Differential global structural changes in the core particle of yeast and mouse proteasome induced by ligand binding

PubMed Central

Arciniega, Marcelino; Beck, Philipp; Lange, Oliver F.; Groll, Michael; Huber, Robert

2014-01-01

Two clusters of configurations of the main proteolytic subunit β5 were identified by principal component analysis of crystal structures of the yeast proteasome core particle (yCP). The apo-cluster encompasses unliganded species and complexes with nonpeptidic ligands, and the pep-cluster comprises complexes with peptidic ligands. The murine constitutive CP structures conform to the yeast system, with the apo-form settled in the apo-cluster and the PR-957 (a peptidic ligand) complex in the pep-cluster. In striking contrast, the murine immune CP classifies into the pep-cluster in both the apo and the PR-957–liganded species. The two clusters differ essentially by multiple small structural changes and a domain motion enabling enclosure of the peptidic ligand and formation of specific hydrogen bonds in the pep-cluster. The immune CP species is in optimal peptide binding configuration also in its apo form. This favors productive ligand binding and may help to explain the generally increased functional activity of the immunoproteasome. Molecular dynamics simulations of the representative murine species are consistent with the experimentally observed configurations. A comparison of all 28 subunits of the unliganded species with the peptidic liganded forms demonstrates a greatly enhanced plasticity of β5 and suggests specific signaling pathways to other subunits. PMID:24979800

Facile Syntheses of Monodisperse Ultra-Small Au Clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bertino, Massimo F.; Sun, Zhong-Ming; Zhang, Rui

2006-11-02

During our effort to synthesize the tetrahedral Au20 cluster, we found a facile synthetic route to prepare monodisperse suspensions of ultra-small Au clusters AuN (N<12) using diphosphine ligands. In our monophasic and single-pot synthesis, a Au precursor ClAu(I)PPh3 and a bidentate phosphine ligand P(Ph)2(CH2)MP(Ph)2 (Ph = phenyl) are dissolved in an organic solvent. Au(I) is reduced slowly by a borane-tert-butylamine complex to form Au clusters coordinated by the diphosphine ligand. The Au clusters are characterized by both high resolution mass spectrometry and UV-Vis absorption spectroscopy. We found that the mean cluster size obtained depends on the chain length M ofmore » the ligand. In particular, a single monodispersed Au11 cluster is obtained with the P(Ph)2(CH2)3P(Ph)2 ligand, whereas P(Ph)2(CH2)MP(Ph)2 ligands with M = 5 and 6 yield Au10 and Au8 clusters. The simplicity of our synthetic method makes it suitable for large-scale production of nearly monodisperse ultrasmall Au clusters. It is suggested that diphosphines provide a set of flexible ligands to allow size-controlled synthesis of Au nanoparticles.« less

Structures of undecagold clusters: Ligand effect

NASA Astrophysics Data System (ADS)

Spivey, Kasi; Williams, Joseph I.; Wang, Lichang

2006-12-01

The most stable structure of undecagold, or Au 11, clusters was predicted from our DFT calculations to be planar [L. Xiao, L. Wang, Chem. Phys. Lett. 392 (2004) 452; L. Xiao, B. Tollberg, X. Hu, L. Wang, J. Chem. Phys. 124 (2005) 114309.]. The structures of ligand protected undecagold clusters were shown to be three-dimensional experimentally. In this work, we used DFT calculations to study the ligand effect on the structures of Au 11 clusters. Our results show that the most stable structure of Au 11 is in fact three-dimensional when SCH 3 ligands are attached. This indicates that the structures of small gold clusters are altered substantially in the presence of ligands.

A grand unified model for liganded gold clusters

NASA Astrophysics Data System (ADS)

Xu, Wen Wu; Zhu, Beien; Zeng, Xiao Cheng; Gao, Yi

2016-12-01

A grand unified model (GUM) is developed to achieve fundamental understanding of rich structures of all 71 liganded gold clusters reported to date. Inspired by the quark model by which composite particles (for example, protons and neutrons) are formed by combining three quarks (or flavours), here gold atoms are assigned three `flavours' (namely, bottom, middle and top) to represent three possible valence states. The `composite particles' in GUM are categorized into two groups: variants of triangular elementary block Au3(2e) and tetrahedral elementary block Au4(2e), all satisfying the duet rule (2e) of the valence shell, akin to the octet rule in general chemistry. The elementary blocks, when packed together, form the cores of liganded gold clusters. With the GUM, structures of 71 liganded gold clusters and their growth mechanism can be deciphered altogether. Although GUM is a predictive heuristic and may not be necessarily reflective of the actual electronic structure, several highly stable liganded gold clusters are predicted, thereby offering GUM-guided synthesis of liganded gold clusters by design.

Construction of (CuX)2n cluster-containing (X = Br, I; n = 1, 2) coordination polymers assembled by dithioethers ArS(CH2)(m)SAr (Ar = Ph, p-Tol; m = 3, 5): effect of the spacer length, aryl group, and metal-to-ligand ratio on the dimensionality, cluster nuclearity, and the luminescence properties of the metal-organic frameworks.

PubMed

Knorr, Michael; Guyon, Fabrice; Khatyr, Abderrahim; Strohmann, Carsten; Allain, Magali; Aly, Shawkat M; Lapprand, Antony; Fortin, Daniel; Harvey, Pierre D

2012-09-17

Reaction of CuI with bis(phenylthio)propane in a 1:1 ratio yields the two-dimensional coordination polymer [{Cu(μ(2)-I)(2)Cu}{μ-PhS(CH(2))(3)SPh}(2)](n) (1). The 2D-sheet structure of 1 is built up by dimeric Cu(2)I(2) units, which are connected via four bridging 1,3-bis(phenylthio)propane ligands. In contrast, treatment of 2 equiv of CuI with 1,3-bis(phenylthio)propane in MeCN solution affords in a self-assembly reaction the strongly luminescent metal-organic 2D-coordination polymer [Cu(4)I(4){μ-PhS(CH(2))(3)Ph}(2)](n) (2), in which cubane-like Cu(4)(μ(3)-I)(4) cluster units are linked by the dithioether ligands. The crystallographically characterized one-dimensional (1D) compound [{Cu(μ(2)-Br)(2)Cu}{μ-PhS(CH(2))(3)SPh}(2)](n) (3) is obtained using CuBr. The outcome of the reaction of PhS(CH(2))(5)SPh with CuI also depends of the metal-to-ligand ratio employed. Mixing CuI and the dithioether in a 2:1 ratio results in formation of [Cu(4)I(4){μ-PhS(CH(2))(5)Ph}(2)](n) (4) in which cubane-like Cu(4)(μ(3)-I)(4) clusters are linked by the bridging dithioether ligand giving rise to a 1D necklace structure. A ribbon-like 1D-polymer with composition [{Cu(μ(2)-I)(2)Cu}{μ-PhS(CH(2))(5)SPh}(2)](n) (5), incorporating rhomboid Cu(2)I(2) units, is produced upon treatment of CuI with 1,5-bis(phenylthio)pentane in a 1:1 ratio. Reaction of CuBr with PhS(CH(2))(5)SPh produces the isomorphous 1D-compound [{Cu(μ(2)-Br)(2)Cu}{μ-PhS(CH(2))(5)SPh}(2)](n) (6). Strongly luminescent [Cu(4)I(4){μ-p-TolS(CH(2))(5)STol-p}(2)](n) (7) is obtained after mixing 1,5-bis(p-tolylthio)pentane with CuI in a 1:2 ratio, and the 2D-polymer [{Cu(μ(2)-I)(2)Cu}(2){μ-p-TolS(CH(2))(5)STol-p}(2)](n) (8) results from reaction in a 1:1 metal-to-ligand ratio. Under the same reaction conditions, 1D-polymeric [{Cu(μ(2)-Br)(2)Cu}{μ-p-TolS(CH(2))(5)STol-p}(2)](n) (9) is formed using CuBr. This study reveals that the structure of the self-assembly process between CuX and ArS(CH(2))(m)SAr ligands is hard to predict. The solid-state luminescence spectra at 298 and 77 K of 2 and 4 exhibit very strong emissions around 535 and 560 nm, respectively, whereas those for 1 and 5 display weaker ones at about 450 nm. The emission lifetimes are longer for the longer wavelength emissions (>1.0 μs arising from the cubane species) and shorter for the shorter wavelength ones (<1.4 μs arising from the rhomboid units). The Br-containing species are found to be weakly fluorescent.

Functional evaluation of carbohydrate-centred glycoclusters by enzyme-linked lectin assay: ligands for concanavalin A.

PubMed

Köhn, Maja; Benito, Juan M; Ortiz Mellet, Carmen; Lindhorst, Thisbe K; García Fernández, José M

2004-06-07

The affinities of the mannose-specific lectin concanavalin A (Con A) towards D-glucose-centred mannosyl clusters differing in the anomeric configuration of the monosaccharide core, nature of the bridging functional groups and valency, have been measured by a competitive enzyme-linked lectin assay. Pentavalent thioether-linked ligands (5 and 7) were prepared by radical addition of 2,3,4,6-tetra-O-acetyl-1-thio-alpha-D-mannopyranose to the corresponding penta-O-allyl-alpha- or -beta-D-glucopyranose, followed by deacetylation. The distinct reactivity of the anomeric position in the D-glucose scaffold was exploited in the preparation of a tetravalent cluster (10) that keeps a reactive aglyconic group for further manipulation, including incorporation of a reporter group or attachment to a solid support. Hydroboration of the double bonds in the penta-O-allyl-alpha-D-glucopyranose derivative and replacement of the hydroxy groups with amine moieties gave a suitable precursor for the preparation of pentavalent and 15-valent mannosides through the thiourea-bridging reaction (17 and 20, respectively). The diastereomeric 1-thiomannose-coated clusters 5 and 7 were demonstrated to be potent ligands for Con A, with IC(50) values for the inhibition of the Con A-yeast mannan association indicative of 6.4- and 5.5-fold increases in binding affinity (valency-corrected values), respectively, relative to the value for methyl alpha-D-mannopyranoside. The tetravalent cluster 10 exhibited a valency-corrected relative lectin-binding potency virtually identical to that of the homologous pentavalent mannoside 7. In sharp contrast, replacement of the 1-thiomannose wedges of 5 with alpha-D-mannopyranosylthioureido units (17) virtually abolished any multivalent or statistic effects, with a dramatic decrease of binding affinity. The 15-valent ligand 20, possessing classical O-glycosidic linkages, exhibited a twofold increase in lectin affinity relative to the penta-O-(thioglycoside) 5; it is less efficient based on the number of mannose units. The results illustrate the potential of carbohydrates as polyfunctional platforms for glycocluster construction and underline the importance of careful design of the overall architecture in optimising glycocluster recognition by specific lectins.

Scanning the potential energy surface for synthesis of dendrimer-wrapped gold clusters: design rules for true single-molecule nanostructures.

PubMed

Thompson, Damien; Hermes, Jens P; Quinn, Aidan J; Mayor, Marcel

2012-04-24

The formation of true single-molecule complexes between organic ligands and nanoparticles is challenging and requires careful design of molecules with size, shape, and chemical properties tailored for the specific nanoparticle. Here we use computer simulations to describe the atomic-scale structure, dynamics, and energetics of ligand-mediated synthesis and interlinking of 1 nm gold clusters. The models help explain recent experimental results and provide insight into how multidentate thioether dendrimers can be employed for synthesis of true single-ligand-nanoparticle complexes and also nanoparticle-molecule-nanoparticle "dumbbell" nanostructures. Electronic structure calculations reveal the individually weak thioether-gold bonds (325 ± 36 meV), which act collectively through the multivalent (multisite) anchoring to stabilize the ligand-nanoparticle complex (∼7 eV total binding energy) and offset the conformational and solvation penalties involved in this "wrapping" process. Molecular dynamics simulations show that the dendrimer is sufficiently flexible to tolerate the strained conformations and desolvation penalties involved in fully wrapping the particle, quantifying the subtle balance between covalent anchoring and noncovalent wrapping in the assembly of ligand-nanoparticle complexes. The computed preference for binding of a single dendrimer to the cluster reveals the prohibitively high dendrimer desolvation barrier (1.5 ± 0.5 eV) to form the alternative double-dendrimer structure. Finally, the models show formation of an additional electron transfer channel between nitrogen and gold for ligands with a central pyridine unit, which gives a stiff binding orientation and explains the recently measured larger interparticle distances for particles synthesized and interlinked using linear ligands with a central pyridine rather than a benzene moiety. The findings stress the importance of organic-inorganic interactions, the control of which is central to the rational engineering and eventual large-scale production of functional building blocks for nano(bio)electronics.

Ligand Rearrangements at Fe/S Cofactors: Slow Isomerization of a Biomimetic [2Fe-2S] Cluster.

PubMed

Bergner, Marie; Roy, Lisa; Dechert, Sebastian; Neese, Frank; Ye, Shengfa; Meyer, Franc

2017-04-18

Ligand exchange plays an important role in the biogenesis of Fe/S clusters, most prominently during cluster transfer from a scaffold protein to its target protein. Although in vivo and in vitro studies have provided some insight into this process, the microscopic details of the ligand exchange steps are mostly unknown. In this work, the kinetics of the ligand rearrangement in a biomimetic [2Fe-2S] cluster with mixed S/N capping ligands have been studied. Two geometrical isomers of the cluster are present in solution, and mechanistic insight into the isomerization process was obtained by variable-temperature 1 H NMR spectroscopy. Combined experimental and computational results reveal that this is an associative process that involves the coordination of a solvent molecule to one of the ferric ions. The cluster isomerizes at least two orders of magnitude faster in its protonated and mixed-valent states. These findings may contribute to a deeper understanding of cluster transfer and sensing processes occurring in Fe/S cluster biogenesis. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A grand unified model for liganded gold clusters

PubMed Central

Xu, Wen Wu; Zhu, Beien; Zeng, Xiao Cheng; Gao, Yi

2016-01-01

A grand unified model (GUM) is developed to achieve fundamental understanding of rich structures of all 71 liganded gold clusters reported to date. Inspired by the quark model by which composite particles (for example, protons and neutrons) are formed by combining three quarks (or flavours), here gold atoms are assigned three ‘flavours' (namely, bottom, middle and top) to represent three possible valence states. The ‘composite particles' in GUM are categorized into two groups: variants of triangular elementary block Au3(2e) and tetrahedral elementary block Au4(2e), all satisfying the duet rule (2e) of the valence shell, akin to the octet rule in general chemistry. The elementary blocks, when packed together, form the cores of liganded gold clusters. With the GUM, structures of 71 liganded gold clusters and their growth mechanism can be deciphered altogether. Although GUM is a predictive heuristic and may not be necessarily reflective of the actual electronic structure, several highly stable liganded gold clusters are predicted, thereby offering GUM-guided synthesis of liganded gold clusters by design. PMID:27910848

Insights into an original pocket-ligand pair classification: a promising tool for ligand profile prediction.

PubMed

Pérot, Stéphanie; Regad, Leslie; Reynès, Christelle; Spérandio, Olivier; Miteva, Maria A; Villoutreix, Bruno O; Camproux, Anne-Claude

2013-01-01

Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely, some key pocket properties for ligand binding.

Insights into an Original Pocket-Ligand Pair Classification: A Promising Tool for Ligand Profile Prediction

PubMed Central

Reynès, Christelle; Spérandio, Olivier; Miteva, Maria A.; Villoutreix, Bruno O.; Camproux, Anne-Claude

2013-01-01

Pockets are today at the cornerstones of modern drug discovery projects and at the crossroad of several research fields, from structural biology to mathematical modeling. Being able to predict if a small molecule could bind to one or more protein targets or if a protein could bind to some given ligands is very useful for drug discovery endeavors, anticipation of binding to off- and anti-targets. To date, several studies explore such questions from chemogenomic approach to reverse docking methods. Most of these studies have been performed either from the viewpoint of ligands or targets. However it seems valuable to use information from both ligands and target binding pockets. Hence, we present a multivariate approach relating ligand properties with protein pocket properties from the analysis of known ligand-protein interactions. We explored and optimized the pocket-ligand pair space by combining pocket and ligand descriptors using Principal Component Analysis and developed a classification engine on this paired space, revealing five main clusters of pocket-ligand pairs sharing specific and similar structural or physico-chemical properties. These pocket-ligand pair clusters highlight correspondences between pocket and ligand topological and physico-chemical properties and capture relevant information with respect to protein-ligand interactions. Based on these pocket-ligand correspondences, a protocol of prediction of clusters sharing similarity in terms of recognition characteristics is developed for a given pocket-ligand complex and gives high performances. It is then extended to cluster prediction for a given pocket in order to acquire knowledge about its expected ligand profile or to cluster prediction for a given ligand in order to acquire knowledge about its expected pocket profile. This prediction approach shows promising results and could contribute to predict some ligand properties critical for binding to a given pocket, and conversely, some key pocket properties for ligand binding. PMID:23840299

Selective binding and lateral clustering of α5β1 and αvβ3 integrins: Unraveling the spatial requirements for cell spreading and focal adhesion assembly

PubMed Central

Schaufler, Viktoria; Czichos-Medda, Helmi; Hirschfeld-Warnecken, Vera; Neubauer, Stefanie; Rechenmacher, Florian; Medda, Rebecca; Kessler, Horst; Geiger, Benjamin; Spatz, Joachim P.; Cavalcanti-Adam, E. Ada

2016-01-01

ABSTRACT Coordination of the specific functions of α5β1 and αvβ3 integrins is crucial for the precise regulation of cell adhesion, spreading and migration, yet the contribution of differential integrin-specific crosstalk to these processes remains unclear. To determine the specific functions of αvβ3 and α5β1 integrins, we used nanoarrays of gold particles presenting immobilized, integrin-selective peptidomimetic ligands. Integrin binding to the peptidomimetics is highly selective, and cells can spread on both ligands. However, spreading is faster and the projected cell area is greater on α5β1 ligand; both depend on ligand spacing. Quantitative analysis of adhesion plaques shows that focal adhesion size is increased in cells adhering to αvβ3 ligand at 30 and 60 nm spacings. Analysis of αvβ3 and α5β1 integrin clusters indicates that fibrillar adhesions are more prominent in cells adhering to α5β1 ligand, while clusters are mostly localized at the cell margins in cells adhering to αvβ3 ligand. αvβ3 integrin clusters are more pronounced on αvβ3 ligand, though they can also be detected in cells adhering to α5β1 ligand. Furthermore, α5β1 integrin clusters are present in cells adhering to α5β1 ligand, and often colocalize with αvβ3 clusters. Taken together, these findings indicate that the activation of αvβ3 integrin by ligand binding is dispensable for initial adhesion and spreading, but essential to formation of stable focal adhesions. PMID:27003228

Identification of stepped changes of binding affinity during interactions between the disintegrin rhodostomin and integrin αIIbβ3 in living cells using optical tweezers

NASA Astrophysics Data System (ADS)

Hsieh, Chia-Fen; Chang, Bo-Jui; Pai, Chyi-Huey; Chen, Hsuan-Yi; Chi, Sien; Hsu, Long; Tsai, Jin-Wu; Lin, Chi-Hung

2004-10-01

Integrin receptors serve as both mechanical links and signal transduction mediators between the cell and its environment. Experimental evidence demonstrates that conformational changes and lateral clustering of the integrin proteins may affect their binding to ligands and regulate downstream cellular responses; however, experimental links between the structural and functional correlations of the ligand-receptor interactions are not yet elucidated. In the present report, we utilized optical tweezers to measure the dynamic binding between the snake venom rhodostomin, coated on a microparticle and functioned as a ligand, and the membrane receptor integrin alpha(IIb)beta(3) expressed on a Chinese Hamster Ovary (CHO) cell. A progressive increase of total binding affinity was found between the bead and CHO cell in the first 300 sec following optical tweezers-guided contact. Further analysis of the cumulative data revealed the presence of "unit binding force" presumably exerted by a single rhodostomin-integrin pair. Interestingly, two such units were found. Among the measurements of less total binding forces, presumably taken at the early stage of ligand-receptor interactions, a unit of 4.15 pN per molecule pair was derived. This unit force dropped to 2.54 pN per molecule pair toward the later stage of interactions when the total binding forces were relatively large. This stepped change of single molecule pair binding affinity was not found when mutant rhodostomin proteins were used as ligands (a single unit of 1.81 pN per pair was found). These results were interpreted along with the current knowledge about the conformational changes of integrins during the "molecule activation" process.

Understanding and Practical Use of Ligand and Metal Exchange Reactions in Thiolate-Protected Metal Clusters to Synthesize Controlled Metal Clusters.

PubMed

Niihori, Yoshiki; Hossain, Sakiat; Sharma, Sachil; Kumar, Bharat; Kurashige, Wataru; Negishi, Yuichi

2017-05-01

It is now possible to accurately synthesize thiolate (SR)-protected gold clusters (Au n (SR) m ) with various chemical compositions with atomic precision. The geometric structure, electronic structure, physical properties, and functions of these clusters are well known. In contrast, the ligand or metal atom exchange reactions between these clusters and other substances have not been studied extensively until recently, even though these phenomena were observed during early studies. Understanding the mechanisms of these reactions could allow desired functional metal clusters to be produced via exchange reactions. Therefore, we have studied the exchange reactions between Au n (SR) m and analogous clusters and other substances for the past four years. The results have enabled us to gain deep understanding of ligand exchange with respect to preferential exchange sites, acceleration means, effect on electronic structure, and intercluster exchange. We have also synthesized several new metal clusters using ligand and metal exchange reactions. In this account, we summarize our research on ligand and metal exchange reactions. © 2017 The Chemical Society of Japan & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular assembly and magnetic dynamics of two novel Dy6 and Dy8 aggregates.

PubMed

Guo, Yun-Nan; Chen, Xiao-Hua; Xue, Shufang; Tang, Jinkui

2012-04-02

Complexation of dysprosium(III) with the heterodonor chelating ligand o-vanillin picolinoylhydrazone (H(2)ovph) in the presence of a carbonato ligand affords two novel Dy(6) and Dy(8) clusters, namely, [Dy(6)(ovph)(4)(Hpvph)(2)Cl(4)(H(2)O)(2)(CO(3))(2)]·CH(3)OH·H(2)O·CH(3)CN (2) and [Dy(8)(ovph)(8)(CO(3))(4)(H(2)O)(8)]·12CH(3)CN·6H(2)O (3). Compound 2 is composed of three petals of the Dy(2) units linked by two carbonato ligands, forming a triangular prism arrangement, while compound 3 possesses an octanuclear core with an unprecedented tub conformation, in which Dy(ovph) fragments are attached to the sides of the carbonato core. The static and dynamic magnetic properties are reported and discussed. In the Dy(6) aggregate, three Dy(2) "skeletons", having been well preserved (see the scheme), contribute to the single-molecule-magnet behavior with a relatively slow tunneling rate, while the Dy(8) cluster only exhibits a rather small relaxation barrier.

Theoretical characterization on the size-dependent electron and hole trapping activity of chloride-passivated CdSe nanoclusters

NASA Astrophysics Data System (ADS)

Cui, Yingqi; Cui, Xianhui; Zhang, Li; Xie, Yujuan; Yang, Mingli

2018-04-01

Ligand passivation is often used to suppress the surface trap states of semiconductor quantum dots (QDs) for their continuous photoluminescence output. The suppression process is related to the electrophilic/nucleophilic activity of surface atoms that varies with the structure and size of QD and the electron donating/accepting nature of ligand. Based on first-principles-based descriptors and cluster models, the electrophilic/nucleophilic activities of bare and chloride-coated CdSe clusters were studied to reveal the suppression mechanism of Cl-passivated QDs and compared to experimental observations. The surface atoms of bare clusters have higher activity than inner atoms and their activity decreases with cluster size. In the ligand-coated clusters, the Cd atom remains as the electrophilic site, while the nucleophilic site of Se atoms is replaced by Cl atoms. The activities of Cd and Cl atoms in the coated clusters are, however, remarkably weaker than those in bare clusters. Cluster size, dangling atoms, ligand coverage, electronegativity of ligand atoms, and solvent (water) were found to have considerable influence on the activity of surface atoms. The suppression of surface trap states in Cl-passivated QDs was attributed to the reduction of electrophilic/nucleophilic activity of Cd/Se/Cl atoms. Both saturation to under-coordinated surface atoms and proper selection for the electron donating/accepting strength of ligands are crucial for eliminating the charge carrier traps. Our calculations predicted a similar suppressing effect of chloride ligands with experiments and provided a simple but effective approach to assess the charge carrier trapping behaviors of semiconductor QDs.

Classification of ligand molecules in PDB with graph match-based structural superposition.

PubMed

Shionyu-Mitsuyama, Clara; Hijikata, Atsushi; Tsuji, Toshiyuki; Shirai, Tsuyoshi

2016-12-01

The fast heuristic graph match algorithm for small molecules, COMPLIG, was improved by adding a structural superposition process to verify the atom-atom matching. The modified method was used to classify the small molecule ligands in the Protein Data Bank (PDB) by their three-dimensional structures, and 16,660 types of ligands in the PDB were classified into 7561 clusters. In contrast, a classification by a previous method (without structure superposition) generated 3371 clusters from the same ligand set. The characteristic feature in the current classification system is the increased number of singleton clusters, which contained only one ligand molecule in a cluster. Inspections of the singletons in the current classification system but not in the previous one implied that the major factors for the isolation were differences in chirality, cyclic conformations, separation of substructures, and bond length. Comparisons between current and previous classification systems revealed that the superposition-based classification was effective in clustering functionally related ligands, such as drugs targeted to specific biological processes, owing to the strictness of the atom-atom matching.

Ab initio metadynamics simulations of oxygen/ligand interactions in organoaluminum clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alnemrat, Sufian; Hooper, Joseph P., E-mail: jphooper@nps.edu

2014-10-14

Car-Parrinello molecular dynamics combined with a metadynamics algorithm is used to study the initial interaction of O{sub 2} with the low-valence organoaluminum clusters Al{sub 4}Cp{sub 4} (Cp=C{sub 5}H{sub 5}) and Al{sub 4}Cp{sub 4}{sup *} (Cp{sup *}=C{sub 5}[CH{sub 3}]{sub 5}). Prior to reaction with the aluminum core, simulations suggest that the oxygen undergoes a hindered crossing of the steric barrier presented by the outer ligand monolayer. A combination of two collective variables based on aluminum/oxygen distance and lateral oxygen displacement was found to produce distinct reactant, product, and transition states for this process. In the methylated cluster with Cp{sup *} ligands,more » a broad transition state of 45 kJ/mol was observed due to direct steric interactions with the ligand groups and considerable oxygen reorientation. In the non-methylated cluster the ligands distort away from the oxidizer, resulting in a barrier of roughly 34 kJ/mol with minimal O{sub 2} reorientation. A study of the oxygen/cluster system fixed in a triplet multiplicity suggests that the spin state does not affect the initial steric interaction with the ligands. The metadynamics approach appears to be a promising means of analyzing the initial steps of such oxidation reactions for ligand-protected clusters.« less

Understanding ligand effects in gold clusters using mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Johnson, Grant E.; Laskin, Julia

This review summarizes recent research on the influence of phosphine ligands on the size, stability, and reactivity of gold clusters synthesized in solution. Sub-nanometer clusters exhibit size- and composition-dependent properties that are unique from those of larger nanoparticles. The highly tunable properties of clusters and their high surface-to-volume ratio make them promising candidates for a variety of technological applications. However, because “each-atom-counts” toward defining cluster properties it is critically important to develop robust synthesis methods to efficiently prepare clusters of predetermined size. For decades phosphines have been known to direct the size-selected synthesis of gold clusters. Despite the preparation ofmore » numerous species it is still not understood how different functional groups at phosphine centers affect the size and properties of gold clusters. Using electrospray ionization mass spectrometry (ESI-MS) it is possible to characterize the effect of ligand substitution on the distribution of clusters formed in solution at defined reaction conditions. In addition, ligand exchange reactions on preformed clusters may be monitored using ESI-MS. Collision induced dissociation (CID) may also be employed to obtain qualitative insight into the fragmentation of mixed ligand clusters and the relative binding energies of differently substituted phosphines. Quantitative ligand binding energies and cluster stability may be determined employing surface induced dissociation (SID) in a custom-built Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR-MS). Rice-Ramsperger-Kassel-Marcus (RRKM) based modeling of the SID data allows dissociation energies and entropy values to be extracted that may be compared with the results of high-level theoretical calculations. The charge reduction and reactivity of atomically precise gold clusters, including partially ligated species generated in the gas-phase by in source CID, on well-defined surfaces may be explored using ion soft landing (SL) in a custom-built instrument combined with in situ time of flight secondary ion mass spectrometry (TOF-SIMS). Jointly, this multipronged experimental approach allows characterization of the full spectrum of relevant phenomena including cluster synthesis, ligand exchange, thermochemistry, surface immobilization, and reactivity. The fundamental insights obtained from this work will facilitate the directed synthesis of gold clusters with predetermined size and properties for specific applications.« less

“Ligands-with-Benefits”: Naphthalene-Substituted Schiff Bases Yielding New Ni II Metal Clusters with Ferromagnetic and Emissive Properties and Undergoing Exciting Transformations

DOE PAGES

Perlepe, Panagiota S.; Cunha-Silva, Luis; Gagnon, Kevin J.; ...

2016-01-20

The initial employment of the fluorescent bridging ligand N-naphthalidene-2-amino-5-chlorobenzoic acid (nacbH 2) in metal cluster chemistry has led to new Ni 12 (1) and Ni 5 (2) clusters with wheel-like and molecular-chain topologies, respectively. The doubly-deprotonated nacb 2- ligands were found to adopt four different coordination modes within 1 and 2. The nature of the ligand has also allowed unexpected organic transformations to occur and ferromagnetic and emission behaviors to emerge. The combined work presented here demonstrates the ability of some "ligands-with-benefits" to yield beautiful structures with exciting topologies and interesting physicochemical properties.

“Ligands-with-Benefits”: Naphthalene-Substituted Schiff Bases Yielding New Ni II Metal Clusters with Ferromagnetic and Emissive Properties and Undergoing Exciting Transformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perlepe, Panagiota S.; Cunha-Silva, Luis; Gagnon, Kevin J.

The initial employment of the fluorescent bridging ligand N-naphthalidene-2-amino-5-chlorobenzoic acid (nacbH 2) in metal cluster chemistry has led to new Ni 12 (1) and Ni 5 (2) clusters with wheel-like and molecular-chain topologies, respectively. The doubly-deprotonated nacb 2- ligands were found to adopt four different coordination modes within 1 and 2. The nature of the ligand has also allowed unexpected organic transformations to occur and ferromagnetic and emission behaviors to emerge. The combined work presented here demonstrates the ability of some "ligands-with-benefits" to yield beautiful structures with exciting topologies and interesting physicochemical properties.

Efficient cluster-based catalysts for asymmetric hydrogenation of α-unsaturated carboxylic acids.

PubMed

Moberg, Viktor; Duquesne, Robin; Contaldi, Simone; Röhrs, Oliver; Nachtigall, Jonny; Damoense, Llewellyn; Hutton, Alan T; Green, Michael; Monari, Magda; Santelia, Daniela; Haukka, Matti; Nordlander, Ebbe

2012-09-24

The new clusters [H(4)Ru(4)(CO)(10)(μ-1,2-P-P)], [H(4)Ru(4)(CO)(10) (1,1-P-P)] and [H(4)Ru(4)(CO)(11)(P-P)] (P-P=chiral diphosphine of the ferrocene-based Josiphos or Walphos ligand families) have been synthesised and characterised. The crystal and molecular structures of eleven clusters reveal that the coordination modes of the diphosphine in the [H(4)Ru(4)(CO)(10)(μ-1,2-P-P)] clusters are different for the Josiphos and the Walphos ligands. The Josiphos ligands bridge a metal-metal bond of the ruthenium tetrahedron in the "conventional" manner, that is, with both phosphine moieties coordinated in equatorial positions relative to a triangular face of the tetrahedron, whereas the phosphine moieties of the Walphos ligands coordinate in one axial and one equatorial position. The differences in the ligand size and the coordination mode between the two types of ligands appear to be reflected in a relative propensity for isomerisation; in solution, the [H(4)Ru(4)(CO)(10)(1,1-Walphos)] clusters isomerise to the corresponding [H(4)Ru(4)(CO)(10)(μ-1,2-Walphos)] clusters, whereas the Josiphos-containing clusters show no tendency to isomerisation in solution. The clusters have been tested as catalysts for asymmetric hydrogenation of four prochiral α-unsaturated carboxylic acids and the prochiral methyl ester (E)-methyl 2-methylbut-2-enoate. High conversion rates (>94%) and selectivities of product formation were observed for almost all catalysts/catalyst precursors. The observed enantioselectivities were low or nonexistent for the Josiphos-containing clusters and catalyst (cluster) recovery was low, suggesting that cluster fragmentation takes place. On the other hand, excellent conversion rates (99-100%), product selectivities (99-100% in most cases) and good enantioselectivities, reaching 90% enantiomeric excess (ee) in certain cases, were observed for the Walphos-containing clusters, and the clusters could be recovered in good yield after completed catalysis. Results from high-pressure NMR and IR studies, catalyst poisoning tests and comparison of catalytic properties of two [H(4)Ru(4)(CO)(10)(μ-1,2-P-P)] clusters (P-P=Walphos ligands) with the analogous mononuclear catalysts [Ru(P-P)(carboxylato)(2)] suggest that these clusters may be the active catalytic species, or direct precursors of an active catalytic cluster species. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tuning the Emission and Quantum Yield of Gold and Silver Nanoclusters Through Ligand Design and Doping

NASA Astrophysics Data System (ADS)

Mishra, Dinesh

Nanoparticles have been extensively studied in the past few decades due to the possibilities they offer in applications ranging from medicine to energy generation. A new class of ultra-small noble metal nanoparticles consisting of tens to hundreds of atoms, commonly known as clusters or nanoclusters, have drawn interest of the research community recently due to their unique optical, electronic and structural properties. Over the past few years, advances have been made in the synthesis of atomically precise noble metal clusters (for example, silver and gold) with distinct optical properties. Their ultra-small size distinguishes them from conventional plasmonic nanoparticles and the properties are very sensitive to the slight variation in the compositon of the cluster, i.e. the number of the metal atoms and/or the nature of the ligands. These clusters are interesting because of their potential applications in field such as sensing, imaging, catalysis, clean energy, photonics, etc. as well as they provide fundamental insight into the evolution of the optical and electronic properties of these clusters. In this project, we explored the strategies to synthesize luminescent metallic clusters of gold and silver and to promote their solubility and stability in aqueous and biological medium. We focused particularly on the thiolate protected clusters due to the higher affinity of gold and silver to sulfur. Lipoic acid (Thioctic acid) is a bio-molecule with a cyclic disulfide ring, which also acts as a chelating ligand. Due to the higher binding affinity of the cyclic disulfide ring to nanocrystal surface, lipoic acid and chemically modified lipoic acid molecules have been widely reported for the synthesis and functionalization of inorganic nanocrystals. Here, we describe the use of bidentate lipoic acid ligands in the one phase growth of luminescent gold and silver nanoclusters. In addition, we have synthesized a new set of monothiol ligands containing PEG and zwitterion for the functionalization of fluorescent clusters. Chapter 1 introduces the fundamental properties of metallic clusters and the origin of these properties from electronic and structural point of view. The optical properties of ultra-small nanocrystals (<2 nm) in comparison to the plasmonic particles is described. In addition, the variation of optical and structural properties from one metal to another as well as one ligand to another is also compared. Chapter 2 describes the synthesis of ultra-small size gold clusters with different optical emission (ranging from blue to red) using photo-activated LA-PEG ligands. The influence of various factors on the growth of the clusters is also studied. Optical properties of the clusters were studied by UV-visible absorption, PL emission and excitation and time resolved fluorescence spectroscopy. XPS and DOSY NMR were used to characterize the oxidation states and sizes of these clusters. The photo-chemical transformation of LA-PEG ligands to thiols and the effect of various experimental parameters such as solvent, oxygen, ligand functional group and effect of acid are described in chapter 3. Thiol yield percentage was quantified using ellman assay. Chapter 4 describes the one phase aqueous synthesis of Ag29 clusters capped with bidentate dihydrolipoic acid (DHLA). We also describe the drastic enhancement of the PL intensity upon gold doping of the Ag29 clusters. Optical properties along with the size characterization by electrospray ionization mass spectrometry is also described. We further describe the growth of these clusters using DHLA-PEG molecules. Chapter 5 describes the synthesis of highly fluorescent Au25-xAgx clusters stabilized with two types of ligands (triphenylphosphine and thiols). We designed a set of monothiolate ligands appended with PEG and zwitterionic moieties. This approach allows to prepare water soluble and stable metallic clusters with enhanced photoluminescence and well defined optical properties. Chapter 6 is the overall summary of our findings and prospects and outlook.

Growth of fluorescence gold clusters using photo-chemically activated ligands

NASA Astrophysics Data System (ADS)

Mishra, Dinesh; Aldeek, Fadi; Michael, Serge; Palui, Goutam; Mattoussi, Hedi

2016-03-01

Ligands made of lipoic acid (LA) appended with a polyethylene glycol (PEG) chain have been used in the aqueous phase growth of luminescent gold clusters with distinct emission from yellow to near-IR, using two different routes. In the first route, the gold-ligand complex was chemically reduced using sodium borohydride in alkaline medium, which gave near- IR luminescent gold clusters with maximum emission around 745 nm. In the second method, LA-PEG ligand was photochemically modified to a mixture of thiols, oligomers and oxygenated species under UV-irradiation, which was then used as both reducing agent and stabilizing ligand. By adjusting the pH, temperature, and time of the reaction, we were able to obtain clusters with two distinct emission properties. Refluxing the gold-ligand complex in alkaline medium in the presence of excess ligand gave yellow emission within the first two hours and the emission shifted to red after overnight reaction. Mass spectrometry and chemical assay were used to understand the photo-chemical transformation of Lipoic Acid (LA). Mass spectroscopic studies showed the photo-irradiated product contains thiols, oligomers (dimers, trimers and tetramers) as well as oxygenated species. The amount of thiol formed under different conditions of irradiation was estimated using Ellman's assay.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yi, Xiu-Chun; Xi, Fu-Gui; Wang, Kun

From a new dicarboxylate ligand, 9H-carbazole-2,7-dicarboxylic acid (2,7-H{sub 2}CDC), three Zn(II) metal-organic frameworks were synthesized in the absence or presence of ditopic N-donor ligands. They are formulated as [Zn{sub 5}(μ{sub 3}-OH){sub 2}(2,7-CDC){sub 4}(DEF){sub 2}] (1) (DEF=N,N-diethylformamide), [Zn{sub 2}(2,7-CDC){sub 2}(DABCO)(H{sub 2}O)]·5DMF·H{sub 2}O (2) (DABCO=1-diaza-bicyclo[2.2.2]octane, DMF=N,N-dimethylformamide), and [Zn{sub 2}(2,7-CDC){sub 2}(bpea)]·3DMA·2 H{sub 2}O (3) (bpea=1,2-bis(4-pyridyl)ethylane, DMA=N,N-dimethylacetamide). Compounds 1 and 3 display the 3D pcu frameworks. In 1 the unusual pentanuclear [Zn{sub 5}(μ{sub 3}-OH){sub 2}(COO){sub 8}] secondary building units (SBUs) are linked by dicarboxylate ligands. Differently, in 3 the well-known paddle–wheel [Zn{sub 2}(COO){sub 4}] SBUs are linked by dicarboxylate and dipyridyl ligands. Compound 2more » shows the rare self-catenated 3D alb-3,6-C2/c net topology based on the dinuclear paddle–wheel SBU and a mononuclear unit. The stability and fluorescent properties of the compounds have been studied. - Graphical abstract: A new dicarboxylate ligand, 9H-carbazole-2,7-dicarboxylic acid, was used to construct Zn(II) metal-organic frameworks, including a novel self-catenated network with the rare 3D alb-3,6-C2/c net and two pcu-type networks based on an unprecedented pentanuclear clusters and the common paddle–wheel units. The compounds show blue fluorescent properties. Display Omitted - Highlights: • MOFs with a new carbazole-based dicarboxylate ligand. • New pentanuclear [Zn{sub 5}(μ{sub 3}-OH){sub 2}(COO){sub 8}] secondary building unit. • The rare self-catenated 3D alb-3,6-C2/c net.« less

Copper chalcogenide clusters stabilized with ferrocene-based diphosphine ligands.

PubMed

Khadka, Chhatra B; Najafabadi, Bahareh Khalili; Hesari, Mahdi; Workentin, Mark S; Corrigan, John F

2013-06-17

The redox-active diphosphine ligand 1,1'-bis(diphenylphosphino)ferrocene (dppf) has been used to stabilize the copper(I) chalcogenide clusters [Cu12(μ4-S)6(μ-dppf)4] (1), [Cu8(μ4-Se)4(μ-dppf)3] (2), [Cu4(μ4-Te)(μ4-η(2)-Te2)(μ-dppf)2] (3), and [Cu12(μ5-Te)4(μ8-η(2)-Te2)2(μ-dppf)4] (4), prepared by the reaction of the copper(I) acetate coordination complex (dppf)CuOAc (5) with 0.5 equiv of E(SiMe3)2 (E = S, Se, Te). Single-crystal X-ray analyses of complexes 1-4 confirm the presence of {Cu(2x)E(x)} cores stabilized by dppf ligands on their surfaces, where the bidentate ligands adopt bridging coordination modes. The redox chemistry of cluster 1 was examined using cyclic voltammetry and compared to the electrochemistry of the free ligand dppf and the corresponding copper(I) acetate coordination complex 5. Cluster 1 shows the expected consecutive oxidations of the ferrocene moieties, Cu(I) centers, and phosphine of the dppf ligand.

Efficient red luminescence from organic-soluble Au25 clusters by ligand structure modification

NASA Astrophysics Data System (ADS)

Mathew, Ammu; Varghese, Elizabeth; Choudhury, Susobhan; Pal, Samir Kumar; Pradeep, T.

2015-08-01

An efficient method to enhance visible luminescence in a visibly non-luminescent organic-soluble 4-(tert butyl)benzyl mercaptan (SBB)-stabilized Au25 cluster has been developed. This method relies mainly on enhancing the surface charge density on the cluster by creating an additional shell of thiolate on the cluster surface, which enhances visible luminescence. The viability of this method has been demonstrated by imparting red luminescence to various ligand-protected quantum clusters (QCs), observable to the naked eye. The bright red luminescent material derived from Au25SBB18 clusters was characterized using UV-vis and luminescence spectroscopy, TEM, SEM/EDS, XPS, TG, ESI and MALDI mass spectrometry, which collectively proposed an uncommon molecular formula of Au29SBB24S, suggested to be due to different stapler motifs protecting the Au25 core. The critical role of temperature on the emergence of luminescence in QCs has been studied. The restoration of the surface ligand shell on the Au25 cluster and subsequent physicochemical modification to the cluster were probed by various mass spectral and spectroscopic techniques. Our results provide fundamental insights into the ligand characteristics determining luminescence in QCs.An efficient method to enhance visible luminescence in a visibly non-luminescent organic-soluble 4-(tert butyl)benzyl mercaptan (SBB)-stabilized Au25 cluster has been developed. This method relies mainly on enhancing the surface charge density on the cluster by creating an additional shell of thiolate on the cluster surface, which enhances visible luminescence. The viability of this method has been demonstrated by imparting red luminescence to various ligand-protected quantum clusters (QCs), observable to the naked eye. The bright red luminescent material derived from Au25SBB18 clusters was characterized using UV-vis and luminescence spectroscopy, TEM, SEM/EDS, XPS, TG, ESI and MALDI mass spectrometry, which collectively proposed an uncommon molecular formula of Au29SBB24S, suggested to be due to different stapler motifs protecting the Au25 core. The critical role of temperature on the emergence of luminescence in QCs has been studied. The restoration of the surface ligand shell on the Au25 cluster and subsequent physicochemical modification to the cluster were probed by various mass spectral and spectroscopic techniques. Our results provide fundamental insights into the ligand characteristics determining luminescence in QCs. Electronic supplementary information (ESI) available: Additional data on characterization of red luminescent Au29 QC and comparison with parent Au25SBB18 are given. See DOI: 10.1039/c5nr03457d

Ligand induced structural isomerism in phosphine coordinated gold clusters revealed by ion mobility mass spectrometry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ligare, Marshall R.; Baker, Erin S.; Laskin, Julia

Structural isomerism in ligated gold clusters is revealed using electrospray ionization ion mobility spectrometry mass spectrometry. Phosphine ligated Au8 clusters are shown to adopt more “extended” type structures with increasing exchange of methyldiphenylphosphine (MePPh2) for triphenylphosphine (PPh3). These ligand-dependant structure-property relationships are critical to applications of clusters in catalysis.

Polyhydrido Copper Clusters: Synthetic Advances, Structural Diversity, and Nanocluster-to-Nanoparticle Conversion.

PubMed

Dhayal, Rajendra S; van Zyl, Werner E; Liu, C W

2016-01-19

Metal hydride clusters have historically been studied to unravel their aesthetically pleasing molecular structures and interesting properties, especially toward hydrogen related applications. Central to this work is the hydride ligand, H¯, the smallest closed-shell spherical anion known. Two new developments in polyhydrido nanocluster chemistry include the determination of heretofore unknown hydride coordination modes and novel structural constructs, and conversion from the molecular entities to rhombus-shaped copper nanoparticles (CuNPs). These advances, together with hydrogen evolution and catalysis, have provided both experimentalists and theorists with a rich scientific directive to further explore. The isolation of hexameric [{(Ph3P)CuH}6] (Stryker reagent) could be regarded as the springboard for the recent emergence of polyhydrido copper cluster chemistry due to its utilization in a variety of organic chemical transformations. The stability of clusters of various nuclearity was improved through phosphine, pyridine, and carbene type ligands. Our focus lies with the isolation of novel copper (poly)hydride clusters using mostly the phosphor-1,1-dithiolato type ligands. We found such chalcogen-stabilized clusters to be exceptionally air and moisture stable over a wide range of nuclearities (Cu7 to Cu32). In this Account, we (i) report on state-of-the-art copper hydride cluster chemistry, especially with regards to the diverse and novel structural types generally, and newly discovered hydride coordination modes in particular, (ii) demonstrate the indispensable power of neutron diffraction for the unambiguous assignment and location of hydride ligand(s) within a cluster, and (iii) prove unique transformations that can occur not only between well characterized high nuclearity clusters, but also how such clusters can transform to uniquely shaped nanoparticles of several nanometers in diameter through copper hydride reduction. The increase in the number of low- to high-nuclearity hydride clusters allows for different means by which they can be classified. We chose a classification based on the coordination mode of hydride ligand within the cluster. This includes copper clusters associated with bridging (μ2-H) and capping (μ3-H) hydride modes, followed by an interstitial (μ4-H) hydride mode that was introduced for the first time into octa- and hepta-nuclear copper clusters stabilized by dichalcogen-type ligands. This breakthrough provided a means to explore higher nuclearity polyhydrido nanoclusters, which contain both capping (μ3-H) and interstitial (μ(4-6)-H) hydrides. The presence of bidentate ligands having mixed S/P dative sites led to air- and moisture-stable copper hydride nanoclusters. The formation of rhombus-shaped nanoparticles (CuNPs) from copper polyhydrides in the presence of excess borohydrides suggests the presence of metal hydrides as intermediates during the formation of nanoparticles.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersson, Gunther G., E-mail: gunther.andersson@flinders.edu.au, E-mail: vladimir.golovko@canterbury.ac.nz, E-mail: greg.metha@adelaide.edu.au; Al Qahtani, Hassan S.; Golovko, Vladimir B., E-mail: gunther.andersson@flinders.edu.au, E-mail: vladimir.golovko@canterbury.ac.nz, E-mail: greg.metha@adelaide.edu.au

Chemically made, atomically precise phosphine-stabilized clusters Au{sub 9}(PPh{sub 3}){sub 8}(NO{sub 3}){sub 3} were deposited on titania and silica from solutions at various concentrations and the samples heated under vacuum to remove the ligands. Metastable induced electron spectroscopy was used to determine the density of states at the surface, and X-ray photoelectron spectroscopy for analysing the composition of the surface. It was found for the Au{sub 9} cluster deposited on titania that the ligands react with the titania substrate. Based on analysis using the singular value decomposition algorithm, the series of MIE spectra can be described as a linear combination ofmore » 3 base spectra that are assigned to the spectra of the substrate, the phosphine ligands on the substrate, and the Au clusters anchored to titania after removal of the ligands. On silica, the Au clusters show significant agglomeration after heat treatment and no interaction of the ligands with the substrate can be identified.« less

Photo-induced transformation process at gold clusters-semiconductor interface: Implications for the complexity of gold clusters-based photocatalysis

NASA Astrophysics Data System (ADS)

Liu, Siqi; Xu, Yi-Jun

2016-03-01

The recent thrust in utilizing atomically precise organic ligands protected gold clusters (Au clusters) as photosensitizer coupled with semiconductors for nano-catalysts has led to the claims of improved efficiency in photocatalysis. Nonetheless, the influence of photo-stability of organic ligands protected-Au clusters at the Au/semiconductor interface on the photocatalytic properties remains rather elusive. Taking Au clusters-TiO2 composites as a prototype, we for the first time demonstrate the photo-induced transformation of small molecular-like Au clusters to larger metallic Au nanoparticles under different illumination conditions, which leads to the diverse photocatalytic reaction mechanism. This transformation process undergoes a diffusion/aggregation mechanism accompanied with the onslaught of Au clusters by active oxygen species and holes resulting from photo-excited TiO2 and Au clusters. However, such Au clusters aggregation can be efficiently inhibited by tuning reaction conditions. This work would trigger rational structural design and fine condition control of organic ligands protected-metal clusters-semiconductor composites for diverse photocatalytic applications with long-term photo-stability.

Di-μ3-chlorido-tetra-μ2-chlorido-dichloridobis(dimethyl­formamide-κO)hexa­kis­(1H-imidazole-κN 3)tetra­cadmium

PubMed Central

Zhu, Run-Qiang

2011-01-01

The centrosymmetric mol­ecule of the title complex, [Cd4Cl8(C3H4N2)6(C3H7NO)2], contains four CdII atoms, six imidazole, two dimethyl­formamide and eight chloride ligands. The structure shows a novel chloride-bridged tetra­nuclear cadmium quasi-cubane cluster. The coordination geometry of all CdII atoms is distorted octa­hedral, with the two metal atoms in the asymmetric unit in different coordination environments. One of the Cd2+ ions is coordinated by five Cl− ions and by one N atom from an imidazole ligand, while the second is coordinated by three chloride ligands, two N atoms from two imidazole ligands and one O atom from a dimethyl­formamide mol­ecule. Inter­molecular N—H⋯Cl hydrogen bonds link the mol­ecules into a two-dimensional polymeric structure parallel to the ab plane. PMID:22058708

Probing the Properties of Polynuclear Superhalogens without Halogen Ligand via ab Initio Calculations: A Case Study on Double-Bridged [Mg2 (CN)5 ](-1) Anions.

PubMed

Li, Jin-Feng; Li, Miao-Miao; Bai, Hongcun; Sun, Yin-Yin; Li, Jian-Li; Yin, Bing

2015-12-01

An ab initio study of the superhalogen properties of eighteen binuclear double-bridged [Mg2 (CN)5 ](-1) clusters is reported herein by using various theoretical methods. High-level CCSD(T) results indicate that all the clusters possess strong superhalogen properties owing to their high vertical electron detachment energies (VDEs), which exceed 6.8 eV (highest: 8.15 eV). The outer valence Green's function method provides inaccurate relative VDE values; hence, this method is not suitable for this kind of polynuclear superhalogens. Both the HF and MP2 results are generally consistent with the CCSD(T) level regarding the relative VDE values and-especially interesting-the average values of the HF and MP2 VDEs are extremely close to the CCSD(T) results. The distributions of the extra electrons of the anions are mainly aggregated into the terminal CN units. These distributions are apparently different from those of previously reported triple-bridged isomers and may be the reason for the decreased VDE values of the clusters. In addition, comparisons of the VDEs of binuclear and mononuclear superhalogens as well as studies of the thermodynamic stabilities with respect to the detachment of various CN(-1) ligands are also performed. These results confirm that polynuclear structures with pseudohalogen ligands can be considered as probable new superhalogens with enhanced properties. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A role for surface hydrophobicity in protein-protein recognition.

PubMed Central

Young, L.; Jernigan, R. L.; Covell, D. G.

1994-01-01

The role of hydrophobicity as a determinant of protein-protein interactions is examined. Surfaces of apo-protein targets comprising 9 classes of enzymes, 7 antibody fragments, hirudin, growth hormone, and retinol-binding protein, and their associated ligands with available X-ray structures for their complexed forms, are scanned to determine clusters of surface-accessible amino acids. Clusters of surface residues are ranked on the basis of the hydrophobicity of their constituent amino acids. The results indicate that the location of the co-crystallized ligand is commonly found to correspond with one of the strongest hydrophobic clusters on the surface of the target molecule. In 25 of 38 cases, the correspondence is exact, with the position of the most hydrophobic cluster coinciding with more than one-third of the surface buried by the bound ligand. The remaining 13 cases demonstrate this correspondence within the top 6 hydrophobic clusters. These results suggest that surface hydrophobicity can be used to identify regions of a protein's surface most likely to interact with a binding ligand. This fast and simple procedure may be useful for identifying small sets of well-defined loci for possible ligand attachment. PMID:8061602

An Atomically Precise Au10 Ag2 Nanocluster with Red-Near-IR Dual Emission.

PubMed

Lei, Zhen; Guan, Zong-Jie; Pei, Xiao-Li; Yuan, Shang-Fu; Wan, Xian-Kai; Zhang, Jin-Yuan; Wang, Quan-Ming

2016-08-01

A red-near-IR dual-emissive nanocluster with the composition [Au10 Ag2 (2-py-C≡C)3 (dppy)6 ](BF4 )5 (1; 2-py-C≡C is 2-pyridylethynyl, dppy=2-pyridyldiphenylphosphine) has been synthesized. Single-crystal X-ray structural analysis reveals that 1 has a trigonal bipyramidal Au10 Ag2 core that contains a planar Au4 (2-py-C≡C)3 unit sandwiched by two Au3 Ag(dppy)3 motifs. Cluster 1 shows intense red-NIR dual emission in solution. The visible emission originates from metal-to-ligand charge transfer (MLCT) from silver atoms to phosphine ligands in the Au3 Ag(dppy)3 motifs, and the intense NIR emission is associated with the participation of 2-pyridylethynyl in the frontier orbitals of the cluster, which is confirmed by a time-dependent density functional theory (TD-DFT) calculation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantum chemistry of the minimal CdSe clusters

NASA Astrophysics Data System (ADS)

Yang, Ping; Tretiak, Sergei; Masunov, Artëm E.; Ivanov, Sergei

2008-08-01

Colloidal quantum dots are semiconductor nanocrystals (NCs) which have stimulated a great deal of research and have attracted technical interest in recent years due to their chemical stability and the tunability of photophysical properties. While internal structure of large quantum dots is similar to bulk, their surface structure and passivating role of capping ligands (surfactants) are not fully understood to date. We apply ab initio wavefunction methods, density functional theory, and semiempirical approaches to study the passivation effects of substituted phosphine and amine ligands on the minimal cluster Cd2Se2, which is also used to benchmark different computational methods versus high level ab initio techniques. Full geometry optimization of Cd2Se2 at different theory levels and ligand coverage is used to understand the affinities of various ligands and the impact of ligands on cluster structure. Most possible bonding patterns between ligands and surface Cd/Se atoms are considered, including a ligand coordinated to Se atoms. The degree of passivation of Cd and Se atoms (one or two ligands attached to one atom) is also studied. The results suggest that B3LYP/LANL2DZ level of theory is appropriate for the system modeling, whereas frequently used semiempirical methods (such as AM1 and PM3) produce unphysical results. The use of hydrogen atom for modeling of the cluster passivating ligands is found to yield unphysical results as well. Hence, the surface termination of II-VI semiconductor NCs with hydrogen atoms often used in computational models should probably be avoided. Basis set superposition error, zero-point energy, and thermal corrections, as well as solvent effects simulated with polarized continuum model are found to produce minor variations on the ligand binding energies. The effects of Cd-Se complex structure on both the electronic band gap (highest occupied molecular orbital-lowest unoccupied molecular orbital energy difference) and ligand binding energies are systematically examined. The role played by positive charges on ligand binding is also explored. The calculated binding energies for various ligands L are found to decrease in the order OPMe3>OPH3>NH2Me>=NH3>=NMe3>PMe3>PH3 for neutral clusters and OPMe3>OPH3>PMe3>=NMe3>=NH2Me>=NH3>PH3 and OPMe3>OPH3>NH2Me>=NMe3>=PMe3>=NH3>PH3 for single and double ligations of positively charged Cd2Se22+ cluster, respectively.

Photo-induced transformation process at gold clusters-semiconductor interface: Implications for the complexity of gold clusters-based photocatalysis

PubMed Central

Liu, Siqi; Xu, Yi-Jun

2016-01-01

The recent thrust in utilizing atomically precise organic ligands protected gold clusters (Au clusters) as photosensitizer coupled with semiconductors for nano-catalysts has led to the claims of improved efficiency in photocatalysis. Nonetheless, the influence of photo-stability of organic ligands protected-Au clusters at the Au/semiconductor interface on the photocatalytic properties remains rather elusive. Taking Au clusters–TiO2 composites as a prototype, we for the first time demonstrate the photo-induced transformation of small molecular-like Au clusters to larger metallic Au nanoparticles under different illumination conditions, which leads to the diverse photocatalytic reaction mechanism. This transformation process undergoes a diffusion/aggregation mechanism accompanied with the onslaught of Au clusters by active oxygen species and holes resulting from photo-excited TiO2 and Au clusters. However, such Au clusters aggregation can be efficiently inhibited by tuning reaction conditions. This work would trigger rational structural design and fine condition control of organic ligands protected-metal clusters-semiconductor composites for diverse photocatalytic applications with long-term photo-stability. PMID:26947754

Characterization of Intermediate Oxidation States in CO2 Activation

NASA Astrophysics Data System (ADS)

Dodson, Leah G.; Thompson, Michael C.; Weber, J. Mathias

2018-04-01

Redox chemistry during the activation of carbon dioxide involves changing the charge state in a CO2 molecular unit. However, such changes are usually not well described by integer formal charges, and one can think of COO functional units as being in intermediate oxidation states. In this article, we discuss the properties of CO2 and CO2-based functional units in various charge states. Besides covering isolated CO2 and its ions, we describe the CO2-based ionic species formate, oxalate, and carbonate. Finally, we provide an overview of CO2-based functional groups and ligands in clusters and metal-organic complexes.

Keeping the ball rolling: fullerene-like molecular clusters.

PubMed

Kong, Xiang-Jian; Long, La-Sheng; Zheng, Zhiping; Huang, Rong-Bin; Zheng, Lan-Sun

2010-02-16

The discovery of fullerenes in 1985 opened a new chapter in the chemistry of highly symmetric molecules. Fullerene-like metal clusters, characterized by (multi)shell-like structures, are one rapidly developing class of molecules that share this shape. In addition to creating aesthetically pleasing molecular structures, the ordered arrangement of metal atoms within such frameworks provides the opportunity to develop materials with properties not readily achieved in corresponding mononuclear or lower-nuclearity complexes. In this Account, we survey the great variety of fullerene-like metal-containing clusters with an emphasis on their synthetic and structural chemistry, a first step in the discussion of this fascinating field of cluster chemistry. We group the compounds of interest into three categories based on the atomic composition of the cluster core: those with formal metal-metal bonding, those characterized by ligand participation, and those supported by polyoxometalate building blocks. The number of clusters in the first group, containing metal-metal bonds, is relatively small. However, because of the unique and complex bonding scenarios observed for some of these species, these metalloid clusters present a number of research questions with significant ramifications. Because these cores contain molecular clusters of precious metals at the nanoscale, they offer an opportunity to study chemical properties at size ranges from the molecular to nanoscale and to gain insights into the electronic structures and properties of nanomaterials of similar chemical compositions. Clusters of the second type, whose core structures are facilitated by ligand participation, could aid in the development of functional materials. Of particular interest are the magnetic clusters containing both transition and lanthanide elements. A series of such heterometallic clusters that we prepared demonstrates diverse magnetic properties including antiferromagnetism, ferrimagnetism, and ferromagnetism. Considering the diversity of their composition, their distinct electronic structures, and the disparate coordination behaviors of the different metal elements, these materials suggest abundant opportunities for designing multifunctional materials with varied structures. The third type of clusters that we discuss are based on polyoxometalates, in particular those containing pentagonal units. However, unlike in fullerene chemistry, which does not allow the use of discrete pentagonal building blocks, the metal oxide-based pentagonal units can be used as fundamental building blocks for constructing various Keplerate structures. These structures also have a variety of functions, including intriguing magnetic properties in some cases. Coupled with different linking groups, such pentagonal units can be used for the assembly of a large number of spherical molecules whose properties can be tuned and optimized. Although this Account focuses on the topological aspects of fullerene-like metal clusters, we hope that this topical review will stimulate more efforts in the exploratory synthesis of new fullerene-like clusters. More importantly, we hope that further study of the bonding interactions and properties of these molecules will lead to the development of new functional materials.

Three 3D metal coordination polymers based on triazol-functionalized rigid ligand: Synthesis, topological structure and properties

NASA Astrophysics Data System (ADS)

Meng, Lingkun; Liu, Kang; Liang, Chen; Guo, Xiaolei; Han, Xu; Ren, Siyuan; Ma, Dingxuan; Li, Guanghua; Shi, Zhan; Feng, Shouhua

2018-02-01

By using a triazol-functionalized tricarboxylate, three novel metal coordination polymers, namely, [Zn2L(OH)]·0.5H2O (1), [Co2L(OH)(H2O)]·5.5H2O (2), [Cu2(HL)] (3) L = ［5-(3-(4-carboxyphenyl)-5-methyl-4H-1,2,4-triazol-4-yl)isophthalate］ were synthesized under hydrothermal reactions. All the compounds were characterized by element analysis, IR spectroscopy, thermogravimetric analysis, power X-ray diffrcation and single-crystal X-ray diffrcation. Structural analysis reveals that compounds 1 and 2 have 3D networks with flu topologies where rigid trizaol-functionalized ligands as 4-connected nodes and Zn4(COO)6 or Co4(COO)6 clusters serves as 8-connected secondary building units. Compound 3 has 3D network with pcu topology where Cu4(COO)4 clusters serve as 6-connected secondary building units. Gas adsorption studies reveal that desolvated compoud 1 exhibits high H2 absorption capacity at 77 K and highly selective separation abilities of CO2 and C3H8 over CH4 at room temperature. The results suggest that 1 has potential application in gas storage and separation. In addition, the magnetic properties of compound 2 were also investigated.

Analysis of ligand-protein exchange by Clustering of Ligand Diffusion Coefficient Pairs (CoLD-CoP)

NASA Astrophysics Data System (ADS)

Snyder, David A.; Chantova, Mihaela; Chaudhry, Saadia

2015-06-01

NMR spectroscopy is a powerful tool in describing protein structures and protein activity for pharmaceutical and biochemical development. This study describes a method to determine weak binding ligands in biological systems by using hierarchic diffusion coefficient clustering of multidimensional data obtained with a 400 MHz Bruker NMR. Comparison of DOSY spectrums of ligands of the chemical library in the presence and absence of target proteins show translational diffusion rates for small molecules upon interaction with macromolecules. For weak binders such as compounds found in fragment libraries, changes in diffusion rates upon macromolecular binding are on the order of the precision of DOSY diffusion measurements, and identifying such subtle shifts in diffusion requires careful statistical analysis. The "CoLD-CoP" (Clustering of Ligand Diffusion Coefficient Pairs) method presented here uses SAHN clustering to identify protein-binders in a chemical library or even a not fully characterized metabolite mixture. We will show how DOSY NMR and the "CoLD-CoP" method complement each other in identifying the most suitable candidates for lysozyme and wheat germ acid phosphatase.

Dispersed metal cluster catalysts by design. Synthesis, characterization, structure, and performance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arslan, Ilke; Dixon, David A.; Gates, Bruce C.

2015-09-30

To understand the class of metal cluster catalysts better and to lay a foundation for the prediction of properties leading to improved catalysts, we have synthesized metal catalysts with well-defined structures and varied the cluster structures and compositions systematically—including the ligands bonded to the metals. These ligands include supports and bulky organics that are being tuned to control both the electron transfer to or from the metal and the accessibility of reactants to influence catalytic properties. We have developed novel syntheses to prepare these well-defined catalysts with atomic-scale control the environment by choice and placement of ligands and applied state-of-themore » art spectroscopic, microscopic, and computational methods to determine their structures, reactivities, and catalytic properties. The ligands range from nearly flat MgO surfaces to enveloping zeolites to bulky calixarenes to provide controlled coverages of the metal clusters, while also enforcing unprecedented degrees of coordinative unsaturation at the metal site—thereby facilitating bonding and catalysis events at exposed metal atoms. With this wide range of ligand properties and our arsenal of characterization tools, we worked to achieve a deep, fundamental understanding of how to synthesize robust supported and ligand-modified metal clusters with controlled catalytic properties, thereby bridging the gap between active site structure and function in unsupported and supported metal catalysts. We used methods of organometallic and inorganic chemistry combined with surface chemistry for the precise synthesis of metal clusters and nanoparticles, characterizing them at various stages of preparation and under various conditions (including catalytic reaction conditions) and determining their structures and reactivities and how their catalytic properties depend on their compositions and structures. Key characterization methods included IR, NMR, and EXAFS spectroscopies to identify ligands on the metals and their reactions; EXAFS spectroscopy and high-resolution STEM to determine cluster framework structures and changes resulting from reactant treatment and locations of metal atoms on support surfaces; X-ray diffraction crystallography to determine full structures of cluster-ligand combinations in the absence of a support, and TEM with tomographic methods to observe individual metal atoms and determine three-dimensional structures of catalysts. Electronic structure calculations were used to verify and interpret spectra and extend the understanding of reactivity beyond what is measurable experimentally.« less

Development of purely structure-based pharmacophores for the topoisomerase I-DNA-ligand binding pocket

NASA Astrophysics Data System (ADS)

Drwal, Malgorzata N.; Agama, Keli; Pommier, Yves; Griffith, Renate

2013-12-01

Purely structure-based pharmacophores (SBPs) are an alternative method to ligand-based approaches and have the advantage of describing the entire interaction capability of a binding pocket. Here, we present the development of SBPs for topoisomerase I, an anticancer target with an unusual ligand binding pocket consisting of protein and DNA atoms. Different approaches to cluster and select pharmacophore features are investigated, including hierarchical clustering and energy calculations. In addition, the performance of SBPs is evaluated retrospectively and compared to the performance of ligand- and complex-based pharmacophores. SBPs emerge as a valid method in virtual screening and a complementary approach to ligand-focussed methods. The study further reveals that the choice of pharmacophore feature clustering and selection methods has a large impact on the virtual screening hit lists. A prospective application of the SBPs in virtual screening reveals that they can be used successfully to identify novel topoisomerase inhibitors.

Mixed-metal cluster chemistry. 28. Core enlargement of tungsten-iridium clusters with alkynyl, ethyndiyl, and butadiyndiyl reagents.

PubMed

Dalton, Gulliver T; Viau, Lydie; Waterman, Susan M; Humphrey, Mark G; Bruce, Michael I; Low, Paul J; Roberts, Rachel L; Willis, Anthony C; Koutsantonis, George A; Skelton, Brian W; White, Allan H

2005-05-02

Reaction of [WIr3(mu-CO)3(CO)8(eta-C5Me5)] (1c) with [W(C[triple bond]CPh)(CO)3(eta-C5H5)] afforded the edge-bridged tetrahedral cluster [W2Ir3(mu4-eta2-C2Ph)(mu-CO)(CO)9(eta-C5H5)(eta-C5Me5)] (3) and the edge-bridged trigonal-bipyramidal cluster [W3Ir3(mu4-eta2-C2Ph)(mu-eta2-C=CHPh)(Cl)(CO)8(eta-C5Me5)(eta-C5H5)2] (4) in poor to fair yield. Cluster 3 forms by insertion of [W(C[triple bond]CPh)(CO)3(eta-C5H5)] into Ir-Ir and W-Ir bonds, accompanied by a change in coordination mode from a terminally bonded alkynyl to a mu4-eta2 alkynyl ligand. Cluster 4 contains an alkynyl ligand interacting with two iridium atoms and two tungsten atoms in a mu4-eta2 fashion, as well as a vinylidene ligand bridging a W-W bond. Reaction of [WIr3(CO)11(eta-C5H5)] (1a) or 1c with [(eta-C5H5)(CO)2 Ru(C[triple bond]C)Ru(CO)2(eta-C5H5)] afforded [Ru2WIr3(mu5-eta2-C2)(mu-CO)3(CO)7(eta-C5H5)2(eta-C5R5)] [R = H (5a), Me (5c)] in low yield, a structural study of 5a revealing a WIr3 butterfly core capped and spiked by Ru atoms; the diruthenium ethyndiyl precursor has undergone Ru-C scission, with insertion of the C2 unit into a W-Ir bond of the cluster precursor. Reaction of [W2Ir2(CO)10(eta-C5H5)2] with the diruthenium ethyndiyl reagent gave [RuW2Ir2{mu4-eta2-(C2C[triple bond]C)Ru(CO)2(eta-C5H5)}(mu-CO)2(CO)6(eta-C5H5)3] (6) in low yield, a structural study of 6 revealing a butterfly W2Ir2 unit capped by a Ru(eta-C5H5) group resulting from Ru-C scission; the terminal C2 of a new ruthenium-bound butadiyndiyl ligand has been inserted into the W-Ir bond. Reaction between 1a, [WIr3(CO)11(eta-C5H4Me)] (1b), or 1c and [(eta-C5H5)(CO)3W(C[triple bond]CC[triple bond]C)W(CO)3(eta-C5H5)] afforded [W2Ir3{mu4-eta2-(C2C[triple bond]C)W(CO)3(eta-C5H5)}(mu-CO)2(CO)2(eta-C5H5)(eta-C5R5)] [R = H (7a), Me (7c); R5 = H4Me (7b)] in good yield, a structural study of 7c revealing it to be a metallaethynyl analogue of 3.

Ligand cluster-based protein network and ePlatton, a multi-target ligand finder.

PubMed

Du, Yu; Shi, Tieliu

2016-01-01

Small molecules are information carriers that make cells aware of external changes and couple internal metabolic and signalling pathway systems with each other. In some specific physiological status, natural or artificial molecules are used to interact with selective biological targets to activate or inhibit their functions to achieve expected biological and physiological output. Millions of years of evolution have optimized biological processes and pathways and now the endocrine and immune system cannot work properly without some key small molecules. In the past thousands of years, the human race has managed to find many medicines against diseases by trail-and-error experience. In the recent decades, with the deepening understanding of life and the progress of molecular biology, researchers spare no effort to design molecules targeting one or two key enzymes and receptors related to corresponding diseases. But recent studies in pharmacogenomics have shown that polypharmacology may be necessary for the effects of drugs, which challenge the paradigm, 'one drug, one target, one disease'. Nowadays, cheminformatics and structural biology can help us reasonably take advantage of the polypharmacology to design next-generation promiscuous drugs and drug combination therapies. 234,591 protein-ligand interactions were extracted from ChEMBL. By the 2D structure similarity, 13,769 ligand emerged from 156,151 distinct ligands which were recognized by 1477 proteins. Ligand cluster- and sequence-based protein networks (LCBN, SBN) were constructed, compared and analysed. For assisting compound designing, exploring polypharmacology and finding possible drug combination, we integrated the pathway, disease, drug adverse reaction and the relationship of targets and ligand clusters into the web platform, ePlatton, which is available at http://www.megabionet.org/eplatton. Although there were some disagreements between the LCBN and SBN, communities in both networks were largely the same with normalized mutual information at 0.9. The study of target and ligand cluster promiscuity underlying the LCBN showed that light ligand clusters were more promiscuous than the heavy one and that highly connected nodes tended to be protein kinases and involved in phosphorylation. ePlatton considerably reduced the redundancy of the ligand set of targets and made it easy to deduce the possible relationship between compounds and targets, pathways and side effects. ePlatton behaved reliably in validation experiments and also fast in virtual screening and information retrieval.Graphical abstractCluster exemplars and ePlatton's mechanism.

The use of a versatile o-vanilloyl hydrazone ligand to prepare SMM-like Dy3 molecular cluster pair.

PubMed

Xue, Shufang; Zhao, Lang; Guo, Yun-Nan; Zhang, Peng; Tang, Jinkui

2012-09-14

A novel lanthanide molecular cluster pair (MCP), displaying single molecule magnet behaviour, was assembled using the novel o-vanilloyl hydrazone ligand, versatile in terms of denticity, tautomerism and the rotatable C-C bond.

Au13(8e): A secondary block for describing a special group of liganded gold clusters containing icosahedral Au13 motifs

NASA Astrophysics Data System (ADS)

Xu, Wen Wu; Zeng, Xiao Cheng; Gao, Yi

2017-05-01

A grand unified model (GUM) has been proposed recently to understand structure anatomy and evolution of liganded gold clusters. In this work, besides the two types of elementary blocks (triangular Au3(2e) and tetrahedral Au4(2e)), we introduce a secondary block, namely, the icosahedral Au13 with 8e valence electrons, noted as Au13(8e). Using this secondary block, structural anatomy and evolution of a special group of liganded gold nanoclusters containing icosahedral Au13 motifs can be conveniently analyzed. In addition, a new ligand-protected cluster Au49(PR3)10(SR)15Cl2 is predicted to exhibit high chemical and thermal stability, suggesting likelihood of its synthesis in the laboratory.

A scalable and accurate method for classifying protein-ligand binding geometries using a MapReduce approach.

PubMed

Estrada, T; Zhang, B; Cicotti, P; Armen, R S; Taufer, M

2012-07-01

We present a scalable and accurate method for classifying protein-ligand binding geometries in molecular docking. Our method is a three-step process: the first step encodes the geometry of a three-dimensional (3D) ligand conformation into a single 3D point in the space; the second step builds an octree by assigning an octant identifier to every single point in the space under consideration; and the third step performs an octree-based clustering on the reduced conformation space and identifies the most dense octant. We adapt our method for MapReduce and implement it in Hadoop. The load-balancing, fault-tolerance, and scalability in MapReduce allow screening of very large conformation spaces not approachable with traditional clustering methods. We analyze results for docking trials for 23 protein-ligand complexes for HIV protease, 21 protein-ligand complexes for Trypsin, and 12 protein-ligand complexes for P38alpha kinase. We also analyze cross docking trials for 24 ligands, each docking into 24 protein conformations of the HIV protease, and receptor ensemble docking trials for 24 ligands, each docking in a pool of HIV protease receptors. Our method demonstrates significant improvement over energy-only scoring for the accurate identification of native ligand geometries in all these docking assessments. The advantages of our clustering approach make it attractive for complex applications in real-world drug design efforts. We demonstrate that our method is particularly useful for clustering docking results using a minimal ensemble of representative protein conformational states (receptor ensemble docking), which is now a common strategy to address protein flexibility in molecular docking. Copyright © 2012 Elsevier Ltd. All rights reserved.

Exhaustive comparison and classification of ligand-binding surfaces in proteins

PubMed Central

Murakami, Yoichi; Kinoshita, Kengo; Kinjo, Akira R; Nakamura, Haruki

2013-01-01

Many proteins function by interacting with other small molecules (ligands). Identification of ligand-binding sites (LBS) in proteins can therefore help to infer their molecular functions. A comprehensive comparison among local structures of LBSs was previously performed, in order to understand their relationships and to classify their structural motifs. However, similar exhaustive comparison among local surfaces of LBSs (patches) has never been performed, due to computational complexity. To enhance our understanding of LBSs, it is worth performing such comparisons among patches and classifying them based on similarities of their surface configurations and electrostatic potentials. In this study, we first developed a rapid method to compare two patches. We then clustered patches corresponding to the same PDB chemical component identifier for a ligand, and selected a representative patch from each cluster. We subsequently exhaustively as compared the representative patches and clustered them using similarity score, PatSim. Finally, the resultant PatSim scores were compared with similarities of atomic structures of the LBSs and those of the ligand-binding protein sequences and functions. Consequently, we classified the patches into ∼2000 well-characterized clusters. We found that about 63% of these clusters are used in identical protein folds, although about 25% of the clusters are conserved in distantly related proteins and even in proteins with cross-fold similarity. Furthermore, we showed that patches with higher PatSim score have potential to be involved in similar biological processes. PMID:23934772

The electronic structure of Au25 clusters: between discrete and continuous

NASA Astrophysics Data System (ADS)

Katsiev, Khabiboulakh; Lozova, Nataliya; Wang, Lu; Sai Krishna, Katla; Li, Ruipeng; Mei, Wai-Ning; Skrabalak, Sara E.; Kumar, Challa S. S. R.; Losovyj, Yaroslav

2016-08-01

Here, an approach based on synchrotron resonant photoemission is employed to explore the transition between quantization and hybridization of the electronic structure in atomically precise ligand-stabilized nanoparticles. While the presence of ligands maintains quantization in Au25 clusters, their removal renders increased hybridization of the electronic states in the vicinity of the Fermi level. These observations are supported by DFT studies.Here, an approach based on synchrotron resonant photoemission is employed to explore the transition between quantization and hybridization of the electronic structure in atomically precise ligand-stabilized nanoparticles. While the presence of ligands maintains quantization in Au25 clusters, their removal renders increased hybridization of the electronic states in the vicinity of the Fermi level. These observations are supported by DFT studies. Electronic supplementary information (ESI) available: Experimental details including chemicals, sample preparation, and characterization methods. Computation techniques, SV-AUC, GIWAXS, XPS, UPS, MALDI-TOF, ESI data of Au25 clusters. See DOI: 10.1039/c6nr02374f

Coupled protein-ligand dynamics in truncated hemoglobin N from atomistic simulations and transition networks.

PubMed

Cazade, Pierre-André; Berezovska, Ganna; Meuwly, Markus

2015-05-01

The nature of ligand motion in proteins is difficult to characterize directly using experiment. Specifically, it is unclear to what degree these motions are coupled. All-atom simulations are used to sample ligand motion in truncated Hemoglobin N. A transition network analysis including ligand- and protein-degrees of freedom is used to analyze the microscopic dynamics. Clustering of two different subsets of MD trajectories highlights the importance of a diverse and exhaustive description to define the macrostates for a ligand-migration network. Monte Carlo simulations on the transition matrices from one particular clustering are able to faithfully capture the atomistic simulations. Contrary to clustering by ligand positions only, including a protein degree of freedom yields considerably improved coarse grained dynamics. Analysis with and without imposing detailed balance agree closely which suggests that the underlying atomistic simulations are converged with respect to sampling transitions between neighboring sites. Protein and ligand dynamics are not independent from each other and ligand migration through globular proteins is not passive diffusion. Transition network analysis is a powerful tool to analyze and characterize the microscopic dynamics in complex systems. This article is part of a Special Issue entitled Recent developments of molecular dynamics. Copyright © 2014 Elsevier B.V. All rights reserved.

Tuning electronic and magnetic properties of Mn-mullite oxide sub-nanoclusters via MnOn polyhedron units.

PubMed

Li, Hui; Cho, Kyeongjae; Li, Shunfang; Wang, Weichao

2018-06-13

Ternary oxide nano-clusters compared to unary metallic and binary ones potentially exhibit more remarkable properties due to their higher stoichiometric flexibility in addition to cluster size variations. Herein, by combining with the structural searching scheme CALYPSO, we have built a series of Mn-mullite oxide clusters (SmxMnyOz)n {(xyz) = (125); (115); n = 1-4, 8} prior to investigation of their geometric and electronic structures via first-principles calculations. In small size regime (n < 4), (SmxMnyOz)n prefer nonstoichiometric (Sm1Mn1O5)n phases composed of nonmagnetic MnO4 tetrahedrons. When n ≧ 4, the clusters tend to develop as stoichiometric (Sm1Mn2O5)n species, including magnetic MnOn polyhedrons and Mn-Mn dimers, which contribute 3d-orbitals (dz2 and/or dx2-y2) around the Fermi levels. The different magnetic behaviors of nonstoichiometric and stoichiometric species originate from the distinct couplings of MnOn polyhedronal units, wherein Mn atoms experience different ligand fields and thus display different spin states. Such findings enable the tuning of electronic properties and potential applications in heterogeneous catalysis, electrochemical catalysis, and the related fields via engineering cluster size and stoichiometry.

Analysis of ligand-protein exchange by Clustering of Ligand Diffusion Coefficient Pairs (CoLD-CoP).

PubMed

Snyder, David A; Chantova, Mihaela; Chaudhry, Saadia

2015-06-01

NMR spectroscopy is a powerful tool in describing protein structures and protein activity for pharmaceutical and biochemical development. This study describes a method to determine weak binding ligands in biological systems by using hierarchic diffusion coefficient clustering of multidimensional data obtained with a 400 MHz Bruker NMR. Comparison of DOSY spectrums of ligands of the chemical library in the presence and absence of target proteins show translational diffusion rates for small molecules upon interaction with macromolecules. For weak binders such as compounds found in fragment libraries, changes in diffusion rates upon macromolecular binding are on the order of the precision of DOSY diffusion measurements, and identifying such subtle shifts in diffusion requires careful statistical analysis. The "CoLD-CoP" (Clustering of Ligand Diffusion Coefficient Pairs) method presented here uses SAHN clustering to identify protein-binders in a chemical library or even a not fully characterized metabolite mixture. We will show how DOSY NMR and the "CoLD-CoP" method complement each other in identifying the most suitable candidates for lysozyme and wheat germ acid phosphatase. Copyright © 2015 Elsevier Inc. All rights reserved.

Nano-confinement inside molecular metal oxide clusters: Dynamics and modified encapsulation behavior

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Zhe; Daemen, Luke L.; Cheng, Yongqiang

Encapsulation behavior, as well as the presence of internal catalytically-active sites, has been spurring the applications of a 3 nm hollow spherical metal oxide cluster {Mo 132} as an encapsulation host and a nano-reactor. Due to its well-defined and tunable cluster structures, and nano-scaled internal void space comparable to the volumes of small molecules, this cluster provides a good model to study the dynamics of materials under ultra-confinement. Neutron scattering studies suggest that bulky internal ligands inside the cluster show slower and limited dynamics compared to their counterparts in the bulk state, revealing the rigid nature of the skeleton ofmore » the internal ligands. Furthermore, NMR studies indicate that the rigid internal ligands that partially cover the interfacial pore on the molybdenum oxide shells are able to block some large guest molecules from going inside the capsule cluster, which provides a convincing protocol for size-selective encapsulation and separation.« less

Nano-confinement inside molecular metal oxide clusters: Dynamics and modified encapsulation behavior

DOE PAGES

Wang, Zhe; Daemen, Luke L.; Cheng, Yongqiang; ...

2016-08-19

Encapsulation behavior, as well as the presence of internal catalytically-active sites, has been spurring the applications of a 3 nm hollow spherical metal oxide cluster {Mo 132} as an encapsulation host and a nano-reactor. Due to its well-defined and tunable cluster structures, and nano-scaled internal void space comparable to the volumes of small molecules, this cluster provides a good model to study the dynamics of materials under ultra-confinement. Neutron scattering studies suggest that bulky internal ligands inside the cluster show slower and limited dynamics compared to their counterparts in the bulk state, revealing the rigid nature of the skeleton ofmore » the internal ligands. Furthermore, NMR studies indicate that the rigid internal ligands that partially cover the interfacial pore on the molybdenum oxide shells are able to block some large guest molecules from going inside the capsule cluster, which provides a convincing protocol for size-selective encapsulation and separation.« less

PDB-Ligand: a ligand database based on PDB for the automated and customized classification of ligand-binding structures.

PubMed

Shin, Jae-Min; Cho, Doo-Ho

2005-01-01

PDB-Ligand (http://www.idrtech.com/PDB-Ligand/) is a three-dimensional structure database of small molecular ligands that are bound to larger biomolecules deposited in the Protein Data Bank (PDB). It is also a database tool that allows one to browse, classify, superimpose and visualize these structures. As of May 2004, there are about 4870 types of small molecular ligands, experimentally determined as a complex with protein or DNA in the PDB. The proteins that a given ligand binds are often homologous and present the same binding structure to the ligand. However, there are also many instances wherein a given ligand binds to two or more unrelated proteins, or to the same or homologous protein in different binding environments. PDB-Ligand serves as an interactive structural analysis and clustering tool for all the ligand-binding structures in the PDB. PDB-Ligand also provides an easier way to obtain a number of different structure alignments of many related ligand-binding structures based on a simple and flexible ligand clustering method. PDB-Ligand will be a good resource for both a better interpretation of ligand-binding structures and the development of better scoring functions to be used in many drug discovery applications.

Kinetic Investigation of Homogeneous H(2)-D(2) Equilibration Catalyzed by Pt-Au Cluster Compounds. Characterization of the Cluster [(H)Pt(AuPPh(3))(9)](NO(3))(2).

PubMed

Rubinstein, Leon I.; Pignolet, Louis H.

1996-11-06

The new Pt-Au hydrido cluster compound [(H)Pt(AuPPh(3))(9)](NO(3))(2) (3) has been synthesized and characterized by NMR, FABMS, and single-crystal X-ray diffraction [triclinic, P&onemacr;, a = 17.0452(1) Å, b = 17.4045(2) Å, c = 55.2353(1) Å, alpha = 89.891(1) degrees, beta = 85.287(1) degrees, gamma = 75.173(1) degrees, V = 15784.0(2) Å(3), Z = 4 (two molecules in asymmetric unit), residual R = 0.089 for 45 929 observed reflections and 3367 variables, Mo Kalpha radiation]. The Pt(AuP)(9) core geometry is a distorted icosahedron with three vertices vacant. The Pt-Au, Au-Au, and Au-P distances are within the normal ranges observed in other Pt-Au clusters. This cluster is a catalyst for H(2)-D(2) equilibration in homogeneous solution phase and has been used in a general mechanistic study of this reaction catalyzed by Pt-Au clusters. We previously proposed that a key step in the mechanism for catalytic H(2)-D(2) equilibration is the dissociation of a PPh(3) ligand to give a cluster with an open Au site for bonding of H(2) or D(2). This was based on qualitative observations that PPh(3) inhibited the rate of HD production with [Pt(AuPPh(3))(8)](NO(3))(2) (1) as catalyst. In order to test this hypothesis, phosphine inhibition (on the rate of HD production) and phosphine ligand exchange kinetic experiments were carried out with [(H)(PPh(3))Pt(AuPPh(3))(7)](NO(3))(2) (2) and 3. In this paper we show that the rate constant for phosphine dissociation determined from the PPh(3) inhibition rate study of H(2)-D(2) equilibration with cluster 2 is nearly identical to the rate constant for dissociative phosphine ligand exchange. The slower rate for H(2)-D(2) equilibration observed with 3 compared with 2 (5.5 x 10(-3) vs 7.7 x 10(-2) turnover s(-1)) is explained by its smaller rate constant for phosphine dissociation (2.8 x 10(-5) vs 2.9 x 10(-4) s(-1)). The fact that clusters 2 and 3 show similar kinetic behaviors suggests that the PPh(3) dissociation step in the catalytic H(2)-D(2) equilibration is general for 18-electron hydrido Pt-AuPPh(3) clusters.

Probing Ligand Effects on the Redox Energies of [4Fe-4S] Clusters Using Broken-Symmetry Density Functional Theory

DOE Office of Scientific and Technical Information (OSTI.GOV)

Niu, Shuqiang; Ichiye, Toshiko

A central issue in understanding redox properties of iron-sulfur proteins is determining the factors that tune the reduction potentials of the Fe-S clusters. Recently, Solomon and coworkers have shown that the Fe-S bond covalency of protein analogs measured by %L, the percent ligand character of the Fe 3d orbitals, from ligand K-edge X-ray absorption spectroscopy (XAS) correlates with the electrochemical redox potentials. Also, Wang and coworkers have measured electron detachment energies for iron-sulfur clusters without environmental perturbations by gas-phase photoelectron spectroscopy (PES). Here the correlations of the ligand character with redox energy and %L character are examined in [Fe₄S₄L₄]2⁻ clustersmore » with different ligands by broken symmetry density functional theory (BS-DFT) calculations using the B3LYP functional together with PES and XAS experimental results. These gas-phase studies assess ligand effects independently of environmental perturbations and thus provide essential information for computational studies of iron-sulfur proteins. The B3LYP oxidation energies agree well with PES data, and the %L character obtained from natural bond orbital analysis correlates with XAS values, although it systematically underestimates them because of basis set effects. The results show that stronger electron-donating terminal ligands increase %Lt, the percent ligand character from terminal ligands, but decrease %Sb, the percent ligand character from the bridging sulfurs. Because the oxidized orbital has significant Fe-Lt antibonding character, the oxidation energy correlates well with %Lt. However, because the reduced orbital has varying contributions of both Fe-Lt and Fe-Sb antibonding character, the reduction energy does not correlate with either %Lt or %Sb. Overall, BSDFT calculations together with XAS and PES experiments can unravel the complex underlying factors in the redox energy and chemical bonding of the [4Fe-4S] clusters in iron-sulfur proteins.« less

A novel extended architecture with 4 6·6 4 topology based on mixed-valence Wells-Dawson arsenotungstate and mixed-ligand Cu(I) units

NASA Astrophysics Data System (ADS)

Tong, Ruizhan; Ren, Xiaoyu; Li, Zuoxi; Liu, Bin; Hu, Huaiming; Xue, Ganglin; Fu, Feng; Wang, Jiwu

2010-09-01

A novel inorganic-organic hybrid compound based on mixed-valence Wells-Dawson arsenotungstate and mixed-ligand Cu(I) units, Cu 8I(imi) 4(bpy) 6(H 2O)[As 2VW 2VW 16VlO 62]·2H 2O ( 1) (bpy=4,4'-bipydine; imi=imidazole), has been hydrothermally synthesized and characterized by elemental analysis, IR spectroscopy, thermal gravimetric analysis, luminescent spectrum and single crystal X-ray diffraction. Single-crystal X-ray diffraction revealed that four terminal and three bridging oxygen atoms of the Wells-Dawson cluster are coordinated to Cu(I) ions and form an unprecedented hepta-supporting polyoxometalate. The functionalized arsenotungstates are further connected by two kinds of tridentate linkers, Imi-Cu-(bpy)-Cu-(bpy)-Cu-(bpy)-Cu-Imi and Imi-Cu-(bpy)-Cu-(bpy)-Cu-H 2O, to construct a 3D framework with 4 6·6 4 topology. The hybrid material has an intense emission at about 397 nm.

Ligand Effects in Aluminum Cluster based Energetic Materials

DTIC Science & Technology

2017-09-01

was recently reported and the effect of their increased steric bulk is discussed here. Experimental results and density functional theory (DFT...analysis show that these clusters are enthalpically more stable than the Cp* variant, due primarily to non -covalent interactions (NCIs) across ligand...C5Me4iPr), two clusters similar to Al4Cp*4, was recently reported and the effect of their increased steric bulk is discussed here. Experimental

Aqueous sulfate separation by crystallization of sulfate–water clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Custelcean, Radu; Williams, Neil J.; Seipp, Charles A.

An effective approach to separating sulfates from aqueous solutions is based on the crystallization of extended [SO 4(H 2O) 5 2-] n sulfate–water clusters with a bis(guanidinium) ligand. The ligand was generated in situ by hydrazone condensation in water, thus avoiding elaborate syntheses, tedious purifications, and organic solvents. Crystallization of sulfate–water clusters represents an alternative to the now established sulfate separation strategies that involve encapsulating the “naked” anion.

Aqueous sulfate separation by crystallization of sulfate–water clusters

DOE PAGES

Custelcean, Radu; Williams, Neil J.; Seipp, Charles A.

2015-08-07

An effective approach to separating sulfates from aqueous solutions is based on the crystallization of extended [SO 4(H 2O) 5 2-] n sulfate–water clusters with a bis(guanidinium) ligand. The ligand was generated in situ by hydrazone condensation in water, thus avoiding elaborate syntheses, tedious purifications, and organic solvents. Crystallization of sulfate–water clusters represents an alternative to the now established sulfate separation strategies that involve encapsulating the “naked” anion.

Classification of ligand molecules in PDB with fast heuristic graph match algorithm COMPLIG.

PubMed

Saito, Mihoko; Takemura, Naomi; Shirai, Tsuyoshi

2012-12-14

A fast heuristic graph-matching algorithm, COMPLIG, was devised to classify the small-molecule ligands in the Protein Data Bank (PDB), which are currently not properly classified on structure basis. By concurrently classifying proteins and ligands, we determined the most appropriate parameter for categorizing ligands to be more than 60% identity of atoms and bonds between molecules, and we classified 11,585 types of ligands into 1946 clusters. Although the large clusters were composed of nucleotides or amino acids, a significant presence of drug compounds was also observed. Application of the system to classify the natural ligand status of human proteins in the current database suggested that, at most, 37% of the experimental structures of human proteins were in complex with natural ligands. However, protein homology- and/or ligand similarity-based modeling was implied to provide models of natural interactions for an additional 28% of the total, which might be used to increase the knowledge of intrinsic protein-metabolite interactions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Low oxidation state aluminum-containing cluster anions: Cp{sup ∗}Al{sub n}H{sup −}, n = 1–3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Xinxing; Ganteför, Gerd; Bowen, Kit, E-mail: AKandalam@wcupa.edu, E-mail: kbowen@jhu.edu

Three new, low oxidation state, aluminum-containing cluster anions, Cp*Al{sub n}H{sup −}, n = 1–3, were prepared via reactions between aluminum hydride cluster anions, Al{sub n}H{sub m}{sup −}, and Cp*H ligands. These were characterized by mass spectrometry, anion photoelectron spectroscopy, and density functional theory based calculations. Agreement between the experimentally and theoretically determined vertical detachment energies and adiabatic detachment energies validated the computed geometrical structures. Reactions between aluminum hydride cluster anions and ligands provide a new avenue for discovering low oxidation state, ligated aluminum clusters.

Quest for highly connected metal-organic framework platforms: rare-earth polynuclear clusters versatility meets net topology needs.

PubMed

Alezi, Dalal; Peedikakkal, Abdul Malik P; Weseliński, Łukasz J; Guillerm, Vincent; Belmabkhout, Youssef; Cairns, Amy J; Chen, Zhijie; Wojtas, Łukasz; Eddaoudi, Mohamed

2015-04-29

Gaining control over the assembly of highly porous rare-earth (RE) based metal-organic frameworks (MOFs) remains challenging. Here we report the latest discoveries on our continuous quest for highly connected nets. The topological exploration based on the noncompatibility of a 12-connected RE polynuclear carboxylate-based cluster, points of extension matching the 12 vertices of the cuboctahedron (cuo), with 3-connected organic ligands led to the discovery of two fascinating and highly connected minimal edge-transitive nets, pek and aea. The reduced symmetry of the employed triangular tricarboxylate ligand, as compared to the prototype highly symmetrical 1,3,5-benzene(tris)benzoic acid guided the concurrent occurrence of nonanuclear [RE9(μ3-OH)12(μ3-O)2(O2C-)12] and hexanuclear [RE6(OH)8(O2C-)8] carboxylate-based clusters as 12-connected and 8-connected molecular building blocks in the structure of a 3-periodic pek-MOF based on a novel (3,8,12)-c trinodal net. The use of a tricarboxylate ligand with modified angles between carboxylate moieties led to the formation of a second MOF containing solely nonanuclear clusters and exhibiting once more a novel and a highly connected (3,12,12)-c trinodal net with aea topology. Notably, it is the first time that RE-MOFs with double six-membered ring (d6R) secondary building units are isolated, representing therefore a critical step forward toward the design of novel and highly coordinated materials using the supermolecular building layer approach while considering the d6Rs as building pillars. Lastly, the potential of these new MOFs for gas separation/storage was investigated by performing gas adsorption studies of various probe gas molecules over a wide range of pressures. Noticeably, pek-MOF-1 showed excellent volumetric CO2 and CH4 uptakes at high pressures.

Strategies, linkers and coordination polymers for high-performance sorbents

DOEpatents

Matzger, Adam J.; Wong-Foy, Antek G.; Lebel, Oliver

2015-09-15

A linking ligand compound includes three bidentate chemical moieties distributed about a central chemical moiety. Another linking ligand compound includes a bidentate linking ligand and a monodentate chemical moiety. Coordination polymers include a plurality of metal clusters linked together by residues of the linking ligand compounds.

A discrete Cu cluster and a 3D MnII-CuII framework based on assembly of Mn2Cu4 clusters: synthesis, structure and magnetic properties.

PubMed

Chakraborty, Anindita; Escuer, Albert; Ribas, Joan; Maji, Tapas Kumar

2016-10-04

The synthesis, single-crystal structure characterization and detailed magnetic study of a homometallic hexanuclear Cu II cluster [Cu 6 (μ 3 -OH) 2 (ppk) 6 (H 2 O) 2 (NO 3 ) 4 ] (1) and a three-dimensional (3D) compound [{MnCu 2 (dpkO 2 H) 2 (dpkO 2 )N 3 }·(NO 3 )·H 2 O] n (2) (ppk = phenyl-2-pyridyl ketoxime; dpk = di-2-pyridyl ketone) consisting of heterometallic Mn II -Cu II hexanuclear cores as secondary building units are reported in this paper. In compound 1, two symmetry-related Cu 3 triangles consisting of a hydroxido-bridged trinuclear unit, [Cu 3 (μ 3 -OH)(ppk) 3 (H 2 O)(NO 3 )] + , are assembled through nitrate bridging giving rise to the homometallic Cu 6 cluster. Compound 2 contains heterometallic {MnCu} cores, which are further connected to each other through an azido bridging ligand in all the crystallographic directions, resulting in a 3D metal-organic framework. Construction of such a heterometallic 3D framework from {MnCu} units is until now, unknown. Magnetic studies of both 1 and 2 were performed in detail and both compounds show dominant antiferromagnetic interaction in the respective clusters. Compound 1 reveals significant spin frustration and anti-symmetric exchange interaction in the trinuclear cores, with a significantly high value of J av (-655 cm -1 ). Furthermore, compound 2 exhibits a dominant antiferromagnetic interaction, which is also supported by an extensive magneto-structural correlation which considers the different magnetic pathways.

Molybdenum-oxide based unique polyprotic nanoacids showing different deprotonations and related assembly processes in solution.

PubMed

Kistler, Melissa L; Liu, Tianbo; Gouzerh, Pierre; Todea, Ana Maria; Müller, Achim

2009-07-14

We report the self-assembly processes in solution of three Keplerate-type molybdenum-oxide based clusters {Mo72V30}, {Mo72Cr30} and {Mo72Fe30} (all with diameters of approximately 2.5 nm). These clusters behave as unique weak polyprotic acids owing to the external water ligands attached to the non-Mo metal centers. Whereas the Cr and Fe clusters have 30 water ligands attached at the 30 M3+ centers pointing outside, {Mo72V30} has 20 water ligands coordinated to vanadium atoms, of which only 10 are pointing outside. The self-assembly processes of the Keplerates leading to supramolecular blackberry-type structures are influenced by the effective charge densities on the cluster surfaces, which can be tuned by the pH values and solvent properties. As expected, {Mo72Cr30} and {Mo72Fe30} behave similarly in aqueous solution due to their analogous structures and in both cases the self-assembly follows the partial deprotonation of the external water ligands attached to the non-Mo metal centers. However, the M-OH2 functionalities differ not only in acidity but also lability, i.e. in different residence times of the H2O ligands. In contrast to {Mo72Cr30} and {Mo72Fe30}, the {Mo72V30} clusters carry a rather large number of negative charges so that their solution properties are different. They exist as discrete macroions in dilute aqueous solution, and form only in mixed water/organic solvent (like acetone) blackberry-type structures whose size increases with acetone content. The comparison of the properties of the clusters allows more general information about the interesting self-assembly phenomenon to be unveiled.

The Design, Synthesis, and Characterization of Open Sites on Metal Clusters

NASA Astrophysics Data System (ADS)

Nigra, Michael Mark

Coordinatively unsaturated corner and edge atoms have been hypothesized to have the highest activity of sites responsible for many catalytic reactions on a metal surface. Recent studies have validated this hypothesis in varied reaction systems. However, quantification of different types of coordinatively unsaturated sites, and elucidation of their individual catalytic rates has remained a largely unresolved challenge when understanding catalysis on metal surfaces. Yet such structure-function knowledge would be invaluable to the design of more active and selective metal-surface catalysts in the future. I investigated the catalytic contributions of undercoordinated sites such as corner and edge atoms are investigated in a model reaction system using organic ligands bound to the gold nanoparticle surface. The catalyst consisted of 4 nm gold nanoparticles on a metal oxide support, using resazurin to resorufin as a model reaction system. My results demonstrate that in this system, corner atom sites are the most undercoordinated sites, and are over an order of magnitude more active when compared to undercoordinated edge atom sites, while terrace sites remain catalytically inactive for the reduction reaction of resazurin to resorufin. Catalytic activity has been also demonstrated for calixarene-bound gold nanoparticles using the reduction of 4-nitrophenol. With the 4-nitrophenol reduction reaction, a comparative study was undertaken to compare calixarene phosphine and calixarene thiol bound 4 nm gold particles. The results of the study suggested that a leached site was responsible for catalysis and not sites on the original gold nanoparticles. Future experiments with calixarene bound gold clusters could investigate ligand effects in reactions where the active site is not a leached or aggregated gold species, possibly in oxidation reactions, where electron-rich gold is hypothesized to be a good catalyst. The results that emphasize the enhanced catalytic activity of undercoordinated sites led me to synthesize small gold clusters consisting of a high fraction of coordinatively unsaturated open sites. This was enabled through an approach that utilized bulky calix[4]arene ligands that are bound to a gold core. Since the size of the calix[4]arene ligand is commensurate with the size of the gold cluster core, the calix[4]arene ligand does not pack closely together on the gold cluster surface. This in turn results in areas of accessible gold atom sites between ligands. Additionally, these calix[4]arene ligands prevent cluster aggregation and electronically tune the gold core in a manner conceptually similar to enzymes affecting reactivity through organic side-chains acting as ligands. I quantified the number of open sites that result from this packing problem on the gold cluster surface, using fluorescence probe chemisorption experiments. The results of these chemisorption measurements support the mechanical model of accessibility whereby accessibility is not dependent on the identity of the functional group, whether it be calixarene phosphines or N-heterocyclic carbenes, bound to the gold surface, but rather to the relative radii of curvature of bound ligands and the gold cluster core. Additional materials characterization was completed with transmission electron microscopy in both bright-field imaging of zeolites, in MCM-22 and delaminated ITQ-2 and UCB-1 materials, and in dark field imaging of glucan coatings on oxide particles. These materials could prove to be interesting materials as to use as supports for the calixarene-bound metal clusters described above or for other metal clusters.

Hydration of a Large Anionic Charge Distribution - Naphthalene-Water Cluster Anions

NASA Astrophysics Data System (ADS)

Weber, J. Mathias; Adams, Christopher L.

2010-06-01

We report the infrared spectra of anionic clusters of naphthalene with up to three water molecules. Comparison of the experimental infrared spectra with theoretically predicted spectra from quantum chemistry calculations allow conclusions regarding the structures of the clusters under study. The first water molecule forms two hydrogen bonds with the π electron system of the naphthalene moiety. Subsequent water ligands interact with both the naphthalene and the other water ligands to form hydrogen bonded networks, similar to other hydrated anion clusters. Naphthalene-water anion clusters illustrate how water interacts with negative charge delocalized over a large π electron system. The clusters are interesting model systems that are discussed in the context of wetting of graphene surfaces and polyaromatic hydrocarbons.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sun, Shengtong; Chevrier, Daniel M.; Zhang, Peng

Amorphous intermediate phases are vital precursors in the crystallization of many biogenic minerals. While inherent short-range orders have been found in amorphous calcium carbonates (ACCs) relating to different crystalline forms, it has never been clarified experimentally whether such orders already exist in very small clusters less than 2 nm in size. Here, we studied the stability and structure of 10,12-pentacosadiynoic acid (PCDA) protected ACC clusters with a core size of ca. 1.4 nm consisting of only seven CaCO 3 units. Ligand concentration and structure are shown to be key factors in stabilizing the ACC clusters. More importantly, even in suchmore » small CaCO 3 entities, a proto-calcite short-range order can be identified but with a relatively high degree of disorder that arises from the very small size of the CaCO 3 core. Our findings support the notion of a structural link between prenucleation clusters, amorphous intermediates, and final crystalline polymorphs, which appears central to the understanding of polymorph selection.« less

Directory of Useful Decoys, Enhanced (DUD-E): Better Ligands and Decoys for Better Benchmarking

PubMed Central

2012-01-01

A key metric to assess molecular docking remains ligand enrichment against challenging decoys. Whereas the directory of useful decoys (DUD) has been widely used, clear areas for optimization have emerged. Here we describe an improved benchmarking set that includes more diverse targets such as GPCRs and ion channels, totaling 102 proteins with 22886 clustered ligands drawn from ChEMBL, each with 50 property-matched decoys drawn from ZINC. To ensure chemotype diversity, we cluster each target’s ligands by their Bemis–Murcko atomic frameworks. We add net charge to the matched physicochemical properties and include only the most dissimilar decoys, by topology, from the ligands. An online automated tool (http://decoys.docking.org) generates these improved matched decoys for user-supplied ligands. We test this data set by docking all 102 targets, using the results to improve the balance between ligand desolvation and electrostatics in DOCK 3.6. The complete DUD-E benchmarking set is freely available at http://dude.docking.org. PMID:22716043

A comprehensive study of catalytic, morphological and electronic properties of ligand-protected gold nanoclusters using XPS, STM, XAFS, and TPD techniques

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wu, Qiyuan; Cen, Jiajie; Zhao, Yue

Ultra-small gold nanoclusters were synthesized via a ligand exchange method and deposited onto different TiO2 supports to study their properties. STM imaging revealed that the as-synthesized gold nanoclusters had 2-D morphology consisting of monolayers of gold atoms. In conclusion, subsequent XPS, XAFS, and CO oxidation TPD results indicated that heat treatments of gold clusters at different temperatures significantly altered their electronic and catalytic properties due to ligand deprotection and cluster agglomeration.

A comprehensive study of catalytic, morphological and electronic properties of ligand-protected gold nanoclusters using XPS, STM, XAFS, and TPD techniques

DOE PAGES

Wu, Qiyuan; Cen, Jiajie; Zhao, Yue; ...

2017-12-08

Ultra-small gold nanoclusters were synthesized via a ligand exchange method and deposited onto different TiO2 supports to study their properties. STM imaging revealed that the as-synthesized gold nanoclusters had 2-D morphology consisting of monolayers of gold atoms. In conclusion, subsequent XPS, XAFS, and CO oxidation TPD results indicated that heat treatments of gold clusters at different temperatures significantly altered their electronic and catalytic properties due to ligand deprotection and cluster agglomeration.

Ligand-free gold atom clusters adsorbed on graphene nano sheets generated by oxidative laser fragmentation in water

NASA Astrophysics Data System (ADS)

Lau, Marcus; Haxhiaj, Ina; Wagener, Philipp; Intartaglia, Romuald; Brandi, Fernando; Nakamura, Junji; Barcikowski, Stephan

2014-08-01

Over three decades after the first synthesis of stabilized Au55-clusters many scientific questions about gold cluster properties are still unsolved and ligand-free colloidal clusters are difficult to fabricate. Here we present a novel route to produce ultra-small gold particles by using a green technique, the laser ablation and fragmentation in water, without using reductive or stabilizing agents at any step of the synthesis. For fabrication only a pulsed laser, a gold-target, pure water, sodium hydroxide and hydrogen peroxide are deployed. The particles are exemplarily hybridized to graphene supports showing that these carbon-free colloidal clusters might serve as versatile building blocks.

Quantum clustering and network analysis of MD simulation trajectories to probe the conformational ensembles of protein-ligand interactions.

PubMed

Bhattacharyya, Moitrayee; Vishveshwara, Saraswathi

2011-07-01

In this article, we present a novel application of a quantum clustering (QC) technique to objectively cluster the conformations, sampled by molecular dynamics simulations performed on different ligand bound structures of the protein. We further portray each conformational population in terms of dynamically stable network parameters which beautifully capture the ligand induced variations in the ensemble in atomistic detail. The conformational populations thus identified by the QC method and verified by network parameters are evaluated for different ligand bound states of the protein pyrrolysyl-tRNA synthetase (DhPylRS) from D. hafniense. The ligand/environment induced re-distribution of protein conformational ensembles forms the basis for understanding several important biological phenomena such as allostery and enzyme catalysis. The atomistic level characterization of each population in the conformational ensemble in terms of the re-orchestrated networks of amino acids is a challenging problem, especially when the changes are minimal at the backbone level. Here we demonstrate that the QC method is sensitive to such subtle changes and is able to cluster MD snapshots which are similar at the side-chain interaction level. Although we have applied these methods on simulation trajectories of a modest time scale (20 ns each), we emphasize that our methodology provides a general approach towards an objective clustering of large-scale MD simulation data and may be applied to probe multistate equilibria at higher time scales, and to problems related to protein folding for any protein or protein-protein/RNA/DNA complex of interest with a known structure.

Emergence of Novel Human Norovirus GII.17 Strains Correlates With Changes in Blockade Antibody Epitopes.

PubMed

Lindesmith, Lisa C; Kocher, Jacob F; Donaldson, Eric F; Debbink, Kari; Mallory, Michael L; Swann, Excel W; Brewer-Jensen, Paul D; Baric, Ralph S

2017-12-05

Human norovirus is a significant public health burden, with >30 genotypes causing endemic levels of disease and strains from the GII.4 genotype causing serial pandemics as the virus evolves new ligand binding and antigenicity features. During 2014-2015, genotype GII.17 cluster IIIb strains emerged as the leading cause of norovirus infection in select global locations. Comparison of capsid sequences indicates that GII.17 is evolving at previously defined GII.4 antibody epitopes. Antigenicity of virus-like particles (VLPs) representative of clusters I, II, and IIIb GII.17 strains were compared by a surrogate neutralization assay based on antibody blockade of ligand binding. Sera from mice immunized with a single GII.17 VLP identified antigenic shifts between each cluster of GII.17 strains. Ligand binding of GII.17 cluster IIIb VLP was blocked only by antisera from mice immunized with cluster IIIb VLPs. Exchange of residues 393-396 from GII.17.2015 into GII.17.1978 ablated ligand binding and altered antigenicity, defining an important varying epitope in GII.17. The capsid sequence changes in GII.17 strains result in loss of blockade antibody binding, indicating that viral evolution, specifically at residues 393-396, may have contributed to the emergence of cluster IIIb strains and the persistence of GII.17 in human populations. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Site-directed mutagenesis of Azotobacter vinelandii ferredoxin I: [Fe-S] cluster-driven protein rearrangement.

PubMed Central

Martín, A E; Burgess, B K; Stout, C D; Cash, V L; Dean, D R; Jensen, G M; Stephens, P J

1990-01-01

Azotobacter vinelandii ferredoxin I is a small protein that contains one [4Fe-4S] cluster and one [3Fe-4S] cluster. Recently the x-ray crystal structure has been redetermined and the fdxA gene, which encodes the protein, has been cloned and sequenced. Here we report the site-directed mutation of Cys-20, which is a ligand of the [4Fe-4S] cluster in the native protein, to alanine and the characterization of the protein product by x-ray crystallographic and spectroscopic methods. The data show that the mutant protein again contains one [4Fe-4S] cluster and one [3Fe-4S] cluster. The new [4Fe-4S] cluster obtains its fourth ligand from Cys-24, a free cysteine in the native structure. The formation of this [4Fe-4S] cluster drives rearrangement of the protein structure. PMID:2153958

Observation of novel photochemistry in the multiphoton ionization of Mo(CO) sub 6 van der Waals clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peifer, W.R.; Garvey, J.F.

1989-07-27

van der Waals clusters of Mo(CO){sub 6} generated in the free-jet expansion of a pulsed beam of seeded helium are subjected to multiphoton ionization and the product ions analyzed by quadrupole mass spectrometry. Oxomolybdenum and dioxomolybdenum ions are observed to be produced with high efficiency. This behavior is in striking contrast to that of metal carbonyl monomers and covalently bound cluster carbonyls, which under complete ligand loss prior to ionization. The observed photochemistry is ascribed to reactions between a photoproduced molybdenum atom and the ligands of neighboring Mo(CO){sub 6} solvent molecules within the van der Waals cluster.

Synthesis, characterization and optical properties of an amino-functionalized gold thiolate cluster: Au10(SPh-pNH2)10.

PubMed

Lavenn, Christophe; Albrieux, Florian; Tuel, Alain; Demessence, Aude

2014-03-15

Research interest in ultra small gold thiolate clusters has been rising in recent years for the challenges they offer to bring together properties of nanoscience and well-defined materials from molecular chemistry. Here, a new atomically well-defined Au10 gold nanocluster surrounded by ten 4-aminothiophenolate ligands is reported. Its synthesis followed the similar conditions reported for the elaboration of Au144(SR)60, but because the reactivity of thiophenol ligands is different from alkanethiol derivates, smaller Au10 clusters were formed. Different techniques, such as ESI-MS, elemental analysis, XRD, TGA, XPS and UV-vis-NIR experiments, have been carried out to determine the Au10(SPh-pNH2)10 formula. Photoemission experiment has been done and reveals that the Au10 clusters are weakly luminescent as opposed to the amino-based ultra-small gold clusters. This observation points out that the emission of gold thiolate clusters is highly dependent on both the structure of the gold core and the type of the ligands at the surface. In addition, ultra-small amino-functionalized clusters offer the opportunity for extended work on self-assembling networks or deposition on substrates for nanotechnologies or catalytic applications. Copyright © 2013 Elsevier Inc. All rights reserved.

Diverse, high-quality test set for the validation of protein-ligand docking performance.

PubMed

Hartshorn, Michael J; Verdonk, Marcel L; Chessari, Gianni; Brewerton, Suzanne C; Mooij, Wijnand T M; Mortenson, Paul N; Murray, Christopher W

2007-02-22

A procedure for analyzing and classifying publicly available crystal structures has been developed. It has been used to identify high-resolution protein-ligand complexes that can be assessed by reconstructing the electron density for the ligand using the deposited structure factors. The complexes have been clustered according to the protein sequences, and clusters have been discarded if they do not represent proteins thought to be of direct interest to the pharmaceutical or agrochemical industry. Rules have been used to exclude complexes containing non-drug-like ligands. One complex from each cluster has been selected where a structure of sufficient quality was available. The final Astex diverse set contains 85 diverse, relevant protein-ligand complexes, which have been prepared in a format suitable for docking and are to be made freely available to the entire research community (http://www.ccdc.cam.ac.uk). The performance of the docking program GOLD against the new set is assessed using a variety of protocols. Relatively unbiased protocols give success rates of approximately 80% for redocking into native structures, but it is possible to get success rates of over 90% with some protocols.

Reactivity of triruthenium thiophyne and furyne clusters: competitive S-C and P-C bond cleavage reactions and the generation of highly unsymmetrical alkyne ligands.

PubMed

Uddin, Md Nazim; Begum, Noorjahan; Hassan, Mohammad R; Hogarth, Graeme; Kabir, Shariff E; Miah, Md Arzu; Nordlander, Ebbe; Tocher, Derek A

2008-11-28

The synthesis and reactivity of the thiophyne and furyne clusters [Ru3(CO)7(mu-dppm)(mu3-eta2-C4H2E)(mu-P(C4H3E)2)(mu-H)] (E = S, O) is reported. Addition of P(C4H3E)3 to [Ru3(CO)10(mu-dppm)] (1) at room temperature in the presence of Me3NO gives simple substitution products [Ru3(CO)9(mu-dppm)(P(C4H3E)3)] (E = S, 2; E = O, 3). Mild thermolysis in the presence of further Me3NO affords the thiophyne and furyne complexes [Ru3(CO)7(mu-dppm)(mu3-eta2-C4H2E)(mu-P(C4H3E)2)(mu-H)] (E = S, 4; E = O, 6) resulting from both carbon-hydrogen and carbon-phosphorus bond activation. In each the C4H2E (E = S, O) ligand donates 4-electrons to the cluster and the rings are tilted with respect to the mu-dppm and the phosphido-bridged open triruthenium unit. Heating 4 at 80 degrees C leads to the formation of the ring-opened cluster [Ru3(CO)5(mu-CO)(mu-dppm)(mu3-eta3-SC4H3)(mu-P(C4H3S)2)] (5) resulting from carbon-sulfur bond scission and carbon-hydrogen bond formation and containing a ring-opened mu3-eta3-1-thia-1,3-butadiene ligand. In contrast, a similar thermolysis of 3 affords the phosphinidene cluster [Ru3(CO)7(mu-dppm)(mu3-eta2-C4H2O)(mu3-P(C4H3O))] (7) resulting from a second phosphorus-carbon bond cleavage and (presumably) elimination of furan. Treatment of 4 and 6 with PPh3 affords the simple phosphine-substituted products [Ru3(CO)6(PPh3)(mu-dppm)(mu3-eta2-C4H2E)(mu-P(C4H3E)2)(mu-H)] (E = S, 8; E = O, 9). Both thiophyne and furyne clusters 4 and 6 readily react with hydrogen bromide to give [Ru3(CO)6Br(mu-Br)(mu-dppm)(mu3-eta2-eta1-C4H2E)(mu-P(C4H3E)2)(mu-H)] (E = S, 10; E = O, 11) containing both terminal and bridging bromides. Here the alkynes bind in a highly unsymmetrical manner with one carbon acting as a bridging alkylidene and the second as a terminally bonded Fisher carbene. As far as we are aware, this binding mode has only previously been noted in ynamine complexes or those with metals in different oxidation states. The crystal structures of seven of these new triruthenium clusters have been carried out, allowing a detailed analysis of the relative orientations of coordinated ligands.

The electronic structure of Au25 clusters: between discrete and continuous.

PubMed

Katsiev, Khabiboulakh; Lozova, Nataliya; Wang, Lu; Sai Krishna, Katla; Li, Ruipeng; Mei, Wai-Ning; Skrabalak, Sara E; Kumar, Challa S S R; Losovyj, Yaroslav

2016-08-21

Here, an approach based on synchrotron resonant photoemission is employed to explore the transition between quantization and hybridization of the electronic structure in atomically precise ligand-stabilized nanoparticles. While the presence of ligands maintains quantization in Au25 clusters, their removal renders increased hybridization of the electronic states in the vicinity of the Fermi level. These observations are supported by DFT studies.

Why do receptor–ligand bonds in cell adhesion cluster into discrete focal-adhesion sites?

DOE PAGES

Gao, Zhiwen; Gao, Yanfei

2016-05-14

We report that cell adhesion often exhibits the clustering of the receptor–ligand bonds into discrete focal-adhesion sites near the contact edge, thus resembling a rosette shape or a contracting membrane anchored by a small number of peripheral forces. The ligands on the extracellular matrix are immobile, and the receptors in the cell plasma membrane consist of two types: high-affinity integrins (that bond to the substrate ligands and are immobile) and low-affinity integrins (that are mobile and not bonded to the ligands). Thus the adhesion energy density is proportional to the high-affinity integrin density. This paper provides a mechanistic explanation formore » the clustering/assembling of the receptor–ligand bonds from two main points: (1) the cellular contractile force leads to the density evolution of these two types of integrins, and results into a large high-affinity integrin density near the contact edge and (2) the front of a propagating crack into a decreasing toughness field will be unstable and wavy. From this fracture mechanics perspective, the chemomechanical equilibrium is reached when a small number of patches with large receptor–ligand bond density are anticipated to form at the cell periphery, as opposed to a uniform distribution of bonds on the entire interface. Finally, cohesive fracture simulations show that the de-adhesion force can be significantly enhanced by this nonuniform bond density field, but the de-adhesion force anisotropy due to the substrate elastic anisotropy is significantly reduced.« less

Why do receptor–ligand bonds in cell adhesion cluster into discrete focal-adhesion sites?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gao, Zhiwen; Gao, Yanfei

We report that cell adhesion often exhibits the clustering of the receptor–ligand bonds into discrete focal-adhesion sites near the contact edge, thus resembling a rosette shape or a contracting membrane anchored by a small number of peripheral forces. The ligands on the extracellular matrix are immobile, and the receptors in the cell plasma membrane consist of two types: high-affinity integrins (that bond to the substrate ligands and are immobile) and low-affinity integrins (that are mobile and not bonded to the ligands). Thus the adhesion energy density is proportional to the high-affinity integrin density. This paper provides a mechanistic explanation formore » the clustering/assembling of the receptor–ligand bonds from two main points: (1) the cellular contractile force leads to the density evolution of these two types of integrins, and results into a large high-affinity integrin density near the contact edge and (2) the front of a propagating crack into a decreasing toughness field will be unstable and wavy. From this fracture mechanics perspective, the chemomechanical equilibrium is reached when a small number of patches with large receptor–ligand bond density are anticipated to form at the cell periphery, as opposed to a uniform distribution of bonds on the entire interface. Finally, cohesive fracture simulations show that the de-adhesion force can be significantly enhanced by this nonuniform bond density field, but the de-adhesion force anisotropy due to the substrate elastic anisotropy is significantly reduced.« less

A comparative analysis of clustering algorithms: O{sub 2} migration in truncated hemoglobin I from transition networks

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cazade, Pierre-André; Berezovska, Ganna; Meuwly, Markus, E-mail: m.meuwly@unibas.ch

2015-01-14

The ligand migration network for O{sub 2}–diffusion in truncated Hemoglobin N is analyzed based on three different clustering schemes. For coordinate-based clustering, the conventional k–means and the kinetics-based Markov Clustering (MCL) methods are employed, whereas the locally scaled diffusion map (LSDMap) method is a collective-variable-based approach. It is found that all three methods agree well in their geometrical definition of the most important docking site, and all experimentally known docking sites are recovered by all three methods. Also, for most of the states, their population coincides quite favourably, whereas the kinetics of and between the states differs. One of themore » major differences between k–means and MCL clustering on the one hand and LSDMap on the other is that the latter finds one large primary cluster containing the Xe1a, IS1, and ENT states. This is related to the fact that the motion within the state occurs on similar time scales, whereas structurally the state is found to be quite diverse. In agreement with previous explicit atomistic simulations, the Xe3 pocket is found to be a highly dynamical site which points to its potential role as a hub in the network. This is also highlighted in the fact that LSDMap cannot identify this state. First passage time distributions from MCL clusterings using a one- (ligand-position) and two-dimensional (ligand-position and protein-structure) descriptor suggest that ligand- and protein-motions are coupled. The benefits and drawbacks of the three methods are discussed in a comparative fashion and highlight that depending on the questions at hand the best-performing method for a particular data set may differ.« less

A comparative analysis of clustering algorithms: O2 migration in truncated hemoglobin I from transition networks.

PubMed

Cazade, Pierre-André; Zheng, Wenwei; Prada-Gracia, Diego; Berezovska, Ganna; Rao, Francesco; Clementi, Cecilia; Meuwly, Markus

2015-01-14

The ligand migration network for O2-diffusion in truncated Hemoglobin N is analyzed based on three different clustering schemes. For coordinate-based clustering, the conventional k-means and the kinetics-based Markov Clustering (MCL) methods are employed, whereas the locally scaled diffusion map (LSDMap) method is a collective-variable-based approach. It is found that all three methods agree well in their geometrical definition of the most important docking site, and all experimentally known docking sites are recovered by all three methods. Also, for most of the states, their population coincides quite favourably, whereas the kinetics of and between the states differs. One of the major differences between k-means and MCL clustering on the one hand and LSDMap on the other is that the latter finds one large primary cluster containing the Xe1a, IS1, and ENT states. This is related to the fact that the motion within the state occurs on similar time scales, whereas structurally the state is found to be quite diverse. In agreement with previous explicit atomistic simulations, the Xe3 pocket is found to be a highly dynamical site which points to its potential role as a hub in the network. This is also highlighted in the fact that LSDMap cannot identify this state. First passage time distributions from MCL clusterings using a one- (ligand-position) and two-dimensional (ligand-position and protein-structure) descriptor suggest that ligand- and protein-motions are coupled. The benefits and drawbacks of the three methods are discussed in a comparative fashion and highlight that depending on the questions at hand the best-performing method for a particular data set may differ.

From lin-benzoguanines to lin-benzohypoxanthines as ligands for Zymomonas mobilis tRNA-guanine transglycosylase: replacement of protein-ligand hydrogen bonding by importing water clusters.

PubMed

Barandun, Luzi Jakob; Immekus, Florian; Kohler, Philipp C; Tonazzi, Sandro; Wagner, Björn; Wendelspiess, Severin; Ritschel, Tina; Heine, Andreas; Kansy, Manfred; Klebe, Gerhard; Diederich, François

2012-07-23

The foodborne illness shigellosis is caused by Shigella bacteria that secrete the highly cytotoxic Shiga toxin, which is also formed by the closely related enterohemorrhagic Escherichia coli (EHEC). It has been shown that tRNA-guanine transglycosylase (TGT) is essential for the pathogenicity of Shigella flexneri. Herein, the molecular recognition properties of a guanine binding pocket in Zymomonas mobilis TGT are investigated with a series of lin-benzohypoxanthine- and lin-benzoguanine-based inhibitors that bear substituents to occupy either the ribose-33 or the ribose-34 pocket. The three inhibitor scaffolds differ by the substituent at C(6) being H, NH(2), or NH-alkyl. These differences lead to major changes in the inhibition constants, pK(a) values, and binding modes. Compared to the lin-benzoguanines, with an exocyclic NH(2) at C(6), the lin-benzohypoxanthines without an exocyclic NH(2) group have a weaker affinity as several ionic protein-ligand hydrogen bonds are lost. X-ray cocrystal structure analysis reveals that a new water cluster is imported into the space vacated by the lacking NH(2) group and by a conformational shift of the side chain of catalytic Asp102. In the presence of an N-alkyl group at C(6) in lin-benzoguanine ligands, this water cluster is largely maintained but replacement of one of the water molecules in the cluster leads to a substantial loss in binding affinity. This study provides new insight into the role of water clusters at enzyme active sites and their challenging substitution by ligand parts, a topic of general interest in contemporary structure-based drug design. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role of binding entropy in the refinement of protein-ligand docking predictions: analysis based on the use of 11 scoring functions.

PubMed

Ruvinsky, Anatoly M

2007-06-01

We present results of testing the ability of eleven popular scoring functions to predict native docked positions using a recently developed method (Ruvinsky and Kozintsev, J Comput Chem 2005, 26, 1089) for estimation the entropy contributions of relative motions to protein-ligand binding affinity. The method is based on the integration of the configurational integral over clusters obtained from multiple docked positions. We use a test set of 100 PDB protein-ligand complexes and ensembles of 101 docked positions generated by (Wang et al. J Med Chem 2003, 46, 2287) for each ligand in the test set. To test the suggested method we compared the averaged root-mean square deviations (RMSD) of the top-scored ligand docked positions, accounting and not accounting for entropy contributions, relative to the experimentally determined positions. We demonstrate that the method increases docking accuracy by 10-21% when used in conjunction with the AutoDock scoring function, by 2-25% with G-Score, by 7-41% with D-Score, by 0-8% with LigScore, by 1-6% with PLP, by 0-12% with LUDI, by 2-8% with F-Score, by 7-29% with ChemScore, by 0-9% with X-Score, by 2-19% with PMF, and by 1-7% with DrugScore. We also compared the performance of the suggested method with the method based on ranking by cluster occupancy only. We analyze how the choice of a clustering-RMSD and a low bound of dense clusters impacts on docking accuracy of the scoring methods. We derive optimal intervals of the clustering-RMSD for 11 scoring functions.

Microsolvation of the acetanilide cation (AA(+)) in a nonpolar solvent: IR spectra of AA(+)-L(n) clusters (L = He, Ar, N2; n ≤ 10).

PubMed

Schmies, Matthias; Patzer, Alexander; Schütz, Markus; Miyazaki, Mitsuhiko; Fujii, Masaaki; Dopfer, Otto

2014-05-07

Infrared photodissociation (IRPD) spectra of mass-selected cluster ions of acetanilide (N-phenylacetamide), AA(+)-Ln, with the ligands L = He (n = 1-2), Ar (n = 1-7), and N2 (n = 1-10) are recorded in the hydride stretch (amide A, νNH, νCH) and fingerprint (amide I-III) ranges of AA(+) in its (2)A'' ground electronic state. Cold AA(+)-Ln clusters are generated in an electron impact ion source, which predominantly produces the most stable isomer of a given cluster ion. Systematic vibrational frequency shifts of the N-H stretch fundamentals (νNH) provide detailed information about the sequential microsolvation process of AA(+) in a nonpolar (L = He and Ar) and quadrupolar (L = N2) solvent. In the most stable AA(+)-Ln clusters, the first ligand forms a hydrogen bond (H-bond) with the N-H proton of trans-AA(+) (t-AA(+)), whereas further ligands bind weakly to the aromatic ring (π-stacking). There is no experimental evidence for complexes with the less stable cis-AA(+) isomer. Quantum chemical calculations at the M06-2X/aug-cc-pVTZ level confirm the cluster growth sequence derived from the IR spectra. The calculated binding energies of De(H) = 720 and 1227 cm(-1) for H-bonded and De(π) = 585 and 715 cm(-1) for π-bonded Ar and N2 ligands in t-AA(+)-L are consistent with the observed photofragmentation branching ratios of AA(+)-Ln. Comparison between charged and neutral AA((+))-L dimers indicates that ionization switches the preferred ion-ligand binding motif from π-stacking to H-bonding. Electron removal from the HOMO of AA(+) delocalized over both the aromatic ring and the amide group significantly strengthens the C[double bond, length as m-dash]O bond and weakens the N-H bond of the amide group.

a Moessbauer Effect and Fenske-Hall Molecular Orbital Study of the Electronic Properties of Organoiron Clusters.

NASA Astrophysics Data System (ADS)

Buhl, Margaret Linn

The electronic properties of trinuclear iron, tetranuclear iron butterfly, iron-cobalt, and iron-copper clusters have been studied experimentally at 78K by the Mossbauer effect and theoretically by Fenske-Hall molecular orbital calculations. The Mossbauer effect isomer shift is very sensitive to the differences in the iron s-electron densities in these clusters and, as expected, decreases as the sum of the iron 4s Mulliken population and the Clementi and Raimondi effective nuclear charge increases. The molecular orbital wave functions and the Mulliken atomic charges are used to calculate the electric field gradient at the metal nuclei and the iron Mossbauer effect quadrupole splittings. The valence contribution was found to be the major component of the electric field gradient in all the clusters studied. In general the calculated value of Delta E_ {Q} is larger than the observed value, as a result of neglect of the valence Sternheimer factor, R. The metal charge depends upon its electronegativity and upon the nature of its Lewis base ligands. The carbonyl ligand carbon charge becomes more positive as the metal electronegativity increases. The oxygen charge becomes more negative as the anionic cluster charge increases, and in so doing, yields the maximum anionic charge separation. The electronic properties of the terminal carbonyl ligands are similar to those of carbon monoxide, whereas the electronic properties of the bridging carbonyl ligands are similar to those of the carbonyl group found in aldehydes and ketones.

Voltage clustering in redox-active ligand complexes: mitigating electronic communication through choice of metal ion

DOE PAGES

Zarkesh, Ryan A.; Ichimura, Andrew S.; Monson, Todd C.; ...

2016-02-01

We used the redox-active bis(imino)acenapthene (BIAN) ligand to synthesize homoleptic aluminum, chromium, and gallium complexes of the general formula (BIAN) 3M. The resulting compounds were characterized using X-ray crystallography, NMR, EPR, magnetic susceptibility and cyclic voltammetry measurements and modeled using both DFT and ab initio wavefunction calculations to compare the orbital contributions of main group elements and transition metals in ligand-based redox events. Ultimately, complexes of this type have the potential to improve the energy density and electrolyte stability of grid-scale energy storage technologies, such as redox flow batteries, through thermodynamically-clustered redox events.

Quantum-chemical study of the effect of ligands on the structure and properties of gold clusters

NASA Astrophysics Data System (ADS)

Golosnaya, M. N.; Pichugina, D. A.; Oleinichenko, A. V.; Kuz'menko, N. E.

2017-02-01

The structures of [Au4(dpmp)2X2]2+clusters, where X =-C≡CH,-CH3,-SCH3,-F,-Cl,-Br,-I, dpmp is bis((diphenylphosphino)methyl)(phenyl)phosphine, are calculated at the level of density functional theory with the PBE functional and a modified Dirac-Coulomb-Breit Hamiltonian in an all-electron basis set (Λ). Using the example of [Au4(dpmp)2(C≡CC6H5)2]2+, the interatomic distances and bond angles calculated by means of PBE0/LANL2DZ, TPSS/LANL2DZ, TPSSh/LANL2DZ, and PBE/Λ are compared to X-ray crystallography data. It is shown that PBE/Λ yields the most accurate calculation of the geometrical parameters of this cluster. The ligand effect on the electronic stability of a cluster and the stability in reactions of decomposition into different fragments is studied, along with the capability of ligand exchange. Stability is predicted for [Au4(dpmp)2F2]2+ and [Au4(dpmp)2(SCH3)2]2+, while [Au4(dpmp)2I2]2+ cluster is unstable and its decomposes into two identical fragments is supposed.

Cargo binding promotes KDEL receptor clustering at the mammalian cell surface

PubMed Central

Becker, Björn; Shaebani, M. Reza; Rammo, Domenik; Bubel, Tobias; Santen, Ludger; Schmitt, Manfred J.

2016-01-01

Transmembrane receptor clustering is a ubiquitous phenomenon in pro- and eukaryotic cells to physically sense receptor/ligand interactions and subsequently translate an exogenous signal into a cellular response. Despite that receptor cluster formation has been described for a wide variety of receptors, ranging from chemotactic receptors in bacteria to growth factor and neurotransmitter receptors in mammalian cells, a mechanistic understanding of the underlying molecular processes is still puzzling. In an attempt to fill this gap we followed a combined experimental and theoretical approach by dissecting and modulating cargo binding, internalization and cellular response mediated by KDEL receptors (KDELRs) at the mammalian cell surface after interaction with a model cargo/ligand. Using a fluorescent variant of ricin toxin A chain as KDELR-ligand (eGFP-RTAH/KDEL), we demonstrate that cargo binding induces dose-dependent receptor cluster formation at and subsequent internalization from the membrane which is associated and counteracted by anterograde and microtubule-assisted receptor transport to preferred docking sites at the plasma membrane. By means of analytical arguments and extensive numerical simulations we show that cargo-synchronized receptor transport from and to the membrane is causative for KDELR/cargo cluster formation at the mammalian cell surface. PMID:27353000

Cargo binding promotes KDEL receptor clustering at the mammalian cell surface

NASA Astrophysics Data System (ADS)

Becker, Björn; Shaebani, M. Reza; Rammo, Domenik; Bubel, Tobias; Santen, Ludger; Schmitt, Manfred J.

2016-06-01

Transmembrane receptor clustering is a ubiquitous phenomenon in pro- and eukaryotic cells to physically sense receptor/ligand interactions and subsequently translate an exogenous signal into a cellular response. Despite that receptor cluster formation has been described for a wide variety of receptors, ranging from chemotactic receptors in bacteria to growth factor and neurotransmitter receptors in mammalian cells, a mechanistic understanding of the underlying molecular processes is still puzzling. In an attempt to fill this gap we followed a combined experimental and theoretical approach by dissecting and modulating cargo binding, internalization and cellular response mediated by KDEL receptors (KDELRs) at the mammalian cell surface after interaction with a model cargo/ligand. Using a fluorescent variant of ricin toxin A chain as KDELR-ligand (eGFP-RTAH/KDEL), we demonstrate that cargo binding induces dose-dependent receptor cluster formation at and subsequent internalization from the membrane which is associated and counteracted by anterograde and microtubule-assisted receptor transport to preferred docking sites at the plasma membrane. By means of analytical arguments and extensive numerical simulations we show that cargo-synchronized receptor transport from and to the membrane is causative for KDELR/cargo cluster formation at the mammalian cell surface.

Clustered Integrin Ligands as a Novel Approach for the Targeting of Non-Viral Vectors

NASA Astrophysics Data System (ADS)

Ng, Quinn Kwan Tai

Gene transfer or gene delivery is described as the process in which foreign DNA is introduced into cells. Over the years, gene delivery has gained the attention of many researchers and has been developed as powerful tools for use in biotechnology and medicine. With the completion of the Human Genome Project, such advances in technology allowed for the identification of diseases ranging from hereditary disorders to acquired ones (cancer) which were thought to be incurable. Gene therapy provides the means necessary to treat or eliminate genetic diseases from its origin, unlike traditional medicine which only treat symptoms. With ongoing clinical trials for gene therapy increasing, the greatest difficulty still lies in developing safe systems which can target cells of interest to provide efficient delivery. Nature, over millions of years of evolution, has provided an example of one of the most efficient delivery systems: viruses. Although the use of viruses for gene delivery has been well studied, the safety issues involving immunogenicity, insertional mutagenesis, high cost, and poor reproducibility has provided problems for their clinical application. From understanding viruses, we gain insight to designing new systems for non-viral gene delivery. One of these techniques utilized by adenoviruses is the clustering of ligands on its surface through the use of a protein called a penton base. Through the use of nanotechnology we can mimic this basic concept in non-viral gene delivery systems. This dissertation research is focused on developing and applying a novel system for displaying the integrin binding ligand (RGD) in a constrained manner to form a clustered integrin ligand binding platform to be used to enhance the targeting and efficiency of non-viral gene delivery vectors. Peptide mixed monolayer protected gold nanoparticles provides a suitable surface for ligand clustering. A relationship between the peptide ratios in the reaction solution used to form these ligand clusters compared to the reacted amounts on the surface of the particle was studied. This provided us the ability to control the size of the clusters formed and the spacing between the integrins for gold nanoparticles of various sizes. We then applied the clustered ligand binding system for targeting of DNA/PEI polyplexes and demonstrated that the use of RGD nanoclusters enhances gene transfer up to 35-fold which was dependent on the density of alphavbeta3 integrins on the cell surface. Cell integrin sensitivity was shown in which cells with higher alpha vbeta3 densities resulting in higher luciferase transgene expression. The targeting of RGD nanoclusters for DNA/PEI polyplexes was further shown in vivo using PET/CT technology which displayed improved targeting towards high level alphavbeta3 integrin expression (U87MG) tumors over medium level alphavbeta 3 integrin expression (HeLa). In addition to studying the clustered integrin binding system, the current non-viral vectors used suffer from stability and toxicity issues in vitro and in vivo. We have applied a new chemistry for synthesizing nanogels utilizing a Traut's reagent initiated Michael addition reaction for modification of diamine containing crosslikers which will allow for the development of stable and cell demanded release of oligonucleotides. We have shown bulk gels made were capable of encapsulating and holding DNA within the gel and were able to synthesize them into nanogels. The combined research shown here using clustered integrin ligands and a new type of nanogel synthesis provides an ideal system for gene delivery in the future.

Role of protein-glutathione contacts in defining glutaredoxin-3 [2Fe-2S] cluster chirality, ligand exchange and transfer chemistry.

PubMed

Sen, Sambuddha; Cowan, J A

2017-10-01

Monothiol glutaredoxins (Grx) serve as intermediate cluster carriers in iron-sulfur cluster trafficking. The [2Fe-2S]-bound holo forms of Grx proteins display cysteinyl coordination from exogenous glutathione (GSH), in addition to contact from protein-derived Cys. Herein, we report mechanistic studies that investigate the role of exogenous glutathione in defining cluster chirality, ligand exchange, and the cluster transfer chemistry of Saccharomyces cerevisiae Grx3. Systematic perturbations were introduced to the glutathione-binding site by substitution of conserved charged amino acids that form crucial electrostatic contacts with the glutathione molecule. Native Grx3 could also be reconstituted in the absence of glutathione, with either DTT, BME or free L-cysteine as the source of the exogenous Fe-S ligand contact, while retaining full functional reactivity. The delivery of the [2Fe-2S] cluster to Grx3 from cluster donor proteins such as Isa, Nfu, and a [2Fe-2S](GS) 4 complex, revealed that electrostatic contacts are of key importance for positioning the exogenous glutathione that in turn influences the chiral environment of the cluster. All Grx3 derivatives were reconstituted by standard chemical reconstitution protocols and found to transfer cluster to apo ferredoxin 1 (Fdx1) at rates comparable to native protein, even when using DTT, BME or free L-cysteine as a thiol source in place of GSH during reconstitution. Kinetic analysis of cluster transfer from holo derivatives to apo Fdx1 has led to a mechanistic model for cluster transfer chemistry of native holo Grx3, and identification of the likely rate-limiting step for the reaction.

A new hexanuclear iron-selenium nitrosyl cluster: primary exploration of the preparation methods, structure, and spectroscopic and electrochemical properties.

PubMed

Wang, Rongming; Xu, Wei; Zhang, Jian; Li, Lijuan

2010-06-07

A new hexanuclear iron-selenium nitrosyl cluster, [(n-Bu)(4)N](2)[Fe(6)Se(6)(NO)(6)] (1), and a hexanuclear iron-sulfur nitrosyl cluster, [(n-Bu)(4)N](2)[Fe(6)S(6)(NO)(6)] (2), were synthesized by the solvent-thermal reactions of [(n-Bu)(4)N][Fe(CO)(3)NO] with selenium or sulfur in methanol, while a tetranuclear iron-sulfur nitrosyl cluster, (Me(4)N)[Fe(4)S(3)(NO)(7)] (3), was also prepared by the solvent-thermal reaction of FeCl(2).4H(2)O with thiourea in the presence of (CH(3))(4)NCl, NaNO(2), and methanol. Complexes 1-3 were characterized by IR, UV-vis, (1)H NMR, electrochemistry, and single-crystal X-ray diffraction analysis. IR spectra of complexes 1 and 2 show the characteristic NO stretching frequencies at 1694 and 1698 cm(-1), respectively, while the absorptions of complex 3 appear at 1799, 1744, and 1710 cm(-1). The UV-vis spectra of complexes 1-3 show different bands in the range of 259-562 nm, which are assigned to the transitions between orbitals delocalized over the Fe-S cluster, the ligand-to-metal charge transfer, pi*(NO)-d(Fe), and the metal-to-ligand charge transfer, d(Fe)-pi*(NO). Single-crystal X-ray structural analysis reveals that complex 1 crystallizes in the monoclinic P2(1)/n space group with two molecules per unit cell. Two parallel "chair-shaped" structures, consisting of three iron and three selenium atoms, are connected by Fe-Se bonds with an average distance of 2.341 A; each iron center is bonded to three selenium atoms and a nitrogen atom from the nitrosyl ligand with a pseudotetrahedral center geometry. Cyclic voltammograms of complexes 1 and 2 display two cathodic and three anodic current peaks with an unusually strong cathodic peak. Further electrochemical investigations demonstrated that the intensity of the unusually strong peak is a result of at least three processes. One is the quasi-reversible reduction, and the other two are from an irreversible electrochemical process, in which the compound goes through a typical electron transfer and chemical reaction mechanism. Compound 3 shows three quasi-reversible reductions.

Dimeric [Mo₂S₁₂]²⁻ Cluster: A Molecular Analogue of MoS₂ Edges for Superior Hydrogen-Evolution Electrocatalysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Zhongjie; Luo, Wenjia; Ma, Lu

2015-12-07

Proton reduction is one of the most fundamental and important reactions in nature. MoS2 edges have been identified as the active sites for hydrogen evolution reaction (HER) electrocatalysis. Designing molecular mimics of MoS2 edge sites is an attractive strategy to understand the underlying catalytic mechanism of different edge sites and improve their activities. Herein we report a dimeric molecular analogue [Mo₂S₁₂]²⁻, as the smallest unit possessing both the terminal and bridging disulfide ligands. Our electrochemical tests show that [Mo₂S₁₂]²⁻ is a superior heterogeneous HER catalyst under acidic conditions. Computations suggest that the bridging disulfide ligand of [Mo₂S₁₂]²⁻ exhibits a hydrogenmore » adsorption free energy near zero (-0.05eV). This work helps shed light on the rational design of HER catalysts and biomimetics of hydrogen-evolving enzymes.« less

Application of chiral critical clusters to assymetric synthesis

DOEpatents

Ferrieri, Richard A.

2002-01-01

Disclosed is a composition, a method of making and a method of using critical clusters for asymmetric synthesis using substantially optically-pure chiral solvent molecules in a supercritical fluid. The solvent molecules are capable of forming a multipoint hydrogen bonded solvate as they encage at least one solute molecule. The encaged solute molecule is capable of reacting to form an optically active chiral center. In another aspect, there is disclosed a method of directing the position of bonding between a solute molecule and a ligand involving encaging the solute molecule and the ligand with polar solvent molecules in a supercritical fluid under conditions of temperature and pressure sufficient to change electric charge distribution in the solute molecule. In yet another aspect, disclosed is a method of making pharmaceutical compounds involving encaging a solute molecule, which is capable of forming a chiral center, and a ligand with polar solvent molecules in a supercritical fluid under conditions of temperature and pressure sufficient to change electric charge distribution of the solute molecule. The solute molecule and ligand are then reacted whereby the ligand bonds to the solute molecule forming a chiral center. Also disclosed is a method for racemic resolution using critical clusters involving encaging racemic mixtures of solute molecules with substantially optically-pure chiral solvent molecules in a supercritical fluid under conditions of temperature and pressure sufficient to form critical clusters. The solvent molecules are capable of multipoint hydrogen bonding with the solute molecules. The encaged solute molecules are then nonenzymatically reacted to enhance the optical purity of the solute molecules.

Synthesis, structure and magnetic study of a novel mixed-valent Co(II)10Co(III)4 shield constructed by mixed pyridine-alcoholate ligands.

PubMed

Peng, Yan; Tian, Chong-Bin; Zhang, Hua-Bin; Li, Zhi-Hua; Lin, Ping; Du, Shao-Wu

2012-04-28

A novel tetradecanuclear mixed-valent cobalt cluster, formulated as [Co(II)(10)Co(III)(4)(OH)(2)O(6)(hmp)(10)(pdm)(4)(CH(3)OH)(2)]·5H(2)O (1), was obtained using mixed ligands of 2-(hydroxymethyl)pyridine (hmpH) and 2,6-pyridinedimethanol (pdmH(2)). The cobalt ions in 1 are connected by ten chelating hmp(-) ligands, four tris-chelating pdm(2-) ligands and six μ(3)-oxide/hydroxide anions, forming a unique shield-like planar structure that is rarely observed for Co-based clusters. Compound 1 displays slight frequency dependence at static zero field below 4.5 K, suggesting that it might be a single molecule magnet (SMM). This journal is © The Royal Society of Chemistry 2012

Analysis of protein-protein docking decoys using interaction fingerprints: application to the reconstruction of CaM-ligand complexes.

PubMed

Uchikoga, Nobuyuki; Hirokawa, Takatsugu

2010-05-11

Protein-protein docking for proteins with large conformational changes was analyzed by using interaction fingerprints, one of the scales for measuring similarities among complex structures, utilized especially for searching near-native protein-ligand or protein-protein complex structures. Here, we have proposed a combined method for analyzing protein-protein docking by taking large conformational changes into consideration. This combined method consists of ensemble soft docking with multiple protein structures, refinement of complexes, and cluster analysis using interaction fingerprints and energy profiles. To test for the applicability of this combined method, various CaM-ligand complexes were reconstructed from the NMR structures of unbound CaM. For the purpose of reconstruction, we used three known CaM-ligands, namely, the CaM-binding peptides of cyclic nucleotide gateway (CNG), CaM kinase kinase (CaMKK) and the plasma membrane Ca2+ ATPase pump (PMCA), and thirty-one structurally diverse CaM conformations. For each ligand, 62000 CaM-ligand complexes were generated in the docking step and the relationship between their energy profiles and structural similarities to the native complex were analyzed using interaction fingerprint and RMSD. Near-native clusters were obtained in the case of CNG and CaMKK. The interaction fingerprint method discriminated near-native structures better than the RMSD method in cluster analysis. We showed that a combined method that includes the interaction fingerprint is very useful for protein-protein docking analysis of certain cases.

Polymorphism of Ag29(BDT)12(TPP)43- cluster: interactions of secondary ligands and their effect on solid state luminescence.

PubMed

Nag, Abhijit; Chakraborty, Papri; Bodiuzzaman, Mohammad; Ahuja, Tripti; Antharjanam, Sudhadevi; Pradeep, Thalappil

2018-05-31

We present the first example of polymorphism (cubic & trigonal) in single crystals of an atomically precise monolayer protected cluster, Ag29(BDT)12(TPP)43-. We demonstrate that C-Hπ interactions of the secondary ligands (TPP) are dominant in a cubic lattice compared to a trigonal lattice, resulting in a greater rigidity of the structure, which in turn, results in a higher luminescence efficiency in it.

Multiheteromacrocycles that Complex Metal Ions. Ninth Progress Report (includes results of last three years), 1 May 1980 -- 30 April 1983

DOE R&D Accomplishments Database

Cram, D. J.

1982-09-15

The overall objective of this research is to design, synthesize, and evaluate cyclic and polycyclic host organic compounds for the abilities to complex and lipophilize guest metal ions, their complexes, and their clusters. Host organic compounds consist of strategically placed solvating, coordinating, and ion-pairing sites tied together by covalent bonds through hydrocarbon units around cavities shaped to be occupied by guest metal ions, or by metal ions plus their ligands. Specificity in complexation is sought by matching the following properties of host and guest: cavity and metal ion sizes; geometric arrangements of binding sites; numbers of binding sites; characters of binding sites; and valences. The hope is to synthesize new classes of compounds useful in the separation of metal ions, their complexes, and their clusters.

Spectroscopic and Computational Investigations of Ligand Binding to IspH: Discovery of Non-diphosphate Inhibitors

DOE Office of Scientific and Technical Information (OSTI.GOV)

O'Dowd, Bing; Williams, Sarah; Wang, Hongxin

Isoprenoid biosynthesis is an important area for anti-infective drug development. One isoprenoid target described is (E)-1-hydroxy-2-methyl-but-2-enyl 4-diphosphate (HMBPP) reductase (IspH), which forms isopentenyl diphosphate and dimethylallyl diphosphate from HMBPP in a 2H + /2e - reduction. IspH contains a 4 Fe-4 S cluster, and in this work, we first investigated how small molecules bound to the cluster by using HYSCORE and NRVS spectroscopies. The results of these, as well as other structural and spectroscopic investigations, led to the conclusion that, in most cases, ligands bound to IspH 4 Fe-4 S clusters by η 1 coordination, forming tetrahedral geometries at themore » unique fourth Fe, ligand side chains preventing further ligand (e.g., H 2 O, O 2 ) binding. Based on these ideas, we used in silico methods to find drug-like inhibitors that might occupy the HMBPP substrate binding pocket and bind to Fe, leading to the discovery of a barbituric acid analogue with a K i value of ≈500 nm against Pseudomonas aeruginosa IspH.« less

Stabilizing subnanometer Ag(0) nanoclusters by thiolate and diphosphine ligands and their crystal structures

NASA Astrophysics Data System (ADS)

Yang, Huayan; Wang, Yu; Zheng, Nanfeng

2013-03-01

The combined use of thiolate and diphosphine as surface ligands helps to stabilize subnanometer Ag(0) nanoclusters, resulting in the successful crystallization of two Ag(0)-containing nanoclusters (Ag16 and Ag32) for X-ray single crystal analysis. Both clusters have core-shell structures with Ag86+ and Ag2212+ as their cores, which are not simply either fragments of face-centered cubic metals or their five-fold twinned counterparts. The clusters display UV-Vis absorption spectra consisting of molecule-like optical transitions.The combined use of thiolate and diphosphine as surface ligands helps to stabilize subnanometer Ag(0) nanoclusters, resulting in the successful crystallization of two Ag(0)-containing nanoclusters (Ag16 and Ag32) for X-ray single crystal analysis. Both clusters have core-shell structures with Ag86+ and Ag2212+ as their cores, which are not simply either fragments of face-centered cubic metals or their five-fold twinned counterparts. The clusters display UV-Vis absorption spectra consisting of molecule-like optical transitions. Electronic supplementary information (ESI) available: Experimental details, more pictures of the structure and XPS spectra of the clusters. CCDC 916463 and 916464. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c3nr34328f

Atomically resolved structure of ligand-protected Au{sub 9} clusters on TiO{sub 2} nanosheets using aberration-corrected STEM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al Qahtani, Hassan S.; Andersson, Gunther G., E-mail: gunther.andersson@flinders.edu.au, E-mail: nakayama.tomonobu@nims.go.jp; Kimoto, Koji

2016-03-21

Triphenylphosphine ligand-protected Au{sub 9} clusters deposited onto titania nanosheets show three different atomic configurations as observed by scanning transmission electron microscopy. The configurations observed are a 3-dimensional structure, corresponding to the previously proposed Au{sub 9} core of the clusters, and two pseudo-2-dimensional (pseudo-2D) structures, newly found by this work. With the help of density functional theory (DFT) calculations, the observed pseudo-2D structures are attributed to the low energy, de-ligated structures formed through interaction with the substrate. The combination of scanning transmission electron microscopy with DFT calculations thus allows identifying whether or not the deposited Au{sub 9} clusters have been de-ligatedmore » in the deposition process.« less

Exploring the Role of Carbonate in the Formation of an Organomanganese Tetramer.

PubMed

Kadassery, Karthika J; Dey, Suman Kr; Friedman, Alan E; Lacy, David C

2017-08-07

The formation of metal-oxygen clusters is an important chemical transformation in biology and catalysis. For example, the biosynthesis of the oxygen-evolving complex in the enzyme photosystem II is a complicated stepwise process that assembles a catalytically active cluster. Herein we describe the role that carbonato ligands have in the formation of the known tetrameric complex [Mn(CO) 3 (μ 3 -OH)] 4 (1). Complex 1 is synthesized in one step via the treatment of Mn 2 (CO) 10 with excess Me 3 NO·2H 2 O. Alternatively, when anhydrous Me 3 NO is used, an OH-free synthetic intermediate (2) with carbonato ligands is produced. Complex 2 produces carbon dioxide, Me 3 NO·2H 2 O, and 1 when treated with water. Labeling studies reveal that the μ 3 -OH ligands in 1 are derived from the water and possibly the carbonato ligands in 2.

GibbsCluster: unsupervised clustering and alignment of peptide sequences.

PubMed

Andreatta, Massimo; Alvarez, Bruno; Nielsen, Morten

2017-07-03

Receptor interactions with short linear peptide fragments (ligands) are at the base of many biological signaling processes. Conserved and information-rich amino acid patterns, commonly called sequence motifs, shape and regulate these interactions. Because of the properties of a receptor-ligand system or of the assay used to interrogate it, experimental data often contain multiple sequence motifs. GibbsCluster is a powerful tool for unsupervised motif discovery because it can simultaneously cluster and align peptide data. The GibbsCluster 2.0 presented here is an improved version incorporating insertion and deletions accounting for variations in motif length in the peptide input. In basic terms, the program takes as input a set of peptide sequences and clusters them into meaningful groups. It returns the optimal number of clusters it identified, together with the sequence alignment and sequence motif characterizing each cluster. Several parameters are available to customize cluster analysis, including adjustable penalties for small clusters and overlapping groups and a trash cluster to remove outliers. As an example application, we used the server to deconvolute multiple specificities in large-scale peptidome data generated by mass spectrometry. The server is available at http://www.cbs.dtu.dk/services/GibbsCluster-2.0. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Synthesis, structure and reactivity of tetranuclear square-type complexes of rhenium and manganese bearing pyrimidine-2-thiolate (pymS) ligands: versatile and efficient precursors for mono- and polynuclear compounds containing M(CO)(3) (M = Re, Mn) fragments.

PubMed

Kabir, S E; Alam, J; Ghosh, S; Kundu, K; Hogarth, G; Tocher, D A; Hossain, G M G; Roesky, H W

2009-06-21

Reactions of M(2)(CO)(10) (M = Re, Mn) with pyrimidine-2-thiol (pymSH) in the presence of Me(3)NO afford the tetranuclear square-type complexes [M(4)(CO)(12)(micro-kappa(3)-pymS)(4)] (, M = Re; , M = Mn). Both consist of four M(CO)(3) (M = Re, Mn) units, pairs of which are joined by tridentate pyrimidine-2-thiolate ligands. Treatment of with a variety of donor ligands results in cleavage of the square to afford mononuclear species with either a mono- or bidentate pyrimidine-2-thiolate ligand. Triphenylphosphine reacts with to give [Mn(CO)(3)(PPh(3))(kappa(2)-pymS)] () in which the pyrimidine-2-thiolate coordinates in a bidentate fashion. With diamines [M(CO)(3)(kappa(2)-L)(kappa(1)-pymS)] () (M = Re, Mn; L = 2,2'- bipy, 1,10-phen, en) result in which the pyrimidine-2-thiolate binds in a monodentate fashion through sulfur. With diphosphines, complexes with different stoichiometries and pyrimidine-2-thiolate binding modes are obtained depending on the nature of the metal and diphosphine. With dppm and dppe, gives [Re(CO)(2)(kappa(1)-pymS)(kappa(2)-dppm)] () and [Re(CO)(2)(kappa(2)-pymS)(kappa(1)-dppe)(2)] (), respectively, whereas affords [Mn(CO)(2)(kappa(2)-pymS)(kappa(1)-dppm)(2)] () and [Mn(CO)(2)(kappa(2)-pyS)(kappa(2)-dppe)] () under similar conditions. Reactions of with [Os(3)(CO)(10)(NCMe)(2)] affords mixed-metal butterfly clusters [MOs(3)(CO)(13)(micro(3)-kappa(2)-pymS)] () in which the group 7 metal occupies a wing-tip position and the pyrimidine-2-thiolate ligand caps a triangular Os(2)M face. With Ru(3)(CO)(12), carbon-sulfur bond cleavage occurs to give the tetranuclear clusters [MRu(3)(CO)(14)(micro(4)-S)(micro-kappa(1):eta(1)-pym)] () bearing both the extruded sulfur and the heterocyclic ring. The molecular structures of , and have been established by X-ray diffraction allowing the binding mode of the pyrimidine-2-thiolate ligands to be probed.

Multivalent ligands control stem cell behaviour in vitro and in vivo

NASA Astrophysics Data System (ADS)

Conway, Anthony; Vazin, Tandis; Spelke, Dawn P.; Rode, Nikhil A.; Healy, Kevin E.; Kane, Ravi S.; Schaffer, David V.

2013-11-01

There is broad interest in designing nanostructured materials that can interact with cells and regulate key downstream functions. In particular, materials with nanoscale features may enable control over multivalent interactions, which involve the simultaneous binding of multiple ligands on one entity to multiple receptors on another and are ubiquitous throughout biology. Cellular signal transduction of growth factor and morphogen cues (which have critical roles in regulating cell function and fate) often begins with such multivalent binding of ligands, either secreted or cell-surface-tethered to target cell receptors, leading to receptor clustering. Cellular mechanisms that orchestrate ligand-receptor oligomerization are complex, however, so the capacity to control multivalent interactions and thereby modulate key signalling events within living systems is currently very limited. Here, we demonstrate the design of potent multivalent conjugates that can organize stem cell receptors into nanoscale clusters and control stem cell behaviour in vitro and in vivo. The ectodomain of ephrin-B2, normally an integral membrane protein ligand, was conjugated to a soluble biopolymer to yield multivalent nanoscale conjugates that potently induce signalling in neural stem cells and promote their neuronal differentiation both in culture and within the brain. Super-resolution microscopy analysis yielded insights into the organization of the receptor-ligand clusters at the nanoscale. We also found that synthetic multivalent conjugates of ephrin-B1 strongly enhance human embryonic and induced pluripotent stem cell differentiation into functional dopaminergic neurons. Multivalent bioconjugates are therefore powerful tools and potential nanoscale therapeutics for controlling the behaviour of target stem cells in vitro and in vivo.

Multiheteromacrocycles that Complex Metal Ions. Sixth Progress Report, 1 May 1979-30 April 1980

DOE R&D Accomplishments Database

Cram, D. J.

1980-01-15

Objective is to design synthesize, and evaluate cyclic and polycyclic host organic compounds for their abilities to complex and lipophilize guest metal ions, their complexes, and their clusters. Host organic compounds consist of strategically placed solvating, coordinating, and ion-pairing sites tied together by covalent bonds through hydrocarbon units around cavities shaped to be occupied by guest metal ions or by metal ions plus their ligands. Specificity in complexation is sought by matching the following properties of host and guest: cavity and metal ion sizes; geometric arrangements of binding sites; number of binding sites; character of binding sites; and valences. During this period, hemispherands based on an aryloxy or cyclic urea unit, spherands based on aryloxyl units only, and their complexes with alkali metals and alkaline earths were investigated. An attempt to separate {sup 6}Li and {sup 7}Li by gel permeation chromatography of lithiospherium chloride failed. (DLC)

Ligand-modified metal clusters for gas separation and purification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Okrut, Alexander; Ouyang, Xiaoying; Runnebaum, Ron

2017-02-21

Provided is an organic ligand-bound metal surface that selects one gaseous species over another. The species can be closely sized molecular species having less than 1 Angstrom difference in kinetic diameter. In one embodiment, the species comprise carbon monoxide and ethylene. Such organic ligand-bound metal surfaces can be successfully used in gas phase separations or purifications, sensing, and in catalysis.

FRET measurements of cell-traction forces and nano-scale clustering of adhesion ligands varied by substrate stiffness.

PubMed

Kong, Hyun Joon; Polte, Thomas R; Alsberg, Eben; Mooney, David J

2005-03-22

The mechanical properties of cell adhesion substrates regulate cell phenotype, but the mechanism of this relation is currently unclear. It may involve the magnitude of traction force applied by the cell, and/or the ability of the cells to rearrange the cell adhesion molecules presented from the material. In this study, we describe a FRET technique that can be used to evaluate the mechanics of cell-material interactions at the molecular level and simultaneously quantify the cell-based nanoscale rearrangement of the material itself. We found that these events depended on the mechanical rigidity of the adhesion substrate. Furthermore, both the proliferation and differentiation of preosteoblasts (MC3T3-E1) correlated to the magnitude of force that cells generate to cluster the cell adhesion ligands, but not the extent of ligand clustering. Together, these data demonstrate the utility of FRET in analyzing cell-material interactions, and suggest that regulation of phenotype with substrate stiffness is related to alterations in cellular traction forces.

Role of excess ligand and effect of thermal treatment in hybrid inorganic-organic EUV resists

NASA Astrophysics Data System (ADS)

Mattson, Eric C.; Rupich, Sara M.; Cabrera, Yasiel; Chabal, Yves J.

2018-03-01

The chemical structure and thermal reactivity of recently discovered inorganic-organic hybrid resist materials are characterized using a combination of in situ and ex situ infrared (IR) spectroscopy and x-ray photoemission spectroscopy (XPS). The materials are comprised of a small HfOx core capped with methacrylic acid ligands that form a combined hybrid cluster, HfMAA. The observed IR modes are consistent with the calculated modes predicted from the previously determined x-ray crystal structure of the HfMAA-12 cluster, but also contain extrinsic hydroxyl groups. We find that the water content of the films is dependent on the concentration of excess ligand added to the solution. The effect of environment used during post-application baking (PAB) is studied and correlated to changes in solubility of the films. In doing so, we find that hydroxylation of the clusters results in formation of additional Hf-O-Hf linkages upon heating, which in turn impacts the solubility of the films.

Insight into Environmental Effects on Bonding and Redox Properties of [4Fe-4S] Clusters in Proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Niu, Shuqiang; Ichiye, Toshiko

The large differences in redox potentials between the HiPIPs and ferredoxins are generally attributed to hydrogen bonds and electrostatic effects from the protein and solvent. Recent ligand K-edge X-ray absorption studies by Solomon and co-workers show that the Fe-S covalencies of [4Fe-4S] clusters in the two proteins differ considerably apparently because of hydrogen bonds from water, indicating electronic effects may be important. However, combined density function theory (DFT) and photoelectron spectroscopy studies by our group and Wang and co-workers indicate that hydrogen bonds tune the potential of [4Fe-4S] clusters by mainly electrostatics. The DFT studies here rationalize both results, namelymore » that the observed change in the Fe-S covalency is due to differences in ligand conformation between the two proteins rather than hydrogen bonds. Moreover, the ligand conformation affects the calculated potentials by 100 mV and, thus, is a heretofore unconsidered means of tuning the potential.« less

Natural-product-derived fragments for fragment-based ligand discovery

NASA Astrophysics Data System (ADS)

Over, Björn; Wetzel, Stefan; Grütter, Christian; Nakai, Yasushi; Renner, Steffen; Rauh, Daniel; Waldmann, Herbert

2013-01-01

Fragment-based ligand and drug discovery predominantly employs sp2-rich compounds covering well-explored regions of chemical space. Despite the ease with which such fragments can be coupled, this focus on flat compounds is widely cited as contributing to the attrition rate of the drug discovery process. In contrast, biologically validated natural products are rich in stereogenic centres and populate areas of chemical space not occupied by average synthetic molecules. Here, we have analysed more than 180,000 natural product structures to arrive at 2,000 clusters of natural-product-derived fragments with high structural diversity, which resemble natural scaffolds and are rich in sp3-configured centres. The structures of the cluster centres differ from previously explored fragment libraries, but for nearly half of the clusters representative members are commercially available. We validate their usefulness for the discovery of novel ligand and inhibitor types by means of protein X-ray crystallography and the identification of novel stabilizers of inactive conformations of p38α MAP kinase and of inhibitors of several phosphatases.

Radical S-Adenosyl-l-methionine Chemistry in the Synthesis of Hydrogenase and Nitrogenase Metal Cofactors*

PubMed Central

Byer, Amanda S.; Shepard, Eric M.; Peters, John W.; Broderick, Joan B.

2015-01-01

Nitrogenase, [FeFe]-hydrogenase, and [Fe]-hydrogenase enzymes perform catalysis at metal cofactors with biologically unusual non-protein ligands. The FeMo cofactor of nitrogenase has a MoFe7S9 cluster with a central carbon, whereas the H-cluster of [FeFe]-hydrogenase contains a 2Fe subcluster coordinated by cyanide and CO ligands as well as dithiomethylamine; the [Fe]-hydrogenase cofactor has CO and guanylylpyridinol ligands at a mononuclear iron site. Intriguingly, radical S-adenosyl-l-methionine enzymes are vital for the assembly of all three of these diverse cofactors. This minireview presents and discusses the current state of knowledge of the radical S-adenosylmethionine enzymes required for synthesis of these remarkable metal cofactors. PMID:25477518

Cysteine as a ligand platform in the biosynthesis of the FeFe hydrogenase H cluster

DOE PAGES

Suess, Daniel L. M.; Bürstel, Ingmar; De La Paz, Liliana; ...

2015-08-31

Hydrogenases catalyze the redox interconversion of protons and H 2, an important reaction for a number of metabolic processes and for solar fuel production. In FeFe hydrogenases, catalysis occurs at the H cluster, a metallocofactor comprising a [4Fe–4S] H subcluster coupled to a [2Fe] H subcluster bound by CO, CN–, and azadithiolate ligands. The [2Fe] H subcluster is assembled by the maturases HydE, HydF, and HydG. HydG is a member of the radical S-adenosyl-L-methionine family of enzymes that transforms Fe and L-tyrosine into an [Fe(CO) 2(CN)] synthon that is incorporated into the H cluster. Though it is thought that themore » site of synthon formation in HydG is the “dangler” Fe of a [5Fe] cluster, many mechanistic aspects of this chemistry remain unresolved including the full ligand set of the synthon, how the dangler Fe initially binds to HydG, and how the synthon is released at the end of the reaction. In order to address these questions, we show in this paper that L-cysteine (Cys) binds the auxiliary [4Fe–4S] cluster of HydG and further chelates the dangler Fe. We demonstrate that a [4Fe–4S] aux[CN] species is generated during HydG catalysis, a process that entails the loss of Cys and the [Fe(CO) 2(CN)] fragment; on this basis, we suggest that Cys likely completes the coordination sphere of the synthon. Finally, through spectroscopic analysis of HydG before and after the synthon is formed, we conclude that Cys serves as the ligand platform on which the synthon is built and plays a role in both Fe 2+ binding and synthon release.« less

Reaction and Aggregation Dynamics of Cell Surface Receptors

NASA Astrophysics Data System (ADS)

Wang, Michelle Dong

This dissertation is composed of both theoretical and experimental studies of cell surface receptor reaction and aggregation. Project I studies the reaction rate enhancement due to surface diffusion of a bulk dissolved ligand with its membrane embedded target, using numerical calculations. The results show that the reaction rate enhancement is determined by ligand surface adsorption and desorption kinetic rates, surface and bulk diffusion coefficients, and geometry. In particular, we demonstrate that the ligand surface adsorption and desorption kinetic rates, rather than their ratio (the equilibrium constant), are important in rate enhancement. The second and third projects are studies of acetylcholine receptor clusters on cultured rat myotubes using fluorescence techniques after labeling the receptors with tetramethylrhodamine -alpha-bungarotoxin. The second project studies when and where the clusters form by making time-lapse movies. The movies are made from overlay of the pseudocolored total internal reflection fluorescence (TIRF) images of the cluster, and the schlieren images of the cell cultures. These movies are the first movies made using TIRF, and they clearly show the cluster formation from the myoblast fusion, the first appearance of clusters, and the eventual disappearance of clusters. The third project studies the fine structural features of individual clusters observed under TIRF. The features were characterized with six parameters by developing a novel fluorescence technique: spatial fluorescence autocorrelation. These parameters were then used to study the feature variations with age, and with treatments of drugs (oligomycin and carbachol). The results show little variation with age. However, drug treatment induced significant changes in some parameters. These changes were different for oligomycin and carbachol, which indicates that the two drugs may eliminate clusters through different mechanisms.

The first octahedral cluster complexes with terminal formate ligands: synthesis, structure, and properties of K4[Re6S8(HCOO)6] and Cs4[Re6S8(HCOO)6].

PubMed

Brylev, Konstantin A; Mironov, Yuri V; Kozlova, Svetlana G; Fedorov, Vladimir E; Kim, Sung-Jin; Pietzsch, Hans-Jürgen; Stephan, Holger; Ito, Akitaka; Ishizaka, Shoji; Kitamura, Noboru

2009-03-02

The hexarhenium anionic cluster complex with terminal formate ligands [Re6S8(HCOO)6]4- was obtained by the room-temperature reaction between [Re6S8(OH)6]4- and formic acid in an aqueous solution. The cluster was crystallized as a potassium or cesium salt and characterized by X-ray single-crystal diffraction and elemental analyses, IR, 1H NMR, UV/vis, and luminescence spectroscopies. In particular, the emission quantum yield of the potassium salt of the Re6 cluster anion in the solid phase was determined for the first time. The electronic structures of [Re6S8(HCOO)6]4- and [Re6S8(OH)6]4- were also elucidated by DFT calculations.

Oxidation catalysis by polyoxometalates fundamental electron-transfer phenomena

Treesearch

Yurii V. Geletii; Rajai H. Atalla; Alan J. Bailey; Laurent Delannoy; Craig L. Hill; Ira A. Weinstock

2002-01-01

Early transition-metal oxygen-anion clusters (polyoxometalates, POMs) are a large and rapidly growing class of versatile and tunable oxidation catalysts. All key molecular properties of these clusters (composition, size, shape, charge density, reduction potential, solubility, etc.) can be systematically altered, and the clusters themselves can serve as tunable ligands...

Synthesis and Ligand-Exchange Reactions of a Tri-Tungsten Cluster with Applications in Biomedical Imaging

ERIC Educational Resources Information Center

Noey, Elizabeth; Curtis, Jeff C.; Tam, Sylvia; Pham, David M.; Jones, Ella F.

2011-01-01

In this experiment students are exposed to concepts in inorganic synthesis and various spectroscopies as applied to a tri-tungsten cluster with applications in biomedical imaging. The tungsten-acetate cluster, Na[W[superscript 3](mu-O)[subscript 2](CH[superscript 3]COO)[superscript 9

Titanium Oxo Cluster with Six Peripheral Ferrocene Units and Its Photocurrent Response Properties for Saccharides.

PubMed

Hou, Jin-Le; Luo, Wen; Guo, Yao; Zhang, Ping; Yang, Shen; Zhu, Qin-Yu; Dai, Jie

2017-06-05

A unique titanium oxo cluster with a ferrocene ligand was synthesized and characterized by single crystal X-ray analysis. Six ferrocene carboxylates coordinate to a D 3d Ti 6 O 6 core to be a redox active cluster 1, [Ti 6 O 6 (O i Pr) 6 (O 2 CFc) 6 ]. An analogue 2, [Ti 6 O 6 (O i Pr) 6 (O 2 C i Bu) 6 ], where the redox active ferrocene group is replaced by isobutyrate, is also reported as a contrast. The six ferrocene moieties in 1 are structurally identical to give a main redox wave at E 1/2 = 0.62 V in dichloromethane investigated by cyclic voltammetry. Photocurrent responses using electrodes of clusters 1 and 2 were studied, and the response properties of 1 are better than those of 2. The electronic spectra and theoretical calculations indicate that charge transfer occurs from ferrocene to Ti(IV) in 1, and the presence of the ferrocene moiety gives efficient electron excitation and charge separation. Cluster 1 is a cooperative system of TiO cluster and redox active ferrocene. Photocurrent response properties of an electrode of 1 for four saccharides, glucose, fructose, maltose, and sucrose, were tested, and only reducing sugars were responsive. The electrode of 2 is also photocurrent responsive to saccharides, but the current densities are lower than those of redox active 1.

Synthesis, Characterization and Application of Water-soluble Gold and Silver Nanoclusters

NASA Astrophysics Data System (ADS)

Kumar, Santosh

The term `nanotechnology' has emerged as a buzzword since the last few decades. It has found widespread applications across disciplines, from medicine to energy. The synthesis of gold and silver nanoclusters has found much excitement, due to their novel material properties. Seminal work by various groups, including ours, has shown that the size of these clusters can be controlled with atomic precision. This control gives access to tuning the optical and electronic properties. The majority of nanoclusters reported thus far are not water soluble, which limit their applications in biology that requires water-solubility. Going from organic to aqueous phase is by no means a simple task, as it is associated with many challenges. Their stability in the presence of oxygen, difficulty in characterization, and separation of pure nanoclusters are some of the major bottlenecks associated with the synthesis of water-soluble gold nanoclusters. Water-soluble gold nanoclusters hold great potential in biological labeling, bio-catalysis and nano-bioconjugates. To overcome this problem, a new ligand with structural rigidity is needed. After considering various possibilities, we chose Captopril as a candidate ligand. In my thesis research, the synthesis of Au25 nanocluster capped with captopril has been reported. Captopril-protected Au25 nanocluster showed significantly higher thermal stability and enhanced chiroptical properties than the Glutathione-capped cluster, which confirms our initial rationale, that the ligand is critical in protecting the nanocluster. The optical absorption properties of these Au25 nanoclusters are studied and compared to the plasmonic nanoparticles. The high thermal stability and solubility of Au25 cluster capped with Captopril motivated us to explore this ligand for the synthesis of other gold clusters. Captopril is a chiral molecule with two chiral centers. The chiral ligand can induce chirality to the overall cluster, even if the core is achiral. Therefore, to obtain Au38 clusters as an enantiomer, the ligand employed should be chiral. The enantioselective synthesis of Au 38 capped with different chiral ligands has been reported and their chiroptical properties have been compared. The synthesis of a series of water-soluble Au nanoclusters has motivated us to study the effect of capping ligands and the core-size on their steady-state and time-resolved fluorescence properties, since the photoluminescence properties are particularly important for bioimaging and biomedical applications of nanoclusters. To gain fundamental insights into the origin of luminescence in nanoclusters, the effect of temperature on the fluorescence properties of these clusters has also been studied. The different sized nanoclusters ranging from a few dozen atoms to hundreds of atoms form a bridge between discrete atoms and the plasmonic nanocrystals; the latter involves essentially collective electron excitation-a phenomenon well explained by classical physics as opposed to quantum physics. The central question is: at what size does this transition from quantum behavior to classical behavior occur? To unravel this, we have successfully synthesized a series of silver nanoclusters. The precise formula assignment and their structural determination are still ongoing. We have successfully demonstrated the application of these water-soluble Au nanoclusters in photodynamic therapy for the treatment of cancer. We have successfully demonstrated that Au nanocluster system can produce singlet oxygen without the presence of any organic photosensitizers. In a collaborative project with Dr. Peteanu's group, the quenching efficiency of organic dyes by these water soluble nanoclusters is studied in different systems. Overall, this thesis outlines the successful synthesis of a family of water-soluble nanoclusters, their optical, chiroptical and fluorescence properties, as well as some applications of these nanoclusters.

Synthesis, Structure and Electrochemistry of Tetranuclear Oxygen-Centered Copper(II) Clusters with Acetylacetone and Benz-pyrazole Hydrolyzed Derivatives as Ligand.

PubMed

Vafazadeh, Rasoul; Willis, Anthony C

2016-01-01

Two copper(II) clusters Cu(4)OCl(6)(pyrazole)4, 1, and Cu(4)OBr(6)(Br-pyrazole)4, 2, have been synthesized by reacting acetylacetone and benzohydrazide (1:1 ratio) with CuX(2) (X = Cl for 1 and X= Br for 2) in methanol solutions. The structures of both clusters have been established by X-ray crystallography. The clusters contain four Cu, one O, six μ(2)-X atoms, and four pyrazole ligands. The pyrazoles was prepared in situ by the reaction of acetylacetone with benzohydrazide in methanol under reflux. In 2, the methine hydrogens of the pyrazole ligands have been replaced by bromine atoms. The four copper atoms encapsulate the central O atom in a tetrahedral arrangement. All copper atoms are five-coordinate and have similar coordination environments with slightly distorted trigonal bipyramidal geometry. The cyclic voltammogram of the clusters 1 and 2 show a one-electron quasi-reversible reduction wave in the region 0.485 to 0.731 V, and a one-electron quasi-reversible oxidation wave in the region 0.767 to 0.898 V. In 1, one irreversible oxidative response is observed on the positive of side of the voltammogram at 1.512 V and this can be assigned to Cu(II) to Cu(III) oxidation.

Nature's polyoxometalate chemistry: X-ray structure of the Mo storage protein loaded with discrete polynuclear Mo-O clusters.

PubMed

Kowalewski, Björn; Poppe, Juliane; Demmer, Ulrike; Warkentin, Eberhard; Dierks, Thomas; Ermler, Ulrich; Schneider, Klaus

2012-06-13

Some N(2)-fixing bacteria prolong the functionality of nitrogenase in molybdenum starvation by a special Mo storage protein (MoSto) that can store more than 100 Mo atoms. The presented 1.6 Å X-ray structure of MoSto from Azotobacter vinelandii reveals various discrete polyoxomolybdate clusters, three covalently and three noncovalently bound Mo(8), three Mo(5-7), and one Mo(3) clusters, and several low occupied, so far undefinable clusters, which are embedded in specific pockets inside a locked cage-shaped (αβ)(3) protein complex. The structurally identical Mo(8) clusters (three layers of two, four, and two MoO(n) octahedra) are distinguishable from the [Mo(8)O(26)](4-) cluster formed in acidic solutions by two displaced MoO(n) octahedra implicating three kinetically labile terminal ligands. Stabilization in the covalent Mo(8) cluster is achieved by Mo bonding to Hisα156-N(ε2) and Gluα129-O(ε1). The absence of covalent protein interactions in the noncovalent Mo(8) cluster is compensated by a more extended hydrogen-bond network involving three pronounced histidines. One displaced MoO(n) octahedron might serve as nucleation site for an inhomogeneous Mo(5-7) cluster largely surrounded by bulk solvent. In the Mo(3) cluster located on the 3-fold axis, the three accurately positioned His140-N(ε2) atoms of the α subunits coordinate to the Mo atoms. The formed polyoxomolybdate clusters of MoSto, not detectable in bulk solvent, are the result of an interplay between self- and protein-driven assembly processes that unite inorganic supramolecular and protein chemistry in a host-guest system. Template, nucleation/protection, and catalyst functions of the polypeptide as well as perspectives for designing new clusters are discussed.

Metal-organic frameworks assembled from lanthanide and 2,5-pyridinedicaboxylate with cubane-like [Ln4(OH)4] building units

NASA Astrophysics Data System (ADS)

Abdelbaky, Mohammed S. M.; Amghouz, Zakariae; Fernández-Zapico, Eva; García-Granda, Santiago; García, José R.

2015-09-01

Lanthanide-organic frameworks based on 2,5-pyridinedicaboxylate (25p) ligand, formulated as [Yb4(OH)4(25p)4(H2O)3]·H2O (25pYb), [Y4(OH)4(25p)4(H2O)3]·H2O (25pY-1) and [Y6(OH)8(25p)5(H2O)2] (25pY-2), have been obtained as single phases under hydrothermal conditions. 25pYb and 25pY-1 are isostructural, and crystallize in the triclinic space group, P-1, with a=8.6075(5) Å, b=14.8478(7) Å, c=15.9164(9) Å, α=86.277(4)°, β=80.196(5)°, γ=81.785(4)°, and a=8.7166(6) Å, b=14.966(1) Å, c=15.966(1) Å, α=86.260(6)°, β=80.036(6)°, γ=81.599(6)°, respectively. 25pY-2 crystallizes in the monoclinic space group, P21/c, with a=24.9117(17) Å, b=13.7340(8) Å, c=14.3385(10) Å, β=100.551(7)°. 25pYb and 25pY-2 have been structurally characterized by single-crystal X-ray diffraction. The 25pYb structure is based on tetranuclear cubane-like [Yb4(OH)4]8+ clusters, which are interconnected to eight neighbouring clusters through teen surrounding 25p ligands leading to neutral 3D framework, while the structure of 25pY-2 is based on two independent cuban-like [Y4(OH)4]8+ clusters, which are joined together through Y1 cation leading to the formation of hexanuclear [Y6(OH)8]10+ clusters, which in turn are joined via Y2 cation resulting in infinite inorganic chain extending along c-axis, and each chain is interconnected to six adjacent chains through 25p ligands leading finally to 3D framework. The luminescence properties of Eu3+ and Tb3+ doped 25pY-1 and 25pY-2 compounds have also been investigated. All materials has been characterized by powder X-ray diffraction, thermal analyses (TG-SDTA-MS), FTIR spectroscopy, C-H-N elemental analysis, scanning electron microscopy (SEM-EDX), and powder X-ray thermodiffraction.

Radical S-Adenosyl-L-methionine Chemistry in the Synthesis of Hydrogenase and Nitrogenase Metal Cofactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Byer, Amanda S.; Shepard, Eric M.; Peters, John W.

Nitrogenase, [FeFe]-hydrogenase, and [Fe]-hydrogenase enzymes perform catalysis at metal cofactors with biologically unusual non-protein ligands. Furthermore, the FeMo cofactor of nitrogenase has a MoFe 7S 9 cluster with a central carbon, whereas the H-cluster of [FeFe]-hydrogenase contains a 2Fe subcluster coordinated by cyanide and CO ligands as well as dithiomethylamine; the [Fe]-hydrogenase cofactor has CO and guanylylpyridinol ligands at a mononuclear iron site. Intriguingly, radical S-adenosyl-L-methionine enzymes are vital for the assembly of all three of these diverse cofactors. Here, in this minireview, we present and discuss the current state of knowledge of the radical S-adenosylmethionine enzymes required for synthesismore » of these remarkable metal cofactors.« less

Radical S-Adenosyl-L-methionine Chemistry in the Synthesis of Hydrogenase and Nitrogenase Metal Cofactors

DOE PAGES

Byer, Amanda S.; Shepard, Eric M.; Peters, John W.; ...

2014-12-04

Nitrogenase, [FeFe]-hydrogenase, and [Fe]-hydrogenase enzymes perform catalysis at metal cofactors with biologically unusual non-protein ligands. Furthermore, the FeMo cofactor of nitrogenase has a MoFe 7S 9 cluster with a central carbon, whereas the H-cluster of [FeFe]-hydrogenase contains a 2Fe subcluster coordinated by cyanide and CO ligands as well as dithiomethylamine; the [Fe]-hydrogenase cofactor has CO and guanylylpyridinol ligands at a mononuclear iron site. Intriguingly, radical S-adenosyl-L-methionine enzymes are vital for the assembly of all three of these diverse cofactors. Here, in this minireview, we present and discuss the current state of knowledge of the radical S-adenosylmethionine enzymes required for synthesismore » of these remarkable metal cofactors.« less

Synthesis and structure of cesium complexes of nitrilotris(methylenephosphonic) acid [Cs-μ6-NH(CH2PO3)3H4] and [Cs2-μ10-NH(CH2PO3H)3] · H2O

NASA Astrophysics Data System (ADS)

Somov, N. V.; Chausov, F. F.; Zakirov, R. M.

2017-07-01

3D coordination polymers cesium nitrilotris(methylenephosphonate) and dicesium nitrilotris( methylenephosphonate) are synthesized and their crystal structure is determined. In the crystal of [Cs-μ6-NH(CH2PO3)3H4] (space group P, Z = 2), cesium atoms occupy two crystallographically inequivalent positions with c.n. = 10 and c.n. = 14. The phosphonate ligand plays the bridging function; its denticity is nine. The crystal packing consists of alternating layers of Cs atoms in different environments with layers of ligand molecules between them. A ligand is bound to three Cs atoms of one layer and three Cs atoms of another layer. In the crystal of [Cs2-μ10-NH(CH2PO3H)3] · H2O (space group P, Z = 2), the complex has a dimeric structure: the bridging phosphonate ligand coordinates Cs to form a three-dimensional Cs4O6 cluster. The denticity of the ligand is equal to nine; the coordination numbers of cesium atoms are seven and nine. Two-dimensional corrugated layers of Cs4O6 clusters lie in the (002) plane, and layers of ligand molecules are located between them. Each ligand molecule coordinates eight Cs atoms of one layer and two Cs atoms of the neighboring layer.

Structural and optical properties of the naked and passivated Al{sub 5}Au{sub 5} bimetallic nanoclusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grande-Aztatzi, Rafael; Formoso, Elena; Matxain, Jon M.

The structural and optical properties of both the naked and passivated bimetallic Al{sub 5}Au{sub 5} nanoclusters have been analyzed based on data obtained from ab initio density functional theory and quantum molecular dynamics simulations. It has been found that the Al{sub 5}Au{sub 5} nanocluster possesses a hollow shaped minimum energy structure with segregated Al and Au layered domains, the former representing the electrophilic domain and the latter the nucleophilic domain. In particular, it has been shown that alkali metal cations attach in the nucleophilic domain and hop from one Au site to the next one in the picoseconds time scale,more » while anions are bound tightly to the Al atoms of the electrophilic domain. Simulating annealing studies are very suggestive of the proneness of the nanocluster towards coalescence into large cluster units, when the cluster is left unprotected by appropriate ligands. Further passivation studies with NaF salt suggest, nonetheless, the possibility of the isolation of the Al{sub 5}Au{sub 5} cluster in molten salts or ionic liquids.« less

An unusual 2p-3d-4f heterometallic coordination polymer featuring Ln8Na and Cu8I clusters as nodes

NASA Astrophysics Data System (ADS)

Zhao, Mingjuan; Chen, Shimin; Huang, Yutian; Dan, Youmeng

2017-01-01

A new cluster-based three-dimensional 2p-3d-4f heterometallic framework {[Ho8Na(OH)6Cu16I2(CPT)24](NO3)9(H2O)6(CH3CN)18}n (1, HCPT = 4-(4-carboxyphenyl)-1,2,4 triazole) has been prepared under solvothermal condition by using a custom-designed bifunctional organic ligand. The single-crystal structure analysis reveals that this framework features novel Ln8Na and Cu8I clusters as nodes, these nodes are further connected by the CPT ligands to give rise to a (6,14)-connected network. The magnetic property of this framework has also been investigated.

Efficient enhancement of magnetic anisotropy by optimizing the ligand-field in a typically tetranuclear dysprosium cluster.

PubMed

Liu, Jiang; Chen, Yan-Cong; Jiang, Zhong-Xia; Liu, Jun-Liang; Jia, Jian-Hua; Wang, Long-Fei; Li, Quan-Wen; Tong, Ming-Liang

2015-05-07

The perturbation to the ligand field around the lanthanide ion may significantly contribute to the magnetic dynamics of single molecule magnets. This can be demonstrated by two typical Dy4 cluster-based single molecular magnets (SMMs), [Dy4X2(μ3-OH)2(μ-OH)2(2,2-bpt)4(H2O)4]X2·2H2O·4EtOH (X = Cl and Br for and , respectively), which were constructed by using 3,5-bis(pyridin-2-yl)-1,2,4-triazole (2,2-bptH) as the polynuclear-chelating ligand. Alternating-current (ac) magnetic susceptibility measurements show that the energy barriers in complexes and were immensely enhanced by comparing with our previous work due to the optimization of the ligand field around Dy(III) ions. Remarkably, their high thermal active barriers at 190 K () and 197 K () under a zero applied external dc magnetic field are also among the highest within the reported tetranuclear lanthanide-based SMMs.

Controlled Expansion of a Strong-Field Iron Nitride Cluster: Multi-Site Ligand Substitution as a Strategy for Activating Interstitial Nitride Nucleophilicity.

PubMed

Drance, Myles J; Mokhtarzadeh, Charles C; Melaimi, Mohand; Agnew, Douglas W; Moore, Curtis E; Rheingold, Arnold L; Figueroa, Joshua S

2018-05-02

Multimetallic clusters have long been investigated as molecular surrogates for reactive sites on metal surfaces. In the case of the μ 4 -nitrido cluster [Fe 4 (μ 4 -N)(CO) 12 ] - , this analogy is limited owing to the electron-withdrawing effect of carbonyl ligands on the iron nitride core. Described here is the synthesis and reactivity of [Fe 4 (μ 4 -N)(CO) 8 (CNAr Mes2 ) 4 ] - , an electron-rich analogue of [Fe 4 (μ 4 -N)(CO) 12 ] - , where the interstitial nitride displays significant nucleophilicity. This characteristic enables rational expansion with main-group and transition-metal centers to yield unsaturated sites. The resulting clusters display surface-like reactivity through coordination-sphere-dependent atom rearrangement and metal-metal cooperativity. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Applying the Power of Reticular Chemistry to Finding the Missing alb-MOF Platform Based on the (6,12)-Coordinated Edge-Transitive Net.

PubMed

Chen, Zhijie; Weseliński, Łukasz J; Adil, Karim; Belmabkhout, Youssef; Shkurenko, Aleksander; Jiang, Hao; Bhatt, Prashant M; Guillerm, Vincent; Dauzon, Emilie; Xue, Dong-Xu; O'Keeffe, Michael; Eddaoudi, Mohamed

2017-03-01

Highly connected and edge-transitive nets are of prime importance in crystal chemistry and are regarded as ideal blueprints for the rational design and construction of metal-organic frameworks (MOFs). We report the design and synthesis of highly connected MOFs based on reticulation of the sole two edge-transitive nets with a vertex figure as double six-membered-ring (d6R) building unit, namely the (4,12)-coordinated shp net (square and hexagonal-prism) and the (6,12)-coordinated alb net (aluminum diboride, hexagonal-prism and trigonal-prism). Decidedly, the combination of our recently isolated 12-connected (12-c) rare-earth (RE) nonanuclear [RE 9 (μ 3 -OH) 12 (μ 3 -O) 2 (O 2 C-) 12 ] carboxylate-based cluster, points of extension matching the 12 vertices of hexagonal-prism d6R, with 4-connected (4-c) square porphyrinic tetracarboxylate ligand led to the formation of the targeted RE-shp-MOF. This is the first time that RE-MOFs based on 12-c molecular building blocks (MBBs), d6R building units, have been deliberately targeted and successfully isolated, paving the way for the long-awaited (6,12)-c MOF with alb topology. Indeed, combination of a custom-designed hexacarboxylate ligand with RE salts led to the formation of the first related alb-MOF, RE-alb-MOF. Intuitively, we successfully transplanted the alb topology to another chemical system and constructed the first indium-based alb-MOF, In-alb-MOF, by employing trinuclear [In 3 (μ 3 -O)(O 2 C-) 6 ] as the requisite 6-connected trigonal-prism and purposely made a dodecacarboxylate ligand as a compatible 12-c MBB. Prominently, the dodecacarboxylate ligand was employed to transplant shp topology into copper-based MOFs by employing the copper paddlewheel [Cu 2 (O 2 C-) 4 ] as the complementary square building unit, affording the first Cu-shp-MOF. We revealed that highly connected edge-transitive nets such shp and alb are ideal for topological transplantation and deliberate construction of related MOFs based on minimal edge-transitive nets.

Catalytic dehydrogenation of alcohol over solid-state molybdenum sulfide clusters with an octahedral metal framework

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kamiguchi, Satoshi, E-mail: kamigu@riken.jp; Organometallic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako City, Saitama 351-0198; Okumura, Kazu

Graphical abstract: - Highlights: • Solid-state molybdenum sulfide clusters catalyzed the dehydrogenation of alcohol. • The dehydrogenation proceeded without the addition of any oxidants. • The catalytic activity developed when the cluster was activated at 300–500 °C in H{sub 2}. • The Lewis-acidic molybdenum atom and basic sulfur ligand were catalytically active. • The clusters function as bifunctional acid–base catalysts. - Abstract: Solid-state molybdenum sulfide clusters with an octahedral metal framework, the superconducting Chevrel phases, are applied to catalysis. A copper salt of a nonstoichiometric sulfur-deficient cluster, Cu{sub x}Mo{sub 6}S{sub 8–δ} (x = 2.94 and δ ≈ 0.3), is storedmore » in air for more than 90 days. When the oxygenated cluster is thermally activated in a hydrogen stream above 300 °C, catalytic activity for the dehydrogenation of primary alcohols to aldehydes and secondary alcohols to ketones develops. The addition of pyridine or benzoic acid decreases the dehydrogenation activity, indicating that both a Lewis-acidic coordinatively unsaturated molybdenum atom and a basic sulfur ligand synergistically act as the catalytic active sites.« less

Integrin Clustering Matters: A Review of Biomaterials Functionalized with Multivalent Integrin-Binding Ligands to Improve Cell Adhesion, Migration, Differentiation, Angiogenesis, and Biomedical Device Integration.

PubMed

Karimi, Fatemeh; O'Connor, Andrea J; Qiao, Greg G; Heath, Daniel E

2018-03-25

Material systems that exhibit tailored interactions with cells are a cornerstone of biomaterial and tissue engineering technologies. One method of achieving these tailored interactions is to biofunctionalize materials with peptide ligands that bind integrin receptors present on the cell surface. However, cell biology research has illustrated that both integrin binding and integrin clustering are required to achieve a full adhesion response. This biophysical knowledge has motivated researchers to develop material systems biofunctionalized with nanoscale clusters of ligands that promote both integrin occupancy and clustering of the receptors. These materials have improved a wide variety of biological interactions in vitro including cell adhesion, proliferation, migration speed, gene expression, and stem cell differentiation; and improved in vivo outcomes including increased angiogenesis, tissue healing, and biomedical device integration. This review first introduces the techniques that enable the fabrication of these nanopatterned materials, describes the improved biological effects that have been achieved, and lastly discusses the current limitations of the technology and where future advances may occur. Although this technology is still in its nascency, it will undoubtedly play an important role in the future development of biomaterials and tissue engineering scaffolds for both in vitro and in vivo applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Titanium Oxo Cluster Model Study of Synergistic Effect of Co-coordinated Dye Ligands on Photocurrent Responses.

PubMed

Hou, Jin-Le; Huo, Peng; Tang, Zheng-Zhen; Cui, Li-Na; Zhu, Qin-Yu; Dai, Jie

2018-05-24

The use of multiple sensitizers in dye sensitized solar cells has been attractive as a promising way to achieve highly efficient photovoltaic performance. However, except for the complementary absorption, synergistic effects among the dye components have not been well understood. Herein, using ferrocene-1-carboxylate (FcCO 2 ) and catechol (Cat) as dye ligands, two titanium oxo clusters (TOCs), [Ti 3 O(O i Pr) 6 (Cat)(FcCO 2 ) 2 ] (1) and [Ti 7 O 4 (O i Pr) 8 (Cat) 5 (FcCO 2 ) 2 ] (2), were synthesized and structurally characterized. Another TOC, [Ti 7 O 3 (O i Pr) 12 (Cat) 4 ( o-BDC)] (3) ( o-BDC = o-benzene dicarboxylate), was also prepared as a contrast. Electronic spectra and theoretical calculations showed that charge transfer occurs from ligands FcCO 2 and Cat to the TiO cluster core and the contribution of redox active FcCO 2 is greater than that of Cat. Using the clusters as TiO-dye pre-anchored precursors, multi-dye sensitized TiO 2 electrodes were prepared. Although the two dyes FcCO 2 and Cat do not complement each other in spectra, a synergistic effect on the enhancement of photocurrent responses was found and discussed in view of the inter-dyes electron communication.

LigSearch: a knowledge-based web server to identify likely ligands for a protein target

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beer, Tjaart A. P. de; Laskowski, Roman A.; Duban, Mark-Eugene

LigSearch is a web server for identifying ligands likely to bind to a given protein. Identifying which ligands might bind to a protein before crystallization trials could provide a significant saving in time and resources. LigSearch, a web server aimed at predicting ligands that might bind to and stabilize a given protein, has been developed. Using a protein sequence and/or structure, the system searches against a variety of databases, combining available knowledge, and provides a clustered and ranked output of possible ligands. LigSearch can be accessed at http://www.ebi.ac.uk/thornton-srv/databases/LigSearch.

A self-assembling luminescent lanthanide molecular nanoparticle with potential for live cell imaging.

PubMed

Yang, Xiaoping; Wang, Shiqing; Zhang, Yali; Liang, Guang; Zhu, Ting; Zhang, Lijie; Huang, Shaoming; Schipper, Desmond; Jones, Richard A

2018-05-28

Four luminescent 32-metal Cd-Tb nanoclusters, [Tb 8 Cd 24 (L 1 ) 12 (OAc) 48 ] ( 1 ), [Tb 8 Cd 24 (L 2 ) 12 (OAc) 48 ] ( 2 ), [Tb 8 Cd 24 (L 3 ) 12 (OAc) 48 ] ( 3 ) and [Tb 8 Cd 24 (L 2 ) 12 (1,4-BDC) 4 (OAc) 38 (OH) 2 ] ( 4 ), were constructed from three specially designed chain-like Schiff base ligands H 2 L 1-3 with flexible carbon-carbon backbones containing 5, 6 and 10 methylene units, respectively. The clusters exhibit drum-like structures and can be imaged using transmission electron microscopy (TEM). In addition to the Schiff base ligands (the primary energy transfer donors), four 1,4-BDC bridging units were successfully introduced into the structure of 4 . In addition to providing increased structural stability, the 1,4-BDC units act as secondary energy transfer donors providing extra energy for lanthanide luminescence, which results in improved luminescence properties when compared to those of the related Cd-Ln nanoclusters without 1,4-BDC units. In vitro investigations on 4 with SGC and PANC cancer cells revealed an accumulation of the molecular nanoparticles in the cells, as confirmed by confocal microscopy. The cytotoxicity of 4 toward the SGC and PANC cells is moderate (IC 50 values of 4 lie in the range of 15-60 μM). ICP-MS analysis reveals that cellular uptakes of 4 in 1000 SGC and PANC cells after treatment for 3 hours are 0.0094 pmol and 0.015 pmol, respectively.

Site specific ligand substitution in cubane-type Mo3FeS(4)(4+) clusters: kinetics and mechanism of reaction and isolation of mixed ligand Cl/SPh complexes.

PubMed

Algarra, Andrés G; Basallote, Manuel G; Fernandez-Trujillo, M J; Llusar, Rosa; Pino-Chamorro, Jose A; Sorribes, Ivan; Vicent, Cristian

2010-04-21

The synthesis, crystal structure and solution characterization of the cubane-type [Mo(3)(FeCl)S(4)(dmpe)(3)Cl(3)] (1) (dmpe = 1,2-bis(dimethylphophane-ethane)) cluster are reported and the ligand substitution processes of chloride by thiophenolate investigated. The kinetics and the intimate mechanism of these substitutions reveal that compound 1 undergoes a number of Fe and Mo site specific ligand substitution reactions in acetonitrile solutions. In particular, PhS(-) coordination at the tetrahedral Fe site proceeds in a single resolved kinetic step whereas such substitutions at the Mo sites proceed more slowly. The effect of the presence of acids in the reaction media is also investigated and reveals that an acid excess hinders substitution reactions both at the Fe and Mo sites; however, an acid-promoted solvolysis of the Fe-Cl bonds is observed. Electrospray ionization (ESI) and tandem (ESI-MS/MS) mass spectrometry allow the identification of all the reaction intermediates proposed on the basis of stopped-flow measurements. The distinctive site specific reactivity made it possible to isolate two new clusters of the Mo(3)FeS(4)(4+) family featuring mixed chlorine/thiophenolate ligands, namely Mo(3)S(4)(FeSPh)(dmpe)(3)Cl(3) (2) and [Mo(3)S(4)(FeSPh)(dmpe)(3)(SPh)(3)] (3). A detailed computational study has also been carried out to understand the details of the mechanism of substitution at the M-Cl (M = Mo and Fe) bonds as well as the solvolysis at the Fe-Cl sites, with particular emphasis on the role of acids on the substitution process. The results of the calculations are in agreement with the experimental observations, thus justifying the non-existence of an accelerating effect of acids on the thiophenolate substitution reaction, which differs from previous proposals for the Fe(4)S(4) and MoFe(3)S(4) clusters and some related compounds.

Monitoring the solid-state electrochemistry of Cu(2,7-AQDC) (AQDC = anthraquinone dicarboxylate) in a lithium battery: coexistence of metal and ligand redox activities in a metal-organic framework.

PubMed

Zhang, Zhongyue; Yoshikawa, Hirofumi; Awaga, Kunio

2014-11-19

By adopting a facile synthetic strategy, we obtained a microporous redox-active metal-organic framework (MOF), namely, Cu(2,7-AQDC) (2,7-H2AQDC = 2,7-anthraquinonedicarboxylic acid) (1), and utilized it as a cathode active material in lithium batteries. With a voltage window of 4.0-1.7 V, both metal clusters and anthraquinone groups in the ligands exhibited reversible redox activity. The valence change of copper cations was clearly evidenced by in situ XANES analysis. By controlling the voltage window of operation, extremely high recyclability of batteries was achieved, suggesting the framework was robust. This MOF is the first example of a porous material showing independent redox activity on both metal cluster nodes and ligand sites.

A Co16 cluster and a 1-D Mn chain complex supported by benzohydroxamic acid.

PubMed

Cao, Yanyuan; Chen, Yanmei; Li, Lei; Gao, Dandan; Liu, Wei; Hu, Hailiang; Li, Wu; Li, Yahong

2013-08-14

The syntheses, crystal structures and magnetic properties are described for a {Co16} cluster [Co(II)16O(OH)2(bha)12(PhCO2)4(Phen)2(MeOH)4]·2MeOH (1) and a 1-D Mn(II) chain complex [Mn(Hbha)2]n·(2MeOH)n (2) (H2bha = benzohydroxamic acid; Phen = 1,10-phenanthroline). The 1 : 1 : 0.5 reaction of Co(O2CMe)2·4H2O, H2bha and 1,10-phenanthroline in MeOH at 100 °C under autogenous pressure gave cluster 1. Complex 2 was obtained from the 1 : 1 reaction mixture of Mn(O2CMe)2·2H2O and H2bha in MeOH under solvothermal conditions. The {Co16} cluster can be thought as a face-centered cube with two wings. The H2bha ligands show hydroximic form in 1 and exhibit hydroxamic mode in 2. The hydroximate ligands in 1 display three distinct binding modes, one of which is novel. Variable-temperature solid-state dc magnetic susceptibility studies have been performed in the 2.0-300 K range for complexes 1 and 2. Antiferromagnetic M(II)···M(II) exchange interactions were found for both 1 and 2. This work also demonstrates that solvothermal method is a potential synthetic approach for the design and growth of high nuclearity clusters or chain complexes of the H2bha ligand.

Polymers for binding of the gram-positive oral pathogen Streptococcus mutans

PubMed Central

Magennis, Eugene P.; Francini, Nora; Mastrotto, Francesca; Catania, Rosa; Redhead, Martin; Fernandez-Trillo, Francisco; Bradshaw, David; Churchley, David; Winzer, Klaus; Alexander, Cameron

2017-01-01

Streptococcus mutans is the most significant pathogenic bacterium implicated in the formation of dental caries and, both directly and indirectly, has been associated with severe conditions such as multiple sclerosis, cerebrovascular and peripheral artery disease. Polymers able to selectively bind S. mutans and/or inhibit its adhesion to oral tissue in a non-lethal manner would offer possibilities for addressing pathogenicity without selecting for populations resistant against bactericidal agents. In the present work two libraries of 2-(dimethylamino)ethyl methacrylate (pDMAEMA)-based polymers were synthesized with various proportions of either N,N,N-trimethylethanaminium cationic- or sulfobetaine zwitterionic groups. These copolymers where initially tested as potential macromolecular ligands for S. mutans NCTC 10449, whilst Escherichia coli MG1655 was used as Gram-negative control bacteria. pDMAEMA-derived materials with high proportions of zwitterionic repeating units were found to be selective for S. mutans, in both isolated and S. mutans–E. coli mixed bacterial cultures. Fully sulfobetainized pDMAEMA was subsequently found to bind/cluster preferentially Gram-positive S. mutans and S. aureus compared to Gram negative E. coli and V. harveyi. A key initial stage of S. mutans pathogenesis involves a lectin-mediated adhesion to the tooth surface, thus the range of potential macromolecular ligands was further expanded by investigating two glycopolymers bearing α-mannopyranoside and β-galactopyranoside pendant units. Results with these polymers indicated that preferential binding to either S. mutans or E. coli can be obtained by modulating the glycosylation pattern of the chosen multivalent ligands without incurring unacceptable cytotoxicity in a model gastrointestinal cell line. Overall, our results allowed to identify a structure–property relationship for the potential antimicrobial polymers investigated, and suggest that preferential binding to Gram-positive S. mutans could be achieved by fine-tuning of the recognition elements in the polymer ligands. PMID:28672031

Dialing in single-site reactivity of a supported calixarene-protected tetrairidium cluster catalyst† †Electronic supplementary information (ESI) available: Detailed characterization of Ir4 clusters, raw kinetic data, time scale analysis, experimental methods, and sample preparation. See DOI: 10.1039/c7sc00686a Click here for additional data file.

PubMed Central

Palermo, Andrew; Solovyov, Andrew; Ertler, Daniel

2017-01-01

A closed Ir4 carbonyl cluster, 1, comprising a tetrahedral metal frame and three sterically bulky tert-butyl-calix[4]arene(OPr)3(OCH2PPh2) (Ph = phenyl; Pr = propyl) ligands at the basal plane, was characterized with variable-temperature 13C NMR spectroscopy, which show the absence of scrambling of the CO ligands at temperatures up to 313 K. This demonstration of distinct sites for the CO ligands was found to extend to the reactivity and catalytic properties, as shown by selective decarbonylation in a reaction with trimethylamine N-oxide (TMAO) as an oxidant, which, reacting in the presence of ethylene, leads to the selective bonding of an ethyl ligand at the apical Ir site. These clusters were supported intact on porous silica and found to catalyze ethylene hydrogenation, and a comparison of the kinetics of the single-hydrogenation reaction and steady-state hydrogenation catalysis demonstrates a unique single-site catalyst—with each site having the same catalytic activity. Reaction orders in the catalytic ethylene hydrogenation reaction of approximately 1/2 and 0 for H2 and C2H4, respectively, nearly match those for conventional noble-metal catalysts. In contrast to oxidative decarbonylation, thermal desorption of CO from silica-supported cluster 1 occurred exclusively at the basal plane, giving rise to sites that do not react with ethylene and are catalytically inactive for ethylene hydrogenation. The evidence of distinctive sites on the cluster catalyst leads to a model that links to hydrogen-transfer catalysis on metals—involving some surface sites that bond to both hydrocarbon and hydrogen and are catalytically engaged (so-called “*” sites) and others, at the basal plane, which bond hydrogen and CO but not hydrocarbon and are reservoir sites (so-called “S” sites). PMID:28959418

Ligand Field Strength Mediates Electron Delocalization in Octahedral [((H)L)2Fe6(L')m](n+) Clusters.

PubMed

Hernández Sánchez, Raúl; Zheng, Shao-Liang; Betley, Theodore A

2015-09-02

To assess the impact of terminal ligand binding on a variety of cluster properties (redox delocalization, ground-state stabilization, and breadth of redox state accessibility), we prepared three electron-transfer series based on the hexanuclear iron cluster [((H)L)2Fe6(L')m](n+) in which the terminal ligand field strength was modulated from weak to strong (L' = DMF, MeCN, CN). The extent of intracore M-M interactions is gauged by M-M distances, spin ground state persistence, and preference for mixed-valence states as determined by electrochemical comproportionation constants. Coordination of DMF to the [((H)L)2Fe6] core leads to weaker Fe-Fe interactions, as manifested by the observation of ground states populated only at lower temperatures (<100 K) and by the greater evidence of valence trapping within the mixed-valence states. Comproportionation constants determined electrochemically (Kc = 10(4)-10(8)) indicate that the redox series exhibits electronic delocalization (class II-III), yet no intervalence charge transfer (IVCT) bands are observable in the near-IR spectra. Ligation of the stronger σ donor acetonitrile results in stabilization of spin ground states to higher temperatures (∼300 K) and a high degree of valence delocalization (Kc = 10(2)-10(8)) with observable IVCT bands. Finally, the anionic cyanide-bound series reveals the highest degree of valence delocalization with the most intense IVCT bands (Kc = 10(12)-10(20)) and spin ground state population beyond room temperature. Across the series, at a given formal oxidation level, the capping ligand on the hexairon cluster dictates the overall properties of the aggregate, modulating the redox delocalization and the persistence of the intracore coupling of the metal sites.

Membrane Localization is Critical for Activation of the PICK1 BAR Domain

PubMed Central

Madsen, Kenneth L.; Eriksen, Jacob; Milan-Lobo, Laura; Han, Daniel S.; Niv, Masha Y.; Ammendrup-Johnsen, Ina; Henriksen, Ulla; Bhatia, Vikram K.; Stamou, Dimitrios; Sitte, Harald H.; McMahon, Harvey T.; Weinstein, Harel; Gether, Ulrik

2013-01-01

The PSD-95/Discs-large/ZO-1 homology (PDZ) domain protein, protein interacting with C kinase 1 (PICK1) contains a C-terminal Bin/amphiphysin/Rvs (BAR) domain mediating recognition of curved membranes; however, the molecular mechanisms controlling the activity of this domain are poorly understood. In agreement with negative regulation of the BAR domain by the N-terminal PDZ domain, PICK1 distributed evenly in the cytoplasm, whereas truncation of the PDZ domain caused BAR domain-dependent redistribution to clusters colocalizing with markers of recycling endosomal compartments. A similar clustering was observed both upon truncation of a short putative α-helical segment in the linker between the PDZ and the BAR domains and upon coexpression of PICK1 with a transmembrane PDZ ligand, including the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluR2 subunit, the GluR2 C-terminus transferred to the single transmembrane protein Tac or the dopamine transporter C-terminus transferred to Tac. In contrast, transfer of the GluR2 C-terminus to cyan fluorescent protein, a cytosolic protein, did not elicit BAR domain-dependent clustering. Instead, localizing PICK1 to the membrane by introducing an N-terminal myristoylation site produced BAR domain-dependent, but ligand-independent, PICK1 clustering. The data support that in the absence of PDZ ligand, the PICK1 BAR domain is inhibited through a PDZ domain-dependent and linker-dependent mechanism. Moreover, they suggest that unmasking of the BAR domain’s membrane-binding capacity is not a consequence of ligand binding to the PDZ domain per se but results from, and coincides with, recruitment of PICK1 to a membrane compartment. PMID:18466293

Laser synthesis and spectroscopy of acetonitrile/silver nanoparticles

NASA Astrophysics Data System (ADS)

Akin, S. T.; Liu, X.; Duncan, M. A.

2015-11-01

Silver nanoparticles with acetonitrile ligands are produced in a laser ablation flow reactor. Excimer laser ablation produces gas phase metal clusters which are thermalized with helium or argon collisions in the flowtube, and reactions with acetonitrile vapor coordinate this ligand to the particle surface. The gaseous mixture is captured in a cryogenic trap; warming produces a solution of excess ligand and coated particles. TEM images reveal particle sizes of 10-30 nm diameter. UV-vis absorption and fluorescence spectra are compared to those of standard silver nanoparticles with surfactant coatings. Deep-UV ligand absorption is strongly enhanced by nanoparticle adsorption.

Applying Pose Clustering and MD Simulations To Eliminate False Positives in Molecular Docking.

PubMed

Makeneni, Spandana; Thieker, David F; Woods, Robert J

2018-03-26

In this work, we developed a computational protocol that employs multiple molecular docking experiments, followed by pose clustering, molecular dynamic simulations (10 ns), and energy rescoring to produce reliable 3D models of antibody-carbohydrate complexes. The protocol was applied to 10 antibody-carbohydrate co-complexes and three unliganded (apo) antibodies. Pose clustering significantly reduced the number of potential poses. For each system, 15 or fewer clusters out of 100 initial poses were generated and chosen for further analysis. Molecular dynamics (MD) simulations allowed the docked poses to either converge or disperse, and rescoring increased the likelihood that the best-ranked pose was an acceptable pose. This approach is amenable to automation and can be a valuable aid in determining the structure of antibody-carbohydrate complexes provided there is no major side chain rearrangement or backbone conformational change in the H3 loop of the CDR regions. Further, the basic protocol of docking a small ligand to a known binding site, clustering the results, and performing MD with a suitable force field is applicable to any protein ligand system.

The role of extended Fe4S4 cluster ligands in mediating sulfite reductase hemoprotein activity.

PubMed

Cepeda, Marisa R; McGarry, Lauren; Pennington, Joseph M; Krzystek, J; Elizabeth Stroupe, M

2018-05-28

The siroheme-containing subunit from the multimeric hemoflavoprotein NADPH-dependent sulfite reductase (SiR/SiRHP) catalyzes the six electron-reduction of SO 3 2- to S 2- . Siroheme is an iron-containing isobacteriochlorin that is found in sulfite and homologous siroheme-containing nitrite reductases. Siroheme does not work alone but is covalently coupled to a Fe 4 S 4 cluster through one of the cluster's ligands. One long-standing hypothesis predicted from this observation is that the environment of one iron-containing cofactor influences the properties of the other. We tested this hypothesis by identifying three amino acids (F437, M444, and T477) that interact with the Fe 4 S 4 cluster and probing the effect of altering them to alanine on the function and structure of the resulting enzymes by use of activity assays, X-ray crystallographic analysis, and EPR spectroscopy. We showed that F437 and M444 gate access for electron transfer to the siroheme-cluster assembly and the direct hydrogen bond between T477 and one of the cluster sulfides is important for determining the geometry of the siroheme active site. Copyright © 2018. Published by Elsevier B.V.

sc-PDB: a database for identifying variations and multiplicity of 'druggable' binding sites in proteins.

PubMed

Meslamani, Jamel; Rognan, Didier; Kellenberger, Esther

2011-05-01

The sc-PDB database is an annotated archive of druggable binding sites extracted from the Protein Data Bank. It contains all-atoms coordinates for 8166 protein-ligand complexes, chosen for their geometrical and physico-chemical properties. The sc-PDB provides a functional annotation for proteins, a chemical description for ligands and the detailed intermolecular interactions for complexes. The sc-PDB now includes a hierarchical classification of all the binding sites within a functional class. The sc-PDB entries were first clustered according to the protein name indifferent of the species. For each cluster, we identified dissimilar sites (e.g. catalytic and allosteric sites of an enzyme). SCOPE AND APPLICATIONS: The classification of sc-PDB targets by binding site diversity was intended to facilitate chemogenomics approaches to drug design. In ligand-based approaches, it avoids comparing ligands that do not share the same binding site. In structure-based approaches, it permits to quantitatively evaluate the diversity of the binding site definition (variations in size, sequence and/or structure). The sc-PDB database is freely available at: http://bioinfo-pharma.u-strasbg.fr/scPDB.

LAR-RPTP Clustering Is Modulated by Competitive Binding between Synaptic Adhesion Partners and Heparan Sulfate

PubMed Central

Won, Seoung Youn; Kim, Cha Yeon; Kim, Doyoun; Ko, Jaewon; Um, Ji Won; Lee, Sung Bae; Buck, Matthias; Kim, Eunjoon; Heo, Won Do; Lee, Jie-Oh; Kim, Ho Min

2017-01-01

The leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) are cellular receptors of heparan sulfate (HS) and chondroitin sulfate (CS) proteoglycans that direct axonal growth and neuronal regeneration. LAR-RPTPs are also synaptic adhesion molecules that form trans-synaptic adhesion complexes by binding to various postsynaptic adhesion ligands, such as Slit- and Trk-like family of proteins (Slitrks), IL-1 receptor accessory protein-like 1 (IL1RAPL1), interleukin-1 receptor accessory protein (IL-1RAcP) and neurotrophin receptor tyrosine kinase C (TrkC), to regulate synaptogenesis. Here, we determined the crystal structure of the human LAR-RPTP/IL1RAPL1 complex and found that lateral interactions between neighboring LAR-RPTP/IL1RAPL1 complexes in crystal lattices are critical for the higher-order assembly and synaptogenic activity of these complexes. Moreover, we found that LAR-RPTP binding to the postsynaptic adhesion ligands, Slitrk3, IL1RAPL1 and IL-1RAcP, but not TrkC, induces reciprocal higher-order clustering of trans-synaptic adhesion complexes. Although LAR-RPTP clustering was induced by either HS or postsynaptic adhesion ligands, the dominant binding of HS to the LAR-RPTP was capable of dismantling pre-established LAR-RPTP-mediated trans-synaptic adhesion complexes. These findings collectively suggest that LAR-RPTP clustering for synaptogenesis is modulated by a complex synapse-organizing protein network. PMID:29081732

Elucidating the Functional Roles of Spatial Organization in Cross-Membrane Signal Transduction by a Hybrid Simulation Method.

PubMed

Chen, Jiawen; Xie, Zhong-Ru; Wu, Yinghao

2016-07-01

The ligand-binding of membrane receptors on cell surfaces initiates the dynamic process of cross-membrane signal transduction. It is an indispensable part of the signaling network for cells to communicate with external environments. Recent experiments revealed that molecular components in signal transduction are not randomly mixed, but spatially organized into distinctive patterns. These patterns, such as receptor clustering and ligand oligomerization, lead to very different gene expression profiles. However, little is understood about the molecular mechanisms and functional impacts of this spatial-temporal regulation in cross-membrane signal transduction. In order to tackle this problem, we developed a hybrid computational method that decomposes a model of signaling network into two simulation modules. The physical process of binding between receptors and ligands on cell surfaces are simulated by a diffusion-reaction algorithm, while the downstream biochemical reactions are modeled by stochastic simulation of Gillespie algorithm. These two processes are coupled together by a synchronization framework. Using this method, we tested the dynamics of a simple signaling network in which the ligand binding of cell surface receptors triggers the phosphorylation of protein kinases, and in turn regulates the expression of target genes. We found that spatial aggregation of membrane receptors at cellular interfaces is able to either amplify or inhibit downstream signaling outputs, depending on the details of clustering mechanism. Moreover, by providing higher binding avidity, the co-localization of ligands into multi-valence complex modulates signaling in very different ways that are closely related to the binding affinity between ligand and receptor. We also found that the temporal oscillation of the signaling pathway that is derived from genetic feedback loops can be modified by the spatial clustering of membrane receptors. In summary, our method demonstrates the functional importance of spatial organization in cross-membrane signal transduction. The method can be applied to any specific signaling pathway in cells.

Crystallization and preliminary X-ray diffraction studies of hyperthermophilic archaeal Rieske-type ferredoxin (ARF) from Sulfolobus solfataricus P1

PubMed Central

Kounosu, Asako; Hasegawa, Kazuya; Iwasaki, Toshio; Kumasaka, Takashi

2010-01-01

The hyperthermophilic archaeal Rieske-type [2Fe–2S] ferredoxin (ARF) from Sulfolobus solfataricus P1 contains a low-potential Rieske-type [2Fe–2S] cluster that has served as a tractable model for ligand-substitution studies on this protein family. Recombinant ARF harbouring a pET30a vector-derived N-­terminal extension region plus a hexahistidine tag has been heterologously overproduced in Escherichia coli, purified and crystallized by the hanging-drop vapour-diffusion method using 0.05 M sodium acetate, 0.05 M HEPES, 2 M ammonium sulfate pH 5.5. The crystals diffracted to 1.85 Å resolution and belonged to the tetragonal space group P43212, with unit-cell parameters a = 60.72, c = 83.31 Å. The asymmetric unit contains one protein molecule. PMID:20606288

Crystallization and preliminary X-ray diffraction studies of hyperthermophilic archaeal Rieske-type ferredoxin (ARF) from Sulfolobus solfataricus P1.

PubMed

Kounosu, Asako; Hasegawa, Kazuya; Iwasaki, Toshio; Kumasaka, Takashi

2010-07-01

The hyperthermophilic archaeal Rieske-type [2Fe-2S] ferredoxin (ARF) from Sulfolobus solfataricus P1 contains a low-potential Rieske-type [2Fe-2S] cluster that has served as a tractable model for ligand-substitution studies on this protein family. Recombinant ARF harbouring a pET30a vector-derived N-terminal extension region plus a hexahistidine tag has been heterologously overproduced in Escherichia coli, purified and crystallized by the hanging-drop vapour-diffusion method using 0.05 M sodium acetate, 0.05 M HEPES, 2 M ammonium sulfate pH 5.5. The crystals diffracted to 1.85 A resolution and belonged to the tetragonal space group P4(3)2(1)2, with unit-cell parameters a = 60.72, c = 83.31 A. The asymmetric unit contains one protein molecule.

Ligand induced ferromagnetism in ZnO nanostructures.

PubMed

Wang, Qian; Sun, Qiang; Jena, P

2008-10-28

Complementary to the experimental finding that ZnO nanoparticles become ferromagnetic when coated with N and S containing ligands such as dodecylamine and dodecanethiol [Garcia et al., Nano Lett. 7, 1489 (2007)], we provide the first theoretical understanding of the origin of magnetism in ligated ZnO nanoparticles as well as the structural properties of the ligated systems by using density functional theory and generalized gradient approximation for exchange and correlation, and a cluster model for the nanoparticles. We show that N or S atoms of the ligand bind to the Zn sites. The accompanying changes in the Zn-O bond length, hybridization between Zn 4s orbitals with N 2p or S 3p orbitals, and consequently the redistribution of charges between Zn and O atoms result in a magnetic system where the 2p electrons in O and N, and 3p electrons in S sites are spin polarized. Furthermore, the sites nearest to the Zn atom attached to the ligand carry bulk of the magnetic moment. Studies, as a function of cluster size, also illustrate that magnetism resides only on the surface. Our results confirm that the use of ligands can pave a new way for introducing magnetism in ZnO nanostructures, which can be used to develop magnetic sensors to detect N and S containing molecules.

Titanium Insertion into CO Bonds in Anionic Ti-CO2 Complexes.

PubMed

Dodson, Leah G; Thompson, Michael C; Weber, J Mathias

2018-03-22

We explore the structures of [Ti(CO 2 ) y ] - cluster anions using infrared photodissociation spectroscopy and quantum chemistry calculations. The existence of spectral signatures of metal carbonyl CO stretching modes shows that insertion of titanium atoms into C-O bonds represents an important reaction during the formation of these clusters. In addition to carbonyl groups, the infrared spectra show that the titanium center is coordinated to oxalato, carbonato, and oxo ligands, which form along with the metal carbonyls. The presence of a metal oxalato ligand promotes C-O bond insertion in these systems. These results highlight the affinity of titanium for C-O bond insertion processes.

Heptacopper(II) and dicopper(II)-adenine complexes: synthesis, structural characterization, and magnetic properties

DOE PAGES

Leite Ferreira, B. J. M.; Brandão, Paula; Dos Santos, A. M.; ...

2015-07-13

The syntheses, crystal structures, and magnetic properties of two new copper(II) complexes with molecular formulas [Cu 7(μ 2-OH 2) 6(μ 3-O) 6(adenine) 6(NO 3) 26H 2O (1) and [Cu 2(μ 2-H 2O) 2(adenine) 2(H 2O) 4](NO 3) 42H 2O (2) are reported. We composed the heptanuclear compound of a central octahedral CuO 6 core sharing edges with six adjacent copper octahedra. In 2, the copper octahedra shares one equatorial edge. In both compounds, these basic copper cluster units are further linked by water bridges and bridging adenine ligands through N3 and N9 donors. All copper(II) centers exhibit Jahn-Teller distorted octahedralmore » coordination characteristic of a d 9 center. Our study of the magnetic properties of the heptacopper complex revealed a dominant ferromagnetic intra-cluster interaction, while the dicopper complex exhibits antiferromagnetic intra-dimer interactions with weakly ferromagnetic inter-dimer interaction.« less

Quantum mechanical design and structures of hexanuclear sandwich complex and its multidecker sandwich clusters (Li6)n([18]annulene)n+1 (n = 1-3).

PubMed

Wang, Shu-Jian; Li, Ying; Wu, Di; Wang, Yin-Feng; Li, Zhi-Ru

2012-09-13

By means of density functional theory, a hexanuclear sandwich complex [18]annulene-Li6-[18]annulene which consists of a central Li6 hexagon ring and large face-capping ligands, [18]annulene, is designed and investigated. The large interaction energy and HOMO-LUMO gap suggest that this novel charge-separated complex is highly stable and may be experimentally synthesized. In addition, the stability found in the [18]annulene-Li6-[18]annulene complex extends to multidecker sandwich clusters (Li6)n([18]annulene)n+1 (n = 2-3). The energy gain upon addition of a [18]annulene-Li6 unit to (Li6)n-1([18]annulene)n is pretty large (96.97-98.22 kcal/mol), indicating that even larger multideckers will also be very stable. Similar to ferrocene, such a hexanuclear sandwich complex could be considered as a versatile building block to find potential applications in different areas of chemistry, such as nanoscience and material science.

Evaluating the component contribution to nonlinear optical performances using stable [Ni4O4] cuboidal clusters as models.

PubMed

Hao, Zhi-Min; Chao, Meng-Yao; Liu, Yan; Song, Ying-Lin; Yang, Jun-Yi; Ding, Lifeng; Zhang, Wen-Hua; Lang, Jian-Ping

2018-06-19

Five stable clusters sharing the cuboidal [Ni4O4] skeleton are subjected to third-order nonlinear optical (NLO) property measurements. Preliminary results suggest that the NLO property is largely defined by the cluster core skeleton and the directly coordinated atoms, with limited contribution from the heavy atoms peripherally attached to the aromatic ligands.

A new family of Ln₇ clusters with an ideal D(3h) metal-centered trigonal prismatic geometry, and SMM and photoluminescence behaviors.

PubMed

Mazarakioti, Eleni C; Poole, Katye M; Cunha-Silva, Luis; Christou, George; Stamatatos, Theocharis C

2014-08-14

The first use of the flexible Schiff base ligand N-salicylidene-2-aminocyclohexanol in metal cluster chemistry has afforded a new family of Ln7 clusters with ideal D(3h) point group symmetry and metal-centered trigonal prismatic topology; solid-state and solution studies revealed SMM and photoluminescence behaviors.

Full control of ligand positioning reveals spatial thresholds for T cell receptor triggering.

PubMed

Cai, Haogang; Muller, James; Depoil, David; Mayya, Viveka; Sheetz, Michael P; Dustin, Michael L; Wind, Shalom J

2018-04-30

Elucidating the rules for receptor triggering in cell-cell and cell-matrix contacts requires precise control of ligand positioning in three dimensions. Here, we use the T cell receptor (TCR) as a model and subject T cells to different geometric arrangements of ligands, using a nanofabricated single-molecule array platform. This comprises monovalent TCR ligands anchored to lithographically patterned nanoparticle clusters surrounded by mobile adhesion molecules on a supported lipid bilayer. The TCR ligand could be co-planar with the supported lipid bilayer (2D), excluding the CD45 transmembrane tyrosine phosphatase, or elevated by 10 nm on solid nanopedestals (3D), allowing closer access of CD45 to engaged TCR. The two configurations resulted in different T cell responses, depending on the lateral spacing between the ligands. These results identify the important contributions of lateral and axial components of ligand positioning and create a more complete foundation for receptor engineering for immunotherapy.

Conversion of the. mu. ketene ligand in (PPN)(Os/sub 3/(CO)/sub 10/(. mu. -I)(. mu. -CH/sub 2/CO)) into enolate, acyl, and vinyl ligands

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bassner, S.L.; Morrison, E.D.; Geoffroy, G.L.

1986-08-20

Free ketene is a valuable organic synthetic reagent, but its utility is somewhat limited by its high reactivity and tendency to dimerize to yield diketene. The ketene ligand is obviously stabilized by metal coordination in a variety of bonding modes, but it is not yet known how coordination influences the chemistry of this important molecule. The authors have studied the reactivity of the coordinated ketene ligand of type II found in the anionic cluster compound (PPN)(Os/sub 3/(CO)/sub 10/(..mu..-I)(..mu..-CH/sub 2/CO)) (1) (PPN/sup +/ = (Ph/sub 3/P)/sub 2/N/sup +/) and herein show that this ligand is readily converted into eta-enolate ligands uponmore » reaction with simple nucleophiles and into vinyl and acetyl ligands upon reaction with electrophiles.« less

Microsolvation of the 5-hydroxyindole cation (5HI+) with nonpolar and quadrupolar ligands: Infrared photodissociation spectra of 5HI+-Ln clusters with L = Ar and N2 (n ≤ 3)

NASA Astrophysics Data System (ADS)

Klyne, Johanna; Dopfer, Otto

2017-07-01

Solvation of biomolecules and their building blocks has a strong influence on their structure and function. Herein we characterize the initial microsolvation of the 5-hydroxyindole cation (5HI+) in its 2A″ ground electronic state with nonpolar and quadrupolar ligands (L = Ar, N2) by infrared photodissociation (IRPD) spectroscopy of cold and mass-selected 5HI+-Ln (n ≤ 3) clusters in a molecular beam and dispersion-corrected density functional theory calculations (B3LYP-D3/aug-cc-pVTZ). The isomer-selective OH and NH stretch frequency shifts (ΔνOH/NH) disentangle the competition between H-bonding to the acidic OH and NH groups and π-stacking to the conjugated bicyclic aromatic π-electron system, the intermolecular interaction strengths, and the cluster growth sequence. For 5HI+-Arn, H-bonding and π-stacking strongly compete, indicating that dispersion forces are important for the interaction of 5HI+ with nonpolar ligands. In contrast, for 5HI+-(N2)n clusters, the H-bonds are much stronger than the π-bonds and largely determine the initial solvation process. In all clusters, the OH…L bonds are stronger than the NH…L bonds followed by the π-bonds. The interaction of 5HI+ with N2 is roughly twice stronger than with Ar, mainly due to the additional quadrupole moment of N2. The nature and strength of the individual interactions are quantified by the noncovalent interaction approach. Comparison of 5HI+-L with the corresponding neutral clusters reveals the strong impact of ionization on the total and relative interaction strengths of the H-bonds and π-bonds. In addition, comparison of 5HI+-L with corresponding clusters of the phenol, indole, and pyrrole radical cations illustrates the effects of substitution of functional groups and the addition of aromatic rings to the various subunits of 5HI on the intermolecular potential.

Stabilization of Reduced Molybdenum-Iron-Sulfur Single and Double Cubane Clusters by Cyanide Ligation

PubMed Central

Pesavento, Russell P.; Berlinguette, Curtis P.; Holm, R. H.

2008-01-01

Recent work has shown that cyanide ligation increases the redox potentials of Fe4S4 clusters, enabling the isolation of [Fe4S4(CN)4]4−, the first synthetic Fe4S4 cluster obtained in the all-ferrous oxidation state (Scott, T. A.; Berlinguette, C. P.; Holm, R. H.; Zhou, H.-C., Proc. Natl. Acad. Sci. USA 2005, 102, 9741). The generality of reduced cluster stabilization has been examined with MoFe3S4 clusters. Reaction of single cubane [(Tp)MoFe3S4(PEt3)3]1+ and edge-bridged double cubane [(Tp)2Mo2Fe6S8(PEt3)4] with cyanide in acetonitrile affords [(Tp)MoFe3S4(CN)3]2− (2) and [(Tp)2Mo2Fe6S8(CN)4]4− (5), respectively. Reduction of 2 with KC14H10 yields [(Tp)MoFe3S4(CN)3]3− (3). Clusters were isolated in ca. 70–90% yields as Et4N+ or Bu4N+ salts; Clusters 3 and 5 contain all-ferrous cores; 3 is the first [MoFe3S4]1+ cluster isolated in substance. The structures of 2 and 3 are very similar; the volume of the reduced cluster core is slightly larger (2.5%), a usual effect upon reduction of cubane-type Fe4S4 and MFe3S4 clusters. Redox potentials and 57Fe isomer shifts of [(Tp)MoFe3S4L3]2−,3 and [(Tp)2Mo2Fe6S8L4]4−,3− clusters with L = CN, PhS, halide, and PEt3 are compared. Clusters with π-donor ligands (L = halide, PhS) exhibit larger isomer shifts and lower (more negative) redox potentials while π-acceptor ligands (L = CN, PEt3) induce smaller isomer shifts and higher (less negative) redox potentials. When potentials of 3/2 and [(Tp)MoFe3S4(SPh)3]3−/2− are compared, cyanide stabilizes 3 by 270 mV vs. the reduced thiolate cluster, commensurate with the 310 mV stabilization of [Fe4S4(CN)4]4− vs. [Fe4S4(SPh)4]4− where four ligands differ. These results demonstrate the efficacy of cyanide stabilization of lower cluster oxidation states. (Tp = hydrotris(pyrazolyl)borate(1−)). PMID:17279830

Stabilization of reduced molybdenum-iron-sulfur single- and double-cubane clusters by cyanide ligation.

PubMed

Pesavento, Russell P; Berlinguette, Curtis P; Holm, R H

2007-01-22

Recent work has shown that cyanide ligation increases the redox potentials of Fe(4)S(4) clusters, enabling the isolation of [Fe(4)S(4)(CN)4]4-, the first synthetic Fe(4)S(4) cluster obtained in the all-ferrous oxidation state (Scott, T. A.; Berlinguette, C. P.; Holm, R. H.; Zhou, H.-C. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 9741). The generality of reduced cluster stabilization has been examined with MoFe(3)S(4) clusters. Reaction of single-cubane [(Tp)MoFe(3)S(4)(PEt(3))3]1+ and edge-bridged double-cubane [(Tp)2Mo(2)Fe(6)S(8)(PEt(3))4] with cyanide in acetonitrile affords [(Tp)MoFe(3)S(4)(CN)3]2- (2) and [(Tp)2Mo(2)Fe(6)S(8)(CN)4]4- (5), respectively. Reduction of 2 with KC(14)H(10) yields [(Tp)MoFe(3)S(4)(CN)3]3- (3). Clusters were isolated in approximately 70-90% yields as Et(4)N+ or Bu(4)N+ salts; clusters 3 and 5 contain all-ferrous cores, and 3 is the first [MoFe(3)S(4)]1+ cluster isolated in substance. The structures of 2 and 3 are very similar; the volume of the reduced cluster core is slightly larger (2.5%), a usual effect upon reduction of cubane-type Fe(4)S(4) and MFe(3)S(4) clusters. Redox potentials and 57Fe isomer shifts of [(Tp)MoFe(3)S(4)L3]2-,3- and [(Tp)2Mo(2)Fe(6)S(8)L(4)]4-,3- clusters with L = CN-, PhS-, halide, and PEt3 are compared. Clusters with pi-donor ligands (L = halide, PhS) exhibit larger isomer shifts and lower (more negative) redox potentials, while pi-acceptor ligands (L = CN, PEt3) induce smaller isomer shifts and higher (less-negative) redox potentials. When the potentials of 3/2 and [(Tp)MoFe(3)S(4)(SPh)3]3-/2- are compared, cyanide stabilizes 3 by 270 mV versus the reduced thiolate cluster, commensurate with the 310 mV stabilization of [Fe(4)S(4)(CN)4]4- versus [Fe(4)S(4)(SPh)4]4- where four ligands differ. These results demonstrate the efficacy of cyanide stabilization of lower cluster oxidation states. (Tp = hydrotris(pyrazolyl)borate(1-)).

Fluorescent probes for tracking the transfer of iron–sulfur cluster and other metal cofactors in biosynthetic reaction pathways

DOE PAGES

Vranish, James N.; Russell, William K.; Yu, Lusa E.; ...

2014-12-05

Iron–sulfur (Fe–S) clusters are protein cofactors that are constructed and delivered to target proteins by elaborate biosynthetic machinery. Mechanistic insights into these processes have been limited by the lack of sensitive probes for tracking Fe–S cluster synthesis and transfer reactions. Here we present fusion protein- and intein-based fluorescent labeling strategies that can probe Fe–S cluster binding. The fluorescence is sensitive to different cluster types ([2Fe–2S] and [4Fe–4S] clusters), ligand environments ([2Fe–2S] clusters on Rieske, ferredoxin (Fdx), and glutaredoxin), and cluster oxidation states. The power of this approach is highlighted with an extreme example in which the kinetics of Fe–S clustermore » transfer reactions are monitored between two Fdx molecules that have identical Fe–S spectroscopic properties. This exchange reaction between labeled and unlabeled Fdx is catalyzed by dithiothreitol (DTT), a result that was confirmed by mass spectrometry. DTT likely functions in a ligand substitution reaction that generates a [2Fe–2S]–DTT species, which can transfer the cluster to either labeled or unlabeled Fdx. The ability to monitor this challenging cluster exchange reaction indicates that real-time Fe–S cluster incorporation can be tracked for a specific labeled protein in multicomponent assays that include several unlabeled Fe–S binding proteins or other chromophores. Such advanced kinetic experiments are required to untangle the intricate networks of transfer pathways and the factors affecting flux through branch points. High sensitivity and suitability with high-throughput methodology are additional benefits of this approach. Lastly, we anticipate that this cluster detection methodology will transform the study of Fe–S cluster pathways and potentially other metal cofactor biosynthetic pathways.« less

Cytochrome C in a dry trehalose matrix: structural and dynamical effects probed by x-ray absorption spectroscopy.

PubMed

Giachini, Lisa; Francia, Francesco; Cordone, Lorenzo; Boscherini, Federico; Venturoli, Giovanni

2007-02-15

We report on the structure and dynamics of the Fe ligand cluster of reduced horse heart cytochrome c in solution, in a dried polyvinyl alcohol (PVA) film, and in two trehalose matrices characterized by different contents of residual water. The effect of the solvent/matrix environment was studied at room temperature using Fe K-edge x-ray absorption fine structure (XAFS) spectroscopy. XAFS data were analyzed by combining ab initio simulations and multi-parameter fitting in an attempt to disentangle structural from disorder parameters. Essentially the same structural and disorder parameters account adequately for the XAFS spectra measured in solution, both in the absence and in the presence of glycerol, and in the PVA film, showing that this polymer interacts weakly with the embedded protein. Instead, incorporation in trehalose leads to severe structural changes, more prominent in the more dried matrix, consisting of 1), an increase up to 0.2 A of the distance between Fe and the imidazole N atom of the coordinating histidine residue and 2), an elongation up to 0.16 A of the distance between Fe and the fourth-shell C atoms of the heme pyrrolic units. These structural distortions are accompanied by a substantial decrease of the relative mean-square displacements of the first ligands. In the extensively dried trehalose matrix, extremely low values of the Debye Waller factors are obtained for the pyrrolic and for the imidazole N atoms. This finding is interpreted as reflecting a drastic hindering in the relative motions of the Fe ligand cluster atoms and an impressive decrease in the static disorder of the local Fe structure. It appears, therefore, that the dried trehalose matrix dramatically perturbs the energy landscape of cytochrome c, giving rise, at the level of local structure, to well-resolved structural distortions and restricting the ensemble of accessible conformational substates.

Adamantyl- and Furanyl-Protected Nanoscale Silver Sulfide Clusters.

PubMed

Bestgen, Sebastian; Yang, Xiaoxun; Issac, Ibrahim; Fuhr, Olaf; Roesky, Peter W; Fenske, Dieter

2016-07-11

The silver salts of 1-adamantanethiol (AdSH) and furan-2-ylmethanethiol (FurCH2 SH) were successfully applied as building blocks for ligand-protected Ag2 S nanoclusters. The reaction of the silver thiolates [AgSAd]x and [AgSCH2 Fur]x with S(SiMe3 )2 and 1,5-bis(diphenylphosphino)pentane (dpppt) afforded three different clusters with 58, 94 and, 190 silver atoms. The intensely colored compounds [Ag58 S13 (SAd)32 ] (1), [Ag94 S34 (SAd)26 (dpppt)6 ] (2), and [Ag190 S58 (SCH2 Fur)74 (dpppt)8 ] (3) were structurally characterized by single-crystal X-ray diffraction and exhibit different cluster core geometries and ligand shells. The diameters of the well-defined sphere-shaped nanoclusters range from 2.2 nm to 3.5 nm. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recruitment of the Adaptor Protein Grb2 to EGFR Tetramers

PubMed Central

2015-01-01

Adaptor protein Grb2 binds phosphotyrosines in the epidermal growth factor (EGF) receptor (EGFR) and thereby links receptor activation to intracellular signaling cascades. Here, we investigated how recruitment of Grb2 to EGFR is affected by the spatial organization and quaternary state of activated EGFR. We used the techniques of image correlation spectroscopy (ICS) and lifetime-detected Förster resonance energy transfer (also known as FLIM-based FRET or FLIM–FRET) to measure ligand-induced receptor clustering and Grb2 binding to activated EGFR in BaF/3 cells. BaF/3 cells were stably transfected with fluorescently labeled forms of Grb2 (Grb2–mRFP) and EGFR (EGFR–eGFP). Following stimulation of the cells with EGF, we detected nanometer-scale association of Grb2–mRFP with EGFR–eGFP clusters, which contained, on average, 4 ± 1 copies of EGFR–eGFP per cluster. In contrast, the pool of EGFR–eGFP without Grb2–mRFP had an average cluster size of 1 ± 0.3 EGFR molecules per punctum. In the absence of EGF, there was no association between EGFR–eGFP and Grb2–mRFP. To interpret these data, we extended our recently developed model for EGFR activation, which considers EGFR oligomerization up to tetramers, to include recruitment of Grb2 to phosphorylated EGFR. The extended model, with adjustment of one new parameter (the ratio of the Grb2 and EGFR copy numbers), is consistent with a cluster size distribution where 2% of EGFR monomers, 5% of EGFR dimers, <1% of EGFR trimers, and 94% of EGFR tetramers are associated with Grb2. Together, our experimental and modeling results further implicate tetrameric EGFR as the key signaling unit and call into question the widely held view that dimeric EGFR is the predominant signaling unit. PMID:24697349

Properties of iron sulfide, hydrosulfide, and mixed sulfide/hydrosulfide cluster anions through photoelectron spectroscopy and density functional theory calculations.

PubMed

Yin, Shi; Bernstein, Elliot R

2016-10-21

A new magnetic-bottle time-of-flight photoelectron spectroscopy (PES) apparatus is constructed in our laboratory. The PES spectra of iron sulfide, hydrosulfide, and mixed sulfide/hydrosulfide [FeS m (SH) n - ; m, n = 0-3, 0 < (m + n) ≤ 3] cluster anions, obtained at 2.331 eV (532 nm) and 3.492 eV (355 nm) photon energies, are reported. The electronic structure and bonding properties of these clusters are additionally investigated at different levels of density functional theory. The most probable structures and ground state spin multiplicity for these cluster anions are tentatively assigned by comparing their theoretical first vertical detachment energies (VDEs) with their respective experiment values. The behavior of S and (SH) as ligands in these iron sulfide, hydrosulfide, and mixed sulfide/hydrosulfide cluster anions is investigated and compared. The experimental first VDEs for Fe(SH) 1-3 - cluster anions are lower than those found for their respective FeS 1-3 - cluster anions. The experimental first VDEs for FeS 1-3 - clusters are observed to increase for the first two S atoms bound to Fe - ; however, due to the formation of an S-S bond for the FeS 3 - cluster, its first VDE is found to be ∼0.41 eV lower than the first VDE for the FeS 2 - cluster. The first VDEs of Fe(SH) 1-3 - cluster anions are observed to increase with the increasing numbers of SH groups. The calculated partial charges of the Fe atom for ground state FeS 1-3 - and Fe(SH) 1-3 - clusters are apparently related to and correlated with their determined first VDEs. The higher first VDE is correlated with a higher, more positive partial charge for the Fe atom of these cluster anions. Iron sulfide/hydrosulfide mixed cluster anions are also explored in this work: the first VDE for FeS(SH) - is lower than that for FeS 2 - , but higher than that for Fe(SH) 2 - ; the first VDEs for FeS 2 (SH) - and FeS(SH) 2 - are close to that for FeS 3 - , but higher than that for Fe(SH) 3 - . The first VDEs of general iron sulfide, hydrosulfide, and mixed sulfide/hydrosulfide clusters [FeS m (SH) n - ; m, n = 0-3, 0 < (m + n) ≤ 3] are dependent on three properties of these anions: 1. the partial charge on the Fe atom, 2. disulfide bond formation (S-S) in the cluster, and 3. the number of hydrosulfide ligands in the cluster. The higher the partial charge on the Fe atom of these clusters, the larger the first VDE; however, cluster S-S bonding and more (SH) ligands in the cluster lower the cluster anion first VDE.

Properties of iron sulfide, hydrosulfide, and mixed sulfide/hydrosulfide cluster anions through photoelectron spectroscopy and density functional theory calculations

NASA Astrophysics Data System (ADS)

Yin, Shi; Bernstein, Elliot R.

2016-10-01

A new magnetic-bottle time-of-flight photoelectron spectroscopy (PES) apparatus is constructed in our laboratory. The PES spectra of iron sulfide, hydrosulfide, and mixed sulfide/hydrosulfide [FeSm(SH)n-; m, n = 0-3, 0 < (m + n) ≤ 3] cluster anions, obtained at 2.331 eV (532 nm) and 3.492 eV (355 nm) photon energies, are reported. The electronic structure and bonding properties of these clusters are additionally investigated at different levels of density functional theory. The most probable structures and ground state spin multiplicity for these cluster anions are tentatively assigned by comparing their theoretical first vertical detachment energies (VDEs) with their respective experiment values. The behavior of S and (SH) as ligands in these iron sulfide, hydrosulfide, and mixed sulfide/hydrosulfide cluster anions is investigated and compared. The experimental first VDEs for Fe(SH)1-3- cluster anions are lower than those found for their respective FeS1-3- cluster anions. The experimental first VDEs for FeS1-3- clusters are observed to increase for the first two S atoms bound to Fe-; however, due to the formation of an S-S bond for the FeS3- cluster, its first VDE is found to be ˜0.41 eV lower than the first VDE for the FeS2- cluster. The first VDEs of Fe(SH)1-3- cluster anions are observed to increase with the increasing numbers of SH groups. The calculated partial charges of the Fe atom for ground state FeS1-3- and Fe(SH)1-3- clusters are apparently related to and correlated with their determined first VDEs. The higher first VDE is correlated with a higher, more positive partial charge for the Fe atom of these cluster anions. Iron sulfide/hydrosulfide mixed cluster anions are also explored in this work: the first VDE for FeS(SH)- is lower than that for FeS2-, but higher than that for Fe(SH)2-; the first VDEs for FeS2(SH)- and FeS(SH)2- are close to that for FeS3-, but higher than that for Fe(SH)3-. The first VDEs of general iron sulfide, hydrosulfide, and mixed sulfide/hydrosulfide clusters [FeSm(SH)n-; m, n = 0-3, 0 < (m + n) ≤ 3] are dependent on three properties of these anions: 1. the partial charge on the Fe atom, 2. disulfide bond formation (S-S) in the cluster, and 3. the number of hydrosulfide ligands in the cluster. The higher the partial charge on the Fe atom of these clusters, the larger the first VDE; however, cluster S-S bonding and more (SH) ligands in the cluster lower the cluster anion first VDE.

SNARE-mediated rapid lysosome fusion in membrane raft clustering and dysfunction of bovine coronary arterial endothelium

PubMed Central

Han, Wei-Qing; Xia, Min; Zhang, Chun; Zhang, Fan; Xu, Ming; Li, Ning-Jun

2011-01-01

The present study attempted to evaluate whether soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) mediate lysosome fusion in response to death receptor activation and contribute to membrane raft (MR) clustering and consequent endothelial dysfunction in coronary arterial endothelial cells. By immunohistochemical analysis, vesicle-associated membrane proteins 2 (VAMP-2, vesicle-SNAREs) were found to be abundantly expressed in the endothelium of bovine coronary arteries. Direct lysosome fusion monitoring by N-(3-triethylammoniumpropyl)-4-[4-(dibutylamino)styryl]pyridinium dibromide (FM1-43) quenching demonstrated that the inhibition of VAMP-2 with tetanus toxin or specific small interfering ribonucleic acid (siRNA) almost completely blocked lysosome fusion to plasma membrane induced by Fas ligand (FasL), a well-known MR clustering stimulator. The involvement of SNAREs was further confirmed by an increased interaction of VAMP-2 with a target-SNARE protein syntaxin-4 after FasL stimulation in coimmunoprecipitation analysis. Also, the inhibition of VAMP-2 with tetanus toxin or VAMP-2 siRNA abolished FasL-induced MR clustering, its colocalization with a NADPH oxidase unit gp91phox, and increased superoxide production. Finally, FasL-induced impairment of endothelium-dependent vasodilation was reversed by the treatment of bovine coronary arteries with tetanus toxin or VAMP-2 siRNA. VAMP-2 is critical to lysosome fusion in MR clustering, and this VAMP-2-mediated lysosome-MR signalosomes contribute to redox regulation of coronary endothelial function. PMID:21926345

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Jinhee; Chen, Ying-Pin; Perry, Zachary

A series of molybdenum- and copper-based MOPs were synthesized through coordination-driven process of a bridging ligand (3,3 -PDBAD, L1) and dimetal paddlewheel clusters. Three conformers of the ligand exist with an ideal bridging angle between the two carboxylate groups of 0° (H2α-L1), 120° (H2β-L1), and of 90° (H2γ-L1), respectively. At ambient or lower temperature, H2L1 and Mo2(OAc)4 or Cu2(OAc)4 were crystallized into a molecular square with γ-L1 and Mo2/Cu2 units. With proper temperature elevation, not only the molecular square with γ-L1 but also a lantern-shaped cage with α-L1 formed simultaneously. Similar to how Watson–Crick pairs stabilize the helical structure ofmore » duplex DNA, the core–shell molecular assembly possesses favorable H-bonding interaction sites. This is dictated by the ligand conformation in the shell, coding for the formation and providing stabilization of the central lantern shaped core, which was not observed without this complementary interaction. On the basis of the crystallographic implications, a heterobimetallic cage was obtained through a postsynthetic metal ion metathesis, showing different reactivity of coordination bonds in the core and shell. As an innovative synthetic strategy, the site-selective metathesis broadens the structural diversity and properties of coordination assemblies.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, J; Chen, YP; Perry, Z

A series of molybdenum- and copper-based MOPs were synthesized through coordination-driven process of a bridging ligand (3,3'-PDBAD, L-1) and dimetal paddlewheel clusters. Three conformers of the ligand exist with an ideal bridging angle between the two carboxylate groups of 0 degrees (H-2 zeta-L(1)), 120 degrees (H-2 beta-L-1), and of 90 degrees (H-2 beta-L-1), respectively. At ambient or lower temperature, (HL1)-L-2 and Mo-2(OAc)(4) or Cu-2(OAc)(4) were crystallized into a molecular square with ?-L-1 and Mo-2/Cu-2 units. With proper temperature elevation, not only the molecular square with ?-L-1 but also a lantern-shaped cage with a-L-1 formed simultaneously. Similar to how Watson-Crick pairsmore » stabilize the helical structure of duplex DNA, the core-shell molecular assembly possesses favorable H-bonding interaction sites. This is dictated by the ligand conformation in the shell, coding for the formation and providing stabilization of the central lantern shaped core, which was not observed without this complementary interaction. On the basis of the crystallographic implications, a heterobimetallic cage was obtained through a postsynthetic metal ion metathesis, showing different reactivity of coordination bonds in the core and shell. As an innovative synthetic strategy, the site-selective metathesis broadens the structural diversity and properties of coordination assemblies.« less

Self-assembly of hybrid organic-inorganic polyoxovanadates: functionalised mixed-valent clusters and molecular cages.

PubMed

Breen, John M; Clérac, Rodolphe; Zhang, Lei; Cloonan, Suzanne M; Kennedy, Elaine; Feeney, Martin; McCabe, Thomas; Williams, D Clive; Schmitt, Wolfgang

2012-03-14

Herein we report the intra- and inter-molecular assembly of a {V(5)O(9)} subunit. This mixed-valent structural motif can be stabilised as [V(5)O(9)(L(1-3))(4)](5-/9-) (1-3) by a range of organoarsonate ligands (L(1)-L(3)) whose secondary functionalities influence its packing arrangement within the crystal structures. Variation of the reaction conditions results in the dodecanuclear cage structure [V(12)O(14)(OH)(4)(L(1))(10)](4-) (4) where two modified convex building units are linked via two dimeric {O(4)V(IV)(OH)(2)V(IV)O(4)} moieties. Bi-functional phosphonate ligands, L(4)-L(6) allow the intramolecular connectivity of the {V(5)O(9)} subunit to give hybrid capsules [V(10)O(18)(L(4-6))(4)](10-) (5-7). The dimensions of the electrophilic cavities of the capsular entities are determined by the incorporated ligand type. Mass spectrometry experiments confirm the stability of the complexes in solution. We investigate and model the temperature-dependent magnetic properties of representative complexes 1, 4, 6 and 7 and provide preliminary cell-viability studies of three different cancer cell lines with respect to Na(8)H(2)[6]·36H(2)O and Na(8)H(2)[7]·2DMF·29H(2)O.

Ag-ligand modified tungstovandates and their efficient catalysis degradation properties for methylene blue

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, Ran; Zhang, Huixia; Liu, Yunping

Two polytungstovandates [Ag(mbpy){sub 2}][Ag{sub 2}(mbpy){sub 3}][VW{sub 5}O{sub 19}]·H{sub 2}O (1) and [Ag(mbpy)]{sub 2}[Ag(mbpy){sub 2}]{sub 4}[VW{sub 12}O{sub 40}] (2) (mbpy =4,4′-dimethyl-2,2′-bipyridyl), had been hydrothermally synthesized and characterized by IR, TG, and single-crystal X-ray diffraction techniques. Single-crystal structural analysis revealed that the polyanionic clusters in two compounds are different: Lindqvist-type in 1 and α-Keggin-type in 2, respectively, while the cationic moieties in them are Ag-mbpy units. The experiments showed that this kind of hybrid crystal materials possesses more efficiently catalytic performance for the degradation of organic dye methylene blue (MB) in water solution under the UV irradiation. The significant degradation rate ofmore » MB can reach 89.9%, 94.9% by crystals 1 and 2 (40 mg) in the course of about 5 min. - Graphical abstract: Two Ag-ligand modified polytungstovandates had been synthesized and characterized, which were active in the catalytic degradation of organic dye methylene blue under the UV irradiation. - Highlights: • Two Ag-ligand modified tungstovandates were synthesized and characterized. • Weak interactions play important roles in constructing crystal frameworks. • Compounds are active to catalyze the degradation of methylene blue.« less

Unified superresolution experiments and stochastic theory provide mechanistic insight into protein ion-exchange adsorptive separations

PubMed Central

Kisley, Lydia; Chen, Jixin; Mansur, Andrea P.; Shuang, Bo; Kourentzi, Katerina; Poongavanam, Mohan-Vivekanandan; Chen, Wen-Hsiang; Dhamane, Sagar; Willson, Richard C.; Landes, Christy F.

2014-01-01

Chromatographic protein separations, immunoassays, and biosensing all typically involve the adsorption of proteins to surfaces decorated with charged, hydrophobic, or affinity ligands. Despite increasingly widespread use throughout the pharmaceutical industry, mechanistic detail about the interactions of proteins with individual chromatographic adsorbent sites is available only via inference from ensemble measurements such as binding isotherms, calorimetry, and chromatography. In this work, we present the direct superresolution mapping and kinetic characterization of functional sites on ion-exchange ligands based on agarose, a support matrix routinely used in protein chromatography. By quantifying the interactions of single proteins with individual charged ligands, we demonstrate that clusters of charges are necessary to create detectable adsorption sites and that even chemically identical ligands create adsorption sites of varying kinetic properties that depend on steric availability at the interface. Additionally, we relate experimental results to the stochastic theory of chromatography. Simulated elution profiles calculated from the molecular-scale data suggest that, if it were possible to engineer uniform optimal interactions into ion-exchange systems, separation efficiencies could be improved by as much as a factor of five by deliberately exploiting clustered interactions that currently dominate the ion-exchange process only accidentally. PMID:24459184

Unified superresolution experiments and stochastic theory provide mechanistic insight into protein ion-exchange adsorptive separations.

PubMed

Kisley, Lydia; Chen, Jixin; Mansur, Andrea P; Shuang, Bo; Kourentzi, Katerina; Poongavanam, Mohan-Vivekanandan; Chen, Wen-Hsiang; Dhamane, Sagar; Willson, Richard C; Landes, Christy F

2014-02-11

Chromatographic protein separations, immunoassays, and biosensing all typically involve the adsorption of proteins to surfaces decorated with charged, hydrophobic, or affinity ligands. Despite increasingly widespread use throughout the pharmaceutical industry, mechanistic detail about the interactions of proteins with individual chromatographic adsorbent sites is available only via inference from ensemble measurements such as binding isotherms, calorimetry, and chromatography. In this work, we present the direct superresolution mapping and kinetic characterization of functional sites on ion-exchange ligands based on agarose, a support matrix routinely used in protein chromatography. By quantifying the interactions of single proteins with individual charged ligands, we demonstrate that clusters of charges are necessary to create detectable adsorption sites and that even chemically identical ligands create adsorption sites of varying kinetic properties that depend on steric availability at the interface. Additionally, we relate experimental results to the stochastic theory of chromatography. Simulated elution profiles calculated from the molecular-scale data suggest that, if it were possible to engineer uniform optimal interactions into ion-exchange systems, separation efficiencies could be improved by as much as a factor of five by deliberately exploiting clustered interactions that currently dominate the ion-exchange process only accidentally.

Optically active red-emitting Cu nanoclusters originating from complexation and redox reaction between copper(ii) and d/l-penicillamine

NASA Astrophysics Data System (ADS)

Long, Tengfei; Guo, Yanjia; Lin, Min; Yuan, Mengke; Liu, Zhongde; Huang, Chengzhi

2016-05-01

Despite a significant surge in the number of investigations into both optically active Au and Ag nanostructures, there is currently only limited knowledge about optically active Cu nanoclusters (CuNCs) and their potential applications. Here, we have succeeded in preparing a pair of optically active red-emitting CuNCs on the basis of complexation and redox reaction between copper(ii) and penicillamine (Pen) enantiomers, in which Pen serves as both a reducing agent and a stabilizing ligand. Significantly, the CuNCs feature unique aggregation induced emission (AIE) characteristics and therefore can serve as pH stimuli-responsive functional materials. Impressively, the ligand chirality plays a dramatic role for the creation of brightly emissive CuNCs, attributed to the conformation of racemic Pen being unfavorable for the electrostatic interaction, and thus suppressing the formation of cluster aggregates. In addition, the clusters display potential toward cytoplasmic staining and labelling due to the high photoluminescence (PL) quantum yields (QYs) and remarkable cellular uptake, in spite that no chirality-dependent effects in autophagy and subcellular localization are observed in the application of chiral cluster enantiomer-based cell imaging.Despite a significant surge in the number of investigations into both optically active Au and Ag nanostructures, there is currently only limited knowledge about optically active Cu nanoclusters (CuNCs) and their potential applications. Here, we have succeeded in preparing a pair of optically active red-emitting CuNCs on the basis of complexation and redox reaction between copper(ii) and penicillamine (Pen) enantiomers, in which Pen serves as both a reducing agent and a stabilizing ligand. Significantly, the CuNCs feature unique aggregation induced emission (AIE) characteristics and therefore can serve as pH stimuli-responsive functional materials. Impressively, the ligand chirality plays a dramatic role for the creation of brightly emissive CuNCs, attributed to the conformation of racemic Pen being unfavorable for the electrostatic interaction, and thus suppressing the formation of cluster aggregates. In addition, the clusters display potential toward cytoplasmic staining and labelling due to the high photoluminescence (PL) quantum yields (QYs) and remarkable cellular uptake, in spite that no chirality-dependent effects in autophagy and subcellular localization are observed in the application of chiral cluster enantiomer-based cell imaging. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr01492e

Elucidating the role of surface passivating ligand structural parameters in hole wave function delocalization in semiconductor cluster molecules.

PubMed

Teunis, Meghan B; Nagaraju, Mulpuri; Dutta, Poulami; Pu, Jingzhi; Muhoberac, Barry B; Sardar, Rajesh; Agarwal, Mangilal

2017-09-28

This article describes the mechanisms underlying electronic interactions between surface passivating ligands and (CdSe) 34 semiconductor cluster molecules (SCMs) that facilitate band-gap engineering through the delocalization of hole wave functions without altering their inorganic core. We show here both experimentally and through density functional theory calculations that the expansion of the hole wave function beyond the SCM boundary into the ligand monolayer depends not only on the pre-binding energetic alignment of interfacial orbitals between the SCM and surface passivating ligands but is also strongly influenced by definable ligand structural parameters such as the extent of their π-conjugation [π-delocalization energy; pyrene (Py), anthracene (Anth), naphthalene (Naph), and phenyl (Ph)], binding mode [dithiocarbamate (DTC, -NH-CS 2 - ), carboxylate (-COO - ), and amine (-NH 2 )], and binding head group [-SH, -SeH, and -TeH]. We observe an unprecedentedly large ∼650 meV red-shift in the lowest energy optical absorption band of (CdSe) 34 SCMs upon passivating their surface with Py-DTC ligands and the trend is found to be Ph- < Naph- < Anth- < Py-DTC. This shift is reversible upon removal of Py-DTC by triethylphosphine gold(i) chloride treatment at room temperature. Furthermore, we performed temperature-dependent (80-300 K) photoluminescence lifetime measurements, which show longer lifetime at lower temperature, suggesting a strong influence of hole wave function delocalization rather than carrier trapping and/or phonon-mediated relaxation. Taken together, knowledge of how ligands electronically interact with the SCM surface is crucial to semiconductor nanomaterial research in general because it allows the tuning of electronic properties of nanomaterials for better charge separation and enhanced charge transfer, which in turn will increase optoelectronic device and photocatalytic efficiencies.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sadeghi, Omid; Falaise, Clément; Molina, Pedro I.

The iron Keggin ion is identified as a structural building block in both magnetite and ferrihydrite, two important iron oxide phases in nature and in technology. Discrete molecular forms of the iron Keggin ion that can be both manipulated in water and chemically converted to the related metal oxides are important for understanding growth mechanisms, in particular non-classical nucleation in which cluster building units are preserved in the aggregation and condensation processes. Here we describe two iron Keggin ion structures, formulated [Bi6FeO4Fe12O12(OH)12(CF3COO)10(H2O)2]3+ and [Bi6FeO4Fe12O12(OH)12(CF3COO)12]1+. Experimental and simulated X-ray scattering studies show indefinite stability of these clusters in water from pHmore » 1-3. The tridecameric iron Keggin-ion core is protected from hydrolysis by a synergistic effect of the capping Bi3+-cations and the trifluoroacetate ligands that respectively bond to the iron and bridge to the bismuth. By introducing electrons to the aqueous solution of clusters, we achieve complete separation of bismuth from the cluster, and the iron Keggin ion rapidly converts to magnetite and/or ferrihydrite, depending on the mechanism of reduction. In this strategy, we take advantage of the easily accessible reduction potential and crystallization energy of bismuth. Reduction was executed in bulk by chemical means, by voltammetry, and by secondary effects of transmission electron microscopy imaging of solutions. Prior, we showed a less stable analogue of the iron Keggin cluster converted to ferrihydrite simply upon dissolution. The prior and currently studied clusters with a range of reactivity provide a chemical system to study molecular cluster metal oxide conversion processes in detail.« less

Heterometal cubane-type MFe(3)S(4) clusters (M = Mo, V) trigonally symmetrized with hydrotris(pyrazolyl)borate(1-) and tris(pyrazolyl)methanesulfonate(1-) capping ligands.

PubMed

Fomitchev, Dmitry V; McLauchlan, Craig C; Holm, R H

2002-02-25

A series of heterometal cubane-type clusters containing [VFe(3)S(4)](2+) and [MoFe(3)S(4)](3+,2+) cores has been prepared. Ligand substitution of [(DMF)(3)VFe(3)S(4)Cl(3)](-) affords [(Tpms)VFe(3)S(4)L(3)](2)(-) (L = Cl(-) (8), EtS(-) (9), p-MeC(6)H(4)S(-), p-MeC(6)H(4)O(-)). A new procedure for the preparation of molybdenum single cubanes is introduced by the reaction of recently reported [(Tp)MoS(S(4))](-) with FeCl(2)/NaSEt to afford [(Tp)MoFe(3)S(4)Cl(3)](-) (1, 75% yield). This procedure is more efficient that the existing multistep synthesis of single cubanes, which generally affords clusters of mirror symmetry. Also prepared were [(Tp)MoFe(3)S(4)L(3)](-) (L = EtS(-) (2), p-MeC(6)H(4)S(-)). Reduction of 1 with borohydride gives [(Tp)MoFe(3)S(4)Cl(3)](2-) (5, 67%). Owing to the nature of the heterometal ligand, all clusters have idealized trigonal symmetry, reflected in their (1)H NMR spectra. Trigonal structures are demonstrated by crystallography of (Bu(4)N)[1,2], (Bu(4)N)(2)[5] x MeCN, and (Me(4)N)(2)[8,9]. The availability of 1 and 5 allows the first comparison of structures and (57)Fe isomer shifts of [MoFe(3)S(4)](3+,2+) in a constant ligand environment. Small increases in most bond distances indicate that an antibonding electron is added in the reduction of 1. Collective synthetic and electrochemical results from this and other studies demonstrate the existence of the series of oxidation states [VFe(3)S(4)](3+,2+,1+) and [MoFe(3)S(4)](4+,3+,2+) whose relative stabilities within a given series are strongly ligand dependent. Isomer shifts indicate that the reduction of 1 largely affects the Fe(3) subcluster and are consistent with the formal descriptions [MoFe(3+)(2)Fe(2+)S(4)](3+) (1) and [MoFe(3+)Fe(2+)(2)S(4)](2+) (5). Reaction of 1 with excess Li(2)S in acetonitrile affords the double cubane [[(Tp)MoFe(3)S(4)Cl(2)](2)(mu(2)(-)S)](2)(-), whose sulfide-bridged structure is supported by two sequential reductions separated by 290 mV, in analogy with previously reported double cubanes of higher charge. Trigonally symmetric single cubanes eliminate isomers in the formation of double cubanes and other cluster structures, and may be of considerable value in the preparation of new types of M-Fe-S clusters. (Tpms = tris(pyrazolyl)methanesulfonate(1-); Tp = hydrotris(pyrazolyl)borate(1-).)

Reversible [4Fe-3S] cluster morphing in an O(2)-tolerant [NiFe] hydrogenase.

PubMed

Frielingsdorf, Stefan; Fritsch, Johannes; Schmidt, Andrea; Hammer, Mathias; Löwenstein, Julia; Siebert, Elisabeth; Pelmenschikov, Vladimir; Jaenicke, Tina; Kalms, Jacqueline; Rippers, Yvonne; Lendzian, Friedhelm; Zebger, Ingo; Teutloff, Christian; Kaupp, Martin; Bittl, Robert; Hildebrandt, Peter; Friedrich, Bärbel; Lenz, Oliver; Scheerer, Patrick

2014-05-01

Hydrogenases catalyze the reversible oxidation of H(2) into protons and electrons and are usually readily inactivated by O(2). However, a subgroup of the [NiFe] hydrogenases, including the membrane-bound [NiFe] hydrogenase from Ralstonia eutropha, has evolved remarkable tolerance toward O(2) that enables their host organisms to utilize H(2) as an energy source at high O(2). This feature is crucially based on a unique six cysteine-coordinated [4Fe-3S] cluster located close to the catalytic center, whose properties were investigated in this study using a multidisciplinary approach. The [4Fe-3S] cluster undergoes redox-dependent reversible transformations, namely iron swapping between a sulfide and a peptide amide N. Moreover, our investigations unraveled the redox-dependent and reversible occurence of an oxygen ligand located at a different iron. This ligand is hydrogen bonded to a conserved histidine that is essential for H(2) oxidation at high O(2). We propose that these transformations, reminiscent of those of the P-cluster of nitrogenase, enable the consecutive transfer of two electrons within a physiological potential range.

Clustering molecular dynamics trajectories for optimizing docking experiments.

PubMed

De Paris, Renata; Quevedo, Christian V; Ruiz, Duncan D; Norberto de Souza, Osmar; Barros, Rodrigo C

2015-01-01

Molecular dynamics simulations of protein receptors have become an attractive tool for rational drug discovery. However, the high computational cost of employing molecular dynamics trajectories in virtual screening of large repositories threats the feasibility of this task. Computational intelligence techniques have been applied in this context, with the ultimate goal of reducing the overall computational cost so the task can become feasible. Particularly, clustering algorithms have been widely used as a means to reduce the dimensionality of molecular dynamics trajectories. In this paper, we develop a novel methodology for clustering entire trajectories using structural features from the substrate-binding cavity of the receptor in order to optimize docking experiments on a cloud-based environment. The resulting partition was selected based on three clustering validity criteria, and it was further validated by analyzing the interactions between 20 ligands and a fully flexible receptor (FFR) model containing a 20 ns molecular dynamics simulation trajectory. Our proposed methodology shows that taking into account features of the substrate-binding cavity as input for the k-means algorithm is a promising technique for accurately selecting ensembles of representative structures tailored to a specific ligand.

Complement activation by ligand-driven juxtaposition of discrete pattern recognition complexes

PubMed Central

Degn, Søren E.; Kjaer, Troels R.; Kidmose, Rune T.; Jensen, Lisbeth; Hansen, Annette G.; Tekin, Mustafa; Jensenius, Jens C.; Andersen, Gregers R.; Thiel, Steffen

2014-01-01

Defining mechanisms governing translation of molecular binding events into immune activation is central to understanding immune function. In the lectin pathway of complement, the pattern recognition molecules (PRMs) mannan-binding lectin (MBL) and ficolins complexed with the MBL-associated serine proteases (MASP)-1 and MASP-2 cleave C4 and C2 to generate C3 convertase. MASP-1 was recently found to be the exclusive activator of MASP-2 under physiological conditions, yet the predominant oligomeric forms of MBL carry only a single MASP homodimer. This prompted us to investigate whether activation of MASP-2 by MASP-1 occurs through PRM-driven juxtaposition on ligand surfaces. We demonstrate that intercomplex activation occurs between discrete PRM/MASP complexes. PRM ligand binding does not directly escort the transition of MASP from zymogen to active enzyme in the PRM/MASP complex; rather, clustering of PRM/MASP complexes directly causes activation. Our results support a clustering-based mechanism of activation, fundamentally different from the conformational model suggested for the classical pathway of complement. PMID:25197071

Hot spot analysis for driving the development of hits into leads in fragment based drug discovery

PubMed Central

Hall, David R.; Ngan, Chi Ho; Zerbe, Brandon S.; Kozakov, Dima; Vajda, Sandor

2011-01-01

Fragment based drug design (FBDD) starts with finding fragment-sized compounds that are highly ligand efficient and can serve as a core moiety for developing high affinity leads. Although the core-bound structure of a protein facilitates the construction of leads, effective design is far from straightforward. We show that protein mapping, a computational method developed to find binding hot spots and implemented as the FTMap server, provides information that complements the fragment screening results and can drive the evolution of core fragments into larger leads with a minimal loss or, in some cases, even a gain in ligand efficiency. The method places small molecular probes, the size of organic solvents, on a dense grid around the protein, and identifies the hot spots as consensus clusters formed by clusters of several probes. The hot spots are ranked based on the number of probe clusters, which predicts the binding propensity of the subsites and hence their importance for drug design. Accordingly, with a single exception the main hot spot identified by FTMap binds the core compound found by fragment screening. The most useful information is provided by the neighboring secondary hot spots, indicating the regions where the core can be extended to increase its affinity. To quantify this information, we calculate the density of probes from mapping, which describes the binding propensity at each point, and show that the change in the correlation between a ligand position and the probe density upon extending or repositioning the core moiety predicts the expected change in ligand efficiency. PMID:22145575

Surface characterization of tin-based inorganic EUV resists

NASA Astrophysics Data System (ADS)

Frederick, Ryan T.; Diulus, J. Trey; Lyubinetsky, Igor; Hutchison, Danielle C.; Olsen, Morgan R.; Nyman, May; Herman, Gregory S.

2018-03-01

Metal oxide nanomaterials have shown promise for use as EUV resists. Recently, significant efforts have focused on tinoxo clusters that have high absorption coefficient Sn centers and radiation sensitive organic ligands. In our studies, we have investigated a β-Keggin butyl-Sn cluster (β-NaSn13), which is charge-neutral and allows studying radiation induced chemistries without interference from counterions. We have used ambient pressure X-ray photoelectron spectroscopy (APXPS) to investigate the contrast properties of the β-NaSn13 in ultrahigh vacuum (UHV) and in the presence of ambient oxygen. These contrast studies indicate that ambient oxygen reduces the dose requirements for the solubility transition of the β-NaSn13 photoresists. APXPS spectra collected before and after the solubility transition shows that ambient oxygen causes a greater loss of butyl ligands from the samples and the formation of more tin oxide for larger doses, suggesting the presence of reactive oxygen species. APXPS was also used to study processes during the post exposure bake, where we compared the differences in film chemistries in ambient oxygen or in UHV. There were only very small differences in the APXPS spectra before exposure and after exposure and the post exposure bake. However, ambient oxygen resulted in some changes for unexposed regions during the post exposure bake; there was a greater ratio of tin oxide to other oxygen species (alkoxy ligands, hydroxyls) for samples annealed in oxygen. These results have significance for EUV and e-beam lithography processing parameters, as well as implications for cluster design and ligand chemistries.

Synthesis and structure of the heterobimetallic Yb(II) complex of composition L2Yb2LiI3 supported with the β-diketiminato ligand [L=Et2NCH2CH2NC(Me)CHC(Me)NCH2CH2NEt2

NASA Astrophysics Data System (ADS)

Nikiforov, Grigori B.; Roesky, Herbert W.; Vidovic, Denis; Magull, Jörg

2003-08-01

The heterobimetallic Yb(II) mixed ligand complex L2Yb2LiI31 has been prepared by the reaction of the lithium salt of the ligand L with the ytterbium diiodide. Compound 1 is characterized by single crystal X-ray structural analysis, multinuclear NMR and mass spectrometry. Complex 1 consists of LYbI and LLi units connected with the central Yb(1) atom. The latter is surrounded by the LYbI and LLi moieties in a sandwich like structure including two bridging iodine atoms. The NCCCN unsaturated system of the ligand in each of the units is almost planar and π coordinated to the Yb(1) atom. These two planar units are tilted to each other and the pendant arms of the β-diketiminato ligand in each moiety are bent. The metal atoms are located out of the NCCCN plane of the ligands and the three metal atoms in complex 1 form almost a straight line.

NRVS and EPR Spectroscopy of 57Fe-enriched [FeFe] Hydrogenase Indicate Stepwise Assembly of the H-cluster†

PubMed Central

Kuchenreuther, Jon M.; Guo, Yisong; Wang, Hongxin; Myers, William K.; George, Simon J.; Boyke, Christine A.; Yoda, Yoshitaka; Alp, E. Ercan; Zhao, Jiyong; Britt, R. David; Swartz, James R.; Cramer, Stephen P.

2013-01-01

The [FeFe] hydrogenase from Clostridium pasteurianum (CpI) harbors four Fe–S clusters that facilitate electron transfer to the H-cluster, a ligand-coordinated six-iron prosthetic group that catalyzes the redox interconversion of protons and H2. Here, we have used 57Fe nuclear resonance vibrational spectroscopy (NRVS) to study the iron centers in CpI, and we compare our data to that for a [4Fe–4S] ferredoxin as well as a model complex resembling the [2Fe]H catalytic domain of the H-cluster. In order to enrich the hydrogenase with 57Fe nuclei, we used cell-free methods to post-translationally mature the enzyme. Specifically, inactive CpI apoprotein with 56Fe-labeled Fe–S clusters was activated in vitro using 57Fe-enriched maturation proteins. This approach enabled us to selectively label the [2Fe]H subcluster with 57Fe, which NRVS confirms by detecting 57Fe–CO and 57Fe–CN normal modes from the H-cluster nonprotein ligands. The NRVS and iron quantification results also suggest that the hydrogenase contains a second 57Fe–S cluster. EPR spectroscopy indicates that this 57Fe-enriched metal center is not the [4Fe– 4S]H subcluster of the H-cluster. This finding demonstrates that the CpI hydrogenase retained an 56Fe-enriched [4Fe–4S]H cluster during in vitro maturation, providing unambiguous evidence for stepwise assembly of the H-cluster. In addition, this work represents the first NRVS characterization of [FeFe] hydrogenases. PMID:23249091

A 4-dimethylaminobenzoate-functionalized Ti6-oxo cluster with a narrow band gap and enhanced photoelectrochemical activity: a combined experimental and computational study.

PubMed

Lv, Hai-Ting; Cui, Ying; Zhang, Yu-Min; Li, Hua-Min; Zou, Guo-Dong; Duan, Rui-Huan; Cao, Jun-Tao; Jing, Qiang-Shan; Fan, Yang

2017-09-28

Organic donor-π-bridge-acceptor (D-π-A) dyes with arylamines as an electron donor have been widely used as photosensitizers for dye-sensitized solar cells (DSSCs). However, titanium-oxo clusters (TOCs) functionalized with this kind of D-π-A structured dye-molecule have rarely been explored. In the present study, the 4-dimethylaminobenzoate-functionalized titanium-oxo cluster [Ti 6 (μ 3 -O) 6 (OiPr) 6 (DMABA) 6 ]·2C 6 H 5 CH 3 (DMABA = 4-dimethylaminobenzoate) was synthesized and structurally characterized by single-crystal X-ray diffraction. For comparison, two other Ti 6 -oxo clusters, namely [Ti 6 (μ 3 -O) 6 (OiPr) 6 (AD) 6 ] (AD = 1-adamantanecarboxylate) and [Ti 6 (μ 3 -O) 2 (μ 2 -O)(μ 2 -OiPr) 4 (OiPr) 10 (DMM) 2 ] (DMM = dimethylmalonate), were also studied. The DMABA-functionalized cluster exhibits a remarkably reduced band gap of ∼2.5 eV and much enhanced photocurrent response in comparison with the other two clusters. The electronic structures and electronic transitions of the clusters were studied by DFT and TDDFT calculations. The computational results suggest that the low-energy transitions of the DMABA-functionalized cluster have a substantial charge-transfer character arising from the DMABA → {Ti 6 } cluster core ligand-to-core charge transfer (LCCT), along with the DMABA-based intra-ligand charge transfer (ILCT). These low-energy charge transfer transitions provide efficient electron injection pathways for photon-to-electron conversion.

X-ray and EPR Characterization of the Auxiliary Fe-S Clusters in the Radical SAM Enzyme PqqE.

PubMed

Barr, Ian; Stich, Troy A; Gizzi, Anthony S; Grove, Tyler L; Bonanno, Jeffrey B; Latham, John A; Chung, Tyler; Wilmot, Carrie M; Britt, R David; Almo, Steven C; Klinman, Judith P

2018-02-27

The Radical SAM (RS) enzyme PqqE catalyzes the first step in the biosynthesis of the bacterial cofactor pyrroloquinoline quinone, forming a new carbon-carbon bond between two side chains within the ribosomally synthesized peptide substrate PqqA. In addition to the active site RS 4Fe-4S cluster, PqqE is predicted to have two auxiliary Fe-S clusters, like the other members of the SPASM domain family. Here we identify these sites and examine their structure using a combination of X-ray crystallography and Mössbauer and electron paramagnetic resonance (EPR) spectroscopies. X-ray crystallography allows us to identify the ligands to each of the two auxiliary clusters at the C-terminal region of the protein. The auxiliary cluster nearest the RS site (AuxI) is in the form of a 2Fe-2S cluster ligated by four cysteines, an Fe-S center not seen previously in other SPASM domain proteins; this assignment is further supported by Mössbauer and EPR spectroscopies. The second, more remote cluster (AuxII) is a 4Fe-4S center that is ligated by three cysteine residues and one aspartate residue. In addition, we examined the roles these ligands play in catalysis by the RS and AuxII clusters using site-directed mutagenesis coupled with EPR spectroscopy. Lastly, we discuss the possible functional consequences that these unique AuxI and AuxII clusters may have in catalysis for PqqE and how these may extend to additional RS enzymes catalyzing the post-translational modification of ribosomally encoded peptides.

Dynamic clustering threshold reduces conformer ensemble size while maintaining a biologically relevant ensemble

NASA Astrophysics Data System (ADS)

Yongye, Austin B.; Bender, Andreas; Martínez-Mayorga, Karina

2010-08-01

Representing the 3D structures of ligands in virtual screenings via multi-conformer ensembles can be computationally intensive, especially for compounds with a large number of rotatable bonds. Thus, reducing the size of multi-conformer databases and the number of query conformers, while simultaneously reproducing the bioactive conformer with good accuracy, is of crucial interest. While clustering and RMSD filtering methods are employed in existing conformer generators, the novelty of this work is the inclusion of a clustering scheme (NMRCLUST) that does not require a user-defined cut-off value. This algorithm simultaneously optimizes the number and the average spread of the clusters. Here we describe and test four inter-dependent approaches for selecting computer-generated conformers, namely: OMEGA, NMRCLUST, RMS filtering and averaged- RMS filtering. The bioactive conformations of 65 selected ligands were extracted from the corresponding protein:ligand complexes from the Protein Data Bank, including eight ligands that adopted dissimilar bound conformations within different receptors. We show that NMRCLUST can be employed to further filter OMEGA-generated conformers while maintaining biological relevance of the ensemble. It was observed that NMRCLUST (containing on average 10 times fewer conformers per compound) performed nearly as well as OMEGA, and both outperformed RMS filtering and averaged- RMS filtering in terms of identifying the bioactive conformations with excellent and good matches (0.5 < RMSD < 1.0 Å). Furthermore, we propose thresholds for OMEGA root-mean square filtering depending on the number of rotors in a compound: 0.8, 1.0 and 1.4 for structures with low (1-4), medium (5-9) and high (10-15) numbers of rotatable bonds, respectively. The protocol employed is general and can be applied to reduce the number of conformers in multi-conformer compound collections and alleviate the complexity of downstream data processing in virtual screening experiments.

Binding constant of cell adhesion receptors and substrate-immobilized ligands depends on the distribution of ligands

NASA Astrophysics Data System (ADS)

Li, Long; Hu, Jinglei; Xu, Guangkui; Song, Fan

2018-01-01

Cell-cell adhesion and the adhesion of cells to tissues and extracellular matrix, which are pivotal for immune response, tissue development, and cell locomotion, depend sensitively on the binding constant of receptor and ligand molecules anchored on the apposing surfaces. An important question remains of whether the immobilization of ligands affects the affinity of binding with cell adhesion receptors. We have investigated the adhesion of multicomponent membranes to a flat substrate coated with immobile ligands using Monte Carlo simulations of a statistical mesoscopic model with biologically relevant parameters. We find that the binding of the adhesion receptors to ligands immobilized on the substrate is strongly affected by the ligand distribution. In the case of ligand clusters, the receptor-ligand binding constant can be significantly enhanced due to the less translational entropy loss of lipid-raft domains in the model cell membranes upon the formation of additional complexes. For ligands randomly or uniformly immobilized on the substrate, the binding constant is rather decreased since the receptors localized in lipid-raft domains have to pay an energetic penalty in order to bind ligands. Our findings help to understand why cell-substrate adhesion experiments for measuring the impact of lipid rafts on the receptor-ligand interactions led to contradictory results.

Structural, spectral and magnetic studies of two Co(II)-N-heterocyclic diphosphonates based on multinuclear units

NASA Astrophysics Data System (ADS)

Zhao, Chen; Ma, Kui-Rong; Zhang, Yu; Kan, Yu-He; Li, Rong-Qing; Hu, Hua-You

2016-01-01

Two examples of Co(II)-N-heterocyclic coordination polymers based on 1-hydroxyethylidenediphosphonic acid (H5L = CH3C(OH)(PO3H2)2), namely 0.5(H3NCH2CH2NH3)·[Co6(Cl2)(H3L)2(H2L)(HL)(2,2‧-bipy)6] 1 and 2(NH4)·[Co3(HL)2(H2O)2(phen)2]·2(H2O) 2, have been solvothermally obtained by introducing the second ligands 2,2‧-bipyridine/1,10-phenanthroline (2,2‧-bipy/phen) and characterized by powder X-ray diffraction (PXRD), elemental analysis, IR, TG-DSC. The single-crystal X-ray diffractions show that compound 1 possesses a 0-D structure with hexa-nuclear cluster [Co6(O-P-O)8] built through single/double O-P-O bridges and compound 2 displays a 1-D ladder-like chain structure with magnetic topology building blocks [Co4(O-P-O)4]n. Then H-bonding and π-π stacking interactions further expand the two low-dimensional structures into three-dimensional supramolecular frameworks. Fluorescent measurements reveal that both the maximum emission peaks of 1-2 are centered at 423 nm, mainly deriving from intraligand π*-π transition state of N-heterocyclic ligand 2,2‧-bipy/phen, respectively. Magnetism data indicate that 1 exhibits antiferromagnetic behavior within hexa-nuclear Co(II) clusters, while 2 shows weak ferromagnetic interactions in 1-D topology Co(II)-chain, showing promising potential as magnetic materials.

The concept of mixed organic ligands in metal-organic frameworks: design, tuning and functions.

PubMed

Yin, Zheng; Zhou, Yan-Ling; Zeng, Ming-Hua; Kurmoo, Mohamedally

2015-03-28

The research on metal-organic frameworks (MOFs) has been developing at an extraordinary pace in its two decades of existence, as judged by the exponential growth of novel structures and the constant expansion of its applicability and research scope. A major part of the research and its success are due to the vital role of the concept of mixed organic ligands in the design, tuning and functions. This perspective, therefore, reviews the recent advances in MOFs based on this concept, which is generally based on employing a small polydentate ligand (here labelled as "nodal ligand") to form either clusters, rods or layers, which are then connected by a second ditopic linker ligand to form the framework. The structures of the materials can be grouped into the following three categories: layer-spacer (usually known as pillared-layer), rod-spacer, and cluster-spacer based MOFs. Depending on the size and geometry of the spacer ligands, interpenetrations of frameworks are occasionally found. These MOFs show a wide range of properties such as (a) crystal-to-crystal transformations upon solvent modifications, post-synthetic metal exchange or ligand reactions, (b) gas sorption, solvent selectivity and purification, (c) specific catalysis, (d) optical properties including colour change, luminescence, non-linear optic, (e) short- and long range magnetic ordering, metamagnetism and reversible ground-state modifications and (f) drug and iodine carriers with controlled release. In the following, we will highlight the importance of the above concept in the design, tuning, and functions of a selection of existing MOFs having mixed organic ligands and their associated structures and properties. The results obtained so far using this concept look very promising for fine-tuning the pore size and shape for selective adsorption and specificity in catalytic reactions, which appears to be one way to propel the advances in the application and commercialization of MOFs.

Benzoate-Induced High-Nuclearity Silver Thiolate Clusters.

PubMed

Su, Yan-Min; Liu, Wei; Wang, Zhi; Wang, Shu-Ao; Li, Yan-An; Yu, Fei; Zhao, Quan-Qin; Wang, Xing-Po; Tung, Chen-Ho; Sun, Di

2018-04-03

Compared with the well-known anion-templated effects in shaping silver thiolate clusters, the influence from the organic ligands in the outer shell is still poorly understood. Herein, three new benzoate-functionalized high-nuclearity silver(I) thiolate clusters are isolated and characterized for the first time in the presence of diverse anion templates such as S 2- , α-[Mo 5 O 18 ] 6- , and MoO 4 2- . Single-crystal X-ray analysis reveals that the nuclearities of the three silver clusters (SD/Ag28, SD/Ag29, SD/Ag30) vary from 32 to 38 to 78 with co-capped tBuS - and benzoate ligands on the surface. SD/Ag28 is a turtle-like cluster comprising a Ag 29 shell caging a Ag 3 S 3 trigon in the center, whereas SD/Ag29 is a prolate Ag 38 sphere templated by the α-[Mo 5 O 18 ] 6- anion. Upon changing from benzoate to methoxyl-substituted benzoate, SD/Ag30 is isolated as a very complicated core-shell spherical cluster composed of a Ag 57 shell and a vase-like Ag 21 S 13 core. Four MoO 4 2- anions are arranged in a supertetrahedron and located in the interstice between the core and shell. Introduction of the bulky benzoate changes elaborately the nuclearity and arrangements of silver polygons on the shell of silver clusters, which is exemplified by comparing SD/Ag28 and a known similar silver thiolate cluster. The three new clusters emit luminescence in the near-infrared (NIR) region and show different thermochromic luminescence properties. This work presents a flexible approach to synthetic studies of high-nuclearity silver clusters decorated by different benzoates, and structural modulations are also achieved. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Impaired synaptic clustering of postsynaptic density proteins and altered signal transmission in hippocampal neurons, and disrupted learning behavior in PDZ1 and PDZ2 ligand binding-deficient PSD-95 knockin mice

PubMed Central

2012-01-01

Background Postsynaptic density (PSD)-95-like membrane-associated guanylate kinases (PSD-MAGUKs) are scaffold proteins in PSDs that cluster signaling molecules near NMDA receptors. PSD-MAGUKs share a common domain structure, including three PDZ (PDZ1/2/3) domains in their N-terminus. While multiple domains enable the PSD-MAGUKs to bind various ligands, the contribution of each PDZ domain to synaptic organization and function is not fully understood. Here, we focused on the PDZ1/2 domains of PSD-95 that bind NMDA-type receptors, and studied the specific roles of the ligand binding of these domains in the assembly of PSD proteins, synaptic properties of hippocampal neurons, and behavior, using ligand binding-deficient PSD-95 cDNA knockin (KI) mice. Results The KI mice showed decreased accumulation of mutant PSD-95, PSD-93 and AMPA receptor subunits in the PSD fraction of the hippocampus. In the hippocampal CA1 region of young KI mice, basal synaptic efficacy was reduced and long-term potentiation (LTP) was enhanced with intact long-term depression. In adult KI mice, there was no significant change in the magnitude of LTP in CA1, but robustly enhanced LTP was induced at the medial perforant path-dentate gyrus synapses, suggesting that PSD-95 has an age- and subregion-dependent role. In a battery of behavioral tests, KI mice showed markedly abnormal anxiety-like behavior, impaired spatial reference and working memory, and impaired remote memory and pattern separation in fear conditioning test. Conclusions These findings reveal that PSD-95 including its ligand binding of the PDZ1/2 domains controls the synaptic clustering of PSD-MAGUKs and AMPA receptors, which may have an essential role in regulating hippocampal synaptic transmission, plasticity, and hippocampus-dependent behavior. PMID:23268962

Impaired synaptic clustering of postsynaptic density proteins and altered signal transmission in hippocampal neurons, and disrupted learning behavior in PDZ1 and PDZ2 ligand binding-deficient PSD-95 knockin mice.

PubMed

Nagura, Hitoshi; Ishikawa, Yasuyuki; Kobayashi, Katsunori; Takao, Keizo; Tanaka, Tomo; Nishikawa, Kouki; Tamura, Hideki; Shiosaka, Sadao; Suzuki, Hidenori; Miyakawa, Tsuyoshi; Fujiyoshi, Yoshinori; Doi, Tomoko

2012-12-26

Postsynaptic density (PSD)-95-like membrane-associated guanylate kinases (PSD-MAGUKs) are scaffold proteins in PSDs that cluster signaling molecules near NMDA receptors. PSD-MAGUKs share a common domain structure, including three PDZ (PDZ1/2/3) domains in their N-terminus. While multiple domains enable the PSD-MAGUKs to bind various ligands, the contribution of each PDZ domain to synaptic organization and function is not fully understood. Here, we focused on the PDZ1/2 domains of PSD-95 that bind NMDA-type receptors, and studied the specific roles of the ligand binding of these domains in the assembly of PSD proteins, synaptic properties of hippocampal neurons, and behavior, using ligand binding-deficient PSD-95 cDNA knockin (KI) mice. The KI mice showed decreased accumulation of mutant PSD-95, PSD-93 and AMPA receptor subunits in the PSD fraction of the hippocampus. In the hippocampal CA1 region of young KI mice, basal synaptic efficacy was reduced and long-term potentiation (LTP) was enhanced with intact long-term depression. In adult KI mice, there was no significant change in the magnitude of LTP in CA1, but robustly enhanced LTP was induced at the medial perforant path-dentate gyrus synapses, suggesting that PSD-95 has an age- and subregion-dependent role. In a battery of behavioral tests, KI mice showed markedly abnormal anxiety-like behavior, impaired spatial reference and working memory, and impaired remote memory and pattern separation in fear conditioning test. These findings reveal that PSD-95 including its ligand binding of the PDZ1/2 domains controls the synaptic clustering of PSD-MAGUKs and AMPA receptors, which may have an essential role in regulating hippocampal synaptic transmission, plasticity, and hippocampus-dependent behavior.

A Cysteine-Rich CCG Domain Contains a Novel [4Fe-4S] Cluster Binding Motif As Deduced From Studies With Subunit B of Heterodisulfide Reductase From Methanothermobacter Marburgensis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hamann, N.; Mander, G.J.; Shokes, J.E.

Heterodisulfide reductase (HDR) of methanogenic archaea with its active-site [4Fe-4S] cluster catalyzes the reversible reduction of the heterodisulfide (CoM-S-S-CoB) of the methanogenic coenzyme M (CoM-SH) and coenzyme B (CoB-SH). CoM-HDR, a mechanistic-based paramagnetic intermediate generated upon half-reaction of the oxidized enzyme with CoM-SH, is a novel type of [4Fe-4S]{sup 3+} cluster with CoM-SH as a ligand. Subunit HdrB of the Methanothermobacter marburgensis HdrABC holoenzyme contains two cysteine-rich sequence motifs (CX{sub 31-39}CCX{sub 35-36}CXXC), designated as CCG domain in the Pfam database and conserved in many proteins. Here we present experimental evidence that the C-terminal CCG domain of HdrB binds this unusualmore » [4Fe-4S] cluster. HdrB was produced in Escherichia coli, and an iron-sulfur cluster was subsequently inserted by in vitro reconstitution. In the oxidized state the cluster without the substrate exhibited a rhombic EPR signal (g{sub zyx} = 2.015, 1.995, and 1.950) reminiscent of the CoM-HDR signal. {sup 57}Fe ENDOR spectroscopy revealed that this paramagnetic species is a [4Fe-4S] cluster with {sup 57}Fe hyperfine couplings very similar to that of CoM-HDR. CoM-{sup 33}SH resulted in a broadening of the EPR signal, and upon addition of CoM-SH the midpoint potential of the cluster was shifted to values observed for CoM-HDR, both indicating binding of CoM-SH to the cluster. Site-directed mutagenesis of all 12 cysteine residues in HdrB identified four cysteines of the C-terminal CCG domain as cluster ligands. Combined with the previous detection of CoM-HDR-like EPR signals in other CCG domain-containing proteins our data indicate a general role of the C-terminal CCG domain in coordination of this novel [4Fe-4S] cluster. In addition, Zn K-edge X-ray absorption spectroscopy identified an isolated Zn site with an S{sub 3}(O/N){sub 1} geometry in HdrB and the HDR holoenzyme. The N-terminal CCG domain is suggested to provide ligands to the Zn site.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dhayal, Rajendra S.; Liao, Jian-Hong; Kahlal, Samia

An air- and moisture-stable nanoscale polyhydrido copper cluster [Cu 32(H) 20{S 2P(O i Pr) 2 } 12 ] (1 H) was synthesized and structurally characterized. The molecular structure of 1 H exhibits a hexacapped pseudo-rhombohedral core of 14 Cu atoms sandwiched between two nestlike triangular cupola fragments of (2x9) Cu atoms in an elongated triangular gyrobicupola polyhedron. The discrete Cu 32 cluster is stabilized by 12 dithiophosphate ligands and a record number of 20 hydride ligands, which were found by high-resolution neutron diffraction to exhibit tri-, tetra-, and pentacoordinated hydrides in capping and interstitial modes. We conclude that this resultmore » was further supported by a density functional theory investigation on the simplified model [Cu 32(H) 20(S 2PH 2) 12].« less

Oxoiron(IV) Tetramethylcyclam Complexes with Axial Carboxylate Ligands: Effect of Tethering the Carboxylate on Reactivity.

PubMed

Bigelow, Jennifer O; England, Jason; Klein, Johannes E M N; Farquhar, Erik R; Frisch, Jonathan R; Martinho, Marlène; Mandal, Debasish; Münck, Eckard; Shaik, Sason; Que, Lawrence

2017-03-20

Oxoiron(IV) species are implicated as reactive intermediates in nonheme monoiron oxygenases, often acting as the agent for hydrogen-atom transfer from substrate. A histidine is the most likely ligand trans to the oxo unit in most enzymes characterized thus far but is replaced by a carboxylate in the case of isopenicillin N synthase. As the effect of a trans carboxylate ligand on the properties of the oxoiron(IV) unit has not been systematically studied, we have synthesized and characterized four oxoiron(IV) complexes supported by the tetramethylcyclam (TMC) macrocycle and having a carboxylate ligand trans to the oxo unit. Two complexes have acetate or propionate axial ligands, while the other two have the carboxylate functionality tethered to the macrocyclic ligand framework by one or two methylene units. Interestingly, these four complexes exhibit substrate oxidation rates that differ by more than 100-fold, despite having E p,c values for the reduction of the Fe═O unit that span a range of only 130 mV. Eyring parameters for 1,4-cyclohexadiene oxidation show that reactivity differences originate from differences in activation enthalpy between complexes with tethered carboxylates and those with untethered carboxylates, in agreement with computational results. As noted previously for the initial subset of four complexes, the logarithms of the oxygen atom transfer rates of 11 complexes of the Fe IV (O)TMC(X) series increase linearly with the observed E p,c values, reflecting the electrophilicity of the Fe═O unit. In contrast, no correlation with E p,c values is observed for the corresponding hydrogen atom transfer (HAT) reaction rates; instead, the HAT rates increase as the computed triplet-quintet spin state gap narrows, consistent with Shaik's two-state-reactivity model. In fact, the two complexes with untethered carboxylates are among the most reactive HAT agents in this series, demonstrating that the axial ligand can play a key role in tuning the HAT reactivity in a nonheme iron enzyme active site.

Self-assembly of high-nuclearity lanthanide-based nanoclusters for potential bioimaging applications

NASA Astrophysics Data System (ADS)

Yang, Xiaoping; Wang, Shiqing; Schipper, Desmond; Zhang, Lijie; Li, Zongping; Huang, Shaoming; Yuan, Daqiang; Chen, Zhongning; Gnanam, Annie J.; Hall, Justin W.; King, Tyler L.; Que, Emily; Dieye, Yakhya; Vadivelu, Jamuna; Brown, Katherine A.; Jones, Richard A.

2016-05-01

Two series of Cd-Ln and Ni-Ln clusters [Ln8Cd24L12(OAc)44(48)Cl4(0)] and [Ln8Ni6L6(OAc)24(EtOH)6(H2O)2] were constructed using a flexible ligand. The Cd-Ln clusters exhibit interesting nano-drum-like structures which allows direct visualization by TEM. Luminex MicroPlex Microspheres loaded with the Cd-Sm cluster were visualized using epifluorescence microscopy. Cytotoxicity studies on A549 and AGS cancer cell lines showed that the materials have mild to moderate cytotoxicity.Two series of Cd-Ln and Ni-Ln clusters [Ln8Cd24L12(OAc)44(48)Cl4(0)] and [Ln8Ni6L6(OAc)24(EtOH)6(H2O)2] were constructed using a flexible ligand. The Cd-Ln clusters exhibit interesting nano-drum-like structures which allows direct visualization by TEM. Luminex MicroPlex Microspheres loaded with the Cd-Sm cluster were visualized using epifluorescence microscopy. Cytotoxicity studies on A549 and AGS cancer cell lines showed that the materials have mild to moderate cytotoxicity. Electronic supplementary information (ESI) available: Full experimental and characterization details for 1-5. CCDC 1007468, 1007469 and 1007472-1007474. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6nr00642f

The Bologna Annotation Resource (BAR 3.0): improving protein functional annotation

PubMed Central

Casadio, Rita

2017-01-01

Abstract BAR 3.0 updates our server BAR (Bologna Annotation Resource) for predicting protein structural and functional features from sequence. We increase data volume, query capabilities and information conveyed to the user. The core of BAR 3.0 is a graph-based clustering procedure of UniProtKB sequences, following strict pairwise similarity criteria (sequence identity ≥40% with alignment coverage ≥90%). Each cluster contains the available annotation downloaded from UniProtKB, GO, PFAM and PDB. After statistical validation, GO terms and PFAM domains are cluster-specific and annotate new sequences entering the cluster after satisfying similarity constraints. BAR 3.0 includes 28 869 663 sequences in 1 361 773 clusters, of which 22.2% (22 241 661 sequences) and 47.4% (24 555 055 sequences) have at least one validated GO term and one PFAM domain, respectively. 1.4% of the clusters (36% of all sequences) include PDB structures and the cluster is associated to a hidden Markov model that allows building template-target alignment suitable for structural modeling. Some other 3 399 026 sequences are singletons. BAR 3.0 offers an improved search interface, allowing queries by UniProtKB-accession, Fasta sequence, GO-term, PFAM-domain, organism, PDB and ligand/s. When evaluated on the CAFA2 targets, BAR 3.0 largely outperforms our previous version and scores among state-of-the-art methods. BAR 3.0 is publicly available and accessible at http://bar.biocomp.unibo.it/bar3. PMID:28453653

Investigation of electronic structure of tri- and tetranuclear molybdenum clusters by X-ray photoelectron and emission spectroscopies and quantum chemical methods

NASA Astrophysics Data System (ADS)

Kryuchkova, Natalya A.; Syrokvashin, Mikhail M.; Gushchin, Artem L.; Korotaev, Evgeniy V.; Kalinkin, Alexander V.; Laricheva, Yuliya A.; Sokolov, Maxim N.

2018-02-01

Charge state studies of compounds [Mo3S4(tu)8(H2O)]Cl4·4H2O (1), [Mo3S4Cl3(dbbpy)3]Cl·5H2O (2), [Mo3S4(CuCl)Cl3(dbbpy)3][CuCl2] (3), containing {Mo3S4}4+ and {Mo3CuS4}5+ cluster cores bearing terminal thiourea (tu) or 4,4‧-di-tert-butyl-2,2‧-bipyridine (dbbpy) ligands, have been performed by X-ray photoelectron and X-ray emission spectroscopies combined with quantum chemical calculations. The best agreement between theory and experiments has been obtained using the B3LYP method. According to the experimental and calculated data, the Mo atoms are in the oxidation state 4+ for all compounds. The energies and shapes of the Cu2p lines indicate formal oxidation states of Cu as 1+. The coordination of Cu(I) to the cluster {Mo3S4} in 3 does not lead to significant changes in the charge state of the molybdenum atoms and the {Mo3S4} unit can be considered as a tridentate metallothia crown ether.

Differential hydrogen/deuterium exchange mass spectrometry analysis of protein–ligand interactions

PubMed Central

Chalmers, Michael J; Busby, Scott A; Pascal, Bruce D; West, Graham M; Griffin, Patrick R

2011-01-01

Functional regulation of ligand-activated receptors is driven by alterations in the conformational dynamics of the protein upon ligand binding. Differential hydrogen/deuterium exchange (HDX) coupled with mass spectrometry has emerged as a rapid and sensitive approach for characterization of perturbations in conformational dynamics of proteins following ligand binding. While this technique is sensitive to detecting ligand interactions and alterations in receptor dynamics, it also can provide important mechanistic insights into ligand regulation. For example, HDX has been used to determine a novel mechanism of ligand activation of the nuclear receptor peroxisome proliferator activated receptor-γ, perform detailed analyses of binding modes of ligands within the ligand-binding pocket of two estrogen receptor isoforms, providing insight into selectivity, and helped classify different types of estrogen receptor-α ligands by correlating their pharmacology with the way they interact with the receptor based solely on hierarchical clustering of receptor HDX signatures. Beyond small-molecule–receptor interactions, this technique has also been applied to study protein–protein complexes, such as mapping antibody–antigen interactions. In this article, we summarize the current state of the differential HDX approaches and the future outlook. We summarize how HDX analysis of protein–ligand interactions has had an impact on biology and drug discovery. PMID:21329427

Changing the ligation of the distal [4Fe4S] cluster in NiFe hydrogenase impairs inter- and intramolecular electron transfers.

PubMed

Dementin, Sébastien; Belle, Valérie; Bertrand, Patrick; Guigliarelli, Bruno; Adryanczyk-Perrier, Géraldine; De Lacey, Antonio L; Fernandez, Victor M; Rousset, Marc; Léger, Christophe

2006-04-19

In NiFe hydrogenases, electrons are transferred from the active site to the redox partner via a chain of three Iron-Sulfur clusters, and the surface-exposed [4Fe4S] cluster has an unusual His(Cys)3 ligation. When this Histidine (H184 in Desulfovibrio fructosovorans) is changed into a cysteine or a glycine, a distal cubane is still assembled but the oxidative activity of the mutants is only 1.5 and 3% of that of the WT, respectively. We compared the activities of the WT and engineered enzymes for H2 oxidation, H+ reduction and H/D exchange, under various conditions: (i) either with the enzyme directly adsorbed onto an electrode or using soluble redox partners, and (ii) in the presence of exogenous ligands whose binding to the exposed Fe of H184G was expected to modulate the properties of the distal cluster. Protein film voltammetry proved particularly useful to unravel the effects of the mutations on inter and intramolecular electron transfer (ET). We demonstrate that changing the coordination of the distal cluster has no effect on cluster assembly, protein stability, active-site chemistry and proton transfer; however, it slows down the first-order rates of ET to and from the cluster. All-sulfur coordination is actually detrimental to ET, and intramolecular (uphill) ET is rate determining in the glycine variant. This demonstrates that although [4Fe4S] clusters are robust chemical constructs, the direct protein ligands play an essential role in imparting their ability to transfer electrons.

Poly[[(μ2-acetato-κ3 O,O′:O′)aqua­bis­(μ3-isonicotinato-κ3 O:O′:N)samarium(III)silver(I)] perchlorate

PubMed Central

Zhu, Li-Cai; Zhu, Si-Ming

2011-01-01

The title compound, {[AgSm(C6H4NO2)2(CH3CO2)(H2O)]ClO4}n, is a three-dimensional heterobimetallic complex constructed from a repeating dimeric unit. Only half of the dimeric moiety is found in the asymmetric unit; the unit cell is completed by crystallographic inversion symmetry. The SmIII ion is eight-coordinated by four O atoms of four different isonicotinate ligands, three O atoms of two different acetate ligands, and one O atom of a water mol­ecule. The two-coordinate AgI ion is bonded to two N atoms of two different isonicotinate anions, thereby connecting the disamarium units. In addition, the isonicotinate ligands also act as bridging ligands, generating a three-dimensional network. The coordinated water mol­ecules link the carboxyl­ate group and acetate ligands by O—H⋯O hydrogen bonding. Another O—H⋯O hydrogen bond is observed in the crystal structure. The perchlorate ion is disordered over two sites with site-occupancy factors of 0.560 (11) and 0.440 (11), whereas the methyl group of the acetate ligand is disordered over two sites with site-occupancy factors of 0.53 (5) and 0.47 (5). PMID:22090841

The use of supramolecular structures as protein ligands.

PubMed

Stopa, Barbara; Jagusiak, Anna; Konieczny, Leszek; Piekarska, Barbara; Rybarska, Janina; Zemanek, Grzegorz; Król, Marcin; Piwowar, Piotr; Roterman, Irena

2013-11-01

Congo red dye as well as other eagerly self-assembling organic molecules which form rod-like or ribbon-like supramolecular structures in water solutions, appears to represent a new class of protein ligands with possible wide-ranging medical applications. Such molecules associate with proteins as integral clusters and preferentially penetrate into areas of low molecular stability. Abnormal, partly unfolded proteins are the main binding target for such ligands, while well packed molecules are generally inaccessible. Of particular interest is the observation that local susceptibility for binding supramolecular ligands may be promoted in some proteins as a consequence of function-derived structural changes, and that such complexation may alter the activity profile of target proteins. Examples are presented in this paper.

Reversing Conventional Reactivity of Mixed Oxo/Alkyl Rare-Earth Complexes: Non-Redox Oxygen Atom Transfer.

PubMed

Hong, Jianquan; Tian, Haiwen; Zhang, Lixin; Zhou, Xigeng; Del Rosal, Iker; Weng, Linhong; Maron, Laurent

2018-01-22

The preferential substitution of oxo ligands over alkyl ones of rare-earth complexes is commonly considered as "impossible" due to the high oxophilicity of metal centers. Now, it has been shown that simply assembling mixed methyl/oxo rare-earth complexes to a rigid trinuclear cluster framework cannot only enhance the activity of the Ln-oxo bond, but also protect the highly reactive Ln-alkyl bond, thus providing a previously unrecognized opportunity to selectively manipulate the oxo ligand in the presence of numerous reactive functionalities. Such trimetallic cluster has proved to be a suitable platform for developing the unprecedented non-redox rare-earth-mediated oxygen atom transfer from ketones to CS 2 and PhNCS. Controlled experiments and computational studies shed light on the driving force for these reactions, emphasizing the importance of the sterical accessibility and multimetallic effect of the cluster framework in promoting reversal of reactivity of rare-earth oxo complexes. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Series of edge-sharing bi-triangle Ln4 clusters with a μ4-NO3- bridge: syntheses, structures, luminescence, and the SMM behavior of the Dy4 analogue.

PubMed

Zou, Hua-Hong; Wang, Rong; Chen, Zi-Lu; Liu, Dong-Cheng; Liang, Fu-Pei

2014-02-14

A series of Ln4 clusters, [Ln4L2(μ3-OH)2(μ4-NO3)(NO3)4(OCH3)(H2O)]·xMeCN·yMeOH (Ln = Gd (1), Tb (2), Dy (3), Ho (4), Er (5), Yb (6), L = 2-{[2-(2-hydroxy-ethoxy)-ethylimino]-methyl}-6-methoxyphenol), have been synthesized by the reaction of Ln(NO)3 and a Schiff-base ligand formed in situ. The six complexes display similar structures, with an overall metal core comprising two edge-sharing triangular Ln3 units linked by a μ4-NO3(-) bridge. The luminescence spectrum of complex 2 shows the characteristic emission of the Tb(III) ions. The magnetic susceptibility studies reveal that the Ln(III) ions are very weakly interacting in all six compounds. Frequency dependence of the ac-susceptibility was found for 3, suggesting a typical single-molecule magnet (SMM) behavior with an anisotropic barrier of 28 K.

Facile design of red-emitting waveguides using hybrid nanocomposites made of inorganic clusters dispersed in SU8 photoresist host

NASA Astrophysics Data System (ADS)

Huby, Nolwenn; Bigeon, John; Lagneaux, Quentin; Amela-Cortes, Maria; Garreau, Alexandre; Molard, Yann; Fade, Julien; Desert, Anthony; Faulques, Eric; Bêche, Bruno; Duvail, Jean-Luc; Cordier, Stéphane

2016-02-01

Integration of stable emissive entities into organic waveguide with minimum scattering is essential to design efficient optically active devices. Here we present a new class of doped nanocomposite waveguides exploiting 1-nm diameter metallic cluster-based building blocks as red-NIR luminescent dyes embedded in a SU8 polymeric matrix, a reference photoresist for organic photonics. These building blocks are [Mo6Ii8(OOCC2F5)a6]2- cluster anionic units with unique chemical and physical features well suited for optical nanocomposites such as a ligand-promoted dispersibility, a large Stokes shift with a broad absorption window and an emission window in the range 600-900 nm. A whole investigation of the nanocomposite has been first performed. Optical characterizations of Cs2[Mo6Ii8(OOCCnF2n+1)a6]@SU8 nanocomposites thin film and waveguiding structures show their relevance as active layers in integrated structures with a significant increase of the refractive index of 3 × 10-2 when the cluster concentration increases up to 4 wt%, while keeping high values for the transmitted power, as shown for different waveguide dimensions and clusters concentrations. The efficiency of photoluminescence propagation is investigated as a function of clusters concentration in the excitation area for several waveguides dimensions. Attenuation coefficient ranges between 5 and 18 dB/cm, values of the same order of magnitude as those obtained in polymeric waveguide doped with QDs or organic dyes. This original, stable and efficient nanocomposite is promising for downscaling complex nanosources and active waveguides in the visible and NIR range.

Structural variation from heterometallic cluster-based 1D chain to heterometallic tetranuclear cluster: Syntheses, structures and magnetic properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Shu-Hua, E-mail: zsh720108@163.com; Zhao, Ru-Xia; Li, He-Ping

Using the solvothermal method, we present the comparative preparation of ([Co{sub 3}Na(dmaep){sub 3}(ehbd)(N{sub 3}){sub 3}]·DMF){sub n} (1) and [Co{sub 2}Na{sub 2}(hmbd){sub 4}(N{sub 3}){sub 2}(DMF){sub 2}] (2), where Hehbd is 3-ethoxy-2-hydroxy-benzaldehyde, Hhmbd is 3-methoxy-2-hydroxy-benzaldehyde, and Hdmaep is 2-dimethylaminomethyl-6-ethoxy-phenol, which was synthesized by an in-situ reaction. Complexes 1 and 2 were characterized by elemental analysis, IR spectroscopy, and X-ray single-crystal diffraction. Complex 1 is a novel heterometallic cluster-based 1-D chain and 2 is a heterometallic tetranuclear cluster. The (Co{sub 3}{sup II}Na) and (Co{sub 2}{sup II}Na{sub 2}) cores display dominant ferromagnetic interaction from the nature of the binding modes through μ{sub 1,1,1}-N{sub 3}{supmore » –} (end-on, EO). - Graphical abstract: Two novel cobalt complexes have been prepared. Compound 1 consists of tetranuclear (Co{sub 3}{sup II}Na) units, which further formed a 1-D chain. Compound 2 is heterometallic tetranuclear cluster. Two complexes display dominant ferromagnetic interaction. - Highlights: • Two new heterometallic complexes have been synthesized by solvothermal method. • The stereospecific blockade of the ligands in the synthesis system seems to be the most important synthetic parameter. • The magnetism studies show that 1 and 2 exhibit ferromagnetic interactions. • Complex 1 shows slowing down of magnetization and not blocking of magnetization.« less

Collision-induced dissociation of [4Fe-4S] cubane cluster complexes: [Fe4S4Cl4 - x(SC2H5)x]2-/1- (x = 0-4)

NASA Astrophysics Data System (ADS)

Fu, You-Jun; Laskin, Julia; Wang, Lai-Sheng

2006-09-01

Collision-induced dissociation (CID) experiments on a series of [4Fe-4S] cluster ions, [Fe4S4Cl4 - x(SC2H5)x]2-/1- (x = 0-4), revealed that their fragmentation channels change with the coordination environment. Among the three Coulomb repulsion related channels for the doubly charged species, the collision induced electron detachment channel was found to become more significant from x = 0 to 4 due to the decreasing electron binding energies and the magnitude of repulsion Coulomb barrier, while both the ligand detachment of Cl- and the fission of the [Fe4S4]2+ core became more and more significant with the increase of the Cl- coordination, and eventually became the dominant channel at x = 0. From the parents containing the SC2H5 ligand, neutral losses of HSC2H5 (62 u) and/or HSCHCH2 (60 u) were observed. It was proposed that inter- and intra-ligand proton transfer could happen during the CID process, resulting in hydrogen coordination to the [4Fe-4S] cluster. In the presence of O2, [Fe4S4Cl3(SC2H5)]2- and [Fe4S4Cl4]2- can form the O2-substituted products [Fe4S4Cl2(SC2H5)O2]- and [Fe4S4Cl3O2]-, respectively. It was shown that the O2 complexation occurs by coordination to the empty iron site of the [4Fe-4S] cubane core after dissociation of one Cl- ligand.

Encapsulating Metal Clusters and Acid Sites within Small Voids: Synthetic Strategies and Catalytic Consequences

NASA Astrophysics Data System (ADS)

Goel, Sarika

The selective encapsulation of metal clusters within zeolites can be used to prepare clusters that are uniform in diameter and to protect them against sintering and contact with feed impurities, while concurrently allowing active sites to select reactants based on their molecular size, thus conferring enzyme-like specificity to chemical catalysis. The apertures in small and medium-pore zeolites preclude the use of post-synthetic protocols to encapsulate the relevant metal precursors because cationic or anionic precursors with their charge-balancing double layer and gaseous complexes cannot diffuse through their windows or channels. We have developed general strategies to encapsulate metal clusters within small-pore zeolites by using metal precursors stabilized by ammonia or organic amine ligands, which stabilize metal precursors against their premature precipitation at the high temperature and pH conditions required for the hydrothermal synthesis of the target zeolite structures and favor interactions between metal precursors and incipient aluminosilicate nuclei during the self-assembly of microporous frameworks. When synthesis temperatures were higher than 400 K, available ligands were unable to prevent the premature precipitation of the metal precursors. In such cases, encapsulation was achieved instead via interzeolite transformations after successfully encapsulating metal precursors or clusters via post-synthesis exchange or ligand protection into parent zeolites and subsequently converting them into the target structures while retaining the encapsulated clusters or precursors. Such strategies led to the successful selective encapsulation of a wide range of metal clusters (Pt, Pd, Ru, Rh, Ir, Re, and Ag) within small-pore (SOD (sodalite), LTA (Linde type A (zeolite A)), GIS (gismondine), and ANA (analcime)) and medium-pore (MFI (ZSM-5)) zeolites. These protocols provide novel and diverse mechanism-based strategies for the design of catalysts with protected active sites. We have demonstrated the selectivity of the encapsulation processes by combining transmission electron microscopy and chemisorptive titrations with rigorous catalytic assessments of the ability of these materials to catalyze reactions of small molecules, which can access the intracrystalline voids, but not of larger molecules that cannot access the metal clusters within such voids. The selective confinement of clusters also prevented their contact with sulfur compounds (e.g., thiophene and H2S), thus allowing reactions to occur at conditions that otherwise render unconfined clusters unreactive. We have also developed synthetic protocols and guiding principles, inspired by mechanistic considerations, for the synthesis of zeolites via interzeolite transformations without the use of organic structure-directing agents (OSDA). More specifically, we have synthesized high-silica MFI (ZSM-5), CHA (chabazite), STF (SSZ-35) and MTW (ZSM-12) zeolites from FAU (faujasite) or BEA (beta) parent materials. Structures with lower framework densities (FAU or BEA) were successfully transformed into thermodynamically-favored, more stable structures with higher framework densities (MFI, CHA, STF, and MTW); to date, target materials with higher Si/Al ratios (Si/Al >10) have not been synthesized via interzeolite transformations without the aid of the OSDA species used to discover these zeolite structures and deemed essential up until now for their successful synthesis. Overcoming kinetic hurdles in such transformations required either the presence of common composite building units (CBU) between parent and target structures or, in their absence, the introduction of small amount of seeds of the daughter structures. The NaOH/SiO2 ratio, H2O/SiO2 ratio and Al content in reagents are used to enforce synchronization between the swelling and local restructuring within parent zeolite domains with the spalling of fragments or building units from seeds of the target structure. The pseudomorphic nature of these seed-mediated transformations, which conserve the volume occupied by the parent crystals and lead to similar size and crystal shape in products, reflect incipient nucleation of target structures occurring at the outer regions of the parent domains and lead to the formation of mesoporosity as a natural consequence of the space-conserving nature of these structural changes and of the higher density of the daughter frameworks. The synthesis mechanism and the guidelines developed enable us to enforce conditions required for the formation of zeolites that previously required OSDA species for their synthesis, thus expanding to a significant extent the diversity of zeolite frameworks that are accessible via these synthesis protocols and providing potential savings in the time and cost involved in the synthesis of some of these zeolite structures.

Synthetic control and empirical prediction of redox potentials for Co 4O 4 cubanes over a 1.4 V range: implications for catalyst design and evaluation of high-valent intermediates in water oxidation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nguyen, Andy I.; Wang, Jianing; Levine, Daniel S.

The oxo-cobalt cubane unit [Co 4O 4] is of interest as a homogeneous oxygen-evolution reaction (OER) catalyst, and as a functional mimic of heterogeneous cobalt oxide OER catalysts. The synthesis of several new cubanes allows evaluation of redox potentials for the [Co 4O 4] cluster, which are highly sensitive to the ligand environment and span a remarkable range of 1.42 V. The [Co III 4O 4] 4+/[Co III 3Co IVO 4 ]5+ and [Co III 3Co IVO 4] 5+/[Co III 2Co IV 2O 4] 6+ redox potentials are reliably predicted by the pKas of the ligands. Hydrogen bonding is alsomore » shown to significantly raise the redox potentials, by ~500 mV. The potential-p K a correlation is used to evaluate the feasibility of various proposed OER catalytic intermediates, including high-valent Co-oxo species. The synthetic methods and structure–reactivity relationships developed by these studies should better guide the design of new cubane-based OER catalysts.« less

Series of coordination polymers based on 4-(5-sulfo-quinolin-8-yloxy) phthalate and bipyridinyl coligands: Structure diversity and properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Feng, Xun; Liu, Jing; College of Chemistry and Chemical Engineering, Luoyang Normal University, Luoyang 471022

2015-10-15

Reactions between later metal salts and conjugational N-hetrocyclic sulfonate/ carboxylic acid under the presence of bipyridyl auxiliary ligands afforded a series of manganese, nickel, zinc, silver, cadmium coordination polymers bearing with phenyl pendant arm attached to quinoline skeletons, and they have been characterized by elements analysis, thermogravimetry, infrared spectroscopy and single-crystal X-ray diffraction studying. The series of polymers show interesting structural diversity in coordination environment, dimensions and topologies. They are all built from 2-D networks constructed from metal cluster through sulfonate or carboxylate groups, as the secondary building unit (SBU). The thermalgravimetric analyses show that they display framework stabilities inmore » solid state. Variable-temperature magnetic susceptibility studies reveal the existence of antiferromagnetic interactions between adjacent Mn (II) ions in 1, and ferromagnetic interactions between Ni(II) ions for 2, respectively. The photo-luminescence properties of 3-5 have also been investigated systemically. - Highlights: • A series of coordination polymers based on later transition metal ions have been obtained. • They contain conjugational N-hetrocyclic sulfonate-carboxylic acid and bipyridyl auxiliary ligands. • They have been characterized systemically. • They exhibit structure diversity and interesting properties.« less

Synthetic control and empirical prediction of redox potentials for Co 4O 4 cubanes over a 1.4 V range: implications for catalyst design and evaluation of high-valent intermediates in water oxidation

DOE PAGES

Nguyen, Andy I.; Wang, Jianing; Levine, Daniel S.; ...

2017-04-07

The oxo-cobalt cubane unit [Co 4O 4] is of interest as a homogeneous oxygen-evolution reaction (OER) catalyst, and as a functional mimic of heterogeneous cobalt oxide OER catalysts. The synthesis of several new cubanes allows evaluation of redox potentials for the [Co 4O 4] cluster, which are highly sensitive to the ligand environment and span a remarkable range of 1.42 V. The [Co III 4O 4] 4+/[Co III 3Co IVO 4 ]5+ and [Co III 3Co IVO 4] 5+/[Co III 2Co IV 2O 4] 6+ redox potentials are reliably predicted by the pKas of the ligands. Hydrogen bonding is alsomore » shown to significantly raise the redox potentials, by ~500 mV. The potential-p K a correlation is used to evaluate the feasibility of various proposed OER catalytic intermediates, including high-valent Co-oxo species. The synthetic methods and structure–reactivity relationships developed by these studies should better guide the design of new cubane-based OER catalysts.« less

Electronic shell structure in Ga12 icosahedra and the relation to the bulk forms of gallium.

PubMed

Schebarchov, D; Gaston, N

2012-07-28

The electronic structure of known cluster compounds with a cage-like icosahedral Ga(12) centre is studied by first-principles theoretical methods, based on density functional theory. We consider these hollow metalloid nanostructures in the context of the polymorphism of the bulk, and identify a close relation to the α phase of gallium. This previously unrecognised connection is established using the electron localisation function, which reveals the ubiquitous presence of radially-pointing covalent bonds around the Ga(12) centre--analogous to the covalent bonds between buckled deltahedral planes in α-Ga. Furthermore, we find prominent superatom shell structure in these clusters, despite their hollow icosahedral motif and the presence of covalent bonds. The exact nature of the electronic shell structure is contrasted with simple electron shell models based on jellium, and we demonstrate how the interplay between gallium dimerisation, ligand- and crystal-field effects can alter the splitting of the partially filled 1F shell. Finally, in the unique compound where the Ga(12) centre is bridged by six phosphorus ligands, the electronic structure most closely resembles that of δ-Ga and there are no well-defined superatom orbitals. The results of this comprehensive study bring new insights into the nature of chemical bonding in metalloid gallium compounds and the relation to bulk gallium metal, and they may also guide the development of more general models for ligand-protected clusters.

Similarities among receptor pockets and among compounds: analysis and application to in silico ligand screening.

PubMed

Fukunishi, Yoshifumi; Mikami, Yoshiaki; Nakamura, Haruki

2005-09-01

We developed a new method to evaluate the distances and similarities between receptor pockets or chemical compounds based on a multi-receptor versus multi-ligand docking affinity matrix. The receptors were classified by a cluster analysis based on calculations of the distance between receptor pockets. A set of low homologous receptors that bind a similar compound could be classified into one cluster. Based on this line of reasoning, we proposed a new in silico screening method. According to this method, compounds in a database were docked to multiple targets. The new docking score was a slightly modified version of the multiple active site correction (MASC) score. Receptors that were at a set distance from the target receptor were not included in the analysis, and the modified MASC scores were calculated for the selected receptors. The choice of the receptors is important to achieve a good screening result, and our clustering of receptors is useful to this purpose. This method was applied to the analysis of a set of 132 receptors and 132 compounds, and the results demonstrated that this method achieves a high hit ratio, as compared to that of a uniform sampling, using a receptor-ligand docking program, Sievgene, which was newly developed with a good docking performance yielding 50.8% of the reconstructed complexes at a distance of less than 2 A RMSD.

Dialing in single-site reactivity of a supported calixarene-protected tetrairidium cluster catalyst

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palermo, Andrew; Solovyov, Andrew; Ertler, Daniel

2017-05-04

A closed Ir 4carbonyl cluster,1, comprising a tetrahedral metal frame and threetert-butyl-calix[4]arene(OPr) 3(OCH 2PPh 2) (Ph = phenyl; Pr = propyl) ligands at the basal plane, was silica supported and consists of “*” and “S” sites, which could be dialed in selectively for controlling ethylene hydrogenation catalysis.

Spin-canting magnetization in an unusual Co4 cluster-based layer compound from a 2,3-dihydroxyquinoxaline ligand.

PubMed

Yang, Chen-I; Chuang, Po-Hsiang; Lee, Gene-Hsiang; Peng, Shie-Ming; Lu, Kuang-Lieh

2012-01-16

The self-assembly of Co(O(2)CPh)(2) with a 2,3-dihydroxyquinoxaline (H(2)dhq) linker has revealed a new two-dimensional cluster-based compound, [Co(4)(OMe)(2)(O(2)CPh)(2)(dhq)(2)(MeOH)(2)](n), which shows spin-canted magnetization and a definite magnetic hysteresis loop.

Clustering Molecular Dynamics Trajectories for Optimizing Docking Experiments

PubMed Central

De Paris, Renata; Quevedo, Christian V.; Ruiz, Duncan D.; Norberto de Souza, Osmar; Barros, Rodrigo C.

2015-01-01

Molecular dynamics simulations of protein receptors have become an attractive tool for rational drug discovery. However, the high computational cost of employing molecular dynamics trajectories in virtual screening of large repositories threats the feasibility of this task. Computational intelligence techniques have been applied in this context, with the ultimate goal of reducing the overall computational cost so the task can become feasible. Particularly, clustering algorithms have been widely used as a means to reduce the dimensionality of molecular dynamics trajectories. In this paper, we develop a novel methodology for clustering entire trajectories using structural features from the substrate-binding cavity of the receptor in order to optimize docking experiments on a cloud-based environment. The resulting partition was selected based on three clustering validity criteria, and it was further validated by analyzing the interactions between 20 ligands and a fully flexible receptor (FFR) model containing a 20 ns molecular dynamics simulation trajectory. Our proposed methodology shows that taking into account features of the substrate-binding cavity as input for the k-means algorithm is a promising technique for accurately selecting ensembles of representative structures tailored to a specific ligand. PMID:25873944

Synthesis, structural characterization, reactivity, and catalytic properties of copper(I) complexes with a series of tetradentate tripodal tris(pyrazolylmethyl)amine ligands.

PubMed

Haldón, Estela; Delgado-Rebollo, Manuela; Prieto, Auxiliadora; Alvarez, Eleuterio; Maya, Celia; Nicasio, M Carmen; Pérez, Pedro J

2014-04-21

Novel tris(pyrazolylmethyl)amine ligands Tpa(Me3), Tpa*(,Br), and Tpa(Br3) have been synthesized and structurally characterized. The coordination chemistries of these three new tetradentate tripodal ligands and the already known Tpa and Tpa* have been explored using different copper(I) salts as starting materials. Cationic copper(I) complexes [Tpa(x)Cu]PF6 (1-4) have been isolated from the reaction of [Cu(NCMe)4]PF6 and 1 equiv of the ligand. Complexes 2 (Tpa(x) = Tpa*) and 3 (Tpa(x) = Tpa(Me3)) have been characterized by X-ray studies. The former is a 1D helical coordination polymer, and the latter is a tetranuclear helicate. In both structures, the Tpa(x) ligand adopts a μ(2):κ(2):κ(1)-coordination mode. However, in solution, all of the four complexes form fluxional species. When CuI is used as the copper(I) source, neutral compounds 5-8 have been obtained. Complexes 6-8 exhibit a 1:1 metal-to-ligand ratio, whereas 5 presents 2:1 stoichiometry. Its solid-state structure has been determined by X-ray diffraction, revealing its 3D polymeric nature. The polymer is composed by the assembly of [Tpa2Cu4I4] units, in which Cu4I4 presents a step-stair structure. The Tpa ligands bridge the Cu4I4 clusters, adopting also a μ(2):κ(2):κ(1)-coordination mode. As observed for the cationic derivatives, the NMR spectra of 5-8 show the equivalence of the three pyrazolyl arms of the ligands in these complexes. The reactivities of cationic copper(I) derivatives 1-4 with PPh3 and CO have been explored. In all cases, 1:1 adducts [Tpa(x)CuL]PF6 [L = PPh3 (9-11), CO (12-15)] have been isolated. The crystal structure of [Tpa*Cu(PPh3)]PF6 (9) has been obtained, showing that the coordination geometry around copper(I) is trigonal-pyramidal with the apical position occupied by the tertiary amine N atom. The Tpa* ligand binds the Cu center to three of its four N atoms, with one pyrazolyl arm remaining uncoordinated. In solution, the carbonyl adducts 13-15 exist as a mixture of two isomers; the four- and five-coordinate species can be distinguished by means of their IR νCO stretching bands. Finally, the catalytic activities of complexes 1-4 have been demonstrated in carbene- and nitrene-transfer reactions.

A Search for CD36 Ligands from Flavor Volatiles in Foods with an Aldehyde Moiety: Identification of Saturated Aliphatic Aldehydes with 9-16 Carbon Atoms as Potential Ligands of the Receptor.

PubMed

Tsuzuki, Satoshi; Amitsuka, Takahiko; Okahashi, Tatsuya; Kimoto, Yusaku; Inoue, Kazuo

2017-08-09

Volatile compounds with an aldehyde moiety such as (Z)-9-octadecenal are potential ligands for cluster of differentiation 36 (CD36), a transmembrane receptor that has recently been shown to play a role in mammalian olfaction. In this study, by performing an assay using a peptide mimic of human CD36, we aimed to discover additional ligands for the receptor from volatiles containing a single aldehyde group commonly found in human foods. Straight-chain, saturated aliphatic aldehydes with 9-16 carbons exhibited CD36 ligand activities, albeit to varying degrees. Notably, the activities of tridecanal and tetradecanal were higher than that of oleic acid, the most potent ligand among the fatty acids tested. Among the aldehydes other than aliphatic aldehydes, only phenylacetaldehyde showed a weak activity. These findings make a contribution to our knowledge of recognition mechanisms for flavor volatiles in foods with an aldehyde group.

Microwave-assisted synthesis of water-soluble, fluorescent gold nanoclusters capped with small organic molecules and a revealing fluorescence and X-ray absorption study

NASA Astrophysics Data System (ADS)

Helmbrecht, C.; Lützenkirchen-Hecht, D.; Frank, W.

2015-03-01

Colourless solutions of blue light-emitting, water-soluble gold nanoclusters (AuNC) were synthesized from gold colloids under microwave irradiation using small organic molecules as ligands. Stabilized by 1,3,5-triaza-7-phosphaadamantane (TPA) or l-glutamine (GLU), fluorescence quantum yields up to 5% were obtained. AuNC are considered to be very promising for biological labelling, optoelectronic devices and light-emitting materials but the structure-property relationships have still not been fully clarified. To expand the knowledge about the AuNC apart from their fluorescent properties they were studied by X-ray absorption spectroscopy elucidating the oxidation state of the nanoclusters' gold atoms. Based on curve fitting of the XANES spectra in comparison to several gold references, optically transparent fluorescent AuNC are predicted to be ligand-stabilized Au5+ species. Additionally, their near edge structure compared with analogous results of polynuclear clusters known from the literature discloses an increasing intensity of the feature close to the absorption edge with decreasing cluster size. As a result, a linear relationship between the cluster size and the X-ray absorption coefficient can be established for the first time.Colourless solutions of blue light-emitting, water-soluble gold nanoclusters (AuNC) were synthesized from gold colloids under microwave irradiation using small organic molecules as ligands. Stabilized by 1,3,5-triaza-7-phosphaadamantane (TPA) or l-glutamine (GLU), fluorescence quantum yields up to 5% were obtained. AuNC are considered to be very promising for biological labelling, optoelectronic devices and light-emitting materials but the structure-property relationships have still not been fully clarified. To expand the knowledge about the AuNC apart from their fluorescent properties they were studied by X-ray absorption spectroscopy elucidating the oxidation state of the nanoclusters' gold atoms. Based on curve fitting of the XANES spectra in comparison to several gold references, optically transparent fluorescent AuNC are predicted to be ligand-stabilized Au5+ species. Additionally, their near edge structure compared with analogous results of polynuclear clusters known from the literature discloses an increasing intensity of the feature close to the absorption edge with decreasing cluster size. As a result, a linear relationship between the cluster size and the X-ray absorption coefficient can be established for the first time. Electronic supplementary information (ESI) available: The deconvoluted reference spectra are given in ESI Fig. 1-9. See DOI: 10.1039/c4nr07051h

An Augmented Pocketome: Detection and Analysis of Small-Molecule Binding Pockets in Proteins of Known 3D Structure.

PubMed

Bhagavat, Raghu; Sankar, Santhosh; Srinivasan, Narayanaswamy; Chandra, Nagasuma

2018-03-06

Protein-ligand interactions form the basis of most cellular events. Identifying ligand binding pockets in proteins will greatly facilitate rationalizing and predicting protein function. Ligand binding sites are unknown for many proteins of known three-dimensional (3D) structure, creating a gap in our understanding of protein structure-function relationships. To bridge this gap, we detect pockets in proteins of known 3D structures, using computational techniques. This augmented pocketome (PocketDB) consists of 249,096 pockets, which is about seven times larger than what is currently known. We deduce possible ligand associations for about 46% of the newly identified pockets. The augmented pocketome, when subjected to clustering based on similarities among pockets, yielded 2,161 site types, which are associated with 1,037 ligand types, together providing fold-site-type-ligand-type associations. The PocketDB resource facilitates a structure-based function annotation, delineation of the structural basis of ligand recognition, and provides functional clues for domains of unknown functions, allosteric proteins, and druggable pockets. Copyright © 2018 Elsevier Ltd. All rights reserved.

Ni(II)/Zn(II)-triazolate clusters based MOFs constructed from a V-shaped dicarboxylate ligand: Magnetic properties and phosphate sensing

NASA Astrophysics Data System (ADS)

Chen, Yong-Qiang; Tian, Yuan; Li, Na; Liu, Sui-Jun

2018-06-01

Two isomorphous metal-organic frameworks (MOFs) {[M2(μ3-OH)(trz)(sdba)(H2O)]·3H2O}∞ (M = Ni for 1, Zn for 2, Htrz = 1,2,4-triazole, H2sdba = 4,4‧-sulfonyldibenzoate) were obtained under the same reaction condition. Both of complexes present a three dimensional 8-c framework with whc1 topology based on M4-(μ3-OH) units. Moreover, the magnetic properties of 1 and anion sensing of 2 were investigated. The magnetic study show that the domain antiferromagnetic interactions exist in 1. However, complex 2 can be considered as a promising chemical sensor for detecting PO43barby means of fluorescence enhancement among various anions in aqueous solutions.

Studies of cluster-assembled materials: From gas phase to condensed phase

NASA Astrophysics Data System (ADS)

Gao, Lin

Clusters, defined as "a number of similar things that occur together" in Webster's dictionary, has different meanings depending on the given subject. To physicists and chemists, the word cluster means "a group of atoms or molecules formed by interactions ranging from very weak van der Waals interactions to strong ionic bonds." Unlike molecules, which are made by nature and are stable under ambient conditions, clusters discovered in a laboratory are often metastable. Molecules have specific stoichiometry, whereas the cluster's composition can usually be altered atom by atom. Thus, clusters can be taken as intrinsically "artificial molecules" with considerably more tunabilities in their properties. Research into the relative stability and instability of clusters has in recent years become a very active research area, especially following the study by Khanna and Castleman that first suggested that by varying size and composition, clusters can expand the periodic table to the 3 rd-dimension; that is, clusters can mimic the chemistry of atoms and may, therefore, be used as the building blocks of new materials. The discovery of Met-Cars has drawn worldwide interests and has been actively investigated by researchers from a variety of fields, including physics, chemistry and material science. However, the unsuccessful search for a solvent capable of isolating Met-Cars has impeded progress in characterizing the material in the condensed state and, hence, limited its potential applications as a novel nanoscale material. An alternative method involving the deposition of mass-gated species and the subsequent structural investigation via Transmission Electron Microscopy (TEM) has been employed. With particularly interesting results, soft-landed deposits of zirconium Met-Cars were found to form a face-centered-cubic (FCC) structure with a lattice parameter ˜ 15A. The production of Met-Cars is conducted with the direct laser vaporization (DLV) of metal/graphite composite pellets. After being mass gated in a reflectron equipped time-of-flight mass spectrometer (TOF-MS) and deposited onto TEM grids, the resultant specimens can be loaded onto high-resolution TEM investigation via electron diffraction. In conclusion, soft-landing of mass selected clusters has been shown to be a successful approach to obtain structural information on Zr-Met-Car cluster-assembled materials collected from the gas phase. TEM images indicate the richness of the morphologies associated with these cluster crystals. However, passivation methods are expected to be examined further to overcome the limited stabilities of these novel clusters. From this initial study, it's shown the promising opportunity to study other Met-Cars species and more cluster-based materials. Experimental results of reactions run with a solvothermal synthesis method obtained while searching for new Zr-C cluster assembled materials, are reported. One unexpected product in single crystal form was isolated and tentatively identified by X-ray diffraction to be [Zr6i O(OH)O12·2(Bu)4], with space group P2 1/n and lattice parameters of a = 12.44 A, b = 22.06 A, c = 18.40 A, alpha = 90°, beta = 105°, gamma = 90°, V = 4875 A3 and R 1 = 3.15% for the total observed data (I ≥ 2 sigma I) and oR2 = 2.82%. This novel hexanuclear Zr(IV)-oxo-hydroxide cluster anion may be the first member in polyoxometalates class with metal atoms from the IVB group and having Oh symmetry. Alternatively, it may be the first member in {[(Zr6Z)X 12]X6}m- class with halides replaced by oxo- and hydroxyl groups and with an increased oxidation state of Zr. It is predicted to bear application potentials directed by both families. This work could suggest a direction in which the preparation of Zr-C cluster-assembled materials in a liquid environment may be eventually fulfilled. 1,3-Bis(diethylphosphino)propane (depp) protected small gold clusters are studied via multiple techniques, including Electrospray Ionization Mass Spectrometry (ESI-MS), Ultraviolet-Visible Spectroscopy (Uv-Vis), Nuclear Magnetic Resonance (NMR) for solution phase and Transmission Electron Microscopy (TEM) for the condensed phase. In particular, undeca-, dodeca- and trideca-gold clusters protected by depp and halogen ligands, i.e. [Au11-13(depp) 4Cl2-4]+, are found to be all predominant and persist in solution for months, while they gradually and spontaneously grow into a monomial trideca-gold clusters series. The unique preferred ligand combination, depp along with Cl, is discussed in terms of the ligand-core interaction and the closed-shell electronic configurations of the Au n (n = 11-13) cores, which enables them to serve as building units for larger cluster-assembled nanoparticles and form Self-Assembled Arrays (SAAs), as discovered by TEM measurements. Such spontaneous-growth behavior and the resultant SAAs observations are correlated by icosahedra-close-packing modes of clusters, following "magic numbers" rules. ˜7 shells of such cluster packing are proposed to be in the SAAs.

SMMRNA: a database of small molecule modulators of RNA

PubMed Central

Mehta, Ankita; Sonam, Surabhi; Gouri, Isha; Loharch, Saurabh; Sharma, Deepak K.; Parkesh, Raman

2014-01-01

We have developed SMMRNA, an interactive database, available at http://www.smmrna.org, with special focus on small molecule ligands targeting RNA. Currently, SMMRNA consists of ∼770 unique ligands along with structural images of RNA molecules. Each ligand in the SMMRNA contains information such as Kd, Ki, IC50, ΔTm, molecular weight (MW), hydrogen donor and acceptor count, XlogP, number of rotatable bonds, number of aromatic rings and 2D and 3D structures. These parameters can be explored using text search, advanced search, substructure and similarity-based analysis tools that are embedded in SMMRNA. A structure editor is provided for 3D visualization of ligands. Advance analysis can be performed using substructure and OpenBabel-based chemical similarity fingerprints. Upload facility for both RNA and ligands is also provided. The physicochemical properties of the ligands were further examined using OpenBabel descriptors, hierarchical clustering, binning partition and multidimensional scaling. We have also generated a 3D conformation database of ligands to support the structure and ligand-based screening. SMMRNA provides comprehensive resource for further design, development and refinement of small molecule modulators for selective targeting of RNA molecules. PMID:24163098

AutoSite: an automated approach for pseudo-ligands prediction—from ligand-binding sites identification to predicting key ligand atoms

PubMed Central

Ravindranath, Pradeep Anand; Sanner, Michel F.

2016-01-01

Motivation: The identification of ligand-binding sites from a protein structure facilitates computational drug design and optimization, and protein function assignment. We introduce AutoSite: an efficient software tool for identifying ligand-binding sites and predicting pseudo ligand corresponding to each binding site identified. Binding sites are reported as clusters of 3D points called fills in which every point is labelled as hydrophobic or as hydrogen bond donor or acceptor. From these fills AutoSite derives feature points: a set of putative positions of hydrophobic-, and hydrogen-bond forming ligand atoms. Results: We show that AutoSite identifies ligand-binding sites with higher accuracy than other leading methods, and produces fills that better matches the ligand shape and properties, than the fills obtained with a software program with similar capabilities, AutoLigand. In addition, we demonstrate that for the Astex Diverse Set, the feature points identify 79% of hydrophobic ligand atoms, and 81% and 62% of the hydrogen acceptor and donor hydrogen ligand atoms interacting with the receptor, and predict 81.2% of water molecules mediating interactions between ligand and receptor. Finally, we illustrate potential uses of the predicted feature points in the context of lead optimization in drug discovery projects. Availability and Implementation: http://adfr.scripps.edu/AutoDockFR/autosite.html Contact: sanner@scripps.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27354702

The Bologna Annotation Resource (BAR 3.0): improving protein functional annotation.

PubMed

Profiti, Giuseppe; Martelli, Pier Luigi; Casadio, Rita

2017-07-03

BAR 3.0 updates our server BAR (Bologna Annotation Resource) for predicting protein structural and functional features from sequence. We increase data volume, query capabilities and information conveyed to the user. The core of BAR 3.0 is a graph-based clustering procedure of UniProtKB sequences, following strict pairwise similarity criteria (sequence identity ≥40% with alignment coverage ≥90%). Each cluster contains the available annotation downloaded from UniProtKB, GO, PFAM and PDB. After statistical validation, GO terms and PFAM domains are cluster-specific and annotate new sequences entering the cluster after satisfying similarity constraints. BAR 3.0 includes 28 869 663 sequences in 1 361 773 clusters, of which 22.2% (22 241 661 sequences) and 47.4% (24 555 055 sequences) have at least one validated GO term and one PFAM domain, respectively. 1.4% of the clusters (36% of all sequences) include PDB structures and the cluster is associated to a hidden Markov model that allows building template-target alignment suitable for structural modeling. Some other 3 399 026 sequences are singletons. BAR 3.0 offers an improved search interface, allowing queries by UniProtKB-accession, Fasta sequence, GO-term, PFAM-domain, organism, PDB and ligand/s. When evaluated on the CAFA2 targets, BAR 3.0 largely outperforms our previous version and scores among state-of-the-art methods. BAR 3.0 is publicly available and accessible at http://bar.biocomp.unibo.it/bar3. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Sensitizing Tb(III) and Eu(III) emission with triarylboron functionalized 1,3-diketonato ligands.

PubMed

Smith, Larissa F; Blight, Barry A; Park, Hee-Jun; Wang, Suning

2014-08-04

Four BMes2Ar (Mes = mesityl, Ar = phenyl or duryl) functionalized 1,3-diketonato ligands have been investigated for use in selective sensitization of Tb(III) and Eu(III) emission. These ligands have the general formula of [R1C(O)CR2C(O)R3](-) (R1 = Ph, R2 = H, R3 = p-Ph-BMes2, L1; R1 = R3 = p-Ph-BMes2, R2 = H, L2; R1 = R3 = Me, R2 = p-Ph-BMes2, L3; R1 = R3 = Me, R2 = p-duryl-BMes2, L4) and belong to class I (L1 and L2) and class II (L3 and L4), respectively. In class I, the boron unit is conjugated with the phenyl linker and the diketone backbone, while in class II, the boron unit, the linker unit, and the diketone unit are nonconjugated with a mutually orthogonal arrangement. To understand the impact of the location of the BMes2Ar unit on the electronic properties of the 1,3-diketone molecules and their ability in activating lanthanide emission, the difluoroboron chelate compounds (1-BF2 to 4-BF2) of ligands L1-L4 were synthesized and examined. The class I ligands were effective in activating Eu(III) emission, while the class II ligands were effective in activating Tb(III) emission. Four Ln(III) complexes, 1Eu, 2Eu, 3Tb, and 4Tb, based on the L1-L4 ligands, respectively, were prepared and examined. The emission quantum efficiency of 1Eu and 2Eu is low (Φ(Eu) ≤ 0.01 in THF, 0.07-0.13 in the solid state), but can be greatly enhanced by the addition of fluoride ions. In contrast, the complex 4Tb has a moderate emission efficiency (Φ(Tb) = 0.14 in THF, 0.47 in the solid state) and experiences a distinct emission quenching upon the addition of fluoride. The selective sensitization of Eu(III) and Tb(III) by L1-L4 and the distinct luminescent response of their Ln(III) complexes toward fluoride ions are caused by the distinct intraligand charge transfer transitions of the two different classes of ligands involving the BMes2 unit.

A web server for analysis, comparison and prediction of protein ligand binding sites.

PubMed

Singh, Harinder; Srivastava, Hemant Kumar; Raghava, Gajendra P S

2016-03-25

One of the major challenges in the field of system biology is to understand the interaction between a wide range of proteins and ligands. In the past, methods have been developed for predicting binding sites in a protein for a limited number of ligands. In order to address this problem, we developed a web server named 'LPIcom' to facilitate users in understanding protein-ligand interaction. Analysis, comparison and prediction modules are available in the "LPIcom' server to predict protein-ligand interacting residues for 824 ligands. Each ligand must have at least 30 protein binding sites in PDB. Analysis module of the server can identify residues preferred in interaction and binding motif for a given ligand; for example residues glycine, lysine and arginine are preferred in ATP binding sites. Comparison module of the server allows comparing protein-binding sites of multiple ligands to understand the similarity between ligands based on their binding site. This module indicates that ATP, ADP and GTP ligands are in the same cluster and thus their binding sites or interacting residues exhibit a high level of similarity. Propensity-based prediction module has been developed for predicting ligand-interacting residues in a protein for more than 800 ligands. In addition, a number of web-based tools have been integrated to facilitate users in creating web logo and two-sample between ligand interacting and non-interacting residues. In summary, this manuscript presents a web-server for analysis of ligand interacting residue. This server is available for public use from URL http://crdd.osdd.net/raghava/lpicom .

Linked supramolecular building blocks for enhanced cluster formation

DOE PAGES

McLellan, Ross; Palacios, Maria A.; Beavers, Christine M.; ...

2015-01-09

Methylene-bridged calix[4]arenes have emerged as extremely versatile ligand supports in the formation of new polymetallic clusters possessing fascinating magnetic properties. Metal ion binding rules established for this building block allow one to partially rationalise the complex assembly process. The ability to covalently link calix[4]arenes at the methylene bridge provides significantly improved control over the introduction of different metal centres to resulting cluster motifs. Clusters assembled from bis-calix[4]arenes and transition metal ions or 3d-4f combinations display characteristic features of the analogous calix[4]arene supported clusters, thereby demonstrating an enhanced and rational approach towards the targeted synthesis of complex and challenging structures.

Electronic structure and optical properties of the thiolate-protected Au28(SMe)20 cluster.

PubMed

Knoppe, Stefan; Malola, Sami; Lehtovaara, Lauri; Bürgi, Thomas; Häkkinen, Hannu

2013-10-10

The recently reported crystal structure of the Au28(TBBT)20 cluster (TBBT: p-tert-butylbenzenethiolate) is analyzed with (time-dependent) density functional theory (TD-DFT). Bader charge analysis reveals a novel trimeric Au3(SR)4 binding motif. The cluster can be formulated as Au14(Au2(SR)3)4(Au3(SR)4)2. The electronic structure of the Au14(6+) core and the ligand-protected cluster were analyzed, and their stability can be explained by formation of distorted eight-electron superatoms. Optical absorption and circular dichroism (CD) spectra were calculated and compared to the experiment. Assignment of handedness of the intrinsically chiral cluster is possible.

Protonation/reduction dynamics at the [4Fe-4S] cluster of the hydrogen-forming cofactor in [FeFe]-hydrogenases.

PubMed

Senger, Moritz; Mebs, Stefan; Duan, Jifu; Shulenina, Olga; Laun, Konstantin; Kertess, Leonie; Wittkamp, Florian; Apfel, Ulf-Peter; Happe, Thomas; Winkler, Martin; Haumann, Michael; Stripp, Sven T

2018-01-31

The [FeFe]-hydrogenases of bacteria and algae are the most efficient hydrogen conversion catalysts in nature. Their active-site cofactor (H-cluster) comprises a [4Fe-4S] cluster linked to a unique diiron site that binds three carbon monoxide (CO) and two cyanide (CN - ) ligands. Understanding microbial hydrogen conversion requires elucidation of the interplay of proton and electron transfer events at the H-cluster. We performed real-time spectroscopy on [FeFe]-hydrogenase protein films under controlled variation of atmospheric gas composition, sample pH, and reductant concentration. Attenuated total reflection Fourier-transform infrared spectroscopy was used to monitor shifts of the CO/CN - vibrational bands in response to redox and protonation changes. Three different [FeFe]-hydrogenases and several protein and cofactor variants were compared, including element and isotopic exchange studies. A protonated equivalent (HoxH) of the oxidized state (Hox) was found, which preferentially accumulated at acidic pH and under reducing conditions. We show that the one-electron reduced state Hred' represents an intrinsically protonated species. Interestingly, the formation of HoxH and Hred' was independent of the established proton pathway to the diiron site. Quantum chemical calculations of the respective CO/CN - infrared band patterns favored a cysteine ligand of the [4Fe-4S] cluster as the protonation site in HoxH and Hred'. We propose that proton-coupled electron transfer facilitates reduction of the [4Fe-4S] cluster and prevents premature formation of a hydride at the catalytic diiron site. Our findings imply that protonation events both at the [4Fe-4S] cluster and at the diiron site of the H-cluster are important in the hydrogen conversion reaction of [FeFe]-hydrogenases.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu Yingya; Grzywa, Maciej; Weil, Matthias

A novel metal-organic framework (MOF) based on a tetranuclear copper cluster and a linear organic ligand formulated as [Cu{sub 4}OCl{sub 6}(DABCO){sub 2}].0.5DABCO.4CH{sub 3}OH (denoted as MFU-5, MFU=Metal-Organic Framework, Ulm University; DABCO=1,4-diazabicyclo[2.2.2]octane), was prepared via solvothermal synthesis. In contrast with common MOF synthesis strategies, MFU-5 is assembled from pre-defined molecular secondary building units, i.e. {l_brace}Cu{sub 4}OCl{sub 6}{r_brace} moieties, which become the nodes of the coordination framework. The title compound was characterized by single crystal X-ray diffraction, variable temperature powder diffraction (VT-XRPD), thermal analysis, as well as IR- and UV/Vis spectroscopy. Crystal data for MFU-5: hexagonal, P6/mcc (no. 192), a=25.645(9), c=17.105(11) A,more » V=9742(8) A{sup 3}, Z=12, 1690 structure factors, R[F{sup 2}>2sigma(F{sup 2})]=0.049. MFU-5 is a 3D metal-organic framework with 1D channels running along the c-axis hosting DABCO and methanol solvent molecules. The framework displays a zeolite-like structure constructed from mso cages, which represents the composite building units in the zeolites SSF, MSO and SZR. Two-fold interpenetration is observed between these building units. TG/DTA-MS and VT-XRPD characterization reveal a stepwise release of methanol and DABCO molecules upon heating, eventually resulting in a structural change into a non-porous material. - Graphical abstract: The metal-organic framework [Cu{sub 4}OCl{sub 6}(DABCO){sub 2}].0.5DABCO.4CH{sub 3}OH (MFU-5) is constructed from a molecular precursor containing {l_brace}Cu{sub 4}OCl{sub 6}{r_brace} secondary building units which become cross-linked into a 3D zeolite-type network with hexagonal symmetry by linear DABCO ligands (DABCO=1,4-diazabicyclo[2.2.2]octane).« less

Synthesis of Cluster-Derived PtFe/SiO(2) Catalysts for the Oxidation of CO

DOE Office of Scientific and Technical Information (OSTI.GOV)

Siani, A.; Alexeev, O.S.; Captain, B.

2009-05-27

Infrared (FTIR) and extended X-ray absorption fine structure (EXAFS) spectroscopy measurements were used to characterize the species formed after impregnation of Pt{sub 5}Fe{sub 2}(COD){sub 2}(CO){sub 12} onto silica, before and after removal of the organic ligands. The results indicate that the Pt{sub 5}Fe{sub 2}(COD){sub 2}(CO){sub 12} cluster adsorbs weakly on the SiO{sub 2} surface. Nevertheless, partial disintegration of the cluster was observed during aging even under He and at room temperature, related to the loss of CO ligands due to their interactions with silanol groups of the support. The organic ligands can be removed from a freshly impregnated cluster bymore » thermal treatment in either He or H{sub 2}, but the surface species formed in each case have different structures. Treatment in He at 350 {sup o}C leads to a complete disintegration of the Pt-Fe bimetallic core and results in the formation of highly dispersed Pt clusters with a nuclearity of six, along with surface Fe oxide-like species. In contrast, bimetallic PtFe nanoparticles with an average size of approximately 1 nm were formed when a similar H{sub 2} treatment was used. In this case, a greater degree of metal dispersion and a larger fraction of Pt-Fe interactions were observed compared to the PtFe/SiO{sub 2} samples prepared by co-impregnation of monometallic salt precursors. Electronic interactions between Pt and Fe atoms in such cluster-derived samples led to an increased electron density on platinum, as indicated by a red shift of the frequencies of FTIR bands for adsorbed NO and CO. These electronic interactions affect the strength of the CO adsorption on platinum. All bimetallic samples were found to be more active than Pt/SiO{sub 2} for the oxidation of CO in air; however, the activity depends strongly on the structure of the surface species, the fraction of Pt-Fe bimetallic contributions, the degree of electronic interactions between Pt and Fe, and the strength of the CO adsorption on platinum.« less

Nucleophilic ring opening of bridging thietane ligands in trirhenium carbonyl cluster complexes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, R.D.; Cortopassi, J.E.; Falloon, S.B.

1992-11-01

The reactions of 3,3-dimethylthietane, SCH{sub 2}CMe{sub 2}CH{sub 2} (3,3-DMT), and thietane, SCH{sub 2}CH{sub 2}CH{sub 2}, with Re{sub 3}(CO){sub 10}[{mu}-SCH{sub 2}CH{sub 2}CH{sub 2}]({mu}-H){sub 3}, 2b. Compound 2a was characterized crystallographically and was found to consist of a trirhenium cluster with three bridging hydride ligands and a bridging thietane ligand coordinated through its sulfur atom. 2a and 2b react with halide ions by ring-opening additions to the 3,3-DMT ligand to yield the complex anions [Re{sub 3}(CO){sub 10}({mu}-SCH{sub 2}CMe{sub 2}CH{sub 2}x)({mu}-h){sub 3}]{sup -} 3A-6A, X = F (71%), Cl(71%), Br(84%), I(87%) and [Re{sub 3}(CO){sub 10}({mu}-SCH{sub 2}CH{sub 2}CH{sub 2}Cl)({mu}-H){sub 3}]{sup -}, 4b (67%). Similarly,more » addition of NMe{sub 3} to 2a and 2b yielded the ring-opened zwitterions Re{sub 3}(CO){sub 10}({mu}-SCH{sub 2}CMe{sub 2}CH{sub 2}NMe{sub 3})({mu}-H){sub 3}, 7 a crystographically. They are zwitterions positively charged at the nitrogen atoms and negatively charged on the trirhenium clusters. Complex 7b was also obtained in a 48% yield from the reaction of Re{sub 3}(C){sub 12}({mu}-H){sub 3} with Me{sub 3}NO in the presence of thietane, but the corresponding reaction using 3,3-DMT yielded only 2a and Re{sub 3}(CO){sub 11}(SCH{sub 2}CMe{sub 2}CH{sub 2})({mu}-H){sub 3}, 8. Attempts to obtain a ring-opening addition to 2a by reaction with PMe{sub 2}Ph yielded only Re{sub 3}(CO){sub 10}(PMe{sub 2}PH){sub 2}({mu}-H){sub 3} by ligand substitution. Attempts to obtain ring opening addition to 8 by reaction with I{sup -} yielded only [Re{sub 3}(CO){sub 11}I({mu}-H){sub 3}]{sup -} by ligand substitution. 20 refs., 3 figs., 10 tabs.« less

Molecular simulations of assembly of functionalized spherical nanoparticles

NASA Astrophysics Data System (ADS)

Seifpour, Arezou

Precise assembly of nanoparticles is crucial for creating spatially engineered materials that can be used for photonics, photovoltaic, and metamaterials applications. One way to control nanoparticle assembly is by functionalizing the nanoparticle with ligands, such as polymers, DNA, and proteins, that can manipulate the interactions between the nanoparticles in the medium the particles are placed in. This thesis research aims to design ligands to provide a new route to the programmable assembly of nanoparticles. We first investigate using Monte Carlo simulation the effect of copolymer ligands on nanoparticle assembly. We first study a single nanoparticle grafted with many copolymer chains to understand how monomer sequence (e.g. alternating ABAB, or diblock AxBx) and chemistry of the copolymers affect the grafted chain conformation at various particle diameters, grafting densities, copolymer chain lengths, and monomer-monomer interactions in an implicit small molecule solvent. We find that the size of the grafted chain varies non-monotonically with increasing blockiness of the monomer sequence for a small particle diameter. From this first study, we selected the two sequences with the most different chain conformations---alternating and diblock---and studied the effect of the sequence and a range of monomer chemistries of the copolymer on the characteristics of assembly of multiple copolymer-functionalized nanoparticles. We find that the alternating sequence produces nanoclusters that are relatively isotropic, whereas diblock sequence tends to form anisotropic structures that are smaller and more compact when the block closer to the surface is attractive and larger loosely held together clusters when the outer block is attractive. Next, we conduct molecular dynamics simulations to study the effect of DNA ligands on nanoparticle assembly. Specifically we investigate the effect of grafted DNA strand composition (e.g. G/C content, placement and sequence) and bidispersity in DNA strand lengths on the thermodynamics and structure of assembly of functionalized nanoparticles. We find that higher G/C content increases cluster dissociation temperature for smaller particles. Placement of G/C block inward along the strand decreases number of neighbors within the assembled cluster. Finally, increased bidispersity in DNA strand lengths leads a distribution of inter-particle distances in the assembled cluster.

Dynamic clustering threshold reduces conformer ensemble size while maintaining a biologically relevant ensemble

PubMed Central

Yongye, Austin B.; Bender, Andreas

2010-01-01

Representing the 3D structures of ligands in virtual screenings via multi-conformer ensembles can be computationally intensive, especially for compounds with a large number of rotatable bonds. Thus, reducing the size of multi-conformer databases and the number of query conformers, while simultaneously reproducing the bioactive conformer with good accuracy, is of crucial interest. While clustering and RMSD filtering methods are employed in existing conformer generators, the novelty of this work is the inclusion of a clustering scheme (NMRCLUST) that does not require a user-defined cut-off value. This algorithm simultaneously optimizes the number and the average spread of the clusters. Here we describe and test four inter-dependent approaches for selecting computer-generated conformers, namely: OMEGA, NMRCLUST, RMS filtering and averaged-RMS filtering. The bioactive conformations of 65 selected ligands were extracted from the corresponding protein:ligand complexes from the Protein Data Bank, including eight ligands that adopted dissimilar bound conformations within different receptors. We show that NMRCLUST can be employed to further filter OMEGA-generated conformers while maintaining biological relevance of the ensemble. It was observed that NMRCLUST (containing on average 10 times fewer conformers per compound) performed nearly as well as OMEGA, and both outperformed RMS filtering and averaged-RMS filtering in terms of identifying the bioactive conformations with excellent and good matches (0.5 < RMSD < 1.0 Å). Furthermore, we propose thresholds for OMEGA root-mean square filtering depending on the number of rotors in a compound: 0.8, 1.0 and 1.4 for structures with low (1–4), medium (5–9) and high (10–15) numbers of rotatable bonds, respectively. The protocol employed is general and can be applied to reduce the number of conformers in multi-conformer compound collections and alleviate the complexity of downstream data processing in virtual screening experiments. Electronic supplementary material The online version of this article (doi:10.1007/s10822-010-9365-1) contains supplementary material, which is available to authorized users. PMID:20499135

Control of the interparticle spacing in superparamagnetic iron oxide nanoparticle clusters by surface ligand engineering

NASA Astrophysics Data System (ADS)

Dan, Wang; Bingbing, Lin; Taipeng, Shen; Jun, Wu; Fuhua, Hao; Chunchao, Xia; Qiyong, Gong; Huiru, Tang; Bin, Song; Hua, Ai

2016-07-01

Polymer-mediated self-assembly of superparamagnetic iron oxide (SPIO) nanoparticles allows modulation of the structure of SPIO nanocrystal cluster and their magnetic properties. In this study, dopamine-functionalized polyesters (DA-polyester) were used to directly control the magnetic nanoparticle spacing and its effect on magnetic resonance relaxation properties of these clusters was investigated. Monodisperse SPIO nanocrystals with different surface coating materials (poly(ɛ-caprolactone), poly(lactic acid)) of different molecular weights containing dopamine (DA) structure (DA-PCL2k, DA-PCL1k, DA-PLA1k)) were prepared via ligand exchange reaction, and these nanocrystals were encapsulated inside amphiphilic polymer micelles to modulate the SPIO nanocrystal interparticle spacing. Small-angle x-ray scattering (SAXS) was applied to quantify the interparticle spacing of SPIO clusters. The results demonstrated that the tailored magnetic nanoparticle clusters featured controllable interparticle spacing providing directly by the different surface coating of SPIO nanocrystals. Systematic modulation of SPIO nanocrystal interparticle spacing can regulate the saturation magnetization (M s) and T 2 relaxation of the aggregation, and lead to increased magnetic resonance (MR) relaxation properties with decreased interparticle spacing. Project supported by the National Key Basic Research Program of China (Grant No. 2013CB933903), the National Key Technology R&D Program of China (Grant No. 2012BAI23B08), and the National Natural Science Foundation of China (Grant Nos. 20974065, 51173117, and 50830107).

Cationic cluster formation versus disproportionation of low-valent indium and gallium complexes of 2,2'-bipyridine

PubMed Central

Lichtenthaler, Martin R.; Stahl, Florian; Kratzert, Daniel; Heidinger, Lorenz; Schleicher, Erik; Hamann, Julian; Himmel, Daniel; Weber, Stefan; Krossing, Ingo

2015-01-01

Group 13 MI compounds often disproportionate into M0 and MIII. Here, however, we show that the reaction of the MI salt of the weakly coordinating alkoxyaluminate [GaI(C6H5F)2]+[Al(ORF)4]− (RF=C(CF3)3) with 2,2'-bipyridine (bipy) yields the paramagnetic and distorted octahedral [Ga(bipy)3]2+•{[Al(ORF)4]−}2 complex salt. While the latter appears to be a GaII compound, both, EPR and DFT investigations assign a ligand-centred [GaIII{(bipy)3}•]2+ radical dication. Surprisingly, the application of the heavier homologue [InI(C6H5F)2]+[Al(ORF)4]− leads to aggregation and formation of the homonuclear cationic triangular and rhombic [In3(bipy)6]3+, [In3(bipy)5]3+ and [In4(bipy)6]4+ metal atom clusters. Typically, such clusters are formed under strongly reductive conditions. Analysing the unexpected redox-neutral cationic cluster formation, DFT studies suggest a stepwise formation of the clusters, possibly via their triplet state and further investigations attribute the overall driving force of the reactions to the strong In−In bonds and the high lattice enthalpies of the resultant ligand stabilized [M3]3+{[Al(ORF)4]−}3 and [M4]4+{[Al(ORF)4]−}4 salts. PMID:26478464

Derivatization of bichromic cyclometalated Ru(II) complexes with hydrophobic substituents.

PubMed

Robson, Kiyoshi C D; Koivisto, Bryan D; Berlinguette, Curtis P

2012-02-06

The syntheses and physical properties of cyclometalated Ru(II) complexes containing a triphenylamine (TPA) unit bearing aliphatic groups are reported. Each member of the series consists of an octahedral Ru(II) center coordinated by a tridentate polypyridyl ligand and a tridentate cyclometalating ligand. One of the chelating ligands contains electron-deficient methyl ester groups, while a TPA unit is attached to the central ring of the adjacent chelating ligand through a thiophene bridge. This study builds on our previous work (Inorg. Chem. 2011, 50, 6019-6028; Inorg. Chem. 2011, 50, 5494-5508) by (i) outlining a synthetic protocol for installing aliphatic groups on the TPA substituents, (ii) examining the role that terminal -O-hexyl and -S-hexyl groups situated on the TPA have on the electrochemical properties, and (iii) demonstrating the potential benefit of installing the TPA on the neutral chelating ligand rather than the anionic chelating ligand. The results reported herein provide important synthetic advances for our broader goal of developing bis-tridentate cyclometalated Ru(II) complexes for light-harvesting applications.

Binding Site and Potency Prediction of Teixobactin and other Lipid II Ligands by Statistical Base Scoring of Conformational Space Maps.

PubMed

Lungu, Claudiu N; Diudea, Mircea V

2018-01-01

Lipid II, a peptidoglycan, is a precursor in bacterial cell synthesis. It has both hydrophilic and lipophilic properties. The molecule translocates a bacterial membrane to deliver and incorporate "building blocks" from disaccharide-pentapeptide into the peptidoglican wall. Lipid II is a valid antibiotic target. A receptor binding pocket may be occupied by a ligand in various plausible conformations, among which only few ones are energetically related to a biological activity in the physiological efficiency domain. This paper reports the mapping of the conformational space of Lipid II in its interaction with Teixobactin and other Lipid II ligands. In order to study computationally the complex between Lipid II and ligands, a docking study was first carried on. Docking site was retrieved form literature. After docking, 5 ligand conformations and further 5 complexes (denoted 00 to 04) for each molecule were taken into account. For each structure, conformational studies were performed. Statistical analysis, conformational analysis and molecular dynamics based clustering were used to predict the potency of these compounds. A score for potency prediction was developed. Appling lipid II classification according to Lipid II conformational energy, a conformation of Teixobactin proved to be energetically favorable, followed by Oritravicin, Dalbavycin, Telvanicin, Teicoplamin and Vancomycin, respectively. Scoring of molecules according to cluster band and PCA produced the same result. Molecules classified according to standard deviations showed Dalbavycin as the most favorable conformation, followed by Teicoplamin, Telvanicin, Teixobactin, Oritravicin and Vancomycin, respectively. Total score showing best energetic efficiency of complex formation shows Teixobactin to have the best conformation (a score of 15 points) followed by Dalbavycin (14 points), Oritravicin (12v points), Telvanicin (10 points), Teicoplamin (9 points), Vancomycin (3 points). Statistical analysis of conformations can be used to predict the efficiency of ligand - target interaction and consecutively to find insight regarding ligand potency and postulate about favorable conformation of ligand and binding site. In this study it was shown that Teixobactin is more efficient in binding with Lipid II compared to Vancomycin, results confirmed by experimental data reported in literature. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Molecular metal catalysts on supports: organometallic chemistry meets surface science.

PubMed

Serna, Pedro; Gates, Bruce C

2014-08-19

Recent advances in the synthesis and characterization of small, essentially molecular metal complexes and metal clusters on support surfaces have brought new insights to catalysis and point the way to systematic catalyst design. We summarize recent work unraveling effects of key design variables of site-isolated catalysts: the metal, metal nuclearity, support, and other ligands on the metals, also considering catalysts with separate, complementary functions on supports. The catalysts were synthesized with the goal of structural simplicity and uniformity to facilitate incisive characterization. Thus, they are essentially molecular species bonded to porous supports chosen for their high degree of uniformity; the supports are crystalline aluminosilicates (zeolites) and MgO. The catalytic species are synthesized in reactions of organometallic precursors with the support surfaces; the precursors include M(L)2(acetylacetonate)1-2, with M = Ru, Rh, Ir, or Au and the ligands L = C2H4, CO, or CH3. Os3(CO)12 and Ir4(CO)12 are used as precursors of supported metal clusters, and some such catalysts are made by ship-in-a-bottle syntheses to trap the clusters in zeolite cages. The simplicity and uniformity of the supported catalysts facilitate precise structure determinations, even in reactive atmospheres and during catalysis. The methods of characterizing catalysts in reactive atmospheres include infrared (IR), extended X-ray absorption fine structure (EXAFS), X-ray absorption near edge structure (XANES), and nuclear magnetic resonance (NMR) spectroscopies, and complementary methods include density functional theory and atomic-resolution aberration-corrected scanning transmission electron microscopy for imaging of individual metal atoms. IR, NMR, XANES, and microscopy data demonstrate the high degrees of uniformity of well-prepared supported species. The characterizations determine the compositions of surface metal complexes and clusters, including the ligands and the metal-support bonding and structure, which identify the supports as ligands with electron-donor properties that influence reactivity and catalysis. Each of the catalyst design variables has been varied independently, illustrated by mononuclear and tetranuclear iridium on zeolite HY and on MgO and by isostructural rhodium and iridium (diethylene or dicarbonyl) complexes on these supports. The data provide examples resolving the roles of the catalyst design variables and place the catalysis science on a firm foundation of organometallic chemistry linked with surface science. Supported molecular catalysts offer the advantages of characterization in the absence of solvents and with surface-science methods that do not require ultrahigh vacuum. Families of supported metal complexes have been made by replacement of ligands with others from the gas phase. Spectroscopically identified catalytic reaction intermediates help to elucidate catalyst performance and guide design. The methods are illustrated for supported complexes and clusters of rhodium, iridium, osmium, and gold used to catalyze reactions of small molecules that facilitate identification of the ligands present during catalysis: alkene dimerization and hydrogenation, H-D exchange in the reaction of H2 with D2, and CO oxidation. The approach is illustrated with the discovery of a highly active and selective MgO-supported rhodium carbonyl dimer catalyst for hydrogenation of 1,3-butadiene to give butenes.

Iron-based magnetic superhalogens with pseudohalogens as ligands: An unbiased structure search

PubMed Central

Ping Ding, Li; Shao, Peng; Lu, Cheng; Hui Zhang, Fang; Wang, Li Ya

2017-01-01

We have performed an unbiased structure search for a series of neutral and anionic FeL4 (L = BO2, CN, NO2, NO3, OH, CH3, NH2, BH4 and Li2H3) clusters using the CALYPSO (Crystal structure Analysis by Particle Swarm Optimization) structure search method. To probe the superhalogen properties of neutral and anionic FeL4 clusters, we used density-functional theory with the B3LYP functional to examine three factors, including distribution of extra electron, pattern of bonding and the nature of the ligands. Theoretical results show that Fe(BO2)4, Fe(NO3)4 and Fe(NO2)4 can be classified as magnetic superhalogen due to that their electron affinities even exceed those of the constituent ligands. The magnetic moment of Fe atom is almost entirly maintained when it is decorated with various ligands except for neutral and anionic (Li2H3)4. Moreover, the current work is also extended to the salt moieties formed by hyperhalogen/superhalogen anion and Na+ ion. It is found that these salts against dissociation into Na + FeL4 are thermodynamic stable except for Na[Fe(OH)4]. These results provides a wealth of electronic structure information about FeL4 magnetic superhalogens and offer insights into the synthesis mechanisms. PMID:28327547

Genomewide Analysis of Aryl Hydrocarbon Receptor Binding Targets Reveals an Extensive Array of Gene Clusters that Control Morphogenetic and Developmental Programs

PubMed Central

Sartor, Maureen A.; Schnekenburger, Michael; Marlowe, Jennifer L.; Reichard, John F.; Wang, Ying; Fan, Yunxia; Ma, Ci; Karyala, Saikumar; Halbleib, Danielle; Liu, Xiangdong; Medvedovic, Mario; Puga, Alvaro

2009-01-01

Background The vertebrate aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates cellular responses to environmental polycyclic and halogenated compounds. The naive receptor is believed to reside in an inactive cytosolic complex that translocates to the nucleus and induces transcription of xenobiotic detoxification genes after activation by ligand. Objectives We conducted an integrative genomewide analysis of AHR gene targets in mouse hepatoma cells and determined whether AHR regulatory functions may take place in the absence of an exogenous ligand. Methods The network of AHR-binding targets in the mouse genome was mapped through a multipronged approach involving chromatin immunoprecipitation/chip and global gene expression signatures. The findings were integrated into a prior functional knowledge base from Gene Ontology, interaction networks, Kyoto Encyclopedia of Genes and Genomes pathways, sequence motif analysis, and literature molecular concepts. Results We found the naive receptor in unstimulated cells bound to an extensive array of gene clusters with functions in regulation of gene expression, differentiation, and pattern specification, connecting multiple morphogenetic and developmental programs. Activation by the ligand displaced the receptor from some of these targets toward sites in the promoters of xenobiotic metabolism genes. Conclusions The vertebrate AHR appears to possess unsuspected regulatory functions that may be potential targets of environmental injury. PMID:19654925

MicroRNA-17-92 cluster promotes the proliferation and the chemokine production of keratinocytes: implication for the pathogenesis of psoriasis.

PubMed

Zhang, Weigang; Yi, Xiuli; An, Yawen; Guo, Sen; Li, Shuli; Song, Pu; Chang, Yuqian; Zhang, Shaolong; Gao, Tianwen; Wang, Gang; Li, Chunying

2018-05-11

Keratinocytes are the main epidermal cell type that constitutes the skin barrier against environmental damages, which emphasizes the balance between the growth and the death of keratinocytes in maintaining skin homeostasis. Aberrant proliferation of keratinocytes and the secretion of inflammatory factors from keratinocytes are related to the formation of chronic inflammatory skin diseases like psoriasis. MicroRNA-17-92 (miRNA-17-92 or miR-17-92) is a miRNA cluster that regulates cell growth and immunity, but the role of miR-17-92 cluster in keratinocytes and its relation to skin diseases have not been well investigated. In the present study, we initially found that miR-17-92 cluster promoted the proliferation and the cell-cycle progression of keratinocytes via suppressing cyclin-dependent kinase inhibitor 2B (CDKN2B). Furthermore, miR-17-92 cluster facilitated the secretion of C-X-C motif chemokine ligand 9 (CXCL9) and C-X-C motif chemokine ligand 10 (CXCL10) from keratinocytes by inhibiting suppressor of cytokine signaling 1 (SOCS1), which enhanced the chemotaxis for T lymphocytes formed by keratinocytes. In addition, we detected increased expression of miR-17-92 cluster in psoriatic lesions and the level of lesional miR-17-92 cluster was positively correlated with the disease severity in psoriasis patients. At last, miR-17-92 cluster was increased in keratinocytes by cytokines through the activation of signal transducers and activators of transcription 1 (STAT1) signaling pathway. Our findings demonstrate that cytokine-induced overexpression of miR-17-92 cluster can promote the proliferation and the immune function of keratinocytes, and thus may contribute to the development of inflammatory skin diseases like psoriasis, which implicates miR-17-92 cluster as a potential therapeutic target for psoriasis and other skin diseases with similar inflammatory pathogenesis.

An electrochemical and photophysical study of a covalently linked inorganic-organic dyad.

PubMed

Kahnt, Axel; Heiniger, Leo-Philipp; Liu, Shi-Xia; Tu, Xiaoyan; Zheng, Zhiping; Hauser, Andreas; Decurtins, Silvio; Guldi, Dirk M

2010-02-22

A molecular donor-acceptor dyad comprising a hexarhenium cluster core, [Re(6)(mu(3)-Se)(8)](2+), and a fullerene moiety which are covalently linked through a pyridine ligand was synthesized and fully characterized. The electrochemical and photophysical properties are reported. The detailed study includes cyclic voltammetry, steady-state absorption and fluorescence spectroscopy, radiation chemistry and transient absorption spectroscopy. A light-induced electron transfer between the inorganic cluster moiety and the fullerene can be excluded. However, a light-induced energy transfer from the rhenium cluster to the fullerene is proposed.

Type I interferon dependence of plasmacytoid dendritic cell activation and migration

PubMed Central

Asselin-Paturel, Carine; Brizard, Géraldine; Chemin, Karine; Boonstra, Andre; O'Garra, Anne; Vicari, Alain; Trinchieri, Giorgio

2005-01-01

Differential expression of Toll-like receptor (TLR) by conventional dendritic cells (cDCs) and plasmacytoid DC (pDCs) has been suggested to influence the type of immune response induced by microbial pathogens. In this study we show that, in vivo, cDCs and pDCs are equally activated by TLR4, -7, and -9 ligands. Type I interferon (IFN) was important for pDC activation in vivo in response to all three TLR ligands, whereas cDCs required type I IFN signaling only for TLR9- and partially for TLR7-mediated activation. Although TLR ligands induced in situ migration of spleen cDC into the T cell area, spleen pDCs formed clusters in the marginal zone and in the outer T cell area 6 h after injection of TLR9 and TLR7 ligands, respectively. In vivo treatment with TLR9 ligands decreased pDC ability to migrate ex vivo in response to IFN-induced CXCR3 ligands and increased their response to CCR7 ligands. Unlike cDCs, the migration pattern of pDCs required type I IFN for induction of CXCR3 ligands and responsiveness to CCR7 ligands. These data demonstrate that mouse pDCs differ from cDCs in the in vivo response to TLR ligands, in terms of pattern and type I IFN requirement for activation and migration. PMID:15795237

Single-molecule toroics in Ising-type lanthanide molecular clusters.

PubMed

Ungur, Liviu; Lin, Shuang-Yan; Tang, Jinkui; Chibotaru, Liviu F

2014-01-01

Single-molecule toroics (SMTs) are defined, by analogy with single-molecule magnets, as bistable molecules with a toroidal magnetic state, and seem to be most promising for future applications in quantum computing and information storage and use as multiferroic materials with magnetoelectric effect. As an interdisciplinary research area that spans chemistry, physics and material sciences, synthetic chemists have produced systems suitable for detailed study by physicists and materials scientists, while ab initio calculations have been playing a major role in the detection of toroidal magnetization and the advancement of this field. In this tutorial review, we demonstrate the research developed in the fascinating and challenging field of molecular-based SMTs with particular focus on how recent studies tend to address the issue of toroidal arrangement of the magnetic moment in these systems. Herein, nine typical SMTs are summarized, showing that the assembly of wheel-shaped complexes with the high symmetry of the molecule unit and strong intra-molecular dipolar interactions using strong anisotropy metal ions represents the most promising route toward the design of a toroidal moment. Furthermore, the linkage of such robust toroidal moment units with ferromagnetic type through appropriate bridging ligands enhances the toroidal magnetic moment per unit cell.

Studies of the spin Hamiltonian parameters and local structure for ZnO:Cu2+.

PubMed

Wu, Shao-Yi; Wei, Li-Hua; Zhang, Zhi-Hong; Wang, Xue-Feng; Hu, Yue-Xia

2008-12-15

The spin Hamiltonian parameters (the g factors and the hyperfine structure constants) and local structure for ZnO:Cu2+ are theoretically studied from the perturbation formulas of these parameters for a 3d9 ion under trigonally distorted tetrahedra. The ligand orbital and spin-orbit coupling contributions are taken into account from the cluster approach due to the significant covalency of the [CuO4](6-) cluster. According to the investigations, the impurity Cu2+ is suggested not to locate on the ideal Zn2+ site in ZnO but to undergo a slight outward displacement (approximately 0.01 angstroms) away from the ligand triangle along C3 axis. The calculated spin Hamiltonian parameters are in good agreement with the observed values. The validity of the above impurity displacement is also discussed.

A comparative DFT study of interactions of Au and small gold clusters Aun (n = 2-4) with CH3S and CH2 radicals

NASA Astrophysics Data System (ADS)

Blaško, Martin; Rajský, Tomáš; Urban, Miroslav

2017-03-01

We compare DFT binding energies (BEs) of Au and small gold clusters interacting with CH3S and CH2 ligands (Aun-L complexes, n = 1-4). The spin state and the binding mechanism in Aun-L varies with the participation of singly occupied non-bonding orbitals or doubly occupied lone-pair orbitals of a ligand and on the number of atoms (even or odd) of Aun. The highest BE, 354 kJ/mol, exhibits the Au3-CH2 complex with the covalent bond in which participate two singly occupied orbitals of the triplet state of CH2. With CH3S the highest BE (277 kJ/mol) is calculated for Au3-SCH3 with the single Au-S bond.

Uranyl-Peroxide Clusters Incorporating Iron Trimers and Bridging by Bisphosphonate- and Carboxylate-Containing Ligands.

PubMed

Qiu, Jie; Dong, Sining; Szymanowski, Jennifer E S; Dobrowolska, Malgorzata; Burns, Peter C

2017-04-03

A hybrid uranium-iron cage nanocluster, [(UO 2 ) 24 (FeOH) 24 (O 2 ) 24 (PO 4 ) 8 (CH(COO)(PO 3 ) 2 ) 24 ] 96- (U 24 Fe 24 ), was synthesized using bridging ligands containing bisphosphonate and carboxylate groups. U 24 Fe 24 contains six tetramers of uranyl hexagonal bipyramids and eight iron trimers, each of which consists of three corner-sharing Fe 3+ octahedra and is stabilized by in situ formed phosphate and 2,2-bis(phosphonato)acetate (C 2 P 2 ) groups. Tetramers and trimers are bridged by 24 C 2 P 2 groups into a cage cluster. Crystals of U 24 Fe 24 present a paramagnetic-like behavior. X-ray scattering showed that U 24 Fe 24 forms in the reactant solution prior to crystallization and is stable upon dissolution in water.

Self-assembly of a tetrahedral 58-nuclear barium vanadium oxide cluster.

PubMed

Kastner, Katharina; Puscher, Bianka; Streb, Carsten

2013-01-07

We report the synthesis and characterization of a molecular barium vanadium oxide cluster featuring high nuclearity and high symmetry. The tetrameric, 2.3 nm cluster H(5)[Ba(10)(NMP)(14)(H(2)O)(8)[V(12)O(33)](4)Br] is based on a bromide-centred, octahedral barium scaffold which is capped by four previously unknown [V(12)O(33)](6-) clusters in a tetrahedral fashion. The compound represents the largest polyoxovanadate-based heterometallic cluster known to date. The cluster is formed in organic solution and it is suggested that the bulky N-methyl-2-pyrrolidone (NMP) solvent ligands allow the isolation of this giant molecule and prevent further condensation to a solid-state metal oxide. The cluster is fully characterized using single-crystal XRD, elemental analysis, ESI mass spectrometry and other spectroscopic techniques.

Self-assembly of metal-organic supramolecules: from a metallamacrocycle and a metal-organic coordination cage to 1D or 2D coordination polymers based on flexible dicarboxylate ligands.

PubMed

Dai, Fangna; Dou, Jianmin; He, Haiyan; Zhao, Xiaoliang; Sun, Daofeng

2010-05-03

To assemble metal-organic supramolecules such as a metallamacrocycle and metal-organic coordination cage (MOCC), a series of flexible dicarboxylate ligands with the appropriate angle, 2,2'-(2,3,5,6-tetramethyl-1,4-phenylene)bis(methylene)bis(sulfanediyl)dibenzoic acid (H(2)L(1)), 2,2'-(2,5-dimethyl-1,4-phenylene)bis(methylene)bis(sulfanediyl)dibenzoic acid (H(2)L(2)), 2,2'-(2,4,6-trimethyl-1,3-phenylene)bis(methylene)bis(sulfanediyl)dinicotinic acid (H(2)L(3)), and 2,2'-(2,4,6-trimethyl-1,3-phenylene)bis(methylene)bis(sulfanediyl)dibenzoic acid (H(2)L(4)), have been designed and synthesized. Using these flexible ligands to assemble with metal ions, six metal-organic supramolecules, Cd(2)(L(1))(2)(dmf)(4)(H(2)O)(2).H(2)O (1), Mn(3)((1)L(2))(2)((2)L(2))(dmf)(2)(H(2)O)(2).5dmf (2), Cu(4)(L(3))(4)(H(2)O)(4).3dmf (3), Cu(4)(L(4))(4)(dmf)(2)(EtOH)(2).8dmf.6H(2)O (4), Mn(4)(L(4))(4)(dmf)(4)(H(2)O)(4).6dmf.H(2)O (5), and Mn(3)(L(4))(3)(dmf)(4).2dmf.3H(2)O (6), possessing a rectangular macrocycle, MOCCs or their extensions, and 1D or 2D coordination polymers, have been isolated. All complexes have been characterized by single-crystal X-ray diffraction, elemental analysis, and thermogravimetric analysis. Complex 1 is a discrete rectangular macrocycle, while complex 2 is a 2D macrocycle-based coordination polymer in which the L(2) ligand adopts both syn and anti conformations. Complexes 3-5 are discrete MOCCs in which two binuclear metal clusters are engaged by four organic ligands. The different geometries of the secondary building units (SBUs) and the axial coordinated solvates on the SBUs result in their different symmetries. Complex 6 is a 1D coordination polymer, extended from a MOCC made up of two metal ions and three L(4) ligands. All of the flexible dicarboxylate ligands adopt a syn conformation except that in complex 2, indicating that the syn conformational ligand is helpful for the formation of a metallamacrocycle and a MOCC. The magnetic properties of complexes 5 and 6 have also been studied.

Surface anisotropy of iron oxide nanoparticles and slabs from first principles: Influence of coatings and ligands as a test of the Heisenberg model

NASA Astrophysics Data System (ADS)

Brymora, Katarzyna; Calvayrac, Florent

2017-07-01

We performed ab initio computations of the magnetic properties of simple iron oxide clusters and slabs. We considered an iron oxide cluster functionalized by a molecule or glued to a gold cluster of the same size. We also considered a magnetite slab coated by cobalt oxide or a mixture of iron oxide and cobalt oxide. The changes in magnetic behavior were explored using constrained magnetic calculations. A possible value for the surface anisotropy was estimated from the fit of a classical Heisenberg model on ab initio results. The value was found to be compatible with estimations obtained by other means, or inferred from experimental results. The addition of a ligand, coating, or of a metallic nanoparticle to the systems degraded the quality of the description by the Heisenberg Hamiltonian. Proposing a change in the anisotropies allowing for the proportion of each transition atom we could get a much better description of the magnetism of series of hybrid cobalt and iron oxide systems.

Autogrid-based clustering of kinases: selection of representative conformations for docking purposes.

PubMed

Marzaro, Giovanni; Ferrarese, Alessandro; Chilin, Adriana

2014-08-01

The selection of the most appropriate protein conformation is a crucial aspect in molecular docking experiments. In order to reduce the errors arising from the use of a single protein conformation, several authors suggest the use of several tridimensional structures for the target. However, the selection of the most appropriate protein conformations still remains a challenging goal. The protein 3D-structures selection is mainly performed based on pairwise root-mean-square-deviation (RMSD) values computation, followed by hierarchical clustering. Herein we report an alternative strategy, based on the computation of only two atom affinity map for each protein conformation, followed by multivariate analysis and hierarchical clustering. This methodology was applied on seven different kinases of pharmaceutical interest. The comparison with the classical RMSD-based strategy was based on cross-docking of co-crystallized ligands. In the case of epidermal growth factor receptor kinase, also the docking performance on 220 known ligands were evaluated, followed by 3D-QSAR studies. In all the cases, the herein proposed methodology outperformed the RMSD-based one.

Theoretical prediction of a new stable structure of Au28(SR)20 cluster

NASA Astrophysics Data System (ADS)

Sun, Xiangxiang; Wang, Pu; Xiong, Lin; Pei, Yong

2018-07-01

A new stable structure of Au28(SR)20 cluster is predicted, which has the same gold core as two known structures but different Au-S framework. The new Au28(SR)20 cluster is proposed to be a key link in the evolution of Au22(SR)18, Au34(SR)22 and Au40(SR)24 clusters. The four clusters belong to a homogenous Au16+6N(SR)16+2N series (N = 1-4). The relative stabilities of the new Au28 isomer structure were confirmed by density functional theory calculations including dispersion corrections (DFT-D). It is found that upon protection of certain SR ligands, the new isomer structure has lower or comparable energies to two known cluster structures.

Studying the Effect of a Composition of the Cluster Core in High-Radiopacity Cluster Complexes of Rhenium on Their Acute Toxicity In Vivo.

PubMed

Pozmogova, T N; Krasil'nikova, A A; Ivanov, A A; Shestopalov, M A; Gyrylova, S N; Shestopalova, L V; Shestopaloiv, A M; Shkurupy, V A

2016-05-01

An in vivo study was performed to evaluate the dependence of acute toxicity of high-radiopacity and luminescent octahedral cluster complexes of rhenium after intravenous injection on a composition of the cluster core. Changes in mouse body weight, water and food consumption, degree of intoxication, and morphological changes in the visceral organs were studied after intravenous injection of the following cluster complexes with various internal ligands (S, Se, or Te): Na4[{Re 6 Te 8 }(CN)6], Na4[{Re 6 Se 8 }(CN)6], and Na4[{Re 6 S 8 }(CN)6]. The Na4[{Re 6 S 8 } (CN)6] cluster complex was shown to be the safest for animals.

Structure of the manganese complex in photosystem II: insights from X-ray spectroscopy.

PubMed Central

Yachandra, Vittal K

2002-01-01

We have used Mn K-edge absorption and Kbeta emission spectroscopy to determine the oxidation states of the Mn complex in the various S states. We have started exploring the new technique of resonant inelastic X-ray scattering spectroscopy; this technique can be characterized as a Raman process that uses K-edge energies (1s to 4p, ca. 6550 eV) to obtain L-edge-like spectra (2p to 3d, ca. 650 eV). The relevance of these data to the oxidation states and structure of the Mn complex is presented. We have obtained extended X-ray absorption fine structure data from the S(0) and S(3) states and observed heterogeneity in the Mn-Mn distances leading us to conclude that there may be three rather than two di-mu-oxo-bridged units present per tetranuclear Mn cluster. In addition, we have obtained data using Ca and Sr X-ray spectroscopy that provide evidence for a heteronuclear Mn-Ca cluster. The possibility of three di-mu-oxo-bridged Mn-Mn moieties and the proximity of Ca is incorporated into developing structural models for the Mn cluster. The involvement of bridging and terminal O ligands of Mn in the mechanism of oxygen evolution is discussed in the context of our X-ray spectroscopy results. PMID:12437873

A Single Crystalline Porphyrinic Titanium MetalOrganic Framework

DTIC Science & Technology

2015-04-28

22, which was synthesized from preformed titanium -oxo carboxylate clusters and porphyrinic ligands. PCN-22 possesses high porosity and photocatalytic...DOI: 10.1039/c5sc00916b www.rsc.org/chemicalscience 3926 | Chem. Sci., 2015, 6, 3926–3930e porphyrinic titanium metal– organic framework† Shuai Yuan...Scott J. Dalgarnoc and Hong-Cai Zhou*a We successfully assembled the photocatalytic titanium -oxo cluster and photosensitizing porphyrinic linker into a

Homochiral coordination polymers with helixes and metal clusters based on lactate derivatives

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Zhong-Xuan, E-mail: xuzhongxuan4201@163.com; Ma, Yu-Lu; Lv, Guo-ling

2017-05-15

Utilizing the lactic acid derivatives (R)-4-(1-carboxyethoxy)benzoic acid (denoted: (R)-H{sub 2}CBA) and (S)-4-(1-carboxyethoxy)benzoic acid (denoted: (S)-H{sub 2}CBA)as chiral linkers to self-assemble with 4, 4′-bipyridine (denoted: BIP) and Cd(II) ions, a couple of three-dimensional homochiral coordination polymers, namely [Cd{sub 3}((R)-CBA){sub 3} (BIP){sub 2}(H{sub 2}O)]·xGuest (1-D) and [Cd{sub 3}((S)-CBA){sub 3}(BIP){sub 2}(H{sub 2}O)]·xGuest (1-L), have been synthesized under solvothermal reaction condition. Single crystal X-ray diffraction analysis reveals the two complexes contain single helical chains based on enantiopure ligands and cadmium clusters. Moreover, some physical characteristics such as PXRD, thermal stability, solid-state circular dichroism (CD) and luminescent were also investigated. - Graphical abstract: Utilizing enantiomericmore » lactic acid derivatives (R)-H{sub 2}CBA and (S)-H{sub 2}CBA to assemble with Cd{sup 2+} ions and ancillary BIP ligands, a couple of 3D homochiral coordination polymers with metal clusters and helical chains have been prepared by hydrothermal reaction. - Highlights: • Chiral lactic acid derivative. • Enantiomeric coordination polymer. • Helical chain. • Trinuclear cadmium cluster.« less

Enhanced electric dipole transition in lanthanide complex with organometallic ruthenocene units.

PubMed

Hasegawa, Yasuchika; Sato, Nao; Hirai, Yuichi; Nakanishi, Takayuki; Kitagawa, Yuichi; Kobayashi, Atsushi; Kato, Masako; Seki, Tomohiro; Ito, Hajime; Fushimi, Koji

2015-05-21

Enhanced luminescence of a lanthanide complex with dynamic polarization of the excited state and molecular motion is introduced. The luminescent lanthanide complex is composed of one Eu(hfa)3 (hfa, hexafluoroacetylacetonate) and two phosphine oxide ligands with ruthenocenyl units Rc, [Eu(hfa)3(RcPO)2] (RcPO = diphenylphosphorylruthenocene). The ruthenocenyl units in the phosphine oxide ligands play an important role of switching for dynamic molecular polarization and motion in liquid media. The oxidation states of the ruthenocenyl unit (Rc(1+)/Rc(1+)) are controlled by potentiostatic polarization. Eu(III) complexes attached with bidentate phosphine oxide ligands containing ruthenocenyl units, [Eu(hfa)3(RcBPO)] (RcBPO = 1,1'-bis(diphenylphosphoryl)ruthenocene), and with bidentate phosphine oxide ligands, [Eu(hfa)3(BIPHEPO)] (BIPHEPO =1,1'-biphenyl-2,2'-diylbis(diphenylphosphine oxide), were also prepared as references. The coordination structures and electrochemical properties were analyzed using single crystal X-ray analysis, cyclic voltammetry, and absorption spectroscopy measurements. The luminescence properties were estimated using an optoelectrochemical cell. Under potentiostatic polarization, a significant enhancement of luminescence was successfully observed for [Eu(hfa)3(RcPO)2], while no spectral change was observed for [Eu(hfa)3(RcBPO)]. In this study, the remarkable enhanced luminescence phenomena of Eu(III) complex based on the dynamic molecular motion under potentiostatic polarization have been performed.

Where Water Is Oxidized to Dioxygen: Structure of the Photosynthetic Mn4Ca Cluster

PubMed Central

Yano, Junko; Kern, Jan; Sauer, Kenneth; Latimer, Matthew J.; Pushkar, Yulia; Biesiadka, Jacek; Loll, Bernhard; Saenger, Wolfram; Messinger, Johannes; Zouni, Athina; Yachandra, Vittal K.

2014-01-01

The oxidation of water to dioxygen is catalyzed within photosystem II (PSII) by a Mn4Ca cluster, the structure of which remains elusive. Polarized extended x-ray absorption fine structure (EXAFS) measurements on PSII single crystals constrain the Mn4Ca cluster geometry to a set of three similar high-resolution structures. Combining polarized EXAFS and x-ray diffraction data, the cluster was placed within PSII, taking into account the overall trend of the electron density of the metal site and the putative ligands. The structure of the cluster from the present study is unlike either the 3.0 or 3.5 angstrom–resolution x-ray structures or other previously proposed models. PMID:17082458

Transition and post-transition metal ions in borate glasses: Borate ligand speciation, cluster formation, and their effect on glass transition and mechanical properties.

PubMed

Möncke, D; Kamitsos, E I; Palles, D; Limbach, R; Winterstein-Beckmann, A; Honma, T; Yao, Z; Rouxel, T; Wondraczek, L

2016-09-28

A series of transition and post-transition metal ion (Mn, Cu, Zn, Pb, Bi) binary borate glasses was studied with special consideration of the cations impact on the borate structure, the cations cross-linking capacity, and more generally, structure-property correlations. Infrared (IR) and Raman spectroscopies were used for the structural characterization. These complementary techniques are sensitive to the short-range order as in the differentiation of tetrahedral and trigonal borate units or regarding the number of non-bridging oxygen ions per unit. Moreover, vibrational spectroscopy is also sensitive to the intermediate-range order and to the presence of superstructural units, such as rings and chains, or the combination of rings. In order to clarify band assignments for the various borate entities, examples are given from pure vitreous B 2 O 3 to meta-, pyro-, ortho-, and even overmodified borate glass compositions. For binary metaborate glasses, the impact of the modifier cation on the borate speciation is shown. High field strength cations such as Zn 2+ enhance the disproportionation of metaborate to polyborate and pyroborate units. Pb 2+ and Bi 3+ induce cluster formation, resulting in PbO n - and BiO n -pseudophases. Both lead and bismuth borate glasses show also a tendency to stabilize very large superstructural units in the form of diborate polyanions. Far-IR spectra reflect on the bonding states of modifier cations in glasses. The frequency of the measured cation-site vibration band was used to obtain the average force constant for the metal-oxygen bonding, F M-O . A linear correlation between glass transition temperature (T g ) and F M-O was shown for the metaborate glass series. The mechanical properties of the glasses also correlate with the force constant F M-O , though for cations of similar force constant the fraction of tetrahedral borate units (N 4 ) strongly affects the thermal and mechanical properties. For paramagnetic Cu- and Mn-borate glasses, N 4 was determined from the IR spectra after deducing the relative absorption coefficient of boron tetrahedral versus boron trigonal units, α = α 4 /α 3 , using NMR literature data of the diamagnetic glasses.

Co5In(BTC)4[B2O4(OH)]2: the first MOF material constructed by borate polyanions and carboxylate mixed ligands.

PubMed

Li, Sa-Ying; Liu, Zhi-Hong

2016-01-07

A novel heterometallic organic-inorganic hybrid MOF material, Co5In(BTC)4[B2O4(OH)]2, has been synthesized under ionothermal conditions. Its structure is characterized as a 3D open framework constructed by the Co2.5In0.5[B2O4(OH)] cluster and the 1,3,5-benzenetricarboxylate ligand. Furthermore, its fluorescent and adsorption properties have also been studied.

The outer mitochondrial membrane protein mitoNEET contains a novel redox-active 2Fe-2S cluster.

PubMed

Wiley, Sandra E; Paddock, Mark L; Abresch, Edward C; Gross, Larry; van der Geer, Peter; Nechushtai, Rachel; Murphy, Anne N; Jennings, Patricia A; Dixon, Jack E

2007-08-17

The outer mitochondrial membrane protein mitoNEET was discovered as a binding target of pioglitazone, an insulin-sensitizing drug of the thiazolidinedione class used to treat type 2 diabetes (Colca, J. R., McDonald, W. G., Waldon, D. J., Leone, J. W., Lull, J. M., Bannow, C. A., Lund, E. T., and Mathews, W. R. (2004) Am. J. Physiol. 286, E252-E260). We have shown that mitoNEET is a member of a small family of proteins containing a 39-amino-acid CDGSH domain. Although the CDGSH domain is annotated as a zinc finger motif, mitoNEET was shown to contain iron (Wiley, S. E., Murphy, A. N., Ross, S. A., van der Geer, P., and Dixon, J. E. (2007) Proc. Natl. Acad. Sci. U. S. A. 104, 5318-5323). Optical and electron paramagnetic resonance spectroscopy showed that it contained a redox-active pH-labile Fe-S cluster. Mass spectrometry showed the loss of 2Fe and 2S upon cofactor extrusion. Spectroscopic studies of recombinant proteins showed that the 2Fe-2S cluster was coordinated by Cys-3 and His-1. The His ligand was shown to be involved in the observed pH lability of the cluster, indicating that loss of this ligand via protonation triggered release of the cluster. mitoNEET is the first identified 2Fe-2S-containing protein located in the outer mitochondrial membrane. Based on the biophysical data and domain fusion analysis, mitoNEET may function in Fe-S cluster shuttling and/or in redox reactions.

Reactivity of Hydride Bridges in High-Spin [3M-3(μ-H)] Clusters (M = FeII, CoII).

PubMed

Lee, Yousoon; Anderton, Kevin J; Sloane, Forrest T; Ermert, David M; Abboud, Khalil A; García-Serres, Ricardo; Murray, Leslie J

2015-08-26

The designed [3M-3(μ-H)] clusters (M = Fe(II), Co(II)) Fe3H3L (1-H) and Co3H3L (2-H) [where L(3-) is a tris(β-diketiminate) cyclophane] were synthesized by treating the corresponding M3Br3L complexes with KBEt3H. From single-crystal X-ray analysis, the hydride ligands are sterically protected by the cyclophane ligand, and these complexes selectively react with CO2 over other unsaturated substrates (e.g., CS2, Me3SiCCH, C2H2, and CH3CN). The reaction of 1-H or 2-H with CO2 at room temperature yielded Fe3(OCHO)(H)2L (1-CO2) or Co3(OCHO)(H)2L (2-CO2), respectively, which evidence the differential reactivity of the hydride ligands within these complexes. The analogous reactions at elevated temperatures revealed a distinct difference in the reactivity pattern for 2-H as compared to 1-H; Fe3(OCHO)3L (1-3CO2) was generated from 1-H, while 2-H afforded only 2-CO2.

A point mutation in the [2Fe–2S] cluster binding region of the NAF-1 protein (H114C) dramatically hinders the cluster donor properties

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tamir, Sagi; Eisenberg-Domovich, Yael; Conlan, Andrea R.

2014-06-01

NAF-1 has been shown to be related with human health and disease, is upregulated in epithelial breast cancer and suppression of its expression significantly suppresses tumor growth. It is shown that replacement of the single His ligand with Cys resulted in dramatic changes to the properties of its 2Fe-2S clusters without any global crystal structural changes. NAF-1 is an important [2Fe–2S] NEET protein associated with human health and disease. A mis-splicing mutation in NAF-1 results in Wolfram Syndrome type 2, a lethal childhood disease. Upregulation of NAF-1 is found in epithelial breast cancer cells, and suppression of NAF-1 expression bymore » knockdown significantly suppresses tumor growth. Key to NAF-1 function is the NEET fold with its [2Fe–2S] cluster. In this work, the high-resolution structure of native NAF-1 was determined to 1.65 Å resolution (R factor = 13.5%) together with that of a mutant in which the single His ligand of its [2Fe–2S] cluster, His114, was replaced by Cys. The NAF-1 H114C mutant structure was determined to 1.58 Å resolution (R factor = 16.0%). All structural differences were localized to the cluster binding site. Compared with native NAF-1, the [2Fe–2S] clusters of the H114C mutant were found to (i) be 25-fold more stable, (ii) have a redox potential that is 300 mV more negative and (iii) have their cluster donation/transfer function abolished. Because no global structural differences were found between the mutant and the native (wild-type) NAF-1 proteins, yet significant functional differences exist between them, the NAF-1 H114C mutant is an excellent tool to decipher the underlying biological importance of the [2Fe–2S] cluster of NAF-1 in vivo.« less

A general and fast scoring function for protein-ligand interactions: a simplified potential approach.

PubMed

Muegge, I; Martin, Y C

1999-03-11

A fast, simplified potential-based approach is presented that estimates the protein-ligand binding affinity based on the given 3D structure of a protein-ligand complex. This general, knowledge-based approach exploits structural information of known protein-ligand complexes extracted from the Brookhaven Protein Data Bank and converts it into distance-dependent Helmholtz free interaction energies of protein-ligand atom pairs (potentials of mean force, PMF). The definition of an appropriate reference state and the introduction of a correction term accounting for the volume taken by the ligand were found to be crucial for deriving the relevant interaction potentials that treat solvation and entropic contributions implicitly. A significant correlation between experimental binding affinities and computed score was found for sets of diverse protein-ligand complexes and for sets of different ligands bound to the same target. For 77 protein-ligand complexes taken from the Brookhaven Protein Data Bank, the calculated score showed a standard deviation from observed binding affinities of 1.8 log Ki units and an R2 value of 0.61. The best results were obtained for the subset of 16 serine protease complexes with a standard deviation of 1.0 log Ki unit and an R2 value of 0.86. A set of 33 inhibitors modeled into a crystal structure of HIV-1 protease yielded a standard deviation of 0.8 log Ki units from measured inhibition constants and an R2 value of 0.74. In contrast to empirical scoring functions that show similar or sometimes better correlation with observed binding affinities, our method does not involve deriving specific parameters that fit the observed binding affinities of protein-ligand complexes of a given training set. We compared the performance of the PMF score, Böhm's score (LUDI), and the SMOG score for eight different test sets of protein-ligand complexes. It was found that for the majority of test sets the PMF score performs best. The strength of the new approach presented here lies in its generality as no knowledge about measured binding affinities is needed to derive atomic interaction potentials. The use of the new scoring function in docking studies is outlined.

Modification of the 5' terminus of oligodeoxyribonucleotides for conjugation with ligands.

PubMed

Asseline, U; Thuong, N T

2001-08-01

Ligands can be introduced at the 5' terminus of an oligonucleotide by adding a linker to the ligand and modifying the 5' terminus of the oligonucleotide. These are then reacted to give the ligand-oligonucleotide conjugate. This unit describes the addition of carboxylated and aminoalkylated linkers, and phosphorothioate, phosphate, and masked thiol groups to the 5' terminus of an oligonucleotide. The addition of linkers to ligands and the final reaction that produces the ligand-conjugated oligonucleotide are described elsewhere in the series. This approach is particularly useful when there is a limited amount of ligand available, when the ligand is sensitive to chemical conditions required for oligonucleotide deprotection, or when the ligand is weakly soluble in solvents required for phosphoramidite- or H-phosphonate-mediated oligonucleotide synthesis.

Superior removal of arsenic from water with zirconium metal-organic framework UiO-66.

PubMed

Wang, Chenghong; Liu, Xinlei; Chen, J Paul; Li, Kang

2015-11-12

In this study, water stable zirconium metal-organic framework (UiO-66) has been synthesized and for the first time applied as an adsorbent to remove aquatic arsenic contamination. The as-synthesized UiO-66 adsorbent functions excellently across a broad pH range of 1 to 10, and achieves a remarkable arsenate uptake capacity of 303 mg/g at the optimal pH, i.e., pH = 2. To the best of our knowledge, this is the highest arsenate As(V) adsorption capacity ever reported, much higher than that of currently available adsorbents (5-280 mg/g, generally less than 100 mg/g). The superior arsenic uptake performance of UiO-66 adsorbent could be attributed to the highly porous crystalline structure containing zirconium oxide clusters, which provides a large contact area and plenty of active sites in unit space. Two binding sites within the adsorbent framework are proposed for arsenic species, i.e., hydroxyl group and benzenedicarboxylate ligand. At equilibrium, seven equivalent arsenic species can be captured by one Zr6 cluster through the formation of Zr-O-As coordination bonds.

Superior removal of arsenic from water with zirconium metal-organic framework UiO-66

PubMed Central

Wang, Chenghong; Liu, Xinlei; Chen, J. Paul; Li, Kang

2015-01-01

In this study, water stable zirconium metal-organic framework (UiO-66) has been synthesized and for the first time applied as an adsorbent to remove aquatic arsenic contamination. The as-synthesized UiO-66 adsorbent functions excellently across a broad pH range of 1 to 10, and achieves a remarkable arsenate uptake capacity of 303 mg/g at the optimal pH, i.e., pH = 2. To the best of our knowledge, this is the highest arsenate As(V) adsorption capacity ever reported, much higher than that of currently available adsorbents (5–280 mg/g, generally less than 100 mg/g). The superior arsenic uptake performance of UiO-66 adsorbent could be attributed to the highly porous crystalline structure containing zirconium oxide clusters, which provides a large contact area and plenty of active sites in unit space. Two binding sites within the adsorbent framework are proposed for arsenic species, i.e., hydroxyl group and benzenedicarboxylate ligand. At equilibrium, seven equivalent arsenic species can be captured by one Zr6 cluster through the formation of Zr-O-As coordination bonds. PMID:26559001

Plasticity of the Binding Site of Renin: Optimized Selection of Protein Structures for Ensemble Docking.

PubMed

Strecker, Claas; Meyer, Bernd

2018-05-29

Protein flexibility poses a major challenge to docking of potential ligands in that the binding site can adopt different shapes. Docking algorithms usually keep the protein rigid and only allow the ligand to be treated as flexible. However, a wrong assessment of the shape of the binding pocket can prevent a ligand from adapting a correct pose. Ensemble docking is a simple yet promising method to solve this problem: Ligands are docked into multiple structures, and the results are subsequently merged. Selection of protein structures is a significant factor for this approach. In this work we perform a comprehensive and comparative study evaluating the impact of structure selection on ensemble docking. We perform ensemble docking with several crystal structures and with structures derived from molecular dynamics simulations of renin, an attractive target for antihypertensive drugs. Here, 500 ns of MD simulations revealed binding site shapes not found in any available crystal structure. We evaluate the importance of structure selection for ensemble docking by comparing binding pose prediction, ability to rank actives above nonactives (screening utility), and scoring accuracy. As a result, for ensemble definition k-means clustering appears to be better suited than hierarchical clustering with average linkage. The best performing ensemble consists of four crystal structures and is able to reproduce the native ligand poses better than any individual crystal structure. Moreover this ensemble outperforms 88% of all individual crystal structures in terms of screening utility as well as scoring accuracy. Similarly, ensembles of MD-derived structures perform on average better than 75% of any individual crystal structure in terms of scoring accuracy at all inspected ensembles sizes.

Can single molecule localization microscopy be used to map closely spaced RGD nanodomains?

PubMed Central

Nicovich, Philip R.; Soeriyadi, Alexander; Nieves, Daniel J.; Gooding, J. Justin; Gaus, Katharina

2017-01-01

Cells sense and respond to nanoscale variations in the distribution of ligands to adhesion receptors. This makes single molecule localization microscopy (SMLM) an attractive tool to map the distribution of ligands on nanopatterned surfaces. We explore the use of SMLM spatial cluster analysis to detect nanodomains of the cell adhesion-stimulating tripeptide arginine-glycine-aspartic acid (RGD). These domains were formed by the phase separation of block copolymers with controllable spacing on the scale of tens of nanometers. We first determined the topology of the block copolymer with atomic force microscopy (AFM) and then imaged the localization of individual RGD peptides with direct stochastic optical reconstruction microscopy (dSTORM). To compare the data, we analyzed the dSTORM data with DBSCAN (density-based spatial clustering application with noise). The ligand distribution and polymer topology are not necessary identical since peptides may attach to the polymer outside the nanodomains and/or coupling and detection of peptides within the nanodomains is incomplete. We therefore performed simulations to explore the extent to which nanodomains could be mapped with dSTORM. We found that successful detection of nanodomains by dSTORM was influenced by the inter-domain spacing and the localization precision of individual fluorophores, and less by non-specific absorption of ligands to the substratum. For example, under our imaging conditions, DBSCAN identification of nanodomains spaced further than 50 nm apart was largely independent of background localisations, while nanodomains spaced closer than 50 nm required a localization precision of ~11 nm to correctly estimate the modal nearest neighbor distance (NDD) between nanodomains. We therefore conclude that SMLM is a promising technique to directly map the distribution and nanoscale organization of ligands and would benefit from an improved localization precision. PMID:28723958

Analysis of a two-domain binding site for the urokinase-type plasminogen activator-plasminogen activator inhibitor-1 complex in low-density-lipoprotein-receptor-related protein.

PubMed

Andersen, O M; Petersen, H H; Jacobsen, C; Moestrup, S K; Etzerodt, M; Andreasen, P A; Thøgersen, H C

2001-07-01

The low-density-lipoprotein-receptor (LDLR)-related protein (LRP) is composed of several classes of domains, including complement-type repeats (CR), which occur in clusters that contain binding sites for a multitude of different ligands. Each approximately 40-residue CR domain contains three conserved disulphide linkages and an octahedral Ca(2+) cage. LRP is a scavenging receptor for ligands from extracellular fluids, e.g. alpha(2)-macroglobulin (alpha(2)M)-proteinase complexes, lipoprotein-containing particles and serine proteinase-inhibitor complexes, like the complex between urokinase-type plasminogen activator (uPA) and the plasminogen activator inhibitor-1 (PAI-1). In the present study we analysed the interaction of the uPA-PAI-1 complex with an ensemble of fragments representing a complete overlapping set of two-domain fragments accounting for the ligand-binding cluster II (CR3-CR10) of LRP. By ligand blotting, solid-state competition analysis and surface-plasmon-resonance analysis, we demonstrate binding to multiple CR domains, but show a preferential interaction between the uPA-PAI-1 complex and a two-domain fragment comprising CR domains 5 and 6 of LRP. We demonstrate that surface-exposed aspartic acid and tryptophan residues at identical positions in the two homologous domains, CR5 and CR6 (Asp(958,CR5), Asp(999,CR6), Trp(953,CR5) and Trp(994,CR6)), are critical for the binding of the complex as well as for the binding of the receptor-associated protein (RAP) - the folding chaperone/escort protein required for transport of LRP to the cell surface. Accordingly, the present work provides (1) an identification of a preferred binding site within LRP CR cluster II; (2) evidence that the uPA-PAI-1 binding site involves residues from two adjacent protein domains; and (3) direct evidence identifying specific residues as important for the binding of uPA-PAI-1 as well as for the binding of RAP.

Novel bimetallic dispersed catalysts for temperature-programmed coal liquefaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chunshan, Song; Kirby, S.; Schmidt, E.

1995-12-31

The objective of this project is to explore bimetallic dispersed catalysts for more efficient coal liquefaction. Coal liquefaction involves cleavage of methylene, dimethylene and ether bridges connecting various aromatic units and the reactions of various oxygen functional groups. This paper describes recent results on (1) hydrodeoxygenation of O-containing polycyclic model compounds using novel organometallic catalyst precursors; and (2) activity and selectivity of dispersed Fe catalysts from organometallic and inorganic precursors for hydrocracking of 4-(1-naphthylmethyl) bibenzyl. The results showed that some iron containing catalysts have higher activity in the sulfur-free form, contrary to conventional wisdom. Adding sulfur to Fe precursors withmore » Cp-ligands decreased the activity of the resulting catalyst. This is in distinct contrast to the cases with iron pentacarbonyl and superfine Fe{sub 2}O{sub 3}, where S addition increased their catalytic activity substantially. A positive correlation between sulfur addition and increased activity can be seen, but a reversed trend between Fe cluster size and hydrocracking conversion could be observed, for carbonyl-type Fe precursors. It is apparent that the activity and selectivity of Fe catalysts for NMBB conversion depends strongly on both the type of ligand environment, the oxidation state and the number of intermetal bonds in the molecular precursor.« less

Extraordinary cluster formation and intramolecular ligand-ligand interactions in cyanoacetylene [corrected] mediated by Mg+*: implications for the atmospheric chemistry of titan and for circumstellar chemistry.

PubMed

Milburn, Rebecca K; Hopkinson, Alan C; Bohme, Diethard K

2005-09-21

Experimental results are reported that track the kinetics of gas-phase reactions initiated by Mg+*, (c-C5H5)Mg+ and (c-C5H5)2Mg+* in hydrogen cyanide and cyanoacetylene. The experiments were performed with a selected-ion flow tube (SIFT) tandem mass spectrometer at a helium buffer-gas pressure of 0.35 +/- 0.01 Torr and at 294 +/- 3 K. The observed chemistries of Mg+* and (c-C5H5)Mg+ are dominated by sequential ligation, while that of (c-C5H5)2Mg+* is by ligand switching. The rate-coefficient measurements for sequential addition of cyanoacetylene to Mg+* indicate an extraordinary pattern in alternating chemical reactivity while multiple-collision induced dissociation experiments revealed an extraordinary stability for the Mg(HC3N)4+* cluster ion. Molecular orbital calculations with density functional theory (DFT) at the B3LYP level, Hartree-Fock (HF) and second-order Mphiller-Plesset (MP2) levels, all performed with a 6-31+G(d) basis set, have been used to calculate structures and energies for the observed Mg(HC3N)1-4(+)* cations. These calculations indicate that the path of formation of Mg(HC3N)4+* involves ligand-ligand interactions leading to two cyclic (HC3N)2 ligands which then interact to form 2,4,6,8-tetracyanosemibullvalene-Mg+ or 1,2,5,6-tetracyano-1,3,5,7-cyclooctatetraene-Mg+ cations. A case is made for the formation of similar complex organomagnesium ions in the upper atmosphere of Titan where subsequent electron-ion recombination may produce cyano derivatives of large unsaturated hydrocarbons. In contrast, circumstellar environments with their much higher relative content of free electrons are less likely to give rise to such chemistry.

What determines catalyst functionality in molecular water oxidation? Dependence on ligands and metal nuclearity in cobalt clusters.

PubMed

Smith, Paul F; Kaplan, Christopher; Sheats, John E; Robinson, David M; McCool, Nicholas S; Mezle, Nicholas; Dismukes, G Charles

2014-02-17

The metal-oxo M4O4 "cubane" topology is of special significance to the field of water oxidation as it represents the merging of bioinspired structural principles derived from natural photosynthesis with successful artificial catalysts known to date. Herein, we directly compare the rates of water oxidation/O2 evolution catalyzed by six cobalt-oxo clusters including the Co4O4 cubanes, Co4O4(OAc)4(py)4 and [Co4O4(OAc)2(bpy)4](2+), using the common Ru(bpy)3(2+)/S2O8(2-) photo-oxidant assay. At pH 8, the first-order rate constants for these cubanes differ by 2-fold, 0.030 and 0.015 s(-1), respectively, reflecting the number of labile carboxylate sites that allow substrate water binding in a pre-equilibrium step before O2 release. Kinetic results reveal a deprotonation step occurs on this pathway and that two electrons are removed before O2 evolution occurs. The Co4O4 cubane core is shown to be the smallest catalytic unit for the intramolecular water oxidation pathway, as neither "incomplete cubane" trimers [Co3O(OH)3(OAc)2(bpy)3](2+) and [Co3O(OH)2(OAc)3(py)5](2+) nor "half cubane" dimers [Co2(OH)2(OAc)3(bpy)2](+) and [Co2(OH)2(OAc)3(py)4](+) were found capable of evolving O2, despite having the same ligand sets as their cubane counterparts. Electrochemical studies reveal that oxidation of both cubanes to formally Co4(3III,IV) (0.7 V vs Ag/AgCl) occurs readily, while neither dimers nor trimers are oxidized below 1.5 V, pointing to appreciably greater charge delocalization in the [Co4O4](5+) core. The origin of catalytic activity by Co4O4 cubanes illustrates three key features for water oxidation: (1) four one-electron redox metals, (2) efficient charge delocalization of the first oxidation step across the Co4O4 cluster, allowing for stabilization of higher oxidizing equivalents, and (3) terminal coordination site for substrate aquo/oxo formation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tang, Chunying; Lu, Jialin; Han, Jingyu

Polymeric lanthanide complexes with thiostannate and polyamine mixed ligands, [Ln(peha)(μ–SnS{sub 4}H)]{sub n} [Ln=La (1a), Nd (1b)] and [(Ln(tepa)(μ–OH)){sub 2}(μ–Sn{sub 2}S{sub 6})]{sub n}nH{sub 2}O [Ln=Nd (2a), Sm (2b), Gd (2c), Dy (2d)] (peha=pentaethylenehexamine, tepa=tetraethylenepentamine) were respectively prepared in peha and tepa coordinative solvents by the solvothermal methods. In 1a and 1b, the Ln{sup 3+} ions are coordinated by a hexadentate peha ligand forming [Ln(peha)]{sup 3+} units. The [SnS{sub 4}H]{sup 3−} anion chelates a [Ln(peha)]{sup 3+} unit via two S atoms and coordinates to another [Ln(peha)]{sup 3+} unit via the third S atom. As a result, the [Ln(peha)]{sup 3+} units are connectedmore » into coordination polymers [Ln(peha)(μ–SnS{sub 4}H)]{sub n} by an unprecedented tridentate μ–η{sup 1},η{sup 2}–SnS{sub 4}H bridging ligands. In 2a–2d, the Ln{sup 3+} ions are coordinated by a pentadentate tepa ligand, and two [Ln(tepa)]{sup 3+} units are joined by two μ–OH bridges to form a binuclear [(Ln(tepa)(μ–OH)){sub 2}]{sup 4+} unit. Behaving as a bidentate μ–η{sup 1}, η{sup 1}–Sn{sub 2}S{sub 6} bridging ligand, the Sn{sub 2}S{sub 6} unit connects [(Ln(tepa)(μ–OH)){sub 2}]{sup 4+} units into a neutral coordination polymer [(Ln(tepa)(μ–OH)){sub 2}(μ–Sn{sub 2}S{sub 6})]{sub n} via the trans S atoms. The Ln{sup 3+} ions are in distorted monocapped square antiprismatic and bicapped trigonal prismatic environments in [(Ln(peha)(μ–SnS{sub 4}H)]{sub n} and [(Ln(tepa)(μ–OH)){sub 2}(μ–Sn{sub 2}S{sub 6})]{sub n}, respectively. The denticities of ethylene polyamine play an important role on the formation and complexation of the thiostannate in the presence of lanthanide ions. Compounds 1a–2d show well-defined absorption edges with band gaps between 2.81 and 3.15 eV. - Graphical abstract: Lanthanide coordination polymers concerning thiostannate ligands were prepared by the solvothermal methods, and μ{sub 3}–SnS{sub 4}H and μ–Sn{sub 2}S{sub 6} ligands to Ln(III) centers were obtained. - Highlights: • Lanthanide coordination polymers were prepared in polyamines with higher denticity. • The μ–η{sup 1},η{sup 2}–SnS{sub 4}H and μ–η{sup 1},η{sup 1}–Sn{sub 2}S{sub 6} ligands to Ln(III) centers were obtained. • Effect of amine on the complexation of Ln(III) with thiostannate is observed.« less

Molecular Clusters: Nanoscale Building Blocks for Solid-State Materials.

PubMed

Pinkard, Andrew; Champsaur, Anouck M; Roy, Xavier

2018-04-17

The programmed assembly of nanoscale building blocks into multicomponent hierarchical structures is a powerful strategy for the bottom-up construction of functional materials. To develop this concept, our team has explored the use of molecular clusters as superatomic building blocks to fabricate new classes of materials. The library of molecular clusters is rich with exciting properties, including diverse functionalization, redox activity, and magnetic ordering, so the resulting cluster-assembled solids, which we term superatomic crystals (SACs), hold the promise of high tunability, atomic precision, and robust architectures among a diverse range of other material properties. Molecular clusters have only seldom been used as precursors for functional materials. Our team has been at the forefront of new developments in this exciting research area, and this Account focuses on our progress toward designing materials from cluster-based precursors. In particular, this Account discusses (1) the design and synthesis of molecular cluster superatomic building blocks, (2) their self-assembly into SACs, and (3) their resulting collective properties. The set of molecular clusters discussed herein is diverse, with different cluster cores and ligand arrangements to create an impressive array of solids. The cluster cores include octahedral M 6 E 8 and cubane M 4 E 4 (M = metal; E = chalcogen), which are typically passivated by a shell of supporting ligands, a feature upon which we have expanded upon by designing and synthesizing more exotic ligands that can be used to direct solid-state assembly. Building from this library, we have designed whole families of binary SACs where the building blocks are held together through electrostatic, covalent, or van der Waals interactions. Using single-crystal X-ray diffraction (SCXRD) to determine the atomic structure, a remarkable range of compositional variability is accessible. We can also use this technique, in tandem with vibrational spectroscopy, to ascertain features about the constituent superatomic building blocks, such as the charge of the cluster cores, by analysis of bond distances from the SCXRD data. The combination of atomic precision and intercluster interactions in these SACs produces novel collective properties, including tunable electrical transport, crystalline thermal conductivity, and ferromagnetism. In addition, we have developed a synthetic strategy to insert redox-active guests into the superstructure of SACs via single-crystal-to-single-crystal intercalation. This intercalation process allows us to tune the optical and electrical transport properties of the superatomic crystal host. These properties are explored using a host of techniques, including Raman spectroscopy, SQUID magnetometry, electrical transport measurements, electronic absorption spectroscopy, differential scanning calorimetry, and frequency-domain thermoreflectance. Superatomic crystals have proven to be both robust and tunable, representing a new method of materials design and architecture. This Account demonstrates how precisely controlling the structure and properties of nanoscale building blocks is key in developing the next generation of functional materials; several examples are discussed and detailed herein.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Chongqi; Harbich, Wolfgang; Sementa, Luca

Ligand-protected Au clusters are non-bleaching fluorescence markers in bio- and medical applications. We show that their fluorescence is an intrinsic property of the Au cluster itself. We find a very intense and sharp fluorescence peak located at λ =739.2 nm (1.68 eV) for Au20 clusters in a Ne matrix held at 6 K. The fluorescence reflects the HOMO-LUMO diabatic bandgap of the cluster. The cluster shows a very rich absorption fine structure reminiscent of well defined molecule-like quantum levels. These levels are resolved since Au20 has only one stable isomer (tetrahedral), therefore our sample is mono-disperse in cluster size andmore » conformation. Density-functional theory (DFT) and time-dependent DFT calculations clarify the nature of optical absorptionand predict both main absorption peaks and intrinsic fluorescence in good agreement with experiment.« less

[Cu13 {S2 CNn Bu2 }6 (acetylide)4 ]+ : A Two-Electron Superatom.

PubMed

Chakrahari, Kiran Kumarvarma; Liao, Jian-Hong; Kahlal, Samia; Liu, Yu-Chiao; Chiang, Ming-Hsi; Saillard, Jean-Yves; Liu, C W

2016-11-14

The first structurally characterized copper cluster with a Cu 13 centered cuboctahedral arrangement, a model of the bulk copper fcc structure, was observed in [Cu 13 (S 2 CN n Bu 2 ) 6 (C≡CR) 4 ](PF 6 ) (R=C(O)OMe, C 6 H 4 F) nanoclusters. Four of the eight triangular faces of the cuboctahedron are capped by acetylide groups in μ 3  fashion, and each of the six square faces is bridged by a dithiolate ligand in μ 2 ,μ 2 fashion, which leads to a truncated tetrahedron of twelve sulfur atoms. DFT calculations are fully consistent with the description of these Cu 13 clusters as two-electron superatoms, that is, a [Cu 13 ] 11+ core passivated by ten monoanionic ligands, with an a 1 HOMO containing two 1S jellium electrons. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Theoretical study of structure, bonding, and electronic behavior of novel sandwich compounds M₃(C6R6)₂ (M = Ni, Pd, Pt; R = H, F).

PubMed

Zhou, Ke

2012-10-01

The correlations between the structural and electronic properties of the monolayer clusters M₃ (where M = Ni, Pd, Pt) and the sandwich complexes M₃(C₆R₆)₂ (where M = Ni, Pd, Pt; R = H, F) were studied by performing quantum-chemical calculations. All of the sandwich complexes are strongly donating and backdonating metal-ligand bonding structures. The influence of the ligand as well as significant variations in the M-C, M-M, and C-C bond lengths and binding energies were examined to obtain a qualitative and quantitative picture of the intramolecular interactions in C₆R₆-M₃. Our theoretical investigations show that the binding energies of these sandwich complexes gradually decrease from Ni to Pt as well as from H to F, which can be explained via the frontier orbitals of the clusters M₃ and C₆R₆.

[Cu 32(H) 20{S 2P(O i Pr) 2 } 12 ]: The Largest Number of Hydrides Recorded in a Molecular Nanocluster by Neutron Diffraction

DOE PAGES

Dhayal, Rajendra S.; Liao, Jian-Hong; Kahlal, Samia; ...

2015-04-20

An air- and moisture-stable nanoscale polyhydrido copper cluster [Cu 32(H) 20{S 2P(O i Pr) 2 } 12 ] (1 H) was synthesized and structurally characterized. The molecular structure of 1 H exhibits a hexacapped pseudo-rhombohedral core of 14 Cu atoms sandwiched between two nestlike triangular cupola fragments of (2x9) Cu atoms in an elongated triangular gyrobicupola polyhedron. The discrete Cu 32 cluster is stabilized by 12 dithiophosphate ligands and a record number of 20 hydride ligands, which were found by high-resolution neutron diffraction to exhibit tri-, tetra-, and pentacoordinated hydrides in capping and interstitial modes. We conclude that this resultmore » was further supported by a density functional theory investigation on the simplified model [Cu 32(H) 20(S 2PH 2) 12].« less

Tie2 and Eph Receptor Tyrosine Kinase Activation and Signaling

PubMed Central

Barton, William A.; Dalton, Annamarie C.; Seegar, Tom C.M.; Himanen, Juha P.

2014-01-01

The Eph and Tie cell surface receptors mediate a variety of signaling events during development and in the adult organism. As other receptor tyrosine kinases, they are activated on binding of extracellular ligands and their catalytic activity is tightly regulated on multiple levels. The Eph and Tie receptors display some unique characteristics, including the requirement of ligand-induced receptor clustering for efficient signaling. Interestingly, both Ephs and Ties can mediate different, even opposite, biological effects depending on the specific ligand eliciting the response and on the cellular context. Here we discuss the structural features of these receptors, their interactions with various ligands, as well as functional implications for downstream signaling initiation. The Eph/ephrin structures are already well reviewed and we only provide a brief overview on the initial binding events. We go into more detail discussing the Tie-angiopoietin structures and recognition. PMID:24478383

Ubiquitination switches EphA2 vesicular traffic from a continuous safeguard to a finite signalling mode

PubMed Central

Sabet, Ola; Stockert, Rabea; Xouri, Georgia; Brüggemann, Yannick; Stanoev, Angel; Bastiaens, Philippe I. H.

2015-01-01

Autocatalytic phosphorylation of receptor tyrosine kinases (RTKs) enables diverse, context-dependent responses to extracellular signals but comes at the price of autonomous, ligand-independent activation. Using a conformational biosensor that reports on the kinase activity of the cell guidance ephrin receptor type-A (EphA2) in living cells, we observe that autonomous EphA2 activation is suppressed by vesicular recycling and dephosphorylation by protein tyrosine phosphatases 1B (PTP1B) near the pericentriolar recycling endosome. This spatial segregation of catalytically superior PTPs from RTKs at the plasma membrane is essential to preserve ligand responsiveness. Ligand-induced clustering, on the other hand, promotes phosphorylation of a c-Cbl docking site and ubiquitination of the receptor, thereby redirecting it to the late endosome/lysosome. We show that this switch from cyclic to unidirectional receptor trafficking converts a continuous suppressive safeguard mechanism into a transient ligand-responsive signalling mode. PMID:26292967

A Pipeline To Enhance Ligand Virtual Screening: Integrating Molecular Dynamics and Fingerprints for Ligand and Proteins.

PubMed

Spyrakis, Francesca; Benedetti, Paolo; Decherchi, Sergio; Rocchia, Walter; Cavalli, Andrea; Alcaro, Stefano; Ortuso, Francesco; Baroni, Massimo; Cruciani, Gabriele

2015-10-26

The importance of taking into account protein flexibility in drug design and virtual ligand screening (VS) has been widely debated in the literature, and molecular dynamics (MD) has been recognized as one of the most powerful tools for investigating intrinsic protein dynamics. Nevertheless, deciphering the amount of information hidden in MD simulations and recognizing a significant minimal set of states to be used in virtual screening experiments can be quite complicated. Here we present an integrated MD-FLAP (molecular dynamics-fingerprints for ligand and proteins) approach, comprising a pipeline of molecular dynamics, clustering and linear discriminant analysis, for enhancing accuracy and efficacy in VS campaigns. We first extracted a limited number of representative structures from tens of nanoseconds of MD trajectories by means of the k-medoids clustering algorithm as implemented in the BiKi Life Science Suite ( http://www.bikitech.com [accessed July 21, 2015]). Then, instead of applying arbitrary selection criteria, that is, RMSD, pharmacophore properties, or enrichment performances, we allowed the linear discriminant analysis algorithm implemented in FLAP ( http://www.moldiscovery.com [accessed July 21, 2015]) to automatically choose the best performing conformational states among medoids and X-ray structures. Retrospective virtual screenings confirmed that ensemble receptor protocols outperform single rigid receptor approaches, proved that computationally generated conformations comprise the same quantity/quality of information included in X-ray structures, and pointed to the MD-FLAP approach as a valuable tool for improving VS performances.

Active Brownian agents with concentration-dependent chemotactic sensitivity.

PubMed

Meyer, Marcel; Schimansky-Geier, Lutz; Romanczuk, Pawel

2014-02-01

We study a biologically motivated model of overdamped, autochemotactic Brownian agents with concentration-dependent chemotactic sensitivity. The agents in our model move stochastically and produce a chemical ligand at their current position. The ligand concentration obeys a reaction-diffusion equation and acts as a chemoattractant for the agents, which bias their motion towards higher concentrations of the dynamically altered chemical field. We explore the impact of concentration-dependent response to chemoattractant gradients on large-scale pattern formation, by deriving a coarse-grained macroscopic description of the individual-based model, and compare the conditions for emergence of inhomogeneous solutions for different variants of the chemotactic sensitivity. We focus primarily on the so-called receptor-law sensitivity, which models a nonlinear decrease of chemotactic sensitivity with increasing ligand concentration. Our results reveal qualitative differences between the receptor law, the constant chemotactic response, and the so-called log law, with respect to stability of the homogeneous solution, as well as the emergence of different patterns (labyrinthine structures, clusters, and bubbles) via spinodal decomposition or nucleation. We discuss two limiting cases, where the model can be reduced to the dynamics of single species: (I) the agent density governed by a density-dependent effective diffusion coefficient and (II) the ligand field with an effective bistable, time-dependent reaction rate. In the end, we turn to single clusters of agents, studying domain growth and determining mean characteristics of the stationary inhomogeneous state. Analytical results are confirmed and extended by large-scale GPU simulations of the individual based model.

C^C* cyclometalated platinum(II) N-heterocyclic carbene complexes with a sterically demanding β-diketonato ligand – synthesis, characterization and photophysical properties.

PubMed

Tenne, M; Metz, S; Wagenblast, G; Münster, Ingo; Strassner, T

2015-05-14

Neutral cyclometalated platinum(ii) N-heterocyclic carbene complexes [Pt(C^C*)(O^O)] with C^C* ligands based on 1-phenyl-1,2,4-triazol-5-ylidene and 4-phenyl-1,2,4-triazol-5-ylidene, as well as acetylacetonato (O^O = acac) and 1,3-bis(2,4,6-trimethylphenyl)propan-1,3-dionato (O^O = mesacac) ancillary ligands were synthesized and characterized. All complexes are emissive at room temperature in a poly(methyl methacrylate) (PMMA) matrix with emission maxima in the blue region of the spectrum. High quantum efficiencies and short decay times were observed for all complexes with mesacac ancillary ligands. The sterically demanding mesityl groups of the mesacac ligand effectively prevent molecular stacking. The emission behavior of these emitters is in general independent of the position of the nitrogen in the backbone of the N-heterocyclic carbene (NHC) unit and a variety of substituents in 4-position of the phenyl unit, meta to the cyclometalating bond.

Microsolvation of the pyrrole cation (Py+) with nonpolar and polar ligands: infrared spectra of Py+-Ln with L = Ar, N2, and H2O (n ≤ 3).

PubMed

Schütz, Markus; Matsumoto, Yoshiteru; Bouchet, Aude; Öztürk, Murat; Dopfer, Otto

2017-02-01

The solvation of aromatic (bio-)molecular building blocks has a strong impact on the intermolecular interactions and function of supramolecular assemblies, proteins, and DNA. Herein we characterize the initial microsolvation process of the heterocyclic aromatic pyrrole cation (Py + ) in its 2 A 2 ground electronic state with nonpolar, quadrupolar, and dipolar ligands (L = Ar, N 2 , and H 2 O) by infrared photodissociation (IRPD) spectroscopy of cold mass-selected Py + -L n (n ≤ 3) clusters in a molecular beam and dispersion-corrected density functional theory calculations at the B3LYP-D3/aug-cc-pVTZ level. Size- and isomer-specific shifts in the NH stretch frequency (Δν NH ) unravel the competition between various ligand binding sites, the strength of the respective intermolecular bonds, and the cluster growth. In Py + -Ar, linear H-bonding of Ar to the acidic NH group (NHAr) is competitive with π-stacking to the aromatic ring, and both Py + -Ar(H) and Py + -Ar(π) are observed. For L = N 2 and H 2 O, the linear NHL H-bond is much more stable than any other binding site and the only observed binding motif. For the Py + -Ar 2 and Py + -(N 2 ) 2 trimers, the H/π isomer with one H-bonded and one π-bonded ligand strongly competes with a 2H isomer with two bifurcated nonlinear NHL bonds. The latter are equivalent for Ar but nonequivalent for N 2 . Py + -H 2 O exhibits a strong and linear NHO H-bond with charge-dipole configuration and C 2v symmetry. IRPD spectra of cold Py + -H 2 O-L clusters with L = Ar and N 2 reveal that Ar prefers π-stacking to the Py + ring, while N 2 forms an OHN 2 H-bond to the H 2 O ligand. The Δν NH frequency shifts in Py + -L n are correlated with the strength of the NHL H-bond and the proton affinity (PA) of L, and a monotonic correlation between Δν NH of the Py + -L(H) dimers and PA is established. Comparison with neutral Py-L dimers reveals the strong impact of the positive charge on the acidity of the NH group, the strength of the NHL H-bond, and the preferred ligand binding motif.

Mössbauer spectroscopy and DFT calculations on all protonation states of the 2Fe-2S cluster of the Rieske protein

NASA Astrophysics Data System (ADS)

Müller, C. S.; Auerbach, H.; Stegmaier, K.; Wolny, J. A.; Schünemann, V.; Pierik, A. J.

2017-11-01

The Thermus thermophilus Rieske protein ( TtRP) contains a 2Fe-2S cluster with one iron (Fe-Cys) coordinated by four sulfur atoms (2xS2- and 2xCys) and one iron (Fe-His) by two sulfur and two nitrogen atoms (2xS2-, His134 and His154). Here, the protein is investigated at three pH values (6.0, 8.5 and 10.5) in order to elucidate the protonation states of the His-ligands. Examination of the effect of protonation on the electronic structure of the cluster via Mössbauer spectroscopy gives a deeper understanding of the coupling of electron transfer to the protonation state of the His-ligands. Two components (1 referring to Fe-Cys and 2 to Fe-His) with parameters typical for a diamagnetic [2Fe-2S]2+ cluster are detected. The Mössbauer parameters and the protonation state clearly correlate: while δ remains almost pH-independent with δ 1 (pH6.0) = 0.23 (± 0.01) mms- 1 and δ 1 (pH10.5) = 0.24 (± 0.01) mms- 1 for Fe-Cys, it decreases for Fe-His from δ 2 (pH6.0) = 0.34 (± 0.01) mms- 1 to δ 2 (pH10.5) = 0.28 (± 0.01) mms- 1. Δ E Q changes from Δ E Q1 (pH6.0) = 0.57 (± 0.01) mms- 1 to Δ E Q1 (pH10.5) = 0.45 (± 0.01) mms- 1 and from Δ E Q2 (pH6.0) = 1.05 (± 0.01) mms- 1 to Δ E Q2 (pH10.5) = 0.71 (± 0.01) mms- 1. Density functional theory (DFT)-calculations based on the crystal structure (pdb 1NYK) (Hunsicker-Wang et al. Biochemistry 42, 7303, 2003) have been performed for the Rieske-cluster with different His-ligand protonation states, reproducing the experimentally observed trend.

A new approach to explore the binding space of polysaccharide-based ligands: selectin antagonists.

PubMed

Calosso, Mickael; Charpentier, Daniel; Vaillancourt, Marc; Bencheqroun, Mohammed; St-Pierre, Gabrielle; Wilkes, Brian C; Guindon, Yvan

2012-12-13

The discovery of molecules that interfere with the binding of a ligand to a receptor remains a topic of great interest in medicinal chemistry. Herein, we report that a monosaccharide unit of a polysaccharide ligand can be replaced advantageously by a conformationally locked acyclic molecular entity. A cyclic component of the selectin ligand Sialyl Lewis(x), GlcNAc, is replaced by an acyclic tether, tartaric esters, which link two saccharide units. The conformational bias of this acyclic tether originates from the minimization of intramolecular dipole-dipole interaction and the gauche effect. The evaluation of the binding of these derivatives to P-selectin was measured by surface plasmon resonance spectroscopy. The results obtained in our pilot study suggest that the discovery of tunable tethers could facilitate the exploration of the carbohydrate recognition domain of various receptors.

Improving estimation of kinetic parameters in dynamic force spectroscopy using cluster analysis

NASA Astrophysics Data System (ADS)

Yen, Chi-Fu; Sivasankar, Sanjeevi

2018-03-01

Dynamic Force Spectroscopy (DFS) is a widely used technique to characterize the dissociation kinetics and interaction energy landscape of receptor-ligand complexes with single-molecule resolution. In an Atomic Force Microscope (AFM)-based DFS experiment, receptor-ligand complexes, sandwiched between an AFM tip and substrate, are ruptured at different stress rates by varying the speed at which the AFM-tip and substrate are pulled away from each other. The rupture events are grouped according to their pulling speeds, and the mean force and loading rate of each group are calculated. These data are subsequently fit to established models, and energy landscape parameters such as the intrinsic off-rate (koff) and the width of the potential energy barrier (xβ) are extracted. However, due to large uncertainties in determining mean forces and loading rates of the groups, errors in the estimated koff and xβ can be substantial. Here, we demonstrate that the accuracy of fitted parameters in a DFS experiment can be dramatically improved by sorting rupture events into groups using cluster analysis instead of sorting them according to their pulling speeds. We test different clustering algorithms including Gaussian mixture, logistic regression, and K-means clustering, under conditions that closely mimic DFS experiments. Using Monte Carlo simulations, we benchmark the performance of these clustering algorithms over a wide range of koff and xβ, under different levels of thermal noise, and as a function of both the number of unbinding events and the number of pulling speeds. Our results demonstrate that cluster analysis, particularly K-means clustering, is very effective in improving the accuracy of parameter estimation, particularly when the number of unbinding events are limited and not well separated into distinct groups. Cluster analysis is easy to implement, and our performance benchmarks serve as a guide in choosing an appropriate method for DFS data analysis.

Second-chance signal transduction explains cooperative flagellar switching.

PubMed

Zot, Henry G; Hasbun, Javier E; Minh, Nguyen Van

2012-01-01

The reversal of flagellar motion (switching) results from the interaction between a switch complex of the flagellar rotor and a torque-generating stationary unit, or stator (motor unit). To explain the steeply cooperative ligand-induced switching, present models propose allosteric interactions between subunits of the rotor, but do not address the possibility of a reaction that stimulates a bidirectional motor unit to reverse direction of torque. During flagellar motion, the binding of a ligand-bound switch complex at the dwell site could excite a motor unit. The probability that another switch complex of the rotor, moving according to steady-state rotation, will reach the same dwell site before that motor unit returns to ground state will be determined by the independent decay rate of the excited-state motor unit. Here, we derive an analytical expression for the energy coupling between a switch complex and a motor unit of the stator complex of a flagellum, and demonstrate that this model accounts for the cooperative switching response without the need for allosteric interactions. The analytical result can be reproduced by simulation when (1) the motion of the rotor delivers a subsequent ligand-bound switch to the excited motor unit, thereby providing the excited motor unit with a second chance to remain excited, and (2) the outputs from multiple independent motor units are constrained to a single all-or-none event. In this proposed model, a motor unit and switch complex represent the components of a mathematically defined signal transduction mechanism in which energy coupling is driven by steady-state and is regulated by stochastic ligand binding. Mathematical derivation of the model shows the analytical function to be a general form of the Hill equation (Hill AV (1910) The possible effects of the aggregation of the molecules of haemoglobin on its dissociation curves. J Physiol 40: iv-vii).

Unexpected self-sorting self-assembly formation of a [4:4] sulfate:ligand cage from a preorganized tripodal urea ligand.

PubMed

Pandurangan, Komala; Kitchen, Jonathan A; Blasco, Salvador; Boyle, Elaine M; Fitzpatrick, Bella; Feeney, Martin; Kruger, Paul E; Gunnlaugsson, Thorfinnur

2015-04-07

The design and synthesis of tripodal ligands 1-3 based upon the N-methyl-1,3,5-benzenetricarboxamide platform appended with three aryl urea arms is reported. This ligand platform gives rise to highly preorganized structures and is ideally suited for binding SO4 (2-) and H2 PO4 (-) ions through multiple hydrogen-bonding interactions. The solid-state crystal structures of 1-3 with SO4 (2-) show the encapsulation of a single anion within a cage structure, whereas the crystal structure of 1 with H2 PO4 (-) showed that two anions are encapsulated. We further demonstrate that ligand 4, based on the same platform but consisting of two bis-urea moieties and a single ammonium moiety, also recognizes SO4 (2-) to form a self-assembled capsule with [4:4] SO4 (2-) :4 stoichiometry in which the anions are clustered within a cavity formed by the four ligands. This is the first example of a self-sorting self-assembled capsule where four tetrahedrally arranged SO4 (2-) ions are embedded within a hydrophobic cavity. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Assembly of bicyclic or monocyclic clusters from [(η5-C5Me5)2Mo2(μ3-S)4(CuMeCN)2]2+ with tetraphosphine or N,P mixed ligands: syntheses, structures and enhanced third-order NLO performances.

PubMed

Ren, Zhi-Gang; Sun, Sha; Dai, Min; Wang, Hui-Fang; Lü, Chun-Ning; Lang, Jian-Ping; Sun, Zhen-Rong

2011-09-07

Reactions of the preformed cluster [(η(5)-C(5)Me(5))(2)Mo(2)(μ(3)-S)(4)Cu(2)(MeCN)(2)](ClO(4))(2) (1) with two tetraphosphine ligands, 1,4-N,N,N',N'-tetra(diphenylphosphanylmethyl)benzene diamine (dpppda) and N,N,N',N'-tetra(diphenylphosphanylmethyl)ethylene diamine (dppeda), produced two bicyclic clusters {[(η(5)-C(5)Me(5))(2)Mo(2)(μ(3)-S)(4)Cu(2)](2)(L)}(ClO(4))(4) (3: L = dpppda; 4: L = dppeda). Analogous reactions of 1 or [(η(5)-C(5)Me(5))(2)Mo(2)(μ(3)-S)(4)Cu(2)(MeCN)(2)](PF(6))(2) (2) with two N,P mixed ligands, N,N-bi(diphenylphosphanylmethyl)-2-aminopyridine (bdppmapy) and N-diphenylphosphanylmethyl-4-aminopyridine (dppmapy), afforded two monocyclic clusters {[(η(5)-C(5)Me(5))(2)Mo(2)(μ(3)-S)(4)Cu(2)](2)(L)(2)}X(4) (5: L = bdppmapy, X = ClO(4); 6: L = dppmapy, X = PF(6)). Compounds 3-6 were fully characterized by elemental analysis, IR spectra, UV-vis spectra, (1)H and (31)P{(1)H} NMR spectra, ESI-MS and single-crystal X-ray crystallography. In the tetracations of 3-6, two cubane-like [Mo(2)(μ(3)-S)(4)Cu(2)] cores are linked either by one dpppda or dppeda bridge to form a bicyclic structure or by a pair of bdppmapy or dppmapy bridges to afford a monocyclic structure. The third-order nonlinear optical (NLO) properties of 1 and 3-6 in MeCN were also investigated by femtosecond degenerate four-wave mixing (DFWM) technique with a 50 fs pulse width at 800 nm. Compounds 3-6 exhibited enhanced third-order NLO performances relative to that of 1. This journal is © The Royal Society of Chemistry 2011

Chiral Silver-Lanthanide Metal-Organic Frameworks Comprised of One-Dimensional Triple Right-Handed Helical Chains Based on [Ln7(μ3-OH)8]13+ Clusters.

PubMed

Guo, Yan; Zhang, Lijuan; Muhammad, Nadeem; Xu, Yan; Zhou, Yunshan; Tang, Fang; Yang, Shaowei

2018-02-05

Three new isostructural chiral silver-lanthanide heterometal-organic frameworks [Ag 3 Ln 7 (μ 3 -OH) 8 (bpdc) 6 (NO 3 ) 3 (H 2 O) 6 ](NO 3 )·2H 2 O [Ln = Eu (1), Tb (2, Sm (3); H 2 bpdc = 2,2'-bipyridine-3,3'-dicarboxylic acid] based on heptanuclear lanthanide clusters [Ln 7 (μ 3 -OH) 8 ] 13+ comprised of one-dimensional triple right-handed helical chains were hydrothermally synthesized. Various means such as UV-vis spectroscopy, IR spectroscopy, elemental analysis, powder X-ray diffraction, and thermogravimetric/differential thermal analysis were used to characterize the compounds, wherein compound 3 was crystallographically characterized. In the structure of compound 3, eight μ 3 -OH - groups link seven Sm 3+ ions, forming a heptanuclear cluster, [Sm 7 (μ 3 -OH) 8 ] 13+ , and the adjacent [Sm 7 (μ 3 -OH) 8 ] 13+ clusters are linked by the carboxylic groups of bpdc 2- ligands, leading to the formation of a one-dimensional triple right-handed helical chain. The adjacent triple right-handed helical chains are further joined together by coordinating the pyridyl N atoms of the bpdc 2- ligands with Ag + , resulting in a chiral three-dimensional silver(I)-lanthanide(III) heterometal-organic framework with one-dimensional channels wherein NO 3 - anions and crystal lattice H 2 O molecules are trapped. The compounds were studied systematically with respect to their photoluminescence properties and energy-transfer mechanism, and it was found that H 2 bpdc (the energy level for the triplet states of the ligand H 2 bpdc is 21505 cm -1 ) can sensitize Eu 3+ luminescence more effectively than Tb 3+ and Sm 3+ luminescence because of effective energy transfer from bpdc 2- to Eu 3+ under excitation in compound 1.

[((H)L)2Fe6(NCMe)m]n+ (m = 0, 2, 4, 6; n = -1, 0, 1, 2, 3, 4, 6): an electron-transfer series featuring octahedral Fe6 clusters supported by a hexaamide ligand platform.

PubMed

Zhao, Qinliang; Harris, T David; Betley, Theodore A

2011-06-01

Using a trinucleating hexaamide ligand platform, the all-ferrous hexanuclear cluster ((H)L)(2)Fe(6) (1) is obtained from reaction of 3 equiv of Fe(2)(Mes)(4) (Mes = 2,4,6-Me(3)C(6)H(2)) with 2 equiv of the ligand ((H)L)H(6). Compound 1 was characterized by X-ray diffraction analysis, (57)Fe Mössbauer, SQUID magnetometry, mass spectrometry, and combustion analysis, providing evidence for an S=6 ground state and delocalized electronic structure. The cyclic voltammogram of [((H)L)(2)Fe(6)](n+) in acetonitrile reveals a rich redox chemistry, featuring five fully reversible redox events that span six oxidation states ([((H)L)(2)Fe(6)](n+), where n=-1→4) within a 1.3 V potential range. Accordingly, each of these species is readily accessed chemically to provide the electron-transfer series [((H)L)(2)Fe(6)(NCMe)(m)][PF(6)](n) (m=0, n=-1 (2); m=2, n=1 (3); m=4, n=2 (4); m=6, n=3 (5); m=6, n=4 (6)). Compounds 2-6 were isolated and characterized by X-ray diffraction, (57)Fe Mössbauer and multinuclear NMR spectroscopy, and combustion analysis. Two-electron oxidation of the tetracationic cluster in 6 by 2 equiv of [NO](+) generates the thermally unstable hexacationic cluster [((H)L)(2)Fe(6)(NCMe)(m)](6+), which is characterized by NMR and (57)Fe Mössbauer spectroscopy. Importantly, several stepwise systematic metrical changes accompany oxidation state changes to the [Fe(6)] core, namely trans ligation of solvent molecules and variation in Mössbauer spectra, spin ground state, and intracluster Fe-Fe separation. The observed metrical changes are rationalized by considering a qualitative, delocalized molecular orbital description, which provides a set of frontier orbitals populated by Fe 3d electrons. © 2011 American Chemical Society

Cell-targeted platinum nanoparticles and nanoparticle clusters.

PubMed

Papst, Stefanie; Brimble, Margaret A; Evans, Clive W; Verdon, Daniel J; Feisst, Vaughan; Dunbar, P Rod; Tilley, Richard D; Williams, David E

2015-06-21

Herein, we report the facile preparation of cell-targeted platinum nanoparticles (PtNPs), through the design of peptides that, as a single molecule added in small concentration during the synthesis, control the size of PtNP clusters during their growth, stabilise the PtNPs in aqueous suspension and enable the functionalisation of the PtNPs with a versatile range of cell-targeting ligands. Water-soluble PtNPs targeted respectively at blood group antigens and at integrin receptors are demonstrated.

Dual effects of water vapor on ceria-supported gold clusters.

PubMed

Li, Zhimin; Li, Weili; Abroshan, Hadi; Ge, Qingjie; Li, Gao; Jin, Rongchao

2018-04-05

Atomically precise nanocatalysts are currently being intensely pursued in catalysis research. Such nanocatalysts can serve as model catalysts for gaining fundamental insights into catalytic processes. In this work we report a discovery that water vapor provokes the mild removal of surface long-chain ligands on 25-atom Au25(SC12H25)18 nanoclusters in a controlled manner. Using the resultant Au25(SC12H25)18-x/CeO2 catalyst and CO oxidation as a probe reaction, we found that the catalytic activity of cluster/CeO2 is enhanced from nearly zero conversion of CO (in the absence of water) to 96.2% (in the presence of 2.3 vol% H2O) at the same temperature (100 °C). The cluster catalysts exhibit high stability during the CO oxidation process under moisture conditions (up to 20 vol% water vapor). Water vapor plays a dual role in gold cluster-catalyzed CO oxidation. FT-IR and XPS analyses in combination with density functional theory (DFT) simulations suggest that the "-SC12H25" ligands are easier to be removed under a water vapor atmosphere, thus generating highly active sites. Moreover, the O22- peroxide species constitutes the active oxygen species in CO oxidation, evidenced by Raman spectroscopy analysis and isotope experiments on the CeO2 and cluster/CeO2. The results also indicate the perimeter sites of the interface of Au25(SC12H25)18-x/CeO2 to be active sites for catalytic CO oxidation. The controlled exposure of active sites under mild conditions is of critical importance for the utilization of clusters in catalysis.

Oxygen-Centered Hexatantalum Tetradecaimido Cluster Complexes

PubMed Central

Krinsky, Jamin L.; Anderson, Laura L.; Arnold, John; Bergman, Robert G.

2008-01-01

The syntheses and characterization of several octahedral hexatantalum cluster compounds of formula (ArN)14Ta6O are described (Ar = Ph, p-MeC6H4, p-MeOC6H4, p-t-BuC6H4, p-BrC6H4, m-ClC6H4). Treatment of Bn3Ta=N-t-Bu (Bn = CH2C6H5) or pentakis(dimethylamido)tantalum with an excess of the appropriate aniline and stoichiometric water or tantalum oxide afforded varying yields of arylimido clusters. The structures of two species were confirmed by X-ray diffraction (XRD), while the identity of the central oxygen atom was elucidated by electrospray mass spectrometry (MS) using 17O/18O-enriched material. The title species are very air- and moisture-sensitive but quite thermally stable in solution. Experimentally determined optical properties and oxidation/reduction potentials, as well as some computational results, indicate that they possess an electronic structure wherein the highest occupied molecular orbitals are ligand-centered, while the lowest unoccupied orbitals are metal-centered and delocalized throughout the tantalum cage. Whereas chemical oxidation resulted in cluster decomposition, reduction with decamethylcobaltocene yielded stable salts of formula [Cp*2Co][(ArN)14Ta6O] (Ar = Ph, Ar = p-MeC6H4). Small-molecule reactivity studies on one of these clusters showed that its imido functionalities are moderately reactive toward oxide donors but inert with respect to metallaheterocycle-forming processes. Clean imido/oxo exchange was observed with aldehydes and ketones, leading cleanly to organic imines with no soluble byproducts being observed. This exchange was also observed with a rhenium oxo compound (generating an imidorhenium complex as the only soluble species). All 14 imido groups were transferred in these reactions, and no mixed-ligand cluster intermediates were ever observed. PMID:18163614

Metal–organic frameworks assembled from lanthanide and 2,5-pyridinedicaboxylate with cubane-like [Ln{sub 4}(OH){sub 4}] building units

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abdelbaky, Mohammed S.M.; Amghouz, Zakariae, E-mail: amghouz.uo@uniovi.es; Servicios Científico-Técnicos, University of Oviedo—CINN, Oviedo 33006

Lanthanide–organic frameworks based on 2,5-pyridinedicaboxylate (25p) ligand, formulated as [Yb{sub 4}(OH){sub 4}(25p){sub 4}(H{sub 2}O){sub 3}]·H{sub 2}O (25pYb), [Y{sub 4}(OH){sub 4}(25p){sub 4}(H{sub 2}O){sub 3}]·H{sub 2}O (25pY-1) and [Y{sub 6}(OH){sub 8}(25p){sub 5}(H{sub 2}O){sub 2}] (25pY-2), have been obtained as single phases under hydrothermal conditions. 25pYb and 25pY-1 are isostructural, and crystallize in the triclinic space group, P-1, with a=8.6075(5) Å, b=14.8478(7) Å, c=15.9164(9) Å, α=86.277(4)°, β=80.196(5)°, γ=81.785(4)°, and a=8.7166(6) Å, b=14.966(1) Å, c=15.966(1) Å, α=86.260(6)°, β=80.036(6)°, γ=81.599(6)°, respectively. 25pY-2 crystallizes in the monoclinic space group, P2{sub 1}/c, with a=24.9117(17) Å, b=13.7340(8) Å, c=14.3385(10) Å, β=100.551(7)°. 25pYb and 25pY-2 have been structurally characterizedmore » by single-crystal X-ray diffraction. The 25pYb structure is based on tetranuclear cubane-like [Yb{sub 4}(OH){sub 4}]{sup 8+} clusters, which are interconnected to eight neighbouring clusters through teen surrounding 25p ligands leading to neutral 3D framework, while the structure of 25pY-2 is based on two independent cuban-like [Y{sub 4}(OH){sub 4}]{sup 8+} clusters, which are joined together through Y1 cation leading to the formation of hexanuclear [Y{sub 6}(OH){sub 8}]{sup 10+} clusters, which in turn are joined via Y2 cation resulting in infinite inorganic chain extending along c-axis, and each chain is interconnected to six adjacent chains through 25p ligands leading finally to 3D framework. The luminescence properties of Eu{sup 3+} and Tb{sup 3+} doped 25pY-1 and 25pY-2 compounds have also been investigated. All materials has been characterized by powder X-ray diffraction, thermal analyses (TG–SDTA–MS), FTIR spectroscopy, C–H–N elemental analysis, scanning electron microscopy (SEM-EDX), and powder X-ray thermodiffraction. - Graphical abstract: Nowadays, lanthanide–organic frameworks (LOFs) attract tremendous attention due to the unique characteristic of lanthanide cations, such as variable coordination numbers and geometries which often lead to novel complex structures, and also to their magnetic and photoluminescence properties. Herein, three LOFs formulated as [Ln{sub 4}(OH){sub 4}(25p){sub 4}(H{sub 2}O){sub 3}]·H{sub 2}O (Ln=Y, Yb) and [Y{sub 6}(OH){sub 8}(25p){sub 5}(H{sub 2}O){sub 2}] have been obtained by hydrothermal method and characterized, and the photoluminescence properties of the Eu and Tb doped compounds are discussed. - Highlights: • Three novel LnOFs has been synthesized and characterized. • Crystal structures are based on tetranuclear cuban-like [Ln{sub 4}(OH){sub 4}]{sup 8+} clusters. • 25pYb and 25pY-1 are based on isolated [Ln{sub 4}(OH){sub 4}]{sup 8+} clusters. • 25pY-2 is based on infinite inorganic chains built up from [Y{sub 4}(OH){sub 4}]{sup 8+} clusters. • Photoluminescence studies show strong red and green light emissions.« less

Stabilizing ultrasmall Au clusters for enhanced photoredox catalysis.

PubMed

Weng, Bo; Lu, Kang-Qiang; Tang, Zichao; Chen, Hao Ming; Xu, Yi-Jun

2018-04-18

Recently, loading ligand-protected gold (Au) clusters as visible light photosensitizers onto various supports for photoredox catalysis has attracted considerable attention. However, the efficient control of long-term photostability of Au clusters on the metal-support interface remains challenging. Herein, we report a simple and efficient method for enhancing the photostability of glutathione-protected Au clusters (Au GSH clusters) loaded on the surface of SiO 2 sphere by utilizing multifunctional branched poly-ethylenimine (BPEI) as a surface charge modifying, reducing and stabilizing agent. The sequential coating of thickness controlled TiO 2 shells can further significantly improve the photocatalytic efficiency, while such structurally designed core-shell SiO 2 -Au GSH clusters-BPEI@TiO 2 composites maintain high photostability during longtime light illumination conditions. This joint strategy via interfacial modification and composition engineering provides a facile guideline for stabilizing ultrasmall Au clusters and rational design of Au clusters-based composites with improved activity toward targeting applications in photoredox catalysis.

Cleavage of Sn-C and S-C(alkyl) bonds on an organotin scaffold: synthesis and characterization of a novel organotin-sulfite cluster bearing methyltin- and dimethyltin fragments.

PubMed

Shankar, Ravi; Jain, Archana; Kociok-Köhn, Gabriele; Mahon, Mary F; Molloy, Kieran C

2010-05-17

Hydrolysis of the mixed-ligand dimethyltin(ethoxy)ethanesulfonate, [Me(2)Sn(OEt)(OSO(2)Et)](n) (1a) in moist hexane proceeds via disproportionation and partial cleavage of Sn-C and S-C bonds to afford a novel oxo-/hydroxo- organotin cluster of the composition [(Me(2)Sn)(MeSn)(4)(OSO(2)Et)(2)(OH)(4)(O)(2)(SO(3))(2)] (1) bearing both mono- and dimethyltin fragments and in situ generated sulfite (SO(3)(2-)) anion in the structural framework. On the other hand, similar reactions with analogous mixed ligand diorganotin precursors, [R(2)Sn(OR(1))(OSO(2)R(1))](n) (R = n-Bu, R(1) = Et (2a); R = Et, R(1) = Me (3a)), result in the formation of tetranuclear diorganotin clusters, [{(n-Bu(2)Sn)(2)(OH)(OSO(2)Et)}O](2) (2) and [(Et(2)Sn)(4)(OH)(O)(2)(OSO(2)Me)(3)] (3), respectively. The activation of the Sn-C or S-C bond is not observed in these cases. These findings provide a preliminary insight into the unusual reactivity of 1a under hydrolytic conditions.

Apoptosis of Trypanosoma musculi co-cultured with LPS activated macrophages: enhanced expression of nitric oxide synthase INF-gamma and caspase.

PubMed

Gugssa, A; Gebru, S; Lee, C M; Baccetti, B; Anderson, W

2005-08-01

Trypanosoma musculi-macrophage co-cultures were studied to investigate the biological role of lipopolysaccharide (LPS) induced cytokines in controlling the proliferation of parasites in vitro. Macrophages, isolated by peritoneal lavage, sustained the growth and proliferation of the parasites. Macrophages activated with LPS were characterized by up-regulation of nitric oxide synthase (iNOS) and phagocytosis of fluorescent latex spheres. Activated macrophages showed marked inhibition of the association and proliferation of the parasites. The LPS treated macrophages produced cytokines, especially interferon gamma (INF-gamma), which was detected by Western blot. Trypanosomes, inhibited from association with macrophages, did not proliferate and instead formed clusters held together by their flagella. Cells in these clusters were apoptotic, as demonstrated by the Apoptag reaction and gel fragmentation assay. In addition, high levels of caspase 8 and caspase 3 were shown in floating trypanosome clusters. The results would suggest that INF-gamma and other cytokines released by activated macrophages, possibly functioning through the INF-gammaR1, Fas ligand, CD95 or other death ligands in the trypanosome plasma membrane initiates the apoptosis cascade in trypanosomes.

MOLA: a bootable, self-configuring system for virtual screening using AutoDock4/Vina on computer clusters.

PubMed

Abreu, Rui Mv; Froufe, Hugo Jc; Queiroz, Maria João Rp; Ferreira, Isabel Cfr

2010-10-28

Virtual screening of small molecules using molecular docking has become an important tool in drug discovery. However, large scale virtual screening is time demanding and usually requires dedicated computer clusters. There are a number of software tools that perform virtual screening using AutoDock4 but they require access to dedicated Linux computer clusters. Also no software is available for performing virtual screening with Vina using computer clusters. In this paper we present MOLA, an easy-to-use graphical user interface tool that automates parallel virtual screening using AutoDock4 and/or Vina in bootable non-dedicated computer clusters. MOLA automates several tasks including: ligand preparation, parallel AutoDock4/Vina jobs distribution and result analysis. When the virtual screening project finishes, an open-office spreadsheet file opens with the ligands ranked by binding energy and distance to the active site. All results files can automatically be recorded on an USB-flash drive or on the hard-disk drive using VirtualBox. MOLA works inside a customized Live CD GNU/Linux operating system, developed by us, that bypass the original operating system installed on the computers used in the cluster. This operating system boots from a CD on the master node and then clusters other computers as slave nodes via ethernet connections. MOLA is an ideal virtual screening tool for non-experienced users, with a limited number of multi-platform heterogeneous computers available and no access to dedicated Linux computer clusters. When a virtual screening project finishes, the computers can just be restarted to their original operating system. The originality of MOLA lies on the fact that, any platform-independent computer available can he added to the cluster, without ever using the computer hard-disk drive and without interfering with the installed operating system. With a cluster of 10 processors, and a potential maximum speed-up of 10x, the parallel algorithm of MOLA performed with a speed-up of 8,64× using AutoDock4 and 8,60× using Vina.

Periodic trends in hexanuclear actinide clusters.

PubMed

Diwu, Juan; Wang, Shuao; Albrecht-Schmitt, Thomas E

2012-04-02

Four new Th(IV), U(IV), and Np(IV) hexanuclear clusters with 1,2-phenylenediphosphonate as the bridging ligand have been prepared by self-assembly at room temperature. The structures of Th(6)Tl(3)[C(6)H(4)(PO(3))(PO(3)H)](6)(NO(3))(7)(H(2)O)(6)·(NO(3))(2)·4H(2)O (Th6-3), (NH(4))(8.11)Np(12)Rb(3.89)[C(6)H(4)(PO(3))(PO(3)H)](12)(NO(3))(24)·15H(2)O (Np6-1), (NH(4))(4)U(12)Cs(8)[C(6)H(4)(PO(3))(PO(3)H)](12)(NO(3))(24)·18H(2)O (U6-1), and (NH(4))(4)U(12)Cs(2)[C(6)H(4)(PO(3))(PO(3)H)](12)(NO(3))(18)·40H(2)O (U6-2) are described and compared with other clusters of containing An(IV) or Ce(IV). All of the clusters share the common formula M(6)(H(2)O)(m)[C(6)H(3)(PO(3))(PO(3)H)](6)(NO(3))(n)((6-n)) (M = Ce, Th, U, Np, Pu). The metal centers are normally nine-coordinate, with five oxygen atoms from the ligand and an additional four either occupied by NO(3)(-) or H(2)O. It was found that the Ce, U, and Pu clusters favor both C(3i) and C(i) point groups, while Th only yields in C(i), and Np only C(3i). In the C(3i) clusters, there are two NO(3)(-) anions bonded to the metal centers. In the C(i) clusters, the number of NO(3)(-) anions varies from 0 to 2. The change in the ionic radius of the actinide ions tunes the cavity size of the clusters. The thorium clusters were found to accept larger ions including Cs(+) and Tl(+), whereas with uranium and later elements, only NH(4)(+) and/or Rb(+) reside in the center of the clusters.

The effect of ligand affinity on integrins' lateral diffusion in cultured cells.

PubMed

Mainali, Dipak; Smith, Emily A

2013-04-01

The role of ligand affinity in altering αPS2CβPS integrins' lateral mobility was studied using single particle tracking (SPT) with ligand-functionalized quantum dots (QDs) and fluorescence recovery after photobleaching (FRAP) with fluorescent protein tagged integrins. Integrins are ubiquitous transmembrane proteins that are vital for numerous cellular functions, including bidirectional signaling and cell anchorage. Wild-type and high ligand affinity mutant (αPS2CβPS-V409D) integrins were studied in S2 cells. As measured by SPT, the integrin mobile fraction decreased by 22% and had a 4× slower diffusion coefficient for αPS2CβPS-V409D compared to wild-type integrins. These differences are partially the result of αPS2CβPS-V409D integrins' increased clustering. For the wild-type integrins, the average of all diffusion coefficients measured by SPT was statistically similar to the ensemble FRAP results. A 75% slower average diffusion coefficient was measured by SPT compared to FRAP for αPS2CβPS-V409D integrins, and this may be the result of SPT measuring only ligand-bound integrins, in contrast all ligand-bound and ligand-unbound integrins are averaged in FRAP measurements. Specific binding of the ligand-functionalized QDs was 99% for integrin expressing cells. The results prove that the ligand binding affinity affects the lateral dynamics of a subset of integrins based on the complementary SPT and FRAP data.

Supramolecular architectures in Co(II) and Cu(II) complexes with thiophene-2-carboxylate and 2-amino-4,6-dimethoxypyrimidine ligands.

PubMed

Karthikeyan, Ammasai; Thomas Muthiah, Packianathan; Perdih, Franc

2016-05-01

The coordination chemistry of mixed-ligand complexes continues to be an active area of research since these compounds have a wide range of applications. Many coordination polymers and metal-organic framworks are emerging as novel functional materials. Aminopyrimidine and its derivatives are flexible ligands with versatile binding and coordination modes which have been proven to be useful in the construction of organic-inorganic hybrid materials and coordination polymers. Thiophenecarboxylic acid, its derivatives and their complexes exhibit pharmacological properties. Cobalt(II) and copper(II) complexes of thiophenecarboxylate have many biological applications, for example, as antifungal and antitumor agents. Two new cobalt(II) and copper(II) complexes incorporating thiophene-2-carboxylate (2-TPC) and 2-amino-4,6-dimethoxypyrimidine (OMP) ligands have been synthesized and characterized by X-ray diffraction studies, namely (2-amino-4,6-dimethoxypyrimidine-κN)aquachlorido(thiophene-2-carboxylato-κO)cobalt(II) monohydrate, [Co(C5H3O2S)Cl(C6H9N3O2)(H2O)]·H2O, (I), and catena-poly[copper(II)-tetrakis(μ-thiophene-2-carboxylato-κ(2)O:O')-copper(II)-(μ-2-amino-4,6-dimethoxypyrimidine-κ(2)N(1):N(3))], [Cu2(C5H3O2S)4(C6H9N3O2)]n, (II). In (I), the Co(II) ion has a distorted tetrahedral coordination environment involving one O atom from a monodentate 2-TPC ligand, one N atom from an OMP ligand, one chloride ligand and one O atom of a water molecule. An additional water molecule is present in the asymmetric unit. The amino group of the coordinated OMP molecule and the coordinated carboxylate O atom of the 2-TPC ligand form an interligand N-H...O hydrogen bond, generating an S(6) ring motif. The pyrimidine molecules also form a base pair [R2(2)(8) motif] via a pair of N-H...N hydrogen bonds. These interactions, together with O-H...O and O-H...Cl hydrogen bonds and π-π stacking interactions, generate a three-dimensional supramolecular architecture. The one-dimensional coordination polymer (II) contains the classical paddle-wheel [Cu2(CH3COO)4(H2O)2] unit, where each carboxylate group of four 2-TPC ligands bridges two square-pyramidally coordinated Cu(II) ions and the apically coordinated OMP ligands bridge the dinuclear copper units. Each dinuclear copper unit has a crystallographic inversion centre, whereas the bridging OMP ligand has crystallographic twofold symmetry. The one-dimensional polymeric chains self-assemble via N-H...O, π-π and C-H...π interactions, generating a three-dimensional supramolecular architecture.

Elucidation of neurophysin/bioligand interactions from molecular modeling.

PubMed

Kaźmierkiewicz, R; Czaplewski, C; Ciarkowski, J

1997-01-01

This is a review of our recent modeling work aimed at: (i) development and assessment of techniques for reliable refinement of low-resolution protein structures and (ii) using these techniques, at solving specific problems pertinent to neurophysin-bioligand interactions. Neurophysins I and II (NPI and NPII) serve in the neurosecretory granules of the posterior pituitary as carrier proteins for the neurophyseal hormones oxytocin (OT) and vasopressin (VP), respectively, until the latter are released into blood. NPs are homologous two-domain, sulphur rich small proteins (93-95 residues, 7 disulphide bridges per monomer), capable of being aggregated. The C2 symmetrical NPI2 and NPII2 homodimers, and the (NPI/OT)2 and (NPII/VP)2 heterotetramers, all believed to be the smallest functional units, were modeled using low-resolution structure information, i.e. the C alpha-carbon coordinates of the homologous NPII/dipeptide complex as a template. The all-atom representations of the models were obtained using the SYBYL suite of programs (by Tripos, Inc.). Subsequently, they were relaxed, using a constrained simulated annealing (CSA) protocol, and submitted to about 100 ps molecular dynamics (MD) in water, using the AMBER 4.1 force field. The (NPI/OT)2 and (NPII/VP)2 structures, averaged after the last 20 ps of MD, were remarkably similar to those recently reported either for NPII/dipeptide or NPII/oxytocin complex in the solid state (Chen et al., 1991, Proc. Natl. Acad. Sci., U.S.A. 88, 4240-4244; Rose et al., 1996, Nature Struct. Biol. 3, 163-169). The results indicate that the 3(10) helices (terminating the amino domains) and the carboxyl domains are more mobile than the remainder of the NP monomers. The hormones become anchored by residues 1-3 and 6 to the host, leaving residues 4-5 and 7-9 exposed on the surface and free to move. A cluster of attractive interactions, extending from the ligand binding site, Tyr-24-Ile-26 of unit 1(2), to the inter-monomer interface Val-36 of unit 1(2), Cys-79 and Ile-72 of unit 2(1), is clearly seen. We suggest that both these interactions as well as the increased mobility of the 3(10) helix and the carboxyl domain may contribute to the allosteric communication between the ligand and the unit1-unit2 interface.

Protein flexibility and conformational entropy in ligand design targeting the carbohydrate recognition domain of galectin-3.

PubMed

Diehl, Carl; Engström, Olof; Delaine, Tamara; Håkansson, Maria; Genheden, Samuel; Modig, Kristofer; Leffler, Hakon; Ryde, Ulf; Nilsson, Ulf J; Akke, Mikael

2010-10-20

Rational drug design is predicated on knowledge of the three-dimensional structure of the protein-ligand complex and the thermodynamics of ligand binding. Despite the fundamental importance of both enthalpy and entropy in driving ligand binding, the role of conformational entropy is rarely addressed in drug design. In this work, we have probed the conformational entropy and its relative contribution to the free energy of ligand binding to the carbohydrate recognition domain of galectin-3. Using a combination of NMR spectroscopy, isothermal titration calorimetry, and X-ray crystallography, we characterized the binding of three ligands with dissociation constants ranging over 2 orders of magnitude. (15)N and (2)H spin relaxation measurements showed that the protein backbone and side chains respond to ligand binding by increased conformational fluctuations, on average, that differ among the three ligand-bound states. Variability in the response to ligand binding is prominent in the hydrophobic core, where a distal cluster of methyl groups becomes more rigid, whereas methyl groups closer to the binding site become more flexible. The results reveal an intricate interplay between structure and conformational fluctuations in the different complexes that fine-tunes the affinity. The estimated change in conformational entropy is comparable in magnitude to the binding enthalpy, demonstrating that it contributes favorably and significantly to ligand binding. We speculate that the relatively weak inherent protein-carbohydrate interactions and limited hydrophobic effect associated with oligosaccharide binding might have exerted evolutionary pressure on carbohydrate-binding proteins to increase the affinity by means of conformational entropy.

CHEMINFORMATICS TOOLS FOR TOXICANT CHARACTERIZATION

EPA Science Inventory

• Continued development of the Shape Signatures method is planed.  This effort will include further development of the Shape Signatures database of PDB-extracted ligands and of the clustering algorithm.

• In addition, we plan to develop an...

• Structure of fluorescent metal clusters on a DNA template.

  NASA Astrophysics Data System (ADS)

  Vdovichev, A. A.; Sych, T. S.; Reveguk, Z. V.; Smirnova, A. A.; Maksimov, D. A.; Ramazanov, R. R.; Kononov, A. I.

  2016-08-01

  Luminescent metal clusters are a subject of growing interest in recent years due to their bright emission from visible to near infrared range. Detailed structure of the fluorescent complexes of Ag and other metal clusters with ligands still remains a challenging task. In this joint experimental and theoretical study we synthesized Ag-DNA complexes on a DNA oligonucleotide emitting in violet- green spectral range. The structure of DNA template was determined by means of various spectral measurements (CD, MS, XPS). Comparison of the experimental fluorescent excitation spectra and calculated absorption spectra for different QM/MM optimized structures allowed us to determine the detailed structure of the green cluster containing three silver atoms in the stem of the DNA hairpin structure stabilized by cytosine-Ag+-cytosine bonds.

• Ligand.Info small-molecule Meta-Database.

  PubMed

  von Grotthuss, Marcin; Koczyk, Grzegorz; Pas, Jakub; Wyrwicz, Lucjan S; Rychlewski, Leszek

  2004-12-01

  Ligand.Info is a compilation of various publicly available databases of small molecules. The total size of the Meta-Database is over 1 million entries. The compound records contain calculated three-dimensional coordinates and sometimes information about biological activity. Some molecules have information about FDA drug approving status or about anti-HIV activity. Meta-Database can be downloaded from the http://Ligand.Info web page. The database can also be screened using a Java-based tool. The tool can interactively cluster sets of molecules on the user side and automatically download similar molecules from the server. The application requires the Java Runtime Environment 1.4 or higher, which can be automatically downloaded from Sun Microsystems or Apple Computer and installed during the first use of Ligand.Info on desktop systems, which support Java (Ms Windows, Mac OS, Solaris, and Linux). The Ligand.Info Meta-Database can be used for virtual high-throughput screening of new potential drugs. Presented examples showed that using a known antiviral drug as query the system was able to find others antiviral drugs and inhibitors.

• Dual-Emitting UiO-66(Zr&Eu) Metal-Organic Framework Films for Ratiometric Temperature Sensing.

  PubMed

  Feng, Ji-Fei; Liu, Tian-Fu; Shi, Jianlin; Gao, Shui-Ying; Cao, Rong

  2018-06-20

  A novel dual-emitting metal-organic framework based on Zr and Eu, named as UiO-66(Zr&Eu), was built using a clever strategy based on secondary building units. With the use of polymers, the obtained UiO-66(Zr&Eu) was subsequently deposited as thin films that can be utilized as smart thermometers. The UiO-66(Zr&Eu) polymer films can be used for the detection of temperature changes in the range of 237-337 K due to the energy transfer between the lanthanide ions (Eu in clusters) and the luminescent ligands, and the relative sensitivity reaches 4.26% K -1 at 337 K. Moreover, the sensitivity can be improved to 19.67% K -1 by changing the film thickness. In addition, the temperature-sensing performance of the films is superior to that of the powders, and the sensor can be reused 3 times without loss of performance.

Structure of choline oxidase in complex with the reaction product glycine betaine.

PubMed

Salvi, Francesca; Wang, Yuan-Fang; Weber, Irene T; Gadda, Giovanni

2014-02-01

Choline oxidase from Arthrobacter globiformis, which is involved in the biosynthesis of glycine betaine from choline, has been extensively characterized in its mechanistic and structural properties. Despite the knowledge gained on the enzyme, the details of substrate access to the active site are not fully understood. The `loop-and-lid' mechanism described for the glucose-methanol-choline enzyme superfamily has not been confirmed for choline oxidase. Instead, a hydrophobic cluster on the solvent-accessible surface of the enzyme has been proposed by molecular dynamics to control substrate access to the active site. Here, the crystal structure of the enzyme was solved in complex with glycine betaine at pH 6.0 at 1.95 Å resolution, allowing a structural description of the ligand-enzyme interactions in the active site. This structure is the first of choline oxidase in complex with a physiologically relevant ligand. The protein structures with and without ligand are virtually identical, with the exception of a loop at the dimer interface, which assumes two distinct conformations. The different conformations of loop 250-255 define different accessibilities of the proposed active-site entrance delimited by the hydrophobic cluster on the other subunit of the dimer, suggesting a role in regulating substrate access to the active site.

75 FR 16424 - Proposed Information Collection; Comment Request; Census Coverage Measurement Final Housing Unit...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-01

... unit is a block cluster, which consists of one or more geographically contiguous census blocks. As in... a number of distinct processes, ranging from forming block clusters, selecting the block clusters... sample of block clusters, while the E Sample is the census of housing units and enumerations in the same...

New ligand platforms featuring boron-rich clusters as organomimetic substituents*,**

PubMed Central

Spokoyny, Alexander M.

2013-01-01

200 years of research with carbon-rich molecules have shaped the development of modern chemistry. Research pertaining to the chemistry of boron-rich species has historically trailed behind its more distinguished neighbor (carbon) in the periodic table. Notably, a potentially rich and, in many cases, unmatched field of coordination chemistry using boronrich clusters remains fundamentally underdeveloped. Our work has been devoted to examining several basic concepts related to the functionalization of icosahedral boron-rich clusters and their use as ligands, aimed at designing fundamentally new hybrid molecular motifs and materials. Particularly interesting are icosahedral carboranes, which can be regarded as 3D analogs of benzene. These species comprise a class of boron-rich clusters that were discovered in the 1950s during the “space race” while researchers were developing energetic materials for rocket fuels. Ultimately, the unique chemical and physical properties of carborane species, such as rigidity, indefinite stability to air and moisture, and 3D aromaticity, may allow one to access a set of properties not normally available in carbon-based chemistry. While technically these species are considered as inorganic clusters, the chemical properties they possess make these boron-rich species suitable for replacing and/or altering structural and functional features of the organic and organometallic molecules—a phenomenon best described as “organomimetic”. Aside from purely fundamental features associated with the organomimetic chemistry of icosahedral carboranes, their use can also provide new avenues in the development of systems relevant to solving current problems associated with energy production, storage, and conversion. PMID:24311823

A neodymium(III)-ammonium complex involving oxalate and carbonate ligands: (NH4)2[Nd2(C2O4)3(CO3)(H2O)].H2O.

PubMed

Trombe, Jean-Christian; Galy, Jean; Enjalbert, Renée

2002-10-01

The title compound, diammonium aqua-mu-carbonato-tri-mu-oxalato-dineodymium(III) hydrate, (NH(4))(2)[Nd(2)(CO(3))(C(2)O(4))(3)(H(2)O)].H(2)O, involving the two ligands oxalate and carbonate, has been prepared hydrothermally as single crystals. The Nd atoms form a tetranuclear unit across the inversion centre at (1/2, 1/2, 1/2). Starting from this tetranuclear unit, the oxalate ligands serve to develop a three-dimensional network. The carbonate group acts as a bis-chelating ligand to two Nd atoms, and is monodentate to a third Nd atom. The oxalate groups are all bis-chelating. The two independent Nd atoms are ninefold coordinated and the coordination polyhedron of these atoms is a distorted monocapped antiprism.

Windmill Co4 {Co4 (μ4 -O)} with 16 Divergent Branches Forming a Family of Metal-Organic Frameworks: Organic Metrics Control Topology, Gas Sorption, and Magnetism.

PubMed

Chen, Qing; Xue, Wei; Lin, Jian-Bin; Wei, Yong-Sheng; Yin, Zheng; Zeng, Ming-Hua; Kurmoo, Mohamedally; Chen, Xiao-Ming

2016-08-16

A series of highly connected metal-organic frameworks (MOFs), [Co8 (O)(OH)4 (H2 O)4 (ina)8 ](NO3 )2 ⋅2 C2 H5 OH⋅4 H2 O (1), [Co8 (O)(OH)4 (H2 O)4 (pba)8 ](NO3 )2 ⋅8 C2 H5 OH⋅28 H2 O (2), and [Co8 (O)(OH)4 (H2 O)4 (pbba)8 ](NO3 )2 ⋅guest (3), in which ina=isonicotinate, pba=4-pyridylbenzoate, and pbba=4-(pyridine-4-yl)phenylbenzoate, is reported. These MOFs contain a new secondary building unit (SBU), with a square Co4 (μ4 -O) central unit having the rare μ4 -O(2-) motif, which is decorated by the other four peripheral cobalt atoms through μ3 -OH in a windmill-like shape. This SBU holds 16 divergent connecting organic ligands, pyridyl-carboxylates, to form three different frameworks. The high porosity of desolvated 2 is shown by the efficient gas absorption of N2 , CO2 , CH4 , and H2 . In addition, 1 and 2 exhibit unusual canted antiferromagnetic behavior with spin-glass-like relaxation, with blocking temperatures that are fairly high, 20 K (1) and 10 K (2), for cobalt materials. The relationship between the metal clusters and linkers has been studied, in which the size and rotational degrees of freedom of the ligands are found to control the topology, gas sorption, and magnetic properties. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Automated docking of ligands to an artificial active site: augmenting crystallographic analysis with computer modeling

NASA Astrophysics Data System (ADS)

Rosenfeld, Robin J.; Goodsell, David S.; Musah, Rabi A.; Morris, Garrett M.; Goodin, David B.; Olson, Arthur J.

2003-08-01

The W191G cavity of cytochrome c peroxidase is useful as a model system for introducing small molecule oxidation in an artificially created cavity. A set of small, cyclic, organic cations was previously shown to bind in the buried, solvent-filled pocket created by the W191G mutation. We docked these ligands and a set of non-binders in the W191G cavity using AutoDock 3.0. For the ligands, we compared docking predictions with experimentally determined binding energies and X-ray crystal structure complexes. For the ligands, predicted binding energies differed from measured values by ± 0.8 kcal/mol. For most ligands, the docking simulation clearly predicted a single binding mode that matched the crystallographic binding mode within 1.0 Å RMSD. For 2 ligands, where the docking procedure yielded an ambiguous result, solutions matching the crystallographic result could be obtained by including an additional crystallographically observed water molecule in the protein model. For the remaining 2 ligands, docking indicated multiple binding modes, consistent with the original electron density, suggesting disordered binding of these ligands. Visual inspection of the atomic affinity grid maps used in docking calculations revealed two patches of high affinity for hydrogen bond donating groups. Multiple solutions are predicted as these two sites compete for polar hydrogens in the ligand during the docking simulation. Ligands could be distinguished, to some extent, from non-binders using a combination of two trends: predicted binding energy and level of clustering. In summary, AutoDock 3.0 appears to be useful in predicting key structural and energetic features of ligand binding in the W191G cavity.

Albumin-stabilized fluorescent silver nanodots

NASA Astrophysics Data System (ADS)

Sych, Tomash; Polyanichko, Alexander; Kononov, Alexei

2017-07-01

Ligand-stabilized Ag nanoclusters (NCs) possess many attractive features including high fluorescence quantum yield, large absorption cross-section, good photostability, large Stokes shift and two-photon absorption cross sections. While plenty of fluorescent clusters have been synthesized on various polymer templates, only a few studies have been reported on the fluorescent Ag clusters on peptides and proteins. We study silver NCs synthesized on different protein matrices, including bovine serum albumin, human serum albumin, egg albumin, equine serum albumin, and lysozyme. Our results show that red-emitting Ag NCs can effectively be stabilized by the disulfide bonds in proteins and that the looser structure of the denatured protein favors formation of the clusters.

Giant Spherical Cluster with I-C140 Fullerene Topology**

PubMed Central

Heinl, Sebastian; Peresypkina, Eugenia; Sutter, Jörg; Scheer, Manfred

2015-01-01

We report on an effective cluster expansion of CuBr-linked aggregates by the increase of the steric bulk of the CpR ligand in the pentatopic molecules [CpRFe(η5-P5)]. Using [CpBIGFe(η5-P5)] (CpBIG=C5(4-nBuC6H4)5), the novel multishell aggregate [{CpBIGFe(η5:2:1:1:1:1:1-P5)}12(CuBr)92] is obtained. It shows topological analogy to the theoretically predicted I-C140 fullerene molecule. The spherical cluster was comprehensively characterized by various methods in solution and in the solid state. PMID:26411255

Aqueous Sulfate Separation by Sequestration of [(SO 4) 2(H 2O) 4] 4 Clusters within Highly Insoluble Imine-Linked Bis-Guanidinium Crystals

DOE PAGES

Custelcean, Radu; Williams, Neil J.; Seipp, Charles A.; ...

2015-12-18

Quantitative removal of sulfate from seawater was achieved by selective crystallization of the anion with a bis(guanidinium) ligand self-assembled in situ through imine condensation of simple components. The resulting crystalline salt has an exceptionally low aqueous solubility, on a par with BaSO 4. Single-crystal X-ray diffraction analysis revealed pairs of sulfate anions clustered together with four water molecules within the crystals.

Structure, Bonding and Surface Chemistry of Metal Oxide Nanoclusters

DTIC Science & Technology

2015-06-23

studies to cobalt and chromium oxides and to both oxides and pure metal clusters of aluminum, using acetonitrile as the ligand. The chromium solutions...seen in molecular beam experiments. The cobalt oxide sample produced a blue solution, and mass spectra had a single main peak at 551 amu. Mass...of cobalt and nickel oxide cluster cations," J. Phys. Chem. A 116, 5398-5404 (2012). DOI: 10.1021/jp302560p. 4. A. M. Ricks, A. D. Brathwaite, M

Photocatalytic polyoxometalate compositions of tungstovanadates and uses as water oxidation catalysts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hill, Craig L.; Gueletii, Iourii V.; Song, Jie

This disclosure relates to photocatalytic polyoxometalate compositions of tungstovanadates and uses as water oxidation catalysts. In certain embodiments, the disclosure relates to compositions comprising water, a complex of a tetra-metal oxide cluster and VW.sub.9O.sub.34 ligands, and a photosensitizer. Typically, the metal oxide cluster is Co. In certain embodiments, the disclosure relates to electrodes and other devices comprising water oxidation catalysts disclosed herein and uses in generating fuels and electrical power from solar energy.

Theoretical Study of the H2-ML(+) Binding Energies

NASA Technical Reports Server (NTRS)

Maitre, Philippe; Bauschlicher, Charles W., Jr.

1993-01-01

The cooperative ligand effects are studied in MLH2(+) and the results are compared to the recent experiments of Kemper et al. The bonding in these compounds is principally electrostatic in origin; however, ligand to metal and metal to ligand donations are important, especially for H2. We show that differences arise among the vanadium, cobalt, and copper complexes which are due to 3d donation to H2. Electron correlation is required to describe the dative interaction, and we find that second order Moller-Plesset perturbation theory (MP2) yields a good description of these systems compared with higher levels of correlation (such as the modified coupled pair functional and coupled cluster approaches) and experiment. However, obtaining quantitative results requires higher levels of theory than MP2.

Solution structure of a repeated unit of the ABA-1 nematode polyprotein allergen of Ascaris reveals a novel fold and two discrete lipid-binding sites.

PubMed

Meenan, Nicola A G; Ball, Graeme; Bromek, Krystyna; Uhrín, Dušan; Cooper, Alan; Kennedy, Malcolm W; Smith, Brian O

2011-04-19

Nematode polyprotein allergens (NPAs) are an unusual class of lipid-binding proteins found only in nematodes. They are synthesized as large, tandemly repetitive polyproteins that are post-translationally cleaved into multiple copies of small lipid binding proteins with virtually identical fatty acid and retinol (Vitamin A)-binding characteristics. They are probably central to transport and distribution of small hydrophobic compounds between the tissues of nematodes, and may play key roles in nutrient scavenging, immunomodulation, and IgE antibody-based responses in infection. In some species the repeating units are diverse in amino acid sequence, but, in ascarid and filarial nematodes, many of the units are identical or near-identical. ABA-1A is the most common repeating unit of the NPA of Ascaris suum, and is closely similar to that of Ascaris lumbricoides, the large intestinal roundworm of humans. Immune responses to NPAs have been associated with naturally-acquired resistance to infection in humans, and the immune repertoire to them is under strict genetic control. The solution structure of ABA-1A was determined by protein nuclear magnetic resonance spectroscopy. The protein adopts a novel seven-helical fold comprising a long central helix that participates in two hollow four-helical bundles on either side. Discrete hydrophobic ligand-binding pockets are found in the N-terminal and C-terminal bundles, and the amino acid sidechains affected by ligand (fatty acid) binding were identified. Recombinant ABA-1A contains tightly-bound ligand(s) of bacterial culture origin in one of its binding sites. This is the first mature, post-translationally processed, unit of a naturally-occurring tandemly-repetitive polyprotein to be structurally characterized from any source, and it belongs to a new structural class. NPAs have no counterparts in vertebrates, so represent potential targets for drug or immunological intervention. The nature of the (as yet) unidentified bacterial ligand(s) may be pertinent to this, as will our characterization of the unusual binding sites.

Construction and optical properties of infinite Cd and finite Cu molecules stairs

NASA Astrophysics Data System (ADS)

Zhao, Qiang; Mao, Wutao; Shen, Zhi; Wang, Qinghong; Zhou, Qian

2017-02-01

Two coordination complexes, namely [(hpdq)(pta)Cd]n (1) and [(pptp)(pta)Cu2Cl] (2) have been synthesized by solvothermal method based on two polypyridyl ligands, 2,3,6,7,10,11-hexakis- (2-pyridyl)dipyrazino[2,3-f:2‧,3‧-h]quinoxaline) (hpdq), 4‧-(4- (3H-pyrrol-3-yl)phenyl)- 2,2‧:6‧,2″- terpyridine (pptp) and auxiliary ligand p-phthalic acid (pta), respectively. Single crystal x-ray diffraction analyses reveal that complexes 1 and 2 assembled based on distinct asymmetric unit comprising one and two respective polypyridyl ligands but one Cd(II) and two Cu(I)ions, respectively. Among them, The asymmetric units in 1 was extended to one dimensional chain via the link of auxiliary ligand pta, just like infinite layers of stairs that connected by cadmium ions as the node. While that in 2 to Zero dimensional tetranuclear structure via the link of auxiliary ligand pta, just like finite four layers of stairs that Copper ion as the node connection. Furthermore, solid fluorescence spectra properties of two complexes were also investigated, and the result shows the fluorescence intensity of complex 1 is stronger than that of the hpdq ligand, but the fluorescence intensity of complex 2 is weaker than that of the pptp ligand. CCDC number of 1and 2 are 1483301 and 1483302.

Synthesis and Characterization of Platinum-Ruthenium-Tin Catalysts

NASA Astrophysics Data System (ADS)

Uffalussy, Karen

Magnesia-supported trimetallic Pt-Ru-Sn catalysts prepared through a cluster and a conventional synthetic route have been investigated in terms of their structural properties and their catalytic activity for the hydrogenation of citral and crotonaldehyde. FTIR results indicate that the majority of the stabilizing ligands remain attached to the PtRu5(μ-SnPh 2)(C)(CO)15 cluster used following impregnation onto the MgO support. Under H2 reduction conditions, partial and full ligand removal are both observed at 473 and 573 K, respectively. HRSTEM analysis shows that cluster-derived samples exhibit significantly smaller average metal particle sizes, as well as narrower particle size distributions than the corresponding conventionally prepared ones. EDX measurements show that in the cluster-derived catalysts, the majority of the metal particles present are trimetallic in nature, with metal compositions similar to those of the original cluster. In contrast, the conventionally prepared materials contain mostly bimetallic and monometallic particles with variable compositions. XPS was used to determine how the variation in method of Sn addition to bimetallic Pt-Ru affects the electronic state for the trimetallic Pt-Ru-Sn/MgO system prepared by impregnation using multimetallic clusters, metal-salts, and the combination of both precursor types. Results show that the PtRu5Sn/MgO material has a significantly higher percentage of Sn0 in comparison to Pt-Ru-Sn/MgO and PtRu5-Sn/MgO, and a corresponding shift in both Pt and Ru peaks can be correlated to this relative change in Sn oxidation state. The formation of smaller metal particles and electronic modification of Pt and Ru by Sn in the cluster-derived catalysts and the presence of the three metals in these particles in close proximity result in higher activity and selectivity to the unsaturated alcohols for the hydrogenation of both citral and crotonaldehyde.

Metal-organophosphine and metal-organophosphonium frameworks with layered honeycomb-like structures.

PubMed

Humphrey, Simon M; Allan, Phoebe K; Oungoulian, Shaunt E; Ironside, Matthew S; Wise, Erica R

2009-04-07

Phosphanotriylbenzenecarboxylic acid (ptbcH(3); P(C(6)H(4)-p-CO(2)H)(3)) and its methyl phosphonium iodide derivative (mptbcH(3)I; {H(3)CP(C(6)H(4)-p-CO(2)H)(3)}I) have been used as organic building blocks in reaction with Zn(ii) salts to obtain a series of related two-dimensional coordination polymers with honeycomb-like networks. The variable coordination number and oxidation states available to phosphorus have been exploited to produce a family of related phosphine coordination materials (PCMs) using a single ligand precursor. The phosphine carboxylate trianion, ptbc(3-), reacted with Zn(ii) to form 3,3-connected undulating hexagonal sheets based on tetrahedral P and Zn nodes, where Zn-ptbc = 1 : 1. When hydroxide was used as an additional framework ligand, Zn(4)(OH)(2) clusters were obtained. The clusters support 6,3-connected bilayers that consist of pairs of fused hexagonal sheets (Zn-ptbc = 2 : 1) with intra-layer pore spaces. The Zn(4)(OH)(2) clusters are also coordinated by solvent, which was preferentially displaced when the bilayer material was synthesized in the presence of ethylene diamine. Treatment of ptbc(3-) with MeI resulted in methylation of the phosphine to give the P(v) phosphonium iodide salt derivative. The formally dianionic methylphosphonium tricarboxylate building block, mptbc(2-), has the same trigonal-pyramidal bridging geometry as the parent phosphine. However, mptbc(2-) reacted with Zn(ii) on a 1 : 1 stoichiometric ratio to give an unusual trilayer sheet polymer that is based exclusively on 3-connected nodes. Solid-state (31)P NMR studies confirmed that the phosphine ligands were resistant to oxidation upon solvothermal reaction under aerobic conditions.

Interchain hydrophobic clustering promotes rigidity in HIV-1 protease flap dynamics: new insights from molecular dynamics.

PubMed

Meher, Biswa Ranjan; Kumar, Mattaparthi Venkata Satish; Bandyopadhyay, Pradipta

2014-01-01

The dynamics of HIV-1 protease (HIV-pr), a drug target for HIV infection, has been studied extensively by both computational and experimental methods. The flap dynamics of HIV-pr is considered to be more important for better ligand binding and enzymatic actions. Moreover, it has been demonstrated that the drug-induced mutations can change the flap dynamics of HIV-pr affecting the binding affinity of the ligands. Therefore, detailed understanding of flap dynamics is essential for designing better inhibitors. Previous computational investigations observed significant variation in the flap opening in nanosecond time scale indicating that the dynamics is highly sensitive to the simulation protocols. To understand the sensitivity of the flap dynamics on the force field and simulation protocol, molecular dynamics simulations of HIV-pr have been performed with two different AMBER force fields, ff99 and ff02. Two different trajectories (20 ns each) were obtained using the ff99 and ff02 force field. The results showed polarizable force field (ff02) make the flap tighter than the nonpolarizable force field (ff99). Some polar interactions and hydrogen bonds involving flap residues were found to be stronger with ff02 force field. The formation of interchain hydrophobic cluster (between flap tip of one chain and active site wall of another chain) was found to be dominant in the semi-open structures obtained from the simulations irrespective of the force field. It is proposed that an inhibitor, which will promote this interchain hydrophobic clustering, may make the flaps more rigid, and presumably the effect of mutation would be small on ligand binding.

Three-Dimensional Biologically Relevant Spectrum (BRS-3D): Shape Similarity Profile Based on PDB Ligands as Molecular Descriptors.

PubMed

Hu, Ben; Kuang, Zheng-Kun; Feng, Shi-Yu; Wang, Dong; He, Song-Bing; Kong, De-Xin

2016-11-17

The crystallized ligands in the Protein Data Bank (PDB) can be treated as the inverse shapes of the active sites of corresponding proteins. Therefore, the shape similarity between a molecule and PDB ligands indicated the possibility of the molecule to bind with the targets. In this paper, we proposed a shape similarity profile that can be used as a molecular descriptor for ligand-based virtual screening. First, through three-dimensional (3D) structural clustering, 300 diverse ligands were extracted from the druggable protein-ligand database, sc-PDB. Then, each of the molecules under scrutiny was flexibly superimposed onto the 300 ligands. Superimpositions were scored by shape overlap and property similarity, producing a 300 dimensional similarity array termed the "Three-Dimensional Biologically Relevant Spectrum (BRS-3D)". Finally, quantitative or discriminant models were developed with the 300 dimensional descriptor using machine learning methods (support vector machine). The effectiveness of this approach was evaluated using 42 benchmark data sets from the G protein-coupled receptor (GPCR) ligand library and the GPCR decoy database (GLL/GDD). We compared the performance of BRS-3D with other 2D and 3D state-of-the-art molecular descriptors. The results showed that models built with BRS-3D performed best for most GLL/GDD data sets. We also applied BRS-3D in histone deacetylase 1 inhibitors screening and GPCR subtype selectivity prediction. The advantages and disadvantages of this approach are discussed.

Triazolylidene-Iridium Complexes with a Pendant Pyridyl Group for Cooperative Metal-Ligand Induced Catalytic Dehydrogenation of Amines.

PubMed

Valencia, Marta; Pereira, Ana; Müller-Bunz, Helge; Belderraín, Tomás R; Pérez, Pedro J; Albrecht, Martin

2017-07-03

Two iridium(III) complexes containing a C,N-bidentate pyridyl-triazolylidene ligand were prepared that are structurally very similar but differ in their pendant substituent. Whereas complex 1 contains a non-coordinating pyridyl unit, complex 2 has a phenyl group on the triazolylidene substituent. The presence of the basic pyridyl unit has distinct effects on the catalytic activity of the complex in the oxidative dehydrogenation of benzylic amines, inducing generally higher rates, higher selectivity towards formation of imines versus secondary amines, and notable quantities of tertiary amines when compared to the phenyl-functionalized analogue. The role of the pyridyl functionality has been elucidated from a set of stoichiometric experiments, which demonstrate hydrogen bonding between the pendant pyridyl unit and the amine protons of the substrate. Such N pyr ⋅⋅⋅H-N interactions are demonstrated by X-ray diffraction analysis, 1 H NMR, and IR spectroscopy, and suggest a pathway of substrate bond-activation that involves concerted substrate binding through the Lewis acidic iridium center and the Lewis basic pyridyl site appended to the triazolylidene ligand, in agreement with ligand-metal cooperative substrate activation. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Atomically precise arrays of fluorescent silver clusters: a modular approach for metal cluster photonics on DNA nanostructures.

PubMed

Copp, Stacy M; Schultz, Danielle E; Swasey, Steven; Gwinn, Elisabeth G

2015-03-24

The remarkable precision that DNA scaffolds provide for arraying nanoscale optical elements enables optical phenomena that arise from interactions of metal nanoparticles, dye molecules, and quantum dots placed at nanoscale separations. However, control of ensemble optical properties has been limited by the difficulty of achieving uniform particle sizes and shapes. Ligand-stabilized metal clusters offer a route to atomically precise arrays that combine desirable attributes of both metals and molecules. Exploiting the unique advantages of the cluster regime requires techniques to realize controlled nanoscale placement of select cluster structures. Here we show that atomically monodisperse arrays of fluorescent, DNA-stabilized silver clusters can be realized on a prototypical scaffold, a DNA nanotube, with attachment sites separated by <10 nm. Cluster attachment is mediated by designed DNA linkers that enable isolation of specific clusters prior to assembly on nanotubes and preserve cluster structure and spectral purity after assembly. The modularity of this approach generalizes to silver clusters of diverse sizes and DNA scaffolds of many types. Thus, these silver cluster nano-optical elements, which themselves have colors selected by their particular DNA templating oligomer, bring unique dimensions of control and flexibility to the rapidly expanding field of nano-optics.

Metal-organic polyhedron based on a Cu(II) paddle-wheel secondary building unit at the truncated octahedron corners.

PubMed

Prakash, M Jaya; Zou, Yang; Hong, Seunghee; Park, Mira; Bui, Minh-Phuong Ngoc; Seong, Gi Hun; Lah, Myoung Soo

2009-02-16

A metal-organic polyhedron of truncated octahedral geometry augmented with a C(4)-symmetric square-planar Cu(II) paddle-wheel node as a secondary building unit can be prepared using a C(3)-symmetric ligand that occupies the face of the octahedral cage, where the three phenyl groups containing a m-carboxylate group in the ligand provide the necessary curvature to form the finite octahedral cage.

Reduction-Triggered Self-Assembly of Nanoscale Molybdenum Oxide Molecular Clusters

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yin, Panchao; Wu, Bin; Li, Tao

A 2.9 nm molybdenum oxide cluster {Mo 132} (Formula: [Mo VI 72Mo V 60O 372(CH 3COO) 30(H 2O) 72] 42-) can be obtained by reducing ammonium molybdate with hydrazine sulfate in weakly acidic CH 3COOH/CH 3COO- buffers. This reaction has been monitored by time-resolved UV-Vis, 1H-NMR, small angle X-ray/neutron scattering, and X-ray absorption near edge structure spectroscopy. The growth of {Mo 132} cluster shows a typical sigmoid curve, suggesting a multi-step assembly mechanism for this reaction. The reaction starts with a lag phase period when partial MoVI centers of molybdate precursors are reduced to form {MoV2(acetate)} structures under the coordinationmore » effect of the acetate groups. Once the concentration of {Mo V 2(acetate)} reaches a critical value, it triggers the assembly of Mo V and Mo VI species into {Mo 132} clusters. Parameters such as the type and amount of reducing agent, the pH, the type of cation, and the type of organic ligand in the reaction buffer, have been studied for the roles they play in the formation of the target clusters.Understanding the formation mechanism of giant molecular clusters is essential for rational design and synthesis of cluster-based nanomaterials with required morphologies and functionalities. Here, typical synthetic reactions of a 2.9 nm spherical molybdenum oxide cluster, {Mo 132} (formula: [Mo VI 72Mo V 60O 372(CH 3COO) 30(H 2O) 72] 42), with systematically varied reaction parameters have been fully explored to determine the morphologies and concentration of products, reduction of metal centers, and chemical environments of the organic ligands. The growth of these clusters shows a typical sigmoid curve, suggesting a general multistep self-assembly mechanism for the formation of giant molecular clusters. The reaction starts with a lag phase period when partial MoVI centers of molybdate precursors are reduced to form {Mo V 2(acetate)} structures under the coordination effect of the acetate groups. Once the concentration of {MoV2(acetate)} reaches a critical value, it triggers the co-assembly of Mo V and Mo VI species into the giant clusters.« less

Reduction-Triggered Self-Assembly of Nanoscale Molybdenum Oxide Molecular Clusters

DOE PAGES

Yin, Panchao; Wu, Bin; Li, Tao; ...

2016-07-26

A 2.9 nm molybdenum oxide cluster {Mo 132} (Formula: [Mo VI 72Mo V 60O 372(CH 3COO) 30(H 2O) 72] 42-) can be obtained by reducing ammonium molybdate with hydrazine sulfate in weakly acidic CH 3COOH/CH 3COO- buffers. This reaction has been monitored by time-resolved UV-Vis, 1H-NMR, small angle X-ray/neutron scattering, and X-ray absorption near edge structure spectroscopy. The growth of {Mo 132} cluster shows a typical sigmoid curve, suggesting a multi-step assembly mechanism for this reaction. The reaction starts with a lag phase period when partial MoVI centers of molybdate precursors are reduced to form {MoV2(acetate)} structures under the coordinationmore » effect of the acetate groups. Once the concentration of {Mo V 2(acetate)} reaches a critical value, it triggers the assembly of Mo V and Mo VI species into {Mo 132} clusters. Parameters such as the type and amount of reducing agent, the pH, the type of cation, and the type of organic ligand in the reaction buffer, have been studied for the roles they play in the formation of the target clusters.Understanding the formation mechanism of giant molecular clusters is essential for rational design and synthesis of cluster-based nanomaterials with required morphologies and functionalities. Here, typical synthetic reactions of a 2.9 nm spherical molybdenum oxide cluster, {Mo 132} (formula: [Mo VI 72Mo V 60O 372(CH 3COO) 30(H 2O) 72] 42), with systematically varied reaction parameters have been fully explored to determine the morphologies and concentration of products, reduction of metal centers, and chemical environments of the organic ligands. The growth of these clusters shows a typical sigmoid curve, suggesting a general multistep self-assembly mechanism for the formation of giant molecular clusters. The reaction starts with a lag phase period when partial MoVI centers of molybdate precursors are reduced to form {Mo V 2(acetate)} structures under the coordination effect of the acetate groups. Once the concentration of {MoV2(acetate)} reaches a critical value, it triggers the co-assembly of Mo V and Mo VI species into the giant clusters.« less

A polyhedron-based metal-organic framework with a reo-e net.

PubMed

Ren, Guojian; Liu, Shuxia; Wei, Feng; Ma, Fengji; Tang, Qun; Li, Shujun

2012-10-14

A polyhedron-based metal-organic framework has been designed and constructed with a reo-e net, which is constructed from trinuclear nickel clusters and mixed ligands (copolymerization pattern). It comprises three kinds of polyhedra, which are the hexahedron, cuboctahedron and rhombicuboctahedron.

Structural diversity in Ni II cluster chemistry: Ni 5, Ni 6, and {NiNa 2} n complexes bearing the Schiff-base ligand N-naphthalidene-2-amino-5-chlorobenzoic acid

DOE PAGES

Perlepe, Panagiota S.; Cunha-Silva, Luis; Bekiari, Vlasoula; ...

2016-05-23

The employment of the fluorescent bridging and chelating ligand N-naphthalidene-2-amino-5-chlorobenzoic acid (nacbH 2) in Ni II cluster chemistry has led to a series of pentanuclear and hexanuclear compounds with different structural motifs, magnetic and optical properties, as well as an interesting 1-D coordination polymer. Synthetic parameters such as the inorganic anion present in the NiX 2 starting materials (X = ClO 4 - or Cl -), the reaction solvent and the nature of the organic base employed for the deprotonation of nacbH 2 were also proved to be structure-directing components. Undoubtedly, the reported results demonstrate the rich coordination chemistry ofmore » nacbH 2 in the presence of Ni II metal ions and the ability of this chelate to adopt a variety of different modes, thus fostering the formation of high-nuclearity molecules with many physical properties.« less

Prediction of Ordered Water Molecules in Protein Binding Sites from Molecular Dynamics Simulations: The Impact of Ligand Binding on Hydration Networks.

PubMed

Rudling, Axel; Orro, Adolfo; Carlsson, Jens

2018-02-26

Water plays a major role in ligand binding and is attracting increasing attention in structure-based drug design. Water molecules can make large contributions to binding affinity by bridging protein-ligand interactions or by being displaced upon complex formation, but these phenomena are challenging to model at the molecular level. Herein, networks of ordered water molecules in protein binding sites were analyzed by clustering of molecular dynamics (MD) simulation trajectories. Locations of ordered waters (hydration sites) were first identified from simulations of high resolution crystal structures of 13 protein-ligand complexes. The MD-derived hydration sites reproduced 73% of the binding site water molecules observed in the crystal structures. If the simulations were repeated without the cocrystallized ligands, a majority (58%) of the crystal waters in the binding sites were still predicted. In addition, comparison of the hydration sites obtained from simulations carried out in the absence of ligands to those identified for the complexes revealed that the networks of ordered water molecules were preserved to a large extent, suggesting that the locations of waters in a protein-ligand interface are mainly dictated by the protein. Analysis of >1000 crystal structures showed that hydration sites bridged protein-ligand interactions in complexes with different ligands, and those with high MD-derived occupancies were more likely to correspond to experimentally observed ordered water molecules. The results demonstrate that ordered water molecules relevant for modeling of protein-ligand complexes can be identified from MD simulations. Our findings could contribute to development of improved methods for structure-based virtual screening and lead optimization.

(Carbonyl-1κC)bis-[2,3(η)-cyclo-penta-dien-yl][μ(3)-(S-methyl trithio-carbonato)methylidyne-1:2:3κC,S'':C:C](triphenyl-phosphine-1κP)(μ(3)-sulfido-1:2:3κS)dicobalt(II)iron(II) trifluoro-methane-sulfonate.

PubMed

Manning, Anthony R; McAdam, C John; Palmer, Anthony J; Simpson, Jim

2008-04-10

The asymmetric unit of the title compound, [FeCo(2)(C(5)H(5))(2)(C(3)H(3)S(3))S(C(18)H(15)P)(CO)]CF(3)SO(3), consists of a triangular irondicobalt cluster cation and a trifluoro-methane-sulfonate anion. In the cation, the FeCo(2) triangle is symmetrically capped on one face by an S atom and on the other by a C atom linked to a methyl trithio-carbonate residue that bridges the Fe-C bond. Each Co atom carries a cyclo-penta-dienyl ligand while the Fe atom coordinates to one carbonyl and one triphenyl-phosphine ligand. In the crystal structure, the cation is linked to the anion by a number of weak non-classical C-H⋯O and C-H⋯F hydrogen bonds and weak S⋯O (3.317 Å) and S⋯F (3.198 Å) inter-actions. The structure is further stabilized by additional inter-molecular C-H⋯O, C-H⋯F and O⋯O (2.942 Å) contacts, together with an unusual S⋯π(Cp) inter-action (S⋯centroid distance = 3.385 Å), generating an extended network.

Circularly Polarized Luminescence in Enantiopure Europium and Terbium Complexes with Modular, All-Oxygen Donor Ligands

PubMed Central

Seitz, Michael; Do, King; Ingram, Andrew J.; Moore, Evan G.; Muller, Gilles; Raymond, Kenneth N.

2009-01-01

Abstract: Circulaly polarized luminescence from terbium(III) complexed and excited by chiral antenna ligands gives strong emission The modular synthesis of three new octadentate, enantiopure ligands are reported - one with the bidentate chelating unit 2-hydroxyisophthalamide (IAM) and two with 1-hydroxy-2-pyridinone (1,2-HOPO) units. A new design principle is introduced for the chiral, non-racemic hexamines which constitute the central backbones for the presented class of ligands. The terbium(III) complex of the IAM ligand, as well as the europium(III) complexes of the 1,2-HOPO ligands are synthesized and characterized by various techniques (NMR, UV, CD, luminescence spectroscopy). All species exhibit excellent stability and moderate to high luminescence efficiency (quantum yields ΦEu = 0.05–0.08 and ΦTb = 0.30–0.57) in aqueous solution at physiological pH. Special focus is put onto the properties of the complexes in regard to circularly polarized luminescence (CPL). The maximum luminescence dissymmetry factors (glum) in aqueous solution are high with |glum|max = 0.08 – 0.40. Together with the very favorable general properties (good stability, high quantum yields, long lifetimes), the presented lanthanide complexes can be considered as good candidates for analytical probes based on CPL in biologically relevant environments. PMID:19639983

Empirical entropic contributions in computational docking: evaluation in APS reductase complexes.

PubMed

Chang, Max W; Belew, Richard K; Carroll, Kate S; Olson, Arthur J; Goodsell, David S

2008-08-01

The results from reiterated docking experiments may be used to evaluate an empirical vibrational entropy of binding in ligand-protein complexes. We have tested several methods for evaluating the vibrational contribution to binding of 22 nucleotide analogues to the enzyme APS reductase. These include two cluster size methods that measure the probability of finding a particular conformation, a method that estimates the extent of the local energetic well by looking at the scatter of conformations within clustered results, and an RMSD-based method that uses the overall scatter and clustering of all conformations. We have also directly characterized the local energy landscape by randomly sampling around docked conformations. The simple cluster size method shows the best performance, improving the identification of correct conformations in multiple docking experiments. 2008 Wiley Periodicals, Inc.

Optical absorption spectra and g factor of MgO: Mn2+explored by ab initio and semi empirical methods

NASA Astrophysics Data System (ADS)

Andreici Eftimie, E.-L.; Avram, C. N.; Brik, M. G.; Avram, N. M.

2018-02-01

In this paper we present a methodology for calculations of the optical absorption spectra, ligand field parameters and g factor for the Mn2+ (3d5) ions doped in MgO host crystal. The proposed technique combines two methods: the ab initio multireference (MR) and the semi empirical ligand field (LF) in the framework of the exchange charge model (ECM) respectively. Both methods of calculations are applied to the [MnO6]10-cluster embedded in an extended point charge field of host matrix ligands based on Gellé-Lepetit procedure. The first step of such investigations was the full optimization of the cubic structure of perfect MgO crystal, followed by the structural optimization of the doped of MgO:Mn2+ system, using periodic density functional theory (DFT). The ab initio MR wave functions approaches, such as complete active space self-consistent field (CASSCF), N-electron valence second order perturbation theory (NEVPT2) and spectroscopy oriented configuration interaction (SORCI), are used for the calculations. The scalar relativistic effects have also been taken into account through the second order Douglas-Kroll-Hess (DKH2) procedure. Ab initio ligand field theory (AILFT) allows to extract all LF parameters and spin-orbit coupling constant from such calculations. In addition, the ECM of ligand field theory (LFT) has been used for modelling theoptical absorption spectra. The perturbation theory (PT) was employed for the g factor calculation in the semi empirical LFT. The results of each of the aforementioned types of calculations are discussed and the comparisons between the results obtained and the experimental results show a reasonable agreement, which justifies this new methodology based on the simultaneous use of both methods. This study establishes fundamental principles for the further modelling of larger embedded cluster models of doped metal oxides.

Force Field Development and Molecular Dynamics of [NiFe] Hydrogenase

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Dayle MA; Xiong, Yijia; Straatsma, TP

2012-05-09

Classical molecular force-field parameters describing the structure and motion of metal clusters in [NiFe] hydrogenase enzymes can be used to compare the dynamics and thermodynamics of [NiFe] under different oxidation, protonation, and ligation circumstances. Using density functional theory (DFT) calculations of small model clusters representative of the active site and the proximal, medial, and distal Fe/S metal centers and their attached protein side chains, we have calculated classical force-field parameters for [NiFe] in reduced and oxidized states, including internal coordinates, force constants, and atom-centered charges. Derived force constants revealed that cysteinate ligands bound to the metal ions are more flexiblemore » in the Ni-B active site, which has a bridging hydroxide ligand, than in the Ni-C active site, which has a bridging hydride. Ten nanosecond all-atom, explicit-solvent MD simulations of [NiFe] hydrogenase in oxidized and reduced catalytic states established the stability of the derived force-field parameters in terms of C{alpha} and metal cluster fluctuations. Average active site structures from the protein MD simulations are consistent with [NiFe] structures from the Protein Data Bank, suggesting that the derived force-field parameters are transferrable to other hydrogenases beyond the structure used for testing. A comparison of experimental H{sub 2}-production rates demonstrated a relationship between cysteinate side chain rotation and activity, justifying the use of a fully dynamic model of [NiFe] metal cluster motion.« less

Copper Sensing Function of Drosophila Metal-Responsive Transcription Factor-1 Is Mediated By a Tetranuclear Cu(I) Cluster

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, X.; Hua, H.; Balamurugan, K.

2009-05-12

Drosophila melanogaster MTF-1 (dMTF-1) is a copper-responsive transcriptional activator that mediates resistance to Cu, as well as Zn and Cd. Here, we characterize a novel cysteine-rich domain which is crucial for sensing excess intracellular copper by dMTF-1. Transgenic flies expressing mutant dMTF-1 containing alanine substitutions of two, four or six cysteine residues within the sequence {sup 547}CNCTNCKCDQTKSCHGGDC{sup 565} are significantly or completely impaired in their ability to protect flies from copper toxicity and fail to up-regulate MtnA (metallothionein) expression in response to excess Cu. In contrast, these flies exhibit wild-type survival in response to copper deprivation thus revealing that themore » cysteine cluster domain is required only for sensing Cu load by dMTF-1. Parallel studies show that the isolated cysteine cluster domain is required to protect a copper-sensitive S. cerevisiae ace1 strain from copper toxicity. Cu(I) ligation by a Cys-rich domain peptide fragment drives the cooperative assembly of a polydentate [Cu{sub 4}-S{sub 6}] cage structure, characterized by a core of trigonally S{sub 3} coordinated Cu(I) ions bound by bridging thiolate ligands. While reminiscent of Cu{sub 4}-L{sub 6} (L = ligand) tetranuclear clusters in copper regulatory transcription factors of yeast, the absence of significant sequence homology is consistent with convergent evolution of a sensing strategy particularly well suited for Cu(I).« less

Footprinting of Inhibitor Interactions of In Silico Identified Inhibitors of Trypanothione Reductase of Leishmania Parasite

PubMed Central

Venkatesan, Santhosh K.; Dubey, Vikash Kumar

2012-01-01

Structure-based virtual screening of NCI Diversity set II compounds was performed to indentify novel inhibitor scaffolds of trypanothione reductase (TR) from Leishmania infantum. The top 50 ranked hits were clustered using the AuPoSOM tool. Majority of the top-ranked compounds were Tricyclic. Clustering of hits yielded four major clusters each comprising varying number of subclusters differing in their mode of binding and orientation in the active site. Moreover, for the first time, we report selected alkaloids and dibenzothiazepines as inhibitors of Leishmania infantum TR. The mode of binding observed among the clusters also potentiates the probable in vitro inhibition kinetics and aids in defining key interaction which might contribute to the inhibition of enzymatic reduction of T[S] 2. The method provides scope for automation and integration into the virtual screening process employing docking softwares, for clustering the small molecule inhibitors based upon protein-ligand interactions. PMID:22550471

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yang, Dong; Xu, Pinghong; Browning, Nigel D.

The initial steps of rhodium cluster formation from zeolite-supported mononuclear Rh(C2H4)2 complexes in H2 at 373 K and 1 bar were investigated by infrared and extended X-ray absorption fine structure spectroscopies and scanning transmission electron microscopy (STEM). The data show that ethylene ligands on the rhodium react with H2 to give supported rhodium hydrides and trigger the formation of rhodium clusters. STEM provided the first images of the smallest rhodium clusters (Rh2) and their further conversion into larger clusters. The samples were investigated in a plug-flow reactor as catalysts for the conversion of ethylene + H2 in a molar ratiomore » of 4:1 at 1 bar and 298 K, with the results showing how the changes in catalyst structure affect the activity and selectivity; the rhodium clusters are more active for hydrogenation of ethylene than the single-site complexes, which are more selective for dimerization of ethylene to give butenes« less

Cell-to-cell variation sets a tissue-rheology–dependent bound on collective gradient sensing

PubMed Central

Camley, Brian A.; Rappel, Wouter-Jan

2017-01-01

When a single cell senses a chemical gradient and chemotaxes, stochastic receptor–ligand binding can be a fundamental limit to the cell’s accuracy. For clusters of cells responding to gradients, however, there is a critical difference: Even genetically identical cells have differing responses to chemical signals. With theory and simulation, we show collective chemotaxis is limited by cell-to-cell variation in signaling. We find that when different cells cooperate, the resulting bias can be much larger than the effects of ligand–receptor binding. Specifically, when a strongly responding cell is at one end of a cell cluster, cluster motion is biased toward that cell. These errors are mitigated if clusters average measurements over times long enough for cells to rearrange. In consequence, fluid clusters are better able to sense gradients: We derive a link between cluster accuracy, cell-to-cell variation, and the cluster rheology. Because of this connection, increasing the noisiness of individual cell motion can actually increase the collective accuracy of a cluster by improving fluidity. PMID:29114053

Cysteine 295 indirectly affects Ni coordination of carbon monoxide dehydrogenase-II C-cluster

DOE Office of Scientific and Technical Information (OSTI.GOV)

Inoue, Takahiro; Takao, Kyosuke; Yoshida, Takashi

2013-11-08

Highlights: •CODH-II harbors a unique [Ni-Fe-S] cluster. •We substituted the ligand residues of Cys{sup 295} and His{sup 261}. •Dramatic decreases in Ni content upon substitutions were observed. •All substitutions did not affect Fe-S clusters assembly. •CO oxidation activity was decreased by the substitutions. -- Abstract: A unique [Ni–Fe–S] cluster (C-cluster) constitutes the active center of Ni-containing carbon monoxide dehydrogenases (CODHs). His{sup 261}, which coordinates one of the Fe atoms with Cys{sup 295}, is suggested to be the only residue required for Ni coordination in the C-cluster. To evaluate the role of Cys{sup 295}, we constructed CODH-II variants. Ala substitution formore » the Cys{sup 295} substitution resulted in the decrease of Ni content and didn’t result in major change of Fe content. In addition, the substitution had no effect on the ability to assemble a full complement of [Fe–S] clusters. This strongly suggests Cys{sup 295} indirectly and His{sup 261} together affect Ni-coordination in the C-cluster.« less

Surface properties of adipocyte lipid-binding protein: Response to lipid binding, and comparison with homologous proteins.

PubMed

LiCata, V J; Bernlohr, D A

1998-12-01

Adipocyte lipid-binding protein (ALBP) is one of a family of intracellular lipid-binding proteins (iLBPs) that bind fatty acids, retinoids, and other hydrophobic ligands. The different members of this family exhibit a highly conserved three-dimensional structure; and where structures have been determined both with (holo) and without (apo) bound lipid, observed conformational changes are extremely small (Banaszak, et al., 1994, Adv. Prot. Chem. 45, 89; Bernlohr, et al., 1997, Annu. Rev. Nutr. 17, 277). We have examined the electrostatic, hydrophobic, and water accessible surfaces of ALBP in the apo form and of holo forms with a variety of bound ligands. These calculations reveal a number of previously unrecognized changes between apo and holo ALBP, including: 1) an increase in the overall protein surface area when ligand binds, 2) expansion of the binding cavity when ligand is bound, 3) clustering of individual residue exposure increases in the area surrounding the proposed ligand entry portal, and 4) ligand-binding dependent variation in the topology of the electrostatic potential in the area surrounding the ligand entry portal. These focused analyses of the crystallographic structures thus reveal a number of subtle but consistent conformational and surface changes that might serve as markers for differential targeting of protein-lipid complexes within the cell. Most changes are consistent from ligand to ligand, however there are some ligand-specific changes. Comparable calculations with intestinal fatty-acid-binding protein and other vertebrate iLBPs show differences in the electrostatic topology, hydrophobic topology, and in localized changes in solvent exposure near the ligand entry portal. These results provide a basis toward understanding the functional and mechanistic differences among these highly structurally homologous proteins. Further, they suggest that iLBPs from different tissues exhibit one of two predominant end-state structural distributions of the ligand entry portal.

Water-soluble Au13 clusters protected by binary thiolates: Structural accommodation and the use for chemosensing

NASA Astrophysics Data System (ADS)

Ding, Weihua; Huang, Chuanqi; Guan, Lingmei; Liu, Xianhu; Luo, Zhixun; Li, Weixue

2017-05-01

Here we report a successful synthesis of water-soluble 13-atoms gold clusters under the monolayer protection of binary thiolates, glutathione and penicillamine, under a molecular formula of Au13(SG)5(PA)7. This monolayer-protected cluster (MPC) finds decent stability and is demonstrated to possess an icosahedral geometry pertaining to structural accommodation in contrast to a planar bare Au13 of local minima energy. Natural bond orbital (NBO) analysis depicts the interaction patterns between gold and the ligands, enlightening to understand the origin of enhanced stability of the Au13 MPCs. Further, the water-soluble Au13 MPCs are found to be a decent candidate for chemosensing and bioimaging.

Giant Spherical Cluster with I-C140 Fullerene Topology.

PubMed

Heinl, Sebastian; Peresypkina, Eugenia; Sutter, Jörg; Scheer, Manfred

2015-11-02

We report on an effective cluster expansion of CuBr-linked aggregates by the increase of the steric bulk of the Cp(R) ligand in the pentatopic molecules [Cp(R)Fe(η(5)-P5)]. Using [Cp(BIG)Fe(η(5)-P5)] (Cp(BIG)=C5(4-nBuC6H4)5), the novel multishell aggregate [{Cp(BIG)Fe(η(5:2:1:1:1:1:1)-P5)}12(CuBr)92] is obtained. It shows topological analogy to the theoretically predicted I-C140 fullerene molecule. The spherical cluster was comprehensively characterized by various methods in solution and in the solid state. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comparative analysis of machine learning methods in ligand-based virtual screening of large compound libraries.

PubMed

Ma, Xiao H; Jia, Jia; Zhu, Feng; Xue, Ying; Li, Ze R; Chen, Yu Z

2009-05-01

Machine learning methods have been explored as ligand-based virtual screening tools for facilitating drug lead discovery. These methods predict compounds of specific pharmacodynamic, pharmacokinetic or toxicological properties based on their structure-derived structural and physicochemical properties. Increasing attention has been directed at these methods because of their capability in predicting compounds of diverse structures and complex structure-activity relationships without requiring the knowledge of target 3D structure. This article reviews current progresses in using machine learning methods for virtual screening of pharmacodynamically active compounds from large compound libraries, and analyzes and compares the reported performances of machine learning tools with those of structure-based and other ligand-based (such as pharmacophore and clustering) virtual screening methods. The feasibility to improve the performance of machine learning methods in screening large libraries is discussed.

Exploration of gated ligand binding recognizes an allosteric site for blocking FABP4-protein interaction.

PubMed

Li, Yan; Li, Xiang; Dong, Zigang

2015-12-28

Fatty acid binding protein 4 (FABP4), reversibly binding to fatty acids and other lipids with high affinities, is a potential target for treatment of cancers. The binding site of FABP4 is buried in an interior cavity and thereby ligand binding/unbinding is coupled with opening/closing of FABP4. It is a difficult task both experimentally and computationally to illuminate the entry or exit pathway, especially with the conformational gating. In this report we combine extensive computer simulations, clustering analysis, and the Markov state model to investigate the binding mechanism of FABP4 and troglitazone. Our simulations capture spontaneous binding and unbinding events as well as the conformational transition of FABP4 between the open and closed states. An allosteric binding site on the protein surface is recognized for the development of novel FABP4 inhibitors. The binding affinity is calculated and compared with the experimental value. The kinetic analysis suggests that ligand residence on the protein surface may delay the binding process. Overall, our results provide a comprehensive picture of ligand diffusion on the protein surface, ligand migration into the buried cavity, and the conformational change of FABP4 at an atomic level.

Ligand-core NLO-phores: a combined experimental and theoretical approach to the two-photon absorption and two-photon excited emission properties of small-ligated silver nanoclusters.

PubMed

Russier-Antoine, Isabelle; Bertorelle, Franck; Calin, Nathalie; Sanader, Željka; Krstić, Marjan; Comby-Zerbino, Clothilde; Dugourd, Philippe; Brevet, Pierre-François; Bonačić-Koutecký, Vlasta; Antoine, Rodolphe

2017-01-19

We report a combined experimental and theoretical study of the two-photon absorption and excited emission properties of monodisperse ligand stabilized Ag 11 , Ag 15 and Ag 31 nanoclusters in aqueous solutions. The nanoclusters were synthesized using a cyclic reduction under oxidative conditions and separated by vertical gel electrophoresis. The two-photon absorption cross-sections of these protected noble metal nanoclusters measured within the biologically attractive 750-900 nm window are several orders of magnitude larger than that reported for commercially available standard organic dyes. The two-photon excited fluorescence spectra are also presented for excitation wavelengths within the same excitation spectral window. They exhibit size-tunability. Because the fundamental photophysical mechanisms underlying these multiphoton processes in ligand protected clusters with only a few metal atoms are not fully understood yet, a theoretical model is proposed to identify the key driving elements. Elements that regulate the dipole moments and the nonlinear optical properties are the nanocluster size, its structure and the charge distribution on both the metal core and the bound ligands. We coined this new class of NLO materials as "Ligand-Core" NLO-phores.

Spectroscopic and computational studies of ionic clusters as models of solvation and atmospheric reactions

NASA Astrophysics Data System (ADS)

Kuwata, Keith T.

Ionic clusters are useful as model systems for the study of fundamental processes in solution and in the atmosphere. Their structure and reactivity can be studied in detail using vibrational predissociation spectroscopy, in conjunction with high level ab initio calculations. This thesis presents the applications of infrared spectroscopy and computation to a variety of gas-phase cluster systems. A crucial component of the process of stratospheric ozone depletion is the action of polar stratospheric clouds (PSCs) to convert the reservoir species HCl and chlorine nitrate (ClONO2) to photochemically labile compounds. Quantum chemistry was used to explore one possible mechanism by which this activation is effected: Cl- + ClONO2 /to Cl2 + NO3- eqno(1)Correlated ab initio calculations predicted that the direct reaction of chloride ion with ClONO2 is facile, which was confirmed in an experimental kinetics study. In the reaction a weakly bound intermediate Cl2-NO3- is formed, with ~70% of the charge localized on the nitrate moiety. This enables the Cl2-NO3- cluster to be well solvated even in bulk solution, allowing (1) to be facile on PSCs. Quantum chemistry was also applied to the hydration of nitrosonium ion (NO+), an important process in the ionosphere. The calculations, in conjunction with an infrared spectroscopy experiment, revealed the structure of the gas-phase clusters NO+(H2O)n. The large degree of covalent interaction between NO+ and the lone pairs of the H2O ligands is contrasted with the weak electrostatic bonding between iodide ion and H2O. Finally, the competition between ion solvation and solvent self-association is explored for the gas-phase clusters Cl/-(H2O)n and Cl-(NH3)n. For the case of water, vibrational predissociation spectroscopy reveals less hydrogen bonding among H2O ligands than predicted by ab initio calculations. Nevertheless, for n /ge 5, cluster structure is dominated by water-water interactions, with Cl- only partially solvated by the water cluster. Preliminary infrared spectra and computations on Cl- (NH3)n indicate that NH3 preferentially binds to Cl- ion instead of forming inter-solvent networks.

Quantum mechanics/molecular mechanics simulation of the ligand vibrations of the water-oxidizing Mn4CaO5 cluster in photosystem II.

PubMed

Nakamura, Shin; Noguchi, Takumi

2016-10-11

During photosynthesis, the light-driven oxidation of water performed by photosystem II (PSII) provides electrons necessary to fix CO 2 , in turn supporting life on Earth by liberating molecular oxygen. Recent high-resolution X-ray images of PSII show that the water-oxidizing center (WOC) is composed of an Mn 4 CaO 5 cluster with six carboxylate, one imidazole, and four water ligands. FTIR difference spectroscopy has shown significant structural changes of the WOC during the S-state cycle of water oxidation, especially within carboxylate groups. However, the roles that these carboxylate groups play in water oxidation as well as how they should be properly assigned in spectra are unresolved. In this study, we performed a normal mode analysis of the WOC using the quantum mechanics/molecular mechanics (QM/MM) method to simulate FTIR difference spectra on the S 1 to S 2 transition in the carboxylate stretching region. By evaluating WOC models with different oxidation and protonation states, we determined that models of high-oxidation states, Mn(III) 2 Mn(IV) 2 , satisfactorily reproduced experimental spectra from intact and Ca-depleted PSII compared with low-oxidation models. It is further suggested that the carboxylate groups bridging Ca and Mn ions within this center tune the reactivity of water ligands bound to Ca by shifting charge via their π conjugation.

Revisiting the Electronic Structure of FeS Monomers Using ab Initio Ligand Field Theory and the Angular Overlap Model.

PubMed

Chilkuri, Vijay Gopal; DeBeer, Serena; Neese, Frank

2017-09-05

Iron-sulfur (FeS) proteins are universally found in nature with actives sites ranging in complexity from simple monomers to multinuclear sites from two up to eight iron atoms. These sites include mononuclear (rubredoxins), dinuclear (ferredoxins and Rieske proteins), trinuclear (e.g., hydrogenases), and tetranuclear (various ferredoxins and high-potential iron-sulfur proteins). The electronic structure of the higher-nuclearity clusters is inherently extremely complex. Hence, it is reasonable to take a bottom-up approach in which clusters of increasing nuclearity are analyzed in terms of the properties of their lower nuclearity constituents. In the present study, the first step is taken by an in-depth analysis of mononuclear FeS systems. Two different FeS molecules with phenylthiolate and methylthiolate as ligands are studied in their oxidized and reduced forms using modern wave function-based ab initio methods. The ab initio electronic spectra and wave function are presented and analyzed in detail. The very intricate electronic structure-geometry relationship in these systems is analyzed using ab initio ligand field theory (AILFT) in conjunction with the angular overlap model (AOM) parametrization scheme. The simple AOM model is used to explain the effect of geometric variations on the electronic structure. Through a comparison of the ab initio computed UV-vis absorption spectra and the available experimental spectra, the low-energy part of the many-particle spectrum is carefully analyzed. We show ab initio calculated magnetic circular dichroism spectra and present a comparison with the experimental spectrum. Finally, AILFT parameters and the ab initio spectra are compared with those obtained experimentally to understand the effect of the increased covalency of the thiolate ligands on the electronic structure of FeS monomers.

Two-Step Nucleation and Growth of InP Quantum Dots via Magic-Sized Cluster Intermediates

DOE PAGES

Gary, Dylan C.; Terban, Maxwell W.; Billinge, Simon J. L.; ...

2015-01-30

We report on the role of magic-sized clusters (MSCs) as key intermediates in the synthesis of indium phosphide quantum dots (InP QDs) from molecular precursors. These observations suggest that previous efforts to control nucleation and growth by tuning precursor reactivity have been undermined by formation of these kinetically persistent MSCs prior to QD formation. The thermal stability of InP MSCs is influenced by the presence of exogenous bases as well as choice of the anionic ligand set. Addition of a primary amine, a common additive in previous InP QD syntheses, to carboxylate terminated MSCs was found to bypass the formationmore » of MSCs, allowing for homogeneous growth of InP QDs through a continuum of isolable sizes. Substitution of the carboxylate ligand set for a phosphonate ligand set increased the thermal stability of one particular InP MSC to 400°C. The structure and optical properties of the MSCs with both carboxylate and phosphonate ligand sets were studied by UV-Vis absorption spectroscopy, powder XRD analysis, and solution ³¹P{¹H} and ¹H NMR spectroscopy. Finally, the carboxylate terminated MSCs were identified as effective single source precursors (SSPs) for the synthesis of high quality InP QDs. Employing InP MSCs as SSPs for QDs effectively decouples the formation of MSCs from the subsequent second nucleation event and growth of InP QDs. The concentration dependence of this SSP reaction, as well as the shape uniformity of particles observed by TEM suggests that the stepwise growth from MSCs directly to QDs proceeds via a second nucleation event rather than an aggregative growth mechanism.« less

Role of Chondroitin Sulfate (CS) Modification in the Regulation of Protein-tyrosine Phosphatase Receptor Type Z (PTPRZ) Activity: PLEIOTROPHIN-PTPRZ-A SIGNALING IS INVOLVED IN OLIGODENDROCYTE DIFFERENTIATION.

PubMed

Kuboyama, Kazuya; Fujikawa, Akihiro; Suzuki, Ryoko; Tanga, Naomi; Noda, Masaharu

2016-08-26

Protein-tyrosine phosphatase receptor type Z (PTPRZ) is predominantly expressed in the developing brain as a CS proteoglycan. PTPRZ has long (PTPRZ-A) and short type (PTPRZ-B) receptor forms by alternative splicing. The extracellular CS moiety of PTPRZ is required for high-affinity binding to inhibitory ligands, such as pleiotrophin (PTN), midkine, and interleukin-34; however, its functional significance in regulating PTPRZ activity remains obscure. We herein found that protein expression of CS-modified PTPRZ-A began earlier, peaking at approximately postnatal days 5-10 (P5-P10), and then that of PTN peaked at P10 at the developmental stage corresponding to myelination onset in the mouse brain. Ptn-deficient mice consistently showed a later onset of the expression of myelin basic protein, a major component of the myelin sheath, than wild-type mice. Upon ligand application, PTPRZ-A/B in cultured oligodendrocyte precursor cells exhibited punctate localization on the cell surface instead of diffuse distribution, causing the inactivation of PTPRZ and oligodendrocyte differentiation. The same effect was observed with the removal of CS chains with chondroitinase ABC but not polyclonal antibodies against the extracellular domain of PTPRZ. These results indicate that the negatively charged CS moiety prevents PTPRZ from spontaneously clustering and that the positively charged ligand PTN induces PTPRZ clustering, potentially by neutralizing electrostatic repulsion between CS chains. Taken altogether, these data indicate that PTN-PTPRZ-A signaling controls the timing of oligodendrocyte precursor cell differentiation in vivo, in which the CS moiety of PTPRZ receptors maintains them in a monomeric active state until its ligand binding. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Functionalization of Cadmium Selenide Quantum Dots with Poly(ethylene glycol): Ligand Exchange, Surface Coverage, and Dispersion Stability.

PubMed

Wenger, Whitney Nowak; Bates, Frank S; Aydil, Eray S

2017-08-22

Semiconductor quantum dots synthesized using rapid mixing of precursors by injection into a hot solution of solvents and surfactants have surface ligands that sterically stabilize the dispersions in nonpolar solvents. Often, these ligands are exchanged to disperse the quantum dots in polar solvents, but quantitative studies of quantum dot surfaces before and after ligand exchange are scarce. We studied exchanging trioctylphosphine (TOP) and trioctylphosphine oxide (TOPO) ligands on as-synthesized CdSe quantum dots dispersed in hexane with a 2000 g/mol thiolated poly(ethylene glycol) (PEG) polymer. Using infrared spectroscopy we quantify the absolute surface concentration of TOP/TOPO and PEG ligands per unit area before and after ligand exchange. While 50-85% of the TOP/TOPO ligands are removed upon ligand exchange, only a few are replaced with PEG. Surprisingly, the remaining TOP/TOPO ligands outnumber the PEG ligands, but these few PEG ligands are sufficient to disperse the quantum dots in polar solvents such as chloroform, tetrahydrofuran, and water. Moreover, as-synthesized quantum dots once easily dispersed in hexane are no longer dispersible in nonpolar solvents after ligand exchange. A subtle coverage-dependent balance between attractive PEG-solvent interactions and repulsive TOP/TOPO-solvent interactions determines the dispersion stability.

The Non-innocent Phenalenyl Unit: An Electronic Nest to Modulate the Catalytic Activity in Hydroamination Reaction

PubMed Central

Mukherjee, Arup; Sen, Tamal K.; Ghorai, Pradip Kr; Mandal, Swadhin K.

2013-01-01

The phenalenyl unit has played intriguing role in different fields of research spanning from chemistry, material chemistry to device physics acting as key electronic reservoir which has not only led to the best organic single component conductor but also created the spin memory device of next generation. Now we show the non-innocent behaviour of phenalenyl unit in modulating the catalytic behaviour in a homogeneous organic transformation. The present study establishes that the cationic state of phenalenyl unit can act as an organic Lewis acceptor unit to influence the catalytic outcome of intermolecular hydroamination reaction of carbodiimides. For the present study, we utilized organoaluminum complexes of phenalenyl ligands in which the phenalenyl unit maintains the closed shell electronic state. The DFT calculation reveals that the energy of LUMO of the catalyst is mainly controlled by phenalenyl ligands which in turn determines the outcome of the catalysis. PMID:24084653

Modeling Conformational Transitions and Energetics of Ligand Binding with the Glutamate Receptor Ligand Binding Domain

NASA Astrophysics Data System (ADS)

Kurnikova, Maria

2009-03-01

Understanding of protein motion and energetics of conformational transitions is crucial to understanding protein function. The glutamate receptor ligand binding domain (GluR2 S1S2) is a two lobe protein, which binds ligand at the interface of two lobes and undergoes conformational transition. The cleft closure conformational transition of S1S2 has been implicated in gating of the ion channel formed by the transmembrane domain of the receptor. In this study we present a composite multi-faceted theoretical analysis of the detailed mechanism of this conformational transition based on rigid cluster decomposition of the protein structure [1] and identifying hydrogen bonds that are responsible for stabilizing the closed conformation [2]. Free energy of the protein reorganization upon ligand binding was calculated using combined Thermodynamic Integration (TI) and Umbrella Sampling (US) simulations [3]. Ligand -- protein interactions in the binding cleft were analyzed using Molecular Dynamics, continuum electrostatics and QM/MM models [4]. All model calculations compare well with corresponding experimental measurements. [4pt] [1] Protein Flexibility using Constraints from Molecular Dynamics Simulations T. Mamonova, B. Hespenheide, R. Straub, M. F. Thorpe, M. G. Kurnikova , Phys. Biol., 2, S137 (2005)[0pt] [2] Theoretical Study of the Glutamate Receptor Ligand Binding Domain Flexibility and Conformational Reorganization T. Mamonova, K. Speranskiy, and M. Kurnikova , Prot.: Struct., Func., Bioinf., 73,656 (2008)[0pt] [3] Energetics of the cleft closing transition and glutamate binding in the Glutamate Receptor ligand Binding Domain T. Mamonova, M. Yonkunas, and M. Kurnikova Biochemistry 47, 11077 (2008)[0pt] [4] On the Binding Determinants of the Glutamate Agonist with the Glutamate Receptor Ligand Binding Domain K. Speranskiy and M. Kurnikova Biochemistry 44, 11208 (2005)

LDL receptor-related protein mediates cell-surface clustering and hepatic sequestration of chylomicron remnants in LDLR-deficient mice.

PubMed

Yu, K C; Chen, W; Cooper, A D

2001-06-01

It has been proposed that in the liver, chylomicron remnants (lipoproteins carrying dietary lipid) may be sequestered before being internalized by hepatocytes. To study this, chylomicron remnants labeled with a fluorescent dye were perfused into isolated livers of LDL receptor-deficient (LDLR-deficient) mice (Ldlr(-/-)) and examined by confocal microscopy. In contrast to livers from normal mice, there was clustering of the chylomicron remnants on the cell surface in the space of DISSE: These remnant clusters colocalized with clusters of LDLR-related protein (LRP) and could be eliminated by low concentrations of receptor-associated protein, an inhibitor of LRP. When competed with ligands of heparan sulfate proteoglycans (HSPGs), the remnant clusters still appeared but were fewer in number, although syndecans (membrane HSPGs) colocalized with the remnant clusters. This suggests that the clustering of remnants is not dependent on syndecans but that the syndecans may modify the binding of remnants. These results establish that sequestration is a novel process, the clustering of remnants in the space of DISSE: The clustering involves remnants binding to the LRP, and this may be stabilized by binding with syndecans, eventually followed by endocytosis.

A Simple Method for Drawing Chiral Mononuclear Octahedral Metal Complexes

ERIC Educational Resources Information Center

Mohamadou, Aminou; Haudrechy, Arnaud

2008-01-01

Octahedral transition-metal complexes are involved in a number of reactions and octahedral coordination geometry, frequently observed for metallic centers, includes important topographical stereochemistry. Depending on the number and nature of different ligands, octahedral coordination units with at least two different monodentate ligands give…

Protein-protected luminescent noble metal quantum clusters: an emerging trend in atomic cluster nanoscience

PubMed Central

Xavier, Paulrajpillai Lourdu; Chaudhari, Kamalesh; Baksi, Ananya; Pradeep, Thalappil

2012-01-01

Noble metal quantum clusters (NMQCs) are the missing link between isolated noble metal atoms and nanoparticles. NMQCs are sub-nanometer core sized clusters composed of a group of atoms, most often luminescent in the visible region, and possess intriguing photo-physical and chemical properties. A trend is observed in the use of ligands, ranging from phosphines to functional proteins, for the synthesis of NMQCs in the liquid phase. In this review, we briefly overview recent advancements in the synthesis of protein protected NMQCs with special emphasis on their structural and photo-physical properties. In view of the protein protection, coupled with direct synthesis and easy functionalization, this hybrid QC-protein system is expected to have numerous optical and bioimaging applications in the future, pointers in this direction are visible in the literature. PMID:22312454

Cluster Organic Frameworks Constructed from Heterometallic Supertetrahedral Cluster Secondary Building Units.

PubMed

Lin, Li-Dan; Li, Xin-Xiong; Qi, Yan-Jie; Ma, Xiang; Zheng, Shou-Tian

2017-04-17

The two novel cluster organic frameworks based on heterometallic supertetrahedral cluster secondary building units (SBUs) [Cd 4 Cu 6 (L) 4 (Ac) 7 (H 2 O) 4 ](Ac)·7H 2 O (1) and [Mn 4 Cu 6 (L) 4 (Ac) 4.5 (H 2 O) 9 ]CuCN(Ac) 3.5 ·H 2 O (2), where H 3 L = 2-(hydroxymethyl)-2-(pyridin-4-yl)-1,3-propanediol and Ac = CH 3 COO - , have been prepared under solvothermal conditions. 1 and 2 are the first cases of cluster organic frameworks containing Cd-Cu/Mn-Cu heterometallic supertetrahedral cluster SBUs. Furthermore, 1 and 2 show an integration of magnetic properties and adsorption properties from both the heterometallic cluster secondary building units and the framework in a porous material.

JADOPPT: java based AutoDock preparing and processing tool.

PubMed

García-Pérez, Carlos; Peláez, Rafael; Therón, Roberto; Luis López-Pérez, José

2017-02-15

AutoDock is a very popular software package for docking and virtual screening. However, currently it is hard work to visualize more than one result from the virtual screening at a time. To overcome this limitation we have designed JADOPPT, a tool for automatically preparing and processing multiple ligand-protein docked poses obtained from AutoDock. It allows the simultaneous visual assessment and comparison of multiple poses through clustering methods. Moreover, it permits the representation of reference ligands with known binding modes, binding site residues, highly scoring regions for the ligand, and the calculated binding energy of the best ranked results. JADOPPT, supplementary material (Case Studies 1 and 2) and video tutorials are available at http://visualanalytics.land/cgarcia/JADOPPT.html. carlosgarcia@usal.es or pelaez@usal.es. Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Hydrogels with tunable stress relaxation regulate stem cell fate and activity

NASA Astrophysics Data System (ADS)

Chaudhuri, Ovijit; Gu, Luo; Klumpers, Darinka; Darnell, Max; Bencherif, Sidi A.; Weaver, James C.; Huebsch, Nathaniel; Lee, Hong-Pyo; Lippens, Evi; Duda, Georg N.; Mooney, David J.

2016-03-01

Natural extracellular matrices (ECMs) are viscoelastic and exhibit stress relaxation. However, hydrogels used as synthetic ECMs for three-dimensional (3D) culture are typically elastic. Here, we report a materials approach to tune the rate of stress relaxation of hydrogels for 3D culture, independently of the hydrogel's initial elastic modulus, degradation, and cell-adhesion-ligand density. We find that cell spreading, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs) are all enhanced in cells cultured in gels with faster relaxation. Strikingly, MSCs form a mineralized, collagen-1-rich matrix similar to bone in rapidly relaxing hydrogels with an initial elastic modulus of 17 kPa. We also show that the effects of stress relaxation are mediated by adhesion-ligand binding, actomyosin contractility and mechanical clustering of adhesion ligands. Our findings highlight stress relaxation as a key characteristic of cell-ECM interactions and as an important design parameter of biomaterials for cell culture.

Identification of metal species by ESI-MS/MS through release of free metals from the corresponding metal-ligand complexes

PubMed Central

Tsednee, Munkhtsetseg; Huang, Yu-Chen; Chen, Yet-Ran; Yeh, Kuo-Chen

2016-01-01

Electrospray ionization-mass spectrometry (ESI-MS) is used to analyze metal species in a variety of samples. Here, we describe an application for identifying metal species by tandem mass spectrometry (ESI-MS/MS) with the release of free metals from the corresponding metal–ligand complexes. The MS/MS data were used to elucidate the possible fragmentation pathways of different metal–deoxymugineic acid (–DMA) and metal–nicotianamine (–NA) complexes and select the product ions with highest abundance that may be useful for quantitative multiple reaction monitoring. This method can be used for identifying different metal–ligand complexes, especially for metal species whose mass spectra peaks are clustered close together. Different metal–DMA/NA complexes were simultaneously identified under different physiological pH conditions with this method. We further demonstrated the application of the technique for different plant samples and with different MS instruments. PMID:27240899

Synthesis, structures and properties of three copper complexes with dibutyldithiocarbamate ligand

NASA Astrophysics Data System (ADS)

Wang, Chen; Niu, Jiao; Li, Jun; Ma, Xiaoxun

2017-05-01

Three copper complexes constructed with sulfur-containing dibutyldithiocarbamate ligand (DDTC), [(Et2NCS2)4Cu2] (1), [(Et2NCS2)(EtO)Cu]2 (2) and [(Et2NCS2)6Cu13I10]n (3) have been synthesized through the reaction of CuI with different mole ratios of DDTC under solution-diffusion conditions. The single crystal X-ray diffraction revealed that divalent Cu cations in complexes 1 and 2 imply that the reactant, Cu(I), was involved in the redox process. They formed binuclear complexes according to bridging S from DDTC ligands and O atoms from ethanol molecules respectively. The mixed valence Cu cations had two types of coordination environments in complex 3 and formed a two-dimensional layered coordination polymer by bridging the five-core Cu(I) clusters and Cu(II). The powder X-ray diffraction, luminescent, thermogravimetric analysis, etc. were also studied in this paper.

Special and general superatoms.

PubMed

Luo, Zhixun; Castleman, A Welford

2014-10-21

Bridging the gap between atoms and macroscopic matter, clusters continue to be a subject of increasing research interest. Among the realm of cluster investigations, an exciting development is the realization that chosen stable clusters can mimic the chemical behavior of an atom or a group of the periodic table of elements. This major finding known as a superatom concept was originated experimentally from the study of aluminum cluster reactivity conducted in 1989 by noting a dramatic size dependence of the reactivity where cluster anions containing a certain number of Al atoms were unreactive toward oxygen while the other species were etched away. This observation was well interpreted by shell closings on the basis of the jellium model, and the related concept (originally termed "unified atom") spawned a wide range of pioneering studies in the 1990s pertaining to the understanding of factors governing the properties of clusters. Under the inspiration of a superatom concept, advances in cluster science in finding stable species not only shed light on magic clusters (i.e., superatomic noble gas) but also enlightened the exploration of stable clusters to mimic the chemical behavior of atoms leading to the discovery of superhalogens, alkaline-earth metals, superalkalis, etc. Among them, certain clusters could enable isovalent isomorphism of precious metals, indicating application potential for inexpensive superatoms for industrial catalysis, while a few superalkalis were found to validate the interesting "harpoon mechanism" involved in the superatomic cluster reactivity; recently also found were the magnetic superatoms of which the cluster-assembled materials could be used in spin electronics. Up to now, extensive studies in cluster science have allowed the stability of superatomic clusters to be understood within a few models, including the jellium model, also aromaticity and Wade-Mingos rules depending on the geometry and metallicity of the cluster. However, the scope of application of the jellium model and modification of the theory to account for nonspherical symmetry and nonmetal-doped metal clusters are still illusive to be further developed. It is still worth mentioning that a superatom concept has also been introduced in ligand-stabilized metal clusters which could also follow the major shell-closing electron count for a spherical, square-well potential. By proposing a new concept named as special and general superatoms, herein we try to summarize all these investigations in series, expecting to provide an overview of this field with a primary focus on the joint undertakings which have given rise to the superatom concept. To be specific, for special superatoms, we limit to clusters under a strict jellium model and simply classify them into groups based on their valence electron counts. While for general superatoms we emphasize on nonmetal-doped metal clusters and ligand-stabilized metal clusters, as well as a few isovalent cluster systems. Hopefully this summary of special and general superatoms benefits the further development of cluster-related theory, and lights up the prospect of using them as building blocks of new materials with tailored properties, such as inexpensive isovalent systems for industrial catalysis, semiconductive superatoms for transistors, and magnetic superatoms for spin electronics.

Macrocycle peptides delineate locked-open inhibition mechanism for microorganism phosphoglycerate mutases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Hao; Dranchak, Patricia; Li, Zhiru

Glycolytic interconversion of phosphoglycerate isomers is catalysed in numerous pathogenic microorganisms by a cofactor-independent mutase (iPGM) structurally distinct from the mammalian cofactor-dependent (dPGM) isozyme. The iPGM active site dynamically assembles through substrate-triggered movement of phosphatase and transferase domains creating a solvent inaccessible cavity. Here we identify alternate ligand binding regions using nematode iPGM to select and enrich lariat-like ligands from an mRNA-display macrocyclic peptide library containing >1012 members. Functional analysis of the ligands, named ipglycermides, demonstrates sub-nanomolar inhibition of iPGM with complete selectivity over dPGM. The crystal structure of an iPGM macrocyclic peptide complex illuminated an allosteric, locked-open inhibition mechanismmore » placing the cyclic peptide at the bi-domain interface. This binding mode aligns the pendant lariat cysteine thiolate for coordination with the iPGM transition metal ion cluster. The extended charged, hydrophilic binding surface interaction rationalizes the persistent challenges these enzymes have presented to small-molecule screening efforts highlighting the important roles of macrocyclic peptides in expanding chemical diversity for ligand discovery.« less

SKATE: a docking program that decouples systematic sampling from scoring.

PubMed

Feng, Jianwen A; Marshall, Garland R

2010-11-15

SKATE is a docking prototype that decouples systematic sampling from scoring. This novel approach removes any interdependence between sampling and scoring functions to achieve better sampling and, thus, improves docking accuracy. SKATE systematically samples a ligand's conformational, rotational and translational degrees of freedom, as constrained by a receptor pocket, to find sterically allowed poses. Efficient systematic sampling is achieved by pruning the combinatorial tree using aggregate assembly, discriminant analysis, adaptive sampling, radial sampling, and clustering. Because systematic sampling is decoupled from scoring, the poses generated by SKATE can be ranked by any published, or in-house, scoring function. To test the performance of SKATE, ligands from the Asetex/CDCC set, the Surflex set, and the Vertex set, a total of 266 complexes, were redocked to their respective receptors. The results show that SKATE was able to sample poses within 2 A RMSD of the native structure for 98, 95, and 98% of the cases in the Astex/CDCC, Surflex, and Vertex sets, respectively. Cross-docking accuracy of SKATE was also assessed by docking 10 ligands to thymidine kinase and 73 ligands to cyclin-dependent kinase. 2010 Wiley Periodicals, Inc.

New insights into the molecular characteristics behind the function of Renilla luciferase.

PubMed

Fanaei-Kahrani, Zahra; Ganjalikhany, Mohamad Reza; Rasa, Seyed Mohammad Mahdi; Emamzadeh, Rahman

2018-02-01

Renilla Luciferase (RLuc) is a blue light emitter protein which can be applied as a valuable tool in medical diagnosis. But due to lack of the crystal structure of RLuc-ligand complex, the functional motions and catalytic mechanism of this enzyme remain largely unknown. In the present study, the active site properties and the ligand-receptor interactions of the native RLuc and its red-shifted light emitting variant (Super RLuc 8) were investigated using molecular docking approach, molecular dynamics (MD) analysis, and MM-PBSA method. The detailed analysis of the main clusters led to identifying a lid-like structure and its functional motions. Furthermore, an induced-fit mechanism is proposed where ligand-binding induces conformational changes of the active site. Our findings give an insight into the deeper understanding of RLuc conformational changes during binding steps and ligand-receptor pattern. Moreover, our work broaden our understanding of how active site geometry is adjusted to support the catalytic activity and red-shifted light emission in Super RLuc 8. © 2017 Wiley Periodicals, Inc.

Gastrointestinal Fibroblasts Have Specialized, Diverse Transcriptional Phenotypes: A Comprehensive Gene Expression Analysis of Human Fibroblasts

PubMed Central

Ishii, Genichiro; Aoyagi, Kazuhiko; Sasaki, Hiroki; Ochiai, Atsushi

2015-01-01

Background Fibroblasts are the principal stromal cells that exist in whole organs and play vital roles in many biological processes. Although the functional diversity of fibroblasts has been estimated, a comprehensive analysis of fibroblasts from the whole body has not been performed and their transcriptional diversity has not been sufficiently explored. The aim of this study was to elucidate the transcriptional diversity of human fibroblasts within the whole body. Methods Global gene expression analysis was performed on 63 human primary fibroblasts from 13 organs. Of these, 32 fibroblasts from gastrointestinal organs (gastrointestinal fibroblasts: GIFs) were obtained from a pair of 2 anatomical sites: the submucosal layer (submucosal fibroblasts: SMFs) and the subperitoneal layer (subperitoneal fibroblasts: SPFs). Using hierarchical clustering analysis, we elucidated identifiable subgroups of fibroblasts and analyzed the transcriptional character of each subgroup. Results In unsupervised clustering, 2 major clusters that separate GIFs and non-GIFs were observed. Organ- and anatomical site-dependent clusters within GIFs were also observed. The signature genes that discriminated GIFs from non-GIFs, SMFs from SPFs, and the fibroblasts of one organ from another organ consisted of genes associated with transcriptional regulation, signaling ligands, and extracellular matrix remodeling. Conclusions GIFs are characteristic fibroblasts with specific gene expressions from transcriptional regulation, signaling ligands, and extracellular matrix remodeling related genes. In addition, the anatomical site- and organ-dependent diversity of GIFs was also discovered. These features of GIFs contribute to their specific physiological function and homeostatic maintenance, and create a functional diversity of the gastrointestinal tract. PMID:26046848

Characterization of Differential Toll-Like Receptor Responses below the Optical Diffraction Limit**

PubMed Central

Aaron, Jesse S.; Carson, Bryan D.; Timlin, Jerilyn A.

2013-01-01

Many membrane receptors are recruited to specific cell surface domains to form nanoscale clusters upon ligand activation. This step appears to be necessary to initiate signaling, including pathways in innate immune system activation. However, virulent pathogens such as Yersinia pestis (the causative agent of plague) are known to evade innate immune detection, in contrast to similar microbes (such as E. coli) that elicit a robust response. This disparity has been partly attributed to the structure of lipopolysaccharides (LPS) on the bacterial cell wall, which are recognized by the innate immune receptor TLR4. As such, we hypothesized that nanoscale differences would exist between the spatial clustering of TLR4 upon binding of LPS derived from Y. pestis and E. coli. Although optical imaging can provide exquisite details of the spatial organization of biomolecules, there is a mismatch between the scale at which receptor clustering occurs (<300 nm) and the optical diffraction limit (>400 nm). The last decade has seen the emergence of super-resolution imaging methods that effectively break the optical diffraction barrier to yield truly nanoscale information in intact biological samples. This study reports the first visualizations of TLR4 distributions on intact cells at image resolutions of <30 nm using a novel, dual-color stochastic optical reconstruction microscopy (STORM) technique. This methodology permits distinction between receptors containing bound LPS from those without at the nanoscale. Importantly, we also show that LPS derived from immuno-stimulatory bacteria resulted in significantly higher LPS-TLR4 cluster sizes and a nearly two-fold greater ligand/receptor colocalization as compared to immuno-evading LPS. PMID:22807232

Structure of transition-metal cluster compounds: Use of an additional orbital resulting from the f, g character of spd bond orbitals*

PubMed Central

Pauling, Linus

1977-01-01

A general theory of the structure of complexes of the transition metals is developed on the basis of the enneacovalence of the metals and the requirements of the electroneutrality principle. An extra orbital may be provided through the small but not negligible amount of f and g character of spd bond orbitals, and an extra electron or electron pair may be accepted in this orbital for a single metal or a cluster to neutralize the positive electric charge resulting from the partial ionic character of the bonds with ligands, such as the carbonyl group. Examples of cluster compounds of cobalt, ruthenium, rhodium, osmium, and gold are discussed. PMID:16592470

Structure of transition-metal cluster compounds: Use of an additional orbital resulting from the f, g character of spd bond orbitals.

PubMed

Pauling, L

1977-12-01

A general theory of the structure of complexes of the transition metals is developed on the basis of the enneacovalence of the metals and the requirements of the electroneutrality principle. An extra orbital may be provided through the small but not negligible amount of f and g character of spd bond orbitals, and an extra electron or electron pair may be accepted in this orbital for a single metal or a cluster to neutralize the positive electric charge resulting from the partial ionic character of the bonds with ligands, such as the carbonyl group. Examples of cluster compounds of cobalt, ruthenium, rhodium, osmium, and gold are discussed.

Fullerene faraday cage keeps magnetic properties of inner cluster pristine.

PubMed

Avdoshenko, Stanislav M

2018-04-21

Any single molecular magnets (SMMs) perspective for application is as good as its magnetization stability in ambient conditions. Endohedral metallofullerenes (EMFs) provide a solid basis for promising SMMs. In this study, we investigated the behavior of functionalized EMFs on a gold surface (EMF-L-Au). Having followed the systems molecular dynamics paths, we observed that the chemically locked inner cluster inside fullerene cage will remain locked even at room temperature due to the ligand-effect. We have located multiple possible minima with different charge arrangements between EMF-L-Au fragments. Remarkably, the charge state of the EMF inner cluster remained virtually constant and so magnetic properties are expected to be untouched. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Self-assembled decanuclear Na(I)2Mn(II)4Mn(III)4 complexes: from discrete clusters to 1-D and 2-D structures, with the Mn(II)4Mn(III)4 unit displaying a large spin ground state and probable SMM behaviour.

PubMed

Langley, Stuart K; Chilton, Nicholas F; Moubaraki, Boujemaa; Murray, Keith S

2011-12-07

The synthesis, magnetic characterization and X-ray crystal structures are reported for five new manganese compounds, [Mn(III)(teaH(2))(sal)]·(1/2)H(2)O (1), [Na(I)(2)Mn(II)(4)Mn(III)(4)(teaH)(6)(sal)(4)(N(3))(2)(MeOH)(4)]·6MeOH (2), [Na(I)(2)Mn(II)(4)Mn(III)(4)(teaH)(6)(sal)(4)(N(3))(2)(MeOH)(2)](n)·7MeOH (3), [Na(I)(2)Mn(II)(4)Mn(III)(4)(teaH)(6)(sal)(4)(N(3))(2)(MeOH)(2)](n)·2MeOH·Et(2)O (4) and [K(I)(2)Mn(II)(4)Mn(III)(4)(teaH)(6)(sal)(4)(N(3))(2)(H(2)O)(2)](n)·5MeOH (5). Complex 1 is a mononuclear compound, formed via the reaction of Mn(NO(3))(2)·4H(2)O, triethanolamine (teaH(3)) and salicylic acid (salH(2)) in a basic methanolic solution. Compound 2 is a mixed-valent hetero-metallic cluster made up of a Mn(8)Na(2) decanuclear core and is formed via the reaction of sodium azide (NaN(3)) with 1. Compounds 3-5 are isolated as 1- or 2-D coordination polymers, each containing the decanuclear Mn(8)M(2) (M = Na(+) or K(+)) core building block as the repeating unit. Compound 3 is isolated when 1 is reacted with NaN(3) over a very short reaction time and forms a 1-D coordination polymer. Each unit displays inter-cluster bridges via the O-atoms of teaH(2-) ligands bonding to the sodium ions of an adjacent cluster. Increasing the reaction time appears to drive the formation of 4 which forms 2-D polymeric sheets and is a packing polymorph of 3. The addition of KMnO(4) and NaN(3) to 1 resulted in compound 5, which also forms a 1-D coordination polymer of the decanuclear core unit. The 1-D chains are now linked via inter-cluster potassium and salicylate bridges. Solid state DC susceptibility measurements were performed on compounds 1-5. The data for 1 are as expected for an S = 2 Mn(III) ion, with the isothermal M vs. H data being fitted by matrix diagonalization methods to give values of g and the axial (D) and rhombic (E) zero field splitting parameters of 2.02, -2.70 cm(-1) and 0.36 cm(-1) respectively. The data for 2-5, each with an identical Mn(II)(4)Mn(III)(4) metallic core, indicates large spin ground states, with likely values of S = 16 (±1) for each. Solid state AC susceptibility measurements confirm the large spin ground state values and is also suggestive of SMM behaviour for 2-5 as observed via the onset of frequency dependent out-of-phase peaks.

Structural insights into the light-driven auto-assembly process of the water-oxidizing Mn 4CaO 5-cluster in photosystem II

DOE PAGES

Zhang, Miao; Bommer, Martin; Chatterjee, Ruchira; ...

2017-07-18

In plants, algae and cyanobacteria, Photosystem II (PSII) catalyzes the light-driven splitting of water at a protein-bound Mn 4CaO 5-cluster, the water-oxidizing complex (WOC). In the photosynthetic organisms, the light-driven formation of the WOC from dissolved metal ions is a key process because it is essential in both initial activation and continuous repair of PSII. Structural information is required for understanding of this chaperone-free metal-cluster assembly. For the first time, we obtained a structure of PSII from Thermosynechococcus elongatus without the Mn 4CaO 5-cluster. Surprisingly, cluster-removal leaves the positions of all coordinating amino acid residues and most nearby water moleculesmore » largely unaffected, resulting in a pre-organized ligand shell for kinetically competent and error-free photo-assembly of the Mn 4CaO 5-cluster. First experiments initiating (i) partial disassembly and (ii) partial re-assembly after complete depletion of the Mn4CaO5-cluster agree with a specific bi-manganese cluster, likely a di-µ-oxo bridged pair of Mn(III) ions, as an assembly intermediate.« less

Structural insights into the light-driven auto-assembly process of the water-oxidizing Mn4CaO5-cluster in photosystem II.

PubMed

Zhang, Miao; Bommer, Martin; Chatterjee, Ruchira; Hussein, Rana; Yano, Junko; Dau, Holger; Kern, Jan; Dobbek, Holger; Zouni, Athina

2017-07-18

In plants, algae and cyanobacteria, Photosystem II (PSII) catalyzes the light-driven splitting of water at a protein-bound Mn 4 CaO 5 -cluster, the water-oxidizing complex (WOC). In the photosynthetic organisms, the light-driven formation of the WOC from dissolved metal ions is a key process because it is essential in both initial activation and continuous repair of PSII. Structural information is required for understanding of this chaperone-free metal-cluster assembly. For the first time, we obtained a structure of PSII from Thermosynechococcus elongatus without the Mn 4 CaO 5 -cluster. Surprisingly, cluster-removal leaves the positions of all coordinating amino acid residues and most nearby water molecules largely unaffected, resulting in a pre-organized ligand shell for kinetically competent and error-free photo-assembly of the Mn 4 CaO 5 -cluster. First experiments initiating (i) partial disassembly and (ii) partial re-assembly after complete depletion of the Mn 4 CaO 5 -cluster agree with a specific bi-manganese cluster, likely a di-µ-oxo bridged pair of Mn(III) ions, as an assembly intermediate.

Triosmium Clusters on a Support: Determination of Structure by X-Ray Absorption Spectroscopy and High-Resolution Microscopy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shareghe, Mehraeen; Chi, Miaofang; Browning, Nigel D.

2011-01-01

The structures of small, robust metal clusters on a solid support were determined by a combination of spectroscopic and microscopic methods: extended X-ray absorption fine structure (EXAFS) spectroscopy, scanning transmission electron microscopy (STEM), and aberration-corrected STEM. The samples were synthesized from [Os{sub 3}(CO){sub 12}] on MgO powder to provide supported clusters intended to be triosmium. The results demonstrate that the supported clusters are robust in the absence of oxidants. Conventional high-angle annular dark-field (HAADF) STEM images demonstrate a high degree of uniformity of the clusters, with root-mean-square (rms) radii of 2.03 {+-} 0.06 {angstrom}. The EXAFS OsOs coordination number ofmore » 2.1 {+-} 0.4 confirms the presence of triosmium clusters on average and correspondingly determines an average rms cluster radius of 2.02 {+-} 0.04 {angstrom}. The high-resolution STEM images show the individual Os atoms in the clusters, confirming the triangular structures of their frames and determining OsOs distances of 2.80 {+-} 0.14 {angstrom}, matching the EXAFS value of 2.89 {+-} 0.06 {angstrom}. IR and EXAFS spectra demonstrate the presence of CO ligands on the clusters. This set of techniques is recommended as optimal for detailed and reliable structural characterization of supported clusters.« less

Ligand-independent pathway that controls stability of interferon alpha receptor

PubMed Central

Liu, Jianghuai; Plotnikov, Alexander; Banerjee, Anamika; Kumar, K.G. Suresh; Ragimbeau, Josiane; Marijanovic, Zrinka; Baker, Darren P.; Pellegrini, Sandra; Fuchs, Serge Y.

2008-01-01

SUMMARY Ligand-specific negative regulation of cytokine-induced signaling relies on down regulation of the cytokine receptors. Down regulation of the IFNAR1 sub-unit of the Type I interferon (IFN) receptor proceeds via lysosomal receptor proteolysis, which is triggered by ubiquitination that depends on IFNAR1 serine phosphorylation. While IFN-inducible phosphorylation, ubiquitination and degradation requires the catalytic activity of the Tyk2 Janus kinase, here we found the ligand- and Tyk2-independent pathway that promotes IFNAR1 phosphorylation, ubiquitination, and degradation when IFNAR1 is expressed at high levels. A major cellular kinase activity that is responsible for IFNAR1 phosphorylation in vitro does not depend on either ligand or Tyk2 activity. Inhibition of ligand-independent IFNAR1 degradation suppresses cell proliferation. We discuss the signaling events that might lead to ubiquitination and degradation of IFNAR1 via ligand-dependent and independent pathways and their potential physiologic significance. PMID:18166147

Heterometallic appended {MMn(III)4} cubanes encapsulated by lacunary polytungstate ligands.

PubMed

Wu, Hai-Hong; Yao, Shuang; Zhang, Zhi-Ming; Li, Yang-Guang; Song, You; Liu, Zhu-Jun; Han, Xin-Bao; Wang, En-Bo

2013-01-14

The heterometallic appended {MMn(III)(4)} (M = Dy(3+) and K(+)) cubanes were firstly trapped by two diamagnetic POM shells, which were robust enough to construct inorganic crystalline tubular materials. Magnetic study reveals the presence of a SMM-like slow magnetic relaxation feature in the heterometallic cluster-containing POM.

Molecular self-recognition: a chiral [Mn(II)6] wheel via donor-acceptor π···π contacts and H-bonds.

PubMed

Barrios, L A; Salinas-Uber, J; Roubeau, O; Teat, S J; Aromí, G

2015-03-18

A multinucleating ligand capable of establishing different types of intermolecular interactions, when combined with acetate groups leads to the assembly of a chiral [Mn(II)3] cluster poised for a process of self-recognition through a combination of perfectly complementary weak forces.

The adapter protein SLP-76 mediates "outside-in" integrin signaling and function in T cells.

PubMed

Baker, R G; Hsu, C J; Lee, D; Jordan, M S; Maltzman, J S; Hammer, D A; Baumgart, T; Koretzky, G A

2009-10-01

The adapter protein SH2 domain-containing leukocyte protein of 76 kDa (SLP-76) is an essential mediator of signaling from the T-cell antigen receptor (TCR). We report here that SLP-76 also mediates signaling downstream of integrins in T cells and that SLP-76-deficient T cells fail to support adhesion to integrin ligands. In response to both TCR and integrin stimulation, SLP-76 relocalizes to surface microclusters that colocalize with phosphorylated signaling proteins. Disruption of SLP-76 recruitment to the protein named LAT (linker for activation of T cells) inhibits SLP-76 clustering downstream of the TCR but not downstream of integrins. Conversely, an SLP-76 mutant unable to bind ADAP (adhesion and degranulation-promoting adapter protein) forms clusters following TCR but not integrin engagement and fails to support T-cell adhesion to integrin ligands. These findings demonstrate that SLP-76 relocalizes to integrin-initiated signaling complexes by a mechanism different from that employed during TCR signaling and that SLP-76 relocalization corresponds to SLP-76-dependent integrin function in T cells.

Complex magnetic orders in small cobalt-benzene molecules.

PubMed

González, J W; Alonso-Lanza, T; Delgado, F; Aguilera-Granja, F; Ayuela, A

2017-06-07

Organometallic clusters based on transition metal atoms are interesting because of their possible applications in spintronics and quantum information processing. In addition to the enhanced magnetism at the nanoscale, the organic ligands may provide a natural shield against unwanted magnetic interactions with the matrices required for applications. Here we show that the organic ligands may lead to non-collinear magnetic order as well as the expected quenching of the magnetic moments. We use different density functional theory (DFT) methods to study the experimentally relevant three cobalt atoms surrounded by benzene rings (Co 3 Bz 3 ). We found that the benzene rings induce a ground state with non-collinear magnetization, with the magnetic moments localized on the cobalt centers and lying on the plane formed by the three cobalt atoms. We further analyze the magnetism of such a cluster using an anisotropic Heisenberg model where the involved parameters are obtained by a comparison with the DFT results. These results may also explain the recent observation of the null magnetic moment of Co 3 Bz 3 + . Moreover, we propose an additional experimental verification based on electron paramagnetic resonance.

Active sites of ligand-protected Au{sub 25} nanoparticle catalysts for CO{sub 2} electroreduction to CO

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alfonso, Dominic R., E-mail: alfonso@netl.doe.gov; Kauffman, Douglas; Matranga, Christopher

2016-05-14

Recent experimental studies have reported the electrochemical reduction of carbon dioxide (CO{sub 2}) into CO at atomically precise negatively charged Au{sub 25}{sup −} nanoclusters. The studies showed CO{sub 2} conversion at remarkably low overpotentials, but the exact mechanisms and nature of the active sites remain unclear. We used first-principles density functional theory and continuum solvation models to examine the role of the cluster during electrochemical CO{sub 2} reduction and analyze the free energies of proposed intermediate species. Contrary to previous assumptions, our results show that the fully ligand protected cluster is not an active CO{sub 2} reduction catalyst because formationmore » of the crucial carboxyl intermediate required very high electrochemical potentials. Instead, our calculations suggest that the reduction process likely occurs on a dethiolated gold site, and adsorbed carboxyl intermediate formation was significantly stabilized at dethiolated gold sites. These findings point to the crucial role of exposed metal sites during electrochemical CO{sub 2} reduction at gold nanocluster catalysts.« less

First principles DFT study of dye-sensitized CdS quantum dots

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jain, Kalpna; Singh, Kh. S.; Kishor, Shyam, E-mail: shyam387@gmail.com

2014-04-24

Dye-sensitized quantum dots (QDs) are considered promising candidates for dye-sensitized solar cells. In order to maximize their efficiency, detailed theoretical studies are important. Here, we report a first principles density functional theory (DFT) investigation of experimentally realized dye - sensitized QD / ligand systems, viz., Cd{sub 16}S{sub 16}, capped with acetate molecules and a coumarin dye. The hybrid B3LYP functional and a 6−311+G(d,p)/LANL2dz basis set are used to study the geometric, energetic and electronic properties of these clusters. There is significant structural rearrangement in all the clusters studied - on the surface for the bare QD, and in the positionsmore » of the acetate / dye ligands for the ligated QDs. The density of states (DOS) of the bare QD shows states in the band gap, which disappear on surface passivation with the acetate molecules. Interestingly, in the dye-sensitised QD, the HOMO is found to be localized mainly on the dye molecule, while the LUMO is on the QD, as required for photo-induced electron injection from the dye to the QD.« less

Crystal engineering on superpolyhedral building blocks in metal-organic frameworks applied in gas adsorption.

PubMed

Chen, Ying Pin; Liu, Tian Fu; Fordham, Stephen; Zhou, Hong Cai

2015-12-01

Two metal-organic frameworks [PCN-426(Ni) and PCN-427(Cu)] have been designed and synthesized to investigate the structure predictability using a SBB (supermolecular building blocks) approach. Tetratopic ligands featuring 120° angular carboxylate moieties were coordinated with a [Ni3(μ3-O)] cluster and a [Cu2O2] unit, respectively. As topologically predicted, 4-connected networks with square coordination adopted the nbo net for the Ni-MOF and ssb net for the Cu-MOF. PCN-426(Ni) was augmented with 12-connected octahedral SBBs, while PCN-427(Cu) was constructed with tetragonal open channels. After a CO2 supercritical drying procedure, the PCN-426(Ni) possessed a Brunauer-Emmett-Teller (BET) surface area as high as 3935 m(2) g(-1) and impressively high N2 uptake of 1500 cm(3) g(-1). This work demonstrates the generalization of the SBB strategy, finding an alternative to inconvenient synthetic processes to achieve the desired structural features.

Two Ti13-oxo-clusters showing non-compact structures, film electrode preparation and photocurrent properties.

PubMed

Hou, Jin-Le; Luo, Wen; Wu, Yin-Yin; Su, Hu-Chao; Zhang, Guang-Lin; Zhu, Qin-Yu; Dai, Jie

2015-12-14

Two benzene dicarboxylate (BDC) and salicylate (SAL) substituted titanium-oxo-clusters, Ti13O10(o-BDC)4(SAL)4(O(i)Pr)16 (1) and Ti13O10(o-BDC)4(SAL-Cl)4(O(i)Pr)16 (2), are prepared by one step in situ solvothermal synthesis. Single crystal analysis shows that the two Ti13 clusters take a paddle arrangement with an S4 symmetry. The non-compact (non-sphere) structure is stabilized by the coordination of BDC and SAL. Film photoelectrodes are prepared by the wet coating process using the solution of the clusters and the photocurrent response properties of the electrodes are studied. It is found that the photocurrent density and photoresponsiveness of the electrodes are related to the number of coating layers and the annealing temperature. Using ligand coordinated titanium-oxo-clusters as the molecular precursors of TiO2 anatase films is found to be effective due to their high solubility, appropriate stability in solution and hence the easy controllability.

Stable and solubilized active Au atom clusters for selective epoxidation of cis-cyclooctene with molecular oxygen

DOE PAGES

Qian, Linping; Wang, Zhen; Beletskiy, Evgeny V.; ...

2017-03-28

Here, the ability of Au catalysts to effect the challenging task of utilizing molecular oxygen for the selective epoxidation of cyclooctene is fascinating. Although supported nanometre-size Au particles are poorly active, here we show that solubilized atomic Au clusters, present in ng ml –1 concentrations and stabilized by ligands derived from the oxidized hydrocarbon products, are active. They can be formed from various Au sources. They generate initiators and propagators to trigger the onset of the auto-oxidation reaction with an apparent turnover frequency of 440 s –1, and continue to generate additional initiators throughout the auto-oxidation cycle without direct participationmore » in the cycle. Spectroscopic characterization suggests that 7–8 atom clusters are effective catalytically. Extension of work based on these understandings leads to the demonstration that these Au clusters are also effective in selective oxidation of cyclohexene, and that solubilized Pt clusters are also capable of generating initiators for cyclooctene epoxidation.« less

Stable and solubilized active Au atom clusters for selective epoxidation of cis-cyclooctene with molecular oxygen

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qian, Linping; Wang, Zhen; Beletskiy, Evgeny V.

Here, the ability of Au catalysts to effect the challenging task of utilizing molecular oxygen for the selective epoxidation of cyclooctene is fascinating. Although supported nanometre-size Au particles are poorly active, here we show that solubilized atomic Au clusters, present in ng ml –1 concentrations and stabilized by ligands derived from the oxidized hydrocarbon products, are active. They can be formed from various Au sources. They generate initiators and propagators to trigger the onset of the auto-oxidation reaction with an apparent turnover frequency of 440 s –1, and continue to generate additional initiators throughout the auto-oxidation cycle without direct participationmore » in the cycle. Spectroscopic characterization suggests that 7–8 atom clusters are effective catalytically. Extension of work based on these understandings leads to the demonstration that these Au clusters are also effective in selective oxidation of cyclohexene, and that solubilized Pt clusters are also capable of generating initiators for cyclooctene epoxidation.« less

Density control of dodecamanganese clusters anchored on silicon(100).

PubMed

Condorelli, Guglielmo G; Motta, Alessandro; Favazza, Maria; Nativo, Paola; Fragalà, Ignazio L; Gatteschi, Dante

2006-04-24

A synthetic strategy to control the density of Mn12 clusters anchored on silicon(100) was investigated. Diluted monolayers suitable for Mn12 anchoring were prepared by Si-grafting mixtures of the methyl 10-undecylenoate precursor ligand with 1-decene spectator spacers. Different ratios of these mixtures were tested. The grafted surfaces were hydrolyzed to reveal the carboxylic groups available for the subsequent exchange with the [Mn12O12(OAc)16(H2O)4]4 H2O2 AcOH cluster. Modified surfaces were analyzed by attenuated total reflection (ATR)-FTIR spectroscopy, X-ray photoemission spectroscopy (XPS), and AFM imaging. Results of XPS and ATR-FTIR spectroscopy show that the surface mole ratio between grafted ester and decene is higher than in the source solution. The surface density of the Mn12 cluster is, in turn, strictly proportional to the ester mole fraction. Well-resolved and isolated clusters were observed by AFM, using a diluted ester/decene 1:1 solution.

Structure and electrochemistry of proteins harboring iron-sulfur clusters of different nuclearities. Part II. [4Fe-4S] and [3Fe-4S] iron-sulfur proteins.

PubMed

Zanello, Piero

2018-06-01

In the context of the plethora of proteins harboring iron-sulfur clusters we have already reviewed structure/electrochemistry of metalloproteins expressing single types of iron-sulfur clusters (namely: {Fe(Cys) 4 }, {[Fe 2 S 2 ](Cys) 4 }, {[Fe 2 S 2 ](Cys) 3 (X)} (X = Asp, Arg, His), {[Fe 2 S 2 ](Cys) 2 (His) 2 }, {[Fe 3 S 4 ](Cys) 3 }, {[Fe 4 S 4 ](Cys) 4 } and {[Fe 4 S 4 ](S γ Cys ) 3 (nonthiolate ligand)} cores) and their synthetic analogs. More recently we are focussing on structure/electrochemistry of metalloproteins harboring iron-sulfur centres of different nuclearities. Having started such a subject with proteins harboring [4Fe-4S] and [2Fe-2S] clusters, we now depict the state of art of proteins containing [4Fe-4S] and [3Fe-4S] clusters. Copyright © 2018 Elsevier Inc. All rights reserved.

LIBRA-WA: a web application for ligand binding site detection and protein function recognition.

PubMed

Toti, Daniele; Viet Hung, Le; Tortosa, Valentina; Brandi, Valentina; Polticelli, Fabio

2018-03-01

Recently, LIBRA, a tool for active/ligand binding site prediction, was described. LIBRA's effectiveness was comparable to similar state-of-the-art tools; however, its scoring scheme, output presentation, dependence on local resources and overall convenience were amenable to improvements. To solve these issues, LIBRA-WA, a web application based on an improved LIBRA engine, has been developed, featuring a novel scoring scheme consistently improving LIBRA's performance, and a refined algorithm that can identify binding sites hosted at the interface between different subunits. LIBRA-WA also sports additional functionalities like ligand clustering and a completely redesigned interface for an easier analysis of the output. Extensive tests on 373 apoprotein structures indicate that LIBRA-WA is able to identify the biologically relevant ligand/ligand binding site in 357 cases (∼96%), with the correct prediction ranking first in 349 cases (∼98% of the latter, ∼94% of the total). The earlier stand-alone tool has also been updated and dubbed LIBRA+, by integrating LIBRA-WA's improved engine for cross-compatibility purposes. LIBRA-WA and LIBRA+ are available at: http://www.computationalbiology.it/software.html. polticel@uniroma3.it. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

A new test set for validating predictions of protein-ligand interaction.

PubMed

Nissink, J Willem M; Murray, Chris; Hartshorn, Mike; Verdonk, Marcel L; Cole, Jason C; Taylor, Robin

2002-12-01

We present a large test set of protein-ligand complexes for the purpose of validating algorithms that rely on the prediction of protein-ligand interactions. The set consists of 305 complexes with protonation states assigned by manual inspection. The following checks have been carried out to identify unsuitable entries in this set: (1) assessing the involvement of crystallographically related protein units in ligand binding; (2) identification of bad clashes between protein side chains and ligand; and (3) assessment of structural errors, and/or inconsistency of ligand placement with crystal structure electron density. In addition, the set has been pruned to assure diversity in terms of protein-ligand structures, and subsets are supplied for different protein-structure resolution ranges. A classification of the set by protein type is available. As an illustration, validation results are shown for GOLD and SuperStar. GOLD is a program that performs flexible protein-ligand docking, and SuperStar is used for the prediction of favorable interaction sites in proteins. The new CCDC/Astex test set is freely available to the scientific community (http://www.ccdc.cam.ac.uk). Copyright 2002 Wiley-Liss, Inc.

Two new coordination polymers constructed by naphthalene-1,4-dicarboxylic acid and 2,4-diamino-6-methyl-triazine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Yamin, E-mail: liyamin@henu.edu.cn; Xiao, Changyu; Zhang, Xudong

2013-08-15

Two new transition metal coordination complexes, ([MnO(nda)](H{sub 2}dmt)(H{sub 2}O)){sub n} (1), [Ag{sub 5}(nda){sub 2.5}(dmt)]{sub n} (2), (H{sub 2}nda=naphthalene-1,4-dicarboxylic acid, dmt=2,4-diamine-6-methyl-1,3,5-triazine) have been hydrothermally synthesized by the reactions of H{sub 2}nda and dmt with the homologous MnCl{sub 2}·4H{sub 2}O and AgNO{sub 3}, respectively, and characterized by single-crystal X-ray diffraction, IR spectra, elemental analysis, thermogravimetric analysis (TGA). The compound 1 exhibits a 3D network comprising 1D metal chain (MnO(CO{sub 2}){sub 2}){sub n} connected by the ligand nda{sup 2−}, featuring a four-connected uninodal diamond -like topology. In compound 2, it is firstly observed that decanuclear silver units as secondary building units to constructmore » 3D network by the ligands dmt and nda{sup 2−}, with a rare 2-nodal (3,8)-connected tfz-d topology ((4{sup 3}){sub 2}(4{sup 6}.6{sup 18}.8{sup 4})). The interactions within each Mn(II)—Mn(II) pair of compound 1 are antiferromagnetic (g=2.07, J=−1.42(1) cm{sup −1}, zj′=−0.73(2) cm{sup −1}). In addition, compound 2 exhibits photoluminescent property at about 472 nm (λ{sub ex}=394 nm). - Graphical abstract: Two new transition metal coordination complexes 1–2 have been hydrothermally synthesized and characterized by single-crystal X-ray diffraction, IR spectra, elemental analysis thermogravimetric analysis (TGA). Highlights: • The compound 1 exhibits a 3D network with four-connected uninodal diamond-like topology. • The first 3D network of 2 with a rare tfz-d topology consists of decanuclear silver clusters as secondary building units. • The magnetic measurement indicates the compound 1 shows antiferromagnetic interactions. • The photoluminescent property of 2 has been measured.« less

Selection of representative embankments based on rough set - fuzzy clustering method

NASA Astrophysics Data System (ADS)

Bin, Ou; Lin, Zhi-xiang; Fu, Shu-yan; Gao, Sheng-song

2018-02-01

The premise condition of comprehensive evaluation of embankment safety is selection of representative unit embankment, on the basis of dividing the unit levee the influencing factors and classification of the unit embankment are drafted.Based on the rough set-fuzzy clustering, the influence factors of the unit embankment are measured by quantitative and qualitative indexes.Construct to fuzzy similarity matrix of standard embankment then calculate fuzzy equivalent matrix of fuzzy similarity matrix by square method. By setting the threshold of the fuzzy equivalence matrix, the unit embankment is clustered, and the representative unit embankment is selected from the classification of the embankment.

(Carbonyl-1κC)bis­[2,3(η5)-cyclo­penta­dien­yl][μ3-(S-methyl trithio­carbonato)methylidyne-1:2:3κ4 C,S′′:C:C](triphenyl­phosphine-1κP)(μ3-sulfido-1:2:3κ3 S)dicobalt(II)iron(II) trifluoro­methane­sulfonate

PubMed Central

Manning, Anthony R.; McAdam, C. John; Palmer, Anthony J.; Simpson, Jim

2008-01-01

The asymmetric unit of the title compound, [FeCo2(C5H5)2(C3H3S3)S(C18H15P)(CO)]CF3SO3, consists of a triangular irondicobalt cluster cation and a trifluoro­methane­sulfonate anion. In the cation, the FeCo2 triangle is symmetrically capped on one face by an S atom and on the other by a C atom linked to a methyl trithio­carbonate residue that bridges the Fe—C bond. Each Co atom carries a cyclo­penta­dienyl ligand while the Fe atom coordinates to one carbonyl and one triphenyl­phosphine ligand. In the crystal structure, the cation is linked to the anion by a number of weak non-classical C—H⋯O and C—H⋯F hydrogen bonds and weak S⋯O (3.317 Å) and S⋯F (3.198 Å) inter­actions. The structure is further stabilized by additional inter­molecular C—H⋯O, C—H⋯F and O⋯O (2.942 Å) contacts, together with an unusual S⋯π(Cp) inter­action (S⋯centroid distance = 3.385 Å), generating an extended network. PMID:21202187

Hierarchical modeling of cluster size in wildlife surveys

USGS Publications Warehouse

Royle, J. Andrew

2008-01-01

Clusters or groups of individuals are the fundamental unit of observation in many wildlife sampling problems, including aerial surveys of waterfowl, marine mammals, and ungulates. Explicit accounting of cluster size in models for estimating abundance is necessary because detection of individuals within clusters is not independent and detectability of clusters is likely to increase with cluster size. This induces a cluster size bias in which the average cluster size in the sample is larger than in the population at large. Thus, failure to account for the relationship between delectability and cluster size will tend to yield a positive bias in estimates of abundance or density. I describe a hierarchical modeling framework for accounting for cluster-size bias in animal sampling. The hierarchical model consists of models for the observation process conditional on the cluster size distribution and the cluster size distribution conditional on the total number of clusters. Optionally, a spatial model can be specified that describes variation in the total number of clusters per sample unit. Parameter estimation, model selection, and criticism may be carried out using conventional likelihood-based methods. An extension of the model is described for the situation where measurable covariates at the level of the sample unit are available. Several candidate models within the proposed class are evaluated for aerial survey data on mallard ducks (Anas platyrhynchos).

The Preparation of an Ultrastable Mesoporous Cr(III)-MOF via Reductive Labilization

DTIC Science & Technology

2015-09-02

of metal clusters from a template MOF with a known structure. Fe(III)-MOFs can serve as practical structural templates because iron resembles chromium ...clusters in PCN-333 are able to accommodate both di- and trivalent metal ions by varying the charges of the terminal ligands, the bridging oxygen atoms, and...molecules in trivalent aqua complexes27 Inert complexes Labile complexes M(OH2) Cr(OH2)6 3+ Ir(OH2)6 3+ V(OH2)6 3+ Fe(OH2)6 3+ Ti(OH2)6 3+ k (s1) 2.4 10

A new (4, 6)-connected Cu(I) coordination polymer based on rare tetranuclear [Cu4I2] clusters: Synthesis, crystal structure, luminescent and photocatalytic properties

NASA Astrophysics Data System (ADS)

Cui, Li-Jing; Liu, Chun-Yan; Bian, Ming; Yu, Li-Jun

2018-03-01

A new Cu(I) coordination polymer, namely [Cu5I3(L)2]n (1 HL = 3-(4-pyridyl)-5-(3-pyridyl)-1,2,4-triazolyl), was solvothermally synthesized using CuI, HL and NaI as the starting materials. Single crystal X-ray structural analysis shows that compound 1 features a (4, 6)-connected 3D framework employing rare tetranuclear [Cu4I2] clusters as building subunits. It exhibits intense metal-to-ligand luminescence and excellent photocatalytic activity on degradation of methylene blue (MB).

Interstaple Dithiol Cross-Linking in Au(25)(SR)(18) Nanomolecules: A Combined Mass Spectrometric and Computational Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Deen; Dass, Amala; Tschumper, Gregory

2011-01-01

A systematic study of cross-linking chemistry of the Au{sub 25}(SR){sub 18} nanomolecule by dithiols of varying chain length, HS-(CH2)n-SH where n = 2, 3, 4, 5, and 6, is presented here. Monothiolated Au{sub 25} has six [RSAuSRAuSR] staple motifs on its surface, and MALDI mass spectrometry data of the ligand exchanged clusters show that propane (C3) and butane (C4) dithiols have ideal chain lengths for interstaple cross-linking and that up to six C3 or C4 dithiols can be facilely exchanged onto the cluster surface. Propanedithiol predominately exchanges with two monothiols at a time, making cross-linking bridges, while butanedithiol can exchangemore » with either one or two monothiols at a time. The extent of cross-linking can be controlled by the Au{sub 25}(SR){sub 18} to dithiol ratio, the reaction time of ligand exchange, or the addition of a hydrophobic tail to the dithiol. MALDI MS suggests that during ethane (C2) dithiol exchange, two ethanedithiols become connected by a disulfide bond; this result is supported by density functional theory (DFT) prediction of the optimal chain length for the intrastaple coupling. Both optical absorption spectroscopy and DFT computations show that the electronic structure of the Au{sub 25} nanomolecule retains its main features after exchange of up to eight monothiol ligands.« less

Conversion events in gene clusters

PubMed Central

2011-01-01

Background Gene clusters containing multiple similar genomic regions in close proximity are of great interest for biomedical studies because of their associations with inherited diseases. However, such regions are difficult to analyze due to their structural complexity and their complicated evolutionary histories, reflecting a variety of large-scale mutational events. In particular, conversion events can mislead inferences about the relationships among these regions, as traced by traditional methods such as construction of phylogenetic trees or multi-species alignments. Results To correct the distorted information generated by such methods, we have developed an automated pipeline called CHAP (Cluster History Analysis Package) for detecting conversion events. We used this pipeline to analyze the conversion events that affected two well-studied gene clusters (α-globin and β-globin) and three gene clusters for which comparative sequence data were generated from seven primate species: CCL (chemokine ligand), IFN (interferon), and CYP2abf (part of cytochrome P450 family 2). CHAP is freely available at http://www.bx.psu.edu/miller_lab. Conclusions These studies reveal the value of characterizing conversion events in the context of studying gene clusters in complex genomes. PMID:21798034

Fe-S Clusters Emerging as Targets of Therapeutic Drugs

PubMed Central

2017-01-01

Fe-S centers exhibit strong electronic plasticity, which is of importance for insuring fine redox tuning of protein biological properties. In accordance, Fe-S clusters are also highly sensitive to oxidation and can be very easily altered in vivo by different drugs, either directly or indirectly due to catabolic by-products, such as nitric oxide species (NOS) or reactive oxygen species (ROS). In case of metal ions, Fe-S cluster alteration might be the result of metal liganding to the coordinating sulfur atoms, as suggested for copper. Several drugs presented through this review are either capable of direct interaction with Fe-S clusters or of secondary Fe-S clusters alteration following ROS or NOS production. Reactions leading to Fe-S cluster disruption are also reported. Due to the recent interest and progress in Fe-S biology, it is very likely that an increasing number of drugs already used in clinics will emerge as molecules interfering with Fe-S centers in the near future. Targeting Fe-S centers could also become a promising strategy for drug development. PMID:29445445

Soft x-ray absorption spectroscopy study of the electronic structures of the MnFe Prussian blue analogs (RbxBay) Mn[3 -(x +2 y )]/2[Fe (CN) 6] H2O

NASA Astrophysics Data System (ADS)

Lee, Eunsook; Seong, Seungho; Kim, Hyun Woo; Kim, D. H.; Thakur, Nidhi; Yusuf, S. M.; Kim, Bongjae; Min, B. I.; Kim, Younghak; Kim, J.-Y.; de Groot, F. M. F.; Kang, J.-S.

2017-11-01

The electronic structures of Prussian blue analog (RbxBay) Mn[3 -(x +2 y )]/2[Fe (CN) 6] cyanides have been investigated by employing soft x-ray absorption spectroscopy (XAS) and magnetic circular dichroism (XMCD) at the Fe and Mn L (2 p ) edges. The measured XAS spectra have been analyzed with the configuration-interaction (CI) cluster model calculations. The valence states of the Fe and Mn ions are found to be Fe2 +-Fe3 + mixed valent, with an average valency of v (Fe )˜2.8 and nearly divalent (Mn2 +), respectively. Our Mn/Fe 2 p XMCD study supports that Mn2 + ions are in the high-spin states while Fe2 +-Fe3 + ions are in the low-spin states. The Fe and Mn 2 p XAS spectra are found to be essentially the same for 80 ≤T ≤ 300 K, suggesting that a simple charge transfer upon cooling from Fe3 +-CN -Mn2 + to Fe2 +-CN -Mn3 + does not occur in (RbxBay) Mn[3 -(x +2 y )]/2[Fe (CN) 6] . According to the CI cluster model analysis, it is necessary to take into account both the ligand-to-metal charge transfer and the metal-to-ligand charge transfer in describing Fe 2 p XAS, while the effect of charge transfer is negligible in describing Mn 2 p XAS. The CI cluster model analysis also shows that the trivalent Fe3 + ions have a strong covalent bonding with the C ≡N ligands and are under a large crystal-field energy of 10 D q ˜3 eV, in contrast to the weak covalency effect and a small 10 D q ˜0.6 eV for the divalent Mn2 + ions.

Atomically Precise Metal Nanoclusters for Catalytic Application

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, Rongchao

2016-11-18

The central goal of this project is to explore the catalytic application of atomically precise gold nanoclusters. By solving the total structures of ligand-protected nanoclusters, we aim to correlate the catalytic properties of metal nanoclusters with their atomic/electronic structures. Such correlation unravel some fundamental aspects of nanocatalysis, such as the nature of particle size effect, origin of catalytic selectivity, particle-support interactions, the identification of catalytically active centers, etc. The well-defined nanocluster catalysts mediate the knowledge gap between single crystal model catalysts and real-world conventional nanocatalysts. These nanoclusters also hold great promise in catalyzing certain types of reactions with extraordinarily highmore » selectivity. These aims are in line with the overall goals of the catalytic science and technology of DOE and advance the BES mission “to support fundamental research to understand, predict, and ultimately control matter and energy at the level of electrons, atoms, and molecules”. Our group has successfully prepared different sized, robust gold nanoclusters protected by thiolates, such as Au 25(SR) 18, Au 28(SR) 20, Au 38(SR) 24, Au 99(SR) 42, Au 144(SR) 60, etc. Some of these nanoclusters have been crystallographically characterized through X-ray crystallography. These ultrasmall nanoclusters (< 2 nm diameter) exhibit discrete electronic structures due to quantum size effect, as opposed to quasicontinuous band structure of conventional metal nanoparticles or bulk metals. The available atomic structures (metal core plus surface ligands) of nanoclusters serve as the basis for structure-property correlations. We have investigated the unique catalytic properties of nanoclusters (i.e. not observed in conventional nanogold catalysts) and revealed the structure-selectivity relationships. Highlights of our works include: i) Effects of ligand, cluster charge state, and size on the catalytic reactivity in CO oxidation, semihydrogenation of alkynes; ii) Size-controlled synthesis of Au-n clusters and structural elucidation; iii) Catalytic mechanisms and correlation with structures of cluster catalyst; iv) Catalytic properties of Au nanorods in chemoselective hydrogenation of nitrobenzaldehyde and visible light driven photocatalytic reactions.« less

A three-dimensional coordination polymer based on 1,2,3-triazole-4,5-dicarboxylic acid (H{sub 3}tda): ([Cd{sub 12}(tda){sub 8}(H{sub 2}O){sub 11}] · (H{sub 2}O)6.25){sub n}

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Xin-Hui, E-mail: iamxhzhou@njupt.edu.cn; Chen, Qiang

The title coordination polymer ([Cd{sub 12}(tda){sub 8}(H{sub 2}O){sub 11}] · (H{sub 2}O){sub 6.25}){sub n} (H{sub 3}tda = 1,2,3-triazole-4,5-dicarboxylic acid), has been hydrothermally synthesized and structurally characterized by single-crystal X-ray diffraction. Complex crystallizes in orthorhombic sp. gr. Pmn2{sub 1} with Z = 4. The Cd{sub 2} unit doublebridged by one carboxylate oxygen atom and two neighboring nitrogen atoms from the tda{sup 3–} ligands are linked by the tda{sup 3–}ligands to lead to the 2D (4,4) network in the ac plane. The almost coplanar Cd{sub 2}(μ{sub 5}-tda){sub 2} unit comprised of two Cd ions double-bridged by two tda{sup 3–} ligands through themore » neighboring nitrogen atoms is connected with the other four Cd{sub 2}(μ{sub 5}-tda){sub 2} units form the undulating 2D network in the ac plane. The (4,4) networks and undulating 2D networks are alternatively connected along the b axis by the tda{sup 3–} ligands coordinating to the Cd ions to form the 3D framework.« less

Why did Nature choose manganese to make oxygen?

PubMed Central

Armstrong, Fraser A

2007-01-01

This paper discusses the suitability of manganese for its function in catalysing the formation of molecular oxygen from water. Manganese is an abundant element. In terms of its inherent properties, Mn has a particularly rich redox chemistry compared with other d-block elements, with several oxidizing states accessible. The most stable-state Mn2+ behaves like a Group 2 element—it is mobile, weakly complexing, easily taken up by cells and redox-inactive in simple aqueous media. Only in the presence of suitable ligands does Mn2+ become oxidized, so it provides an uncomplicated building unit for the oxygen-evolving centre (OEC). The intermediate oxidation states Mn(III) and Mn(IV) are strongly complexed by O2− and form robust mixed-valence poly-oxo clusters in which the Mn(IV)/Mn(III) ratio can be elevated, one electron at a time, accumulating oxidizing potential and capacity. The OEC is a Mn4CaOx cluster that undergoes sequential oxidations by P680+ at potentials above 1 V, ultimately to a super-oxidized level that includes one Mn(V) or a Mn(IV)-oxyl radical. The latter is powerfully oxidizing and provides the crucial ‘power stroke’ necessary to generate an O–O bond. This leaves a centre still rich in Mn(IV), ensuring a rapid follow-through to O2. PMID:17971329

Characterization of the diffusion of epidermal growth factor receptor clusters by single particle tracking.

PubMed

Boggara, Mohan; Athmakuri, Krishna; Srivastava, Sunit; Cole, Richard; Kane, Ravi S

2013-02-01

A number of studies have shown that receptors of the epidermal growth factor receptor family (ErbBs) exist as higher-order oligomers (clusters) in cell membranes in addition to their monomeric and dimeric forms. Characterizing the lateral diffusion of such clusters may provide insights into their dynamics and help elucidate their functional relevance. To that end, we used single particle tracking to study the diffusion of clusters of the epidermal growth factor (EGF) receptor (EGFR; ErbB1) containing bound fluorescently-labeled ligand, EGF. EGFR clusters had a median diffusivity of 6.8×10(-11)cm(2)/s and were found to exhibit different modes of transport (immobile, simple, confined, and directed) similar to that previously reported for single EGFR molecules. Disruption of actin filaments increased the median diffusivity of EGFR clusters to 10.3×10(-11)cm(2)/s, while preserving the different modes of diffusion. Interestingly, disruption of microtubules rendered EGFR clusters nearly immobile. Our data suggests that microtubules may play an important role in the diffusion of EGFR clusters either directly or perhaps indirectly via other mechanisms. To our knowledge, this is the first report probing the effect of the cytoskeleton on the diffusion of EGFR clusters in the membranes of live cells. Copyright © 2012 Elsevier B.V. All rights reserved.

Cluster management.

PubMed

Katz, R

1992-11-01

Cluster management is a management model that fosters decentralization of management, develops leadership potential of staff, and creates ownership of unit-based goals. Unlike shared governance models, there is no formal structure created by committees and it is less threatening for managers. There are two parts to the cluster management model. One is the formation of cluster groups, consisting of all staff and facilitated by a cluster leader. The cluster groups function for communication and problem-solving. The second part of the cluster management model is the creation of task forces. These task forces are designed to work on short-term goals, usually in response to solving one of the unit's goals. Sometimes the task forces are used for quality improvement or system problems. Clusters are groups of not more than five or six staff members, facilitated by a cluster leader. A cluster is made up of individuals who work the same shift. For example, people with job titles who work days would be in a cluster. There would be registered nurses, licensed practical nurses, nursing assistants, and unit clerks in the cluster. The cluster leader is chosen by the manager based on certain criteria and is trained for this specialized role. The concept of cluster management, criteria for choosing leaders, training for leaders, using cluster groups to solve quality improvement issues, and the learning process necessary for manager support are described.

Redox Behavior of the S-Adenosylmethionine (SAM)-Binding Fe-S Cluster in Methylthiotransferase RimO, toward Understanding Dual SAM Activity.

PubMed

Molle, Thibaut; Moreau, Yohann; Clemancey, Martin; Forouhar, Farhad; Ravanat, Jean-Luc; Duraffourg, Nicolas; Fourmond, Vincent; Latour, Jean-Marc; Gambarelli, Serge; Mulliez, Etienne; Atta, Mohamed

2016-10-18

RimO, a radical-S-adenosylmethionine (SAM) enzyme, catalyzes the specific C 3 methylthiolation of the D89 residue in the ribosomal S 12 protein. Two intact iron-sulfur clusters and two SAM cofactors both are required for catalysis. By using electron paramagnetic resonance, Mössbauer spectroscopies, and site-directed mutagenesis, we show how two SAM molecules sequentially bind to the unique iron site of the radical-SAM cluster for two distinct chemical reactions in RimO. Our data establish that the two SAM molecules bind the radical-SAM cluster to the unique iron site, and spectroscopic evidence obtained under strongly reducing conditions supports a mechanism in which the first molecule of SAM causes the reoxidation of the reduced radical-SAM cluster, impeding reductive cleavage of SAM to occur and allowing SAM to methylate a HS - ligand bound to the additional cluster. Furthermore, by using density functional theory-based methods, we provide a description of the reaction mechanism that predicts the attack of the carbon radical substrate on the methylthio group attached to the additional [4Fe-4S] cluster.

Improved Prediction of Bovine Leucocyte Antigens (BoLA) Presented Ligands by Use of Mass-Spectrometry-Determined Ligand and in Vitro Binding Data

PubMed Central

2017-01-01

Peptide binding to MHC class I molecules is the single most selective step in antigen presentation and the strongest single correlate to peptide cellular immunogenicity. The cost of experimentally characterizing the rules of peptide presentation for a given MHC-I molecule is extensive, and predictors of peptide–MHC interactions constitute an attractive alternative. Recently, an increasing amount of MHC presented peptides identified by mass spectrometry (MS ligands) has been published. Handling and interpretation of MS ligand data is, in general, challenging due to the polyspecificity nature of the data. We here outline a general pipeline for dealing with this challenge and accurately annotate ligands to the relevant MHC-I molecule they were eluted from by use of GibbsClustering and binding motif information inferred from in silico models. We illustrate the approach here in the context of MHC-I molecules (BoLA) of cattle. Next, we demonstrate how such annotated BoLA MS ligand data can readily be integrated with in vitro binding affinity data in a prediction model with very high and unprecedented performance for identification of BoLA-I restricted T-cell epitopes. The prediction model is freely available at http://www.cbs.dtu.dk/services/NetMHCpan/NetBoLApan. The approach has here been applied to the BoLA-I system, but the pipeline is readily applicable to MHC systems in other species. PMID:29115832

Improved Prediction of Bovine Leucocyte Antigens (BoLA) Presented Ligands by Use of Mass-Spectrometry-Determined Ligand and in Vitro Binding Data.

PubMed

Nielsen, Morten; Connelley, Tim; Ternette, Nicola

2018-01-05

Peptide binding to MHC class I molecules is the single most selective step in antigen presentation and the strongest single correlate to peptide cellular immunogenicity. The cost of experimentally characterizing the rules of peptide presentation for a given MHC-I molecule is extensive, and predictors of peptide-MHC interactions constitute an attractive alternative. Recently, an increasing amount of MHC presented peptides identified by mass spectrometry (MS ligands) has been published. Handling and interpretation of MS ligand data is, in general, challenging due to the polyspecificity nature of the data. We here outline a general pipeline for dealing with this challenge and accurately annotate ligands to the relevant MHC-I molecule they were eluted from by use of GibbsClustering and binding motif information inferred from in silico models. We illustrate the approach here in the context of MHC-I molecules (BoLA) of cattle. Next, we demonstrate how such annotated BoLA MS ligand data can readily be integrated with in vitro binding affinity data in a prediction model with very high and unprecedented performance for identification of BoLA-I restricted T-cell epitopes. The prediction model is freely available at http://www.cbs.dtu.dk/services/NetMHCpan/NetBoLApan . The approach has here been applied to the BoLA-I system, but the pipeline is readily applicable to MHC systems in other species.

Structural direction of hybrid organic-inorganic materials: Synthesis of vanadium oxyfluoride, copper vanadate, and copper molybdate solid state materials through solvuthermal and solution methods

NASA Astrophysics Data System (ADS)

Deburgomaster, Paul

The vast structural complexity of inorganic oxides with structure directing organocations, nitrogen containing ligands and organophosphonate ligands was explored. The hydrothermal reaction conditions utilized herein include the variables of temperature, pH, fill volume and stoichiometry. The systems studied included: (1) the complex materials rendered from reactions of organoamine cations on the structure of vanadium oxides, oxyfluorides and fluorides. As with other systems, the influence of the mineralizer HF was not limited to pH as fluorine incorporation was not uncommon. In specific cases this coincided with reduction of vanadium sites. (2) The copper-organonitrogen ligand/vanadium oxide/aromatic phosphonate system has been studied. The rigid aromatic di- and tri-phosphonate tethers have provided a series of materials which are structurally distinct from the previously investigated aliphatic series. The inclusion of copper-coordinated nitrogen bi- and tri-dentate ligands also provided structural diversity. Product composition was highly influenced by the HF/V ratio. A similar study was conducted with the ligand 1,4-carboxy-phenylphosphonic acid. (3) The preparation of a series of bimetallic organic-inorganic hybrid materials of the M(II)/VxOy/organonitrogen ligand class was further evidence of the utility of thermodynamically driven hydrothermal synthesis. (4) While decomposition of the spherical Keplerate molybdenum clusters is encountered under hydrothermal conditions, this highly soluble form of molybdate was investigated for the development of hybrid organic-inorganic room temperature solution synthesis.

The coordination- and photochemistry of copper(i) complexes: variation of N^N ligands from imidazole to tetrazole.

PubMed

Bergmann, Larissa; Braun, Carolin; Nieger, Martin; Bräse, Stefan

2018-01-02

The prediction of coordination modes is of high importance when structure-property relationships are discussed. Herein, the coordination chemistry of copper(i) with pyridine-amines with a varying number of coordinating N-atoms, namely pyridine-benzimidazole, -triazole and -tetrazole, or their deprotonated analogues, and different phosphines was systematically studied and the photoluminescence properties of all synthesized complexes examined and related to DFT data. Each complex was characterized by single-crystal X-ray analysis and elemental analysis, and a set of prediction rules derived for the coordination chemistry of copper(i) with these ligands. A mononuclear cationic coordination motif was found for PPh 3 or DPEPhos with all N^N ligands, which exhibits blue to green luminescence of MLCT character d(Cu) → π*(pyridine-amine ligand) with quantum yields up to 46%. With the deprotonated N^N ligands, mononuclear neutral complexes were only expected with DPEPhos. The emission's nature of this complex type is strongly dependent on the electronic effects of the N^N ligand and was characterized as (ML + IL)CT transition. In contrast to the high quantum yields up to 78% for the tetrazolate complexes (as reported before), the triazolate and imidazolate based complexes show much lower emission efficiencies below 10%. Besides the mononuclear copper(i) complexes, cluster-type complexes were obtained, which show moderate luminescence in the blue to green region of the visible spectrum (469-505 nm).

Bio-nanocapsule-based scaffold improves the sensitivity and ligand-binding capacity of mammalian receptors on the sensor chip.

PubMed

Iijima, Masumi; Yoshimoto, Nobuo; Niimi, Tomoaki; Maturana, Andrés D; Kuroda, Shun'ichi

2016-06-01

Mammalian receptors are recognized as target molecules for drug discovery, and chemical libraries have been screened for both potential antagonists and agonists mainly by ligand-binding assays using immobilized receptors. A bio-nanocapsule (BNC) of approximately 30 nm that displays a tandem form of the protein A-derived immunoglobulin G (IgG) Fc-binding Z domains (denoted as ZZ-BNC) has been developed for both clustering and oriented immobilization of IgGs on the solid phase of immunosensors. In this study, human IgG1 Fc-fused vascular endothelial growth factor (VEGF) receptor was immobilized through ZZ-BNC on the sensor chip of quartz crystal microbalance (ZZ-BNC-coating). When compared with direct adsorption and protein A-coating, the sensor chip showed higher sensitivity (∽46- and ∽165-fold, respectively) and larger ligand-binding capacity (∽4- and ∽18-fold, respectively). Furthermore, the number of VEGF molecules bound to its receptor increased from 0.20 (direct adsorption) to 2.06 by ZZ-BNC-coating, strongly suggesting that ZZ-BNC reduced the steric hindrance near ligand recognition sites through oriented immobilization. Similarly, the sensitivity and ligand-binding capacity of leptin and prolactin receptors were both enhanced at a level comparable to that observed for the VEGF receptor. Thus, the combination of ZZ-BNC and Fc-fused receptors could significantly improve the function of ligand-binding assays. Copyright © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Computer-Aided Drug Discovery: Molecular Docking of Diminazene Ligands to DNA Minor Groove

ERIC Educational Resources Information Center

Kholod, Yana; Hoag, Erin; Muratore, Katlynn; Kosenkov, Dmytro

2018-01-01

The reported project-based laboratory unit introduces upper-division undergraduate students to the basics of computer-aided drug discovery as a part of a computational chemistry laboratory course. The students learn to perform model binding of organic molecules (ligands) to the DNA minor groove with computer-aided drug discovery (CADD) tools. The…

Synthesis, characterization and single crystal structures of chiral Schiff base and its tetranuclear palladium complex with Pdsbnd Osbnd Pd bridging and Pdsbnd Pd bonds

NASA Astrophysics Data System (ADS)

Rajegowda, H. R.; Kumar, P. Raghavendra; Hosamani, Amar; Butcher, R. J.; Naveen, S.; Lokanath, N. K.

2018-03-01

A new chiral Schiff base ligand 2-{N-[(2S)-(1-hydroxy-3-phenylpropan-2-yl]ethanimidoyl} phenol ((S)sbnd H2L) was obtained by acid catalyzed condensation of (2S)-(-)-2-amino-3-phenyl-1-propanol with 2‧-hydroxyacetophenone. The palladium complex was prepared by treating a solution of (S)sbnd H2L in acetone with a solution of Na2PdCl4 in water in 1:1 M ratio. The new ligand and its complex were characterized by FT-IR, 1H, 13C{1H} NMR spectroscopy, polarimetry and elemental analysis and their molecular structures were determined by single crystal X-ray diffraction. Both the compounds crystallizes in monoclinic system in the space group P21. There exists an intra [Osbnd H ⋯N (1.62(5) Å)] and intermolecular [Osbnd H ⋯O (1.53(5) Å) and Csbnd H ⋯O (2.59 Å)] hydrogen bonding and secondary interactions in the crystal of (S)sbnd H2L. The structure of the palladium complex was found very interesting wherein the ligand coordinated to metal center as tridentate dianionic (O-, N, O-) fashion, (S)-L, resulting in a tetranuclear palladium cluster, [Pd4((S)-L)4]. In these supramolecular structures phenolate oxygen coordinated to Pd(II) ion as Pdsbnd O terminal bonds [1.934(12) - 1.977(11) Å] and the alkoxide oxygen coordinated as Pdsbnd Osbnd Pd bridging bonds [1.993(11) - 2.012(12) Å]. The Pdsbnd N bond lengths found were in the range of 1.949(13) to 1.919(12) Å. There exists two asymmetric tetranuclear complex molecules in its crystal lattice. There exists very strong metal-metal bond interaction, Pd(2)sbnd Pd(3) [3.0410(18) Å] and Pd(6)sbnd Pd(7) [3.0517(19) Å] respectively in the two asymmetric units.

Influence of ionic liquids on the syntheses and structures of Mn(II) coordination polymers based on multidentate N-heterocyclic aromatic ligands and bridging carboxylate ligands.

PubMed

Qin, Jian-Hua; Wang, Hua-Rui; Pan, Qi; Zang, Shuang-Quan; Hou, Hongwei; Fan, Yaoting

2015-10-28

Seven Mn(ii) coordination polymers, namely {[Mn2(ptptp)Cl2(H2O)3]·H2O}n (1), {[Mn(μ-ptptp)3]2[Mn3(μ3-Cl)]2}·2Cl·16H2O (2), {[Mn2(ptptp)(ip)2(H2O)3]·H2O}n (3), {[Mn2(ptptp)(5-CH3-ip)2(H2O)3]·H2O}n (4), {[Mn4(ptptp)(5-Br-ip)3(H2O)3]·4H2O}n (5), {[Mn2(ptptp)(Hbtc)(H2O)2]·2H2O}n (6) and {[Mn2(ptptp)(tdc)(H2O)2]·1.5H2O}n (7), have been prepared based on multidentate N-heterocyclic aromatic ligands and bridging carboxylate ligands (H2ptptp = 2-(5-{6-[5-(pyrazin-2-yl)-1H-1,2,4-triazol-3-yl]pyridin-2-yl}-1H-1,2,4-triazol-3-yl)pyrazine; R-isophthalic acids, H2ip-R: R = -H (3), -CH3 (4), -Br (5); H3btc = trimesic acid (6); H2tdc = thiophene-2,5-dicarboxylic acid (7)), in order to further probe the multiple roles of [RMI]Br ionic liquids in the hydro/solvothermal synthesis (RMI = 1-alkyl-3-methylimidazolium, R = ethyl, or propyl, or butyl). The successful syntheses of complexes 2-6 suggest that in hydro/solvothermal synthesis the addition of a small amount of [RMI]Br plays a crucial role. Complex 1 exhibits single right-handed helices constructed by ptptp ligands and Mn(ii) ions. Complex 2 possesses octanuclear helicate structures in which two propeller-shaped [Mn(μ-ptptp)3](4-) units embrace two [Mn3(μ3-Cl)](5+) cluster cores inside. Complexes 3 and 4 are isostructural and display a 1D double chain formed by two kinds of pseudo meso-helices: (Mn-ptptp)n and (Mn-5-R-ip)n. Complex 5 has a 2D structure containing 1D Mn(ii) ion chains formed through carboxylates and [ptptp](2-)-N,N bridges. Complex 6 shows a 2D structure formed by a meso-helix (Mn-ptptp)n and the partly deprotonated Hbtc ligands. Complex 7 features a heterochiral [2 + 2] coaxially nested double-helical column formed by using the outer double-helices (Mn-ptptp)n as a template to encapsulate the inner double-helices (Mn-tdc)n with opposite orientation. All complexes were characterized by elemental analysis, IR spectroscopy, thermogravimetric analysis, single-crystal X-ray crystallography and powder X-ray diffraction. The magnetic properties of 1-7 were also investigated.

Ligand placement based on prior structures: the guided ligand-replacement method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Klei, Herbert E.; Bristol-Myers Squibb, Princeton, NJ 08543-4000; Moriarty, Nigel W., E-mail: nwmoriarty@lbl.gov

2014-01-01

A new module, Guided Ligand Replacement (GLR), has been developed in Phenix to increase the ease and success rate of ligand placement when prior protein-ligand complexes are available. The process of iterative structure-based drug design involves the X-ray crystal structure determination of upwards of 100 ligands with the same general scaffold (i.e. chemotype) complexed with very similar, if not identical, protein targets. In conjunction with insights from computational models and assays, this collection of crystal structures is analyzed to improve potency, to achieve better selectivity and to reduce liabilities such as absorption, distribution, metabolism, excretion and toxicology. Current methods formore » modeling ligands into electron-density maps typically do not utilize information on how similar ligands bound in related structures. Even if the electron density is of sufficient quality and resolution to allow de novo placement, the process can take considerable time as the size, complexity and torsional degrees of freedom of the ligands increase. A new module, Guided Ligand Replacement (GLR), was developed in Phenix to increase the ease and success rate of ligand placement when prior protein–ligand complexes are available. At the heart of GLR is an algorithm based on graph theory that associates atoms in the target ligand with analogous atoms in the reference ligand. Based on this correspondence, a set of coordinates is generated for the target ligand. GLR is especially useful in two situations: (i) modeling a series of large, flexible, complicated or macrocyclic ligands in successive structures and (ii) modeling ligands as part of a refinement pipeline that can automatically select a reference structure. Even in those cases for which no reference structure is available, if there are multiple copies of the bound ligand per asymmetric unit GLR offers an efficient way to complete the model after the first ligand has been placed. In all of these applications, GLR leverages prior knowledge from earlier structures to facilitate ligand placement in the current structure.« less

Lithium formate ion clusters formation during electrospray ionization: Evidence of magic number clusters by mass spectrometry and ab initio calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shukla, Anil; Bogdanov, Bogdan

2015-02-14

Small cationic and anionic clusters of lithium formate were generated by electrospray ionization and their fragmentations were studied by tandem mass spectrometry. Singly as well as multiply charged clusters were formed with the general formulae, (HCOOLi)nLi+, (HCOOLi)nLimm+, (HCOOLi)nHCOO- and (HCOOLi)n(HCOO)mm-. Several magic number cluster ions were observed in both the positive and negative ion modes although more predominant in the positive ion mode with (HCOOLi)3Li+ being the most abundant and stable cluster ions. Fragmentations of singly charged clusters proceed first by the loss of a dimer unit ((HCOOLi)2) followed by sequential loss of monomer units (HCOOLi). In the case ofmore » positive cluster ions, all fragmentations lead to the magic cluster (HCOOLi)3Li+ at higher collision energies which later fragments to dimer and monomer ions in lower abundance. Quantum mechanical calculations performed for smaller cluster ions showed that the trimer ion has a closed ring structure similar to the phenalenylium structure with three closed rings connected to the lithium ion. Further additions of monomer units result in similar symmetric structures for hexamer and nonamer cluster ions. Thermochemical calculations show that trimer cluster ion is relatively more stable than neighboring cluster ions, supporting the experimental observation of a magic number cluster with enhanced stability.« less

Force loading explains spatial sensing of ligands by cells

NASA Astrophysics Data System (ADS)

Oria, Roger; Wiegand, Tina; Escribano, Jorge; Elosegui-Artola, Alberto; Uriarte, Juan Jose; Moreno-Pulido, Cristian; Platzman, Ilia; Delcanale, Pietro; Albertazzi, Lorenzo; Navajas, Daniel; Trepat, Xavier; García-Aznar, José Manuel; Cavalcanti-Adam, Elisabetta Ada; Roca-Cusachs, Pere

2017-12-01

Cells can sense the density and distribution of extracellular matrix (ECM) molecules by means of individual integrin proteins and larger, integrin-containing adhesion complexes within the cell membrane. This spatial sensing drives cellular activity in a variety of normal and pathological contexts. Previous studies of cells on rigid glass surfaces have shown that spatial sensing of ECM ligands takes place at the nanometre scale, with integrin clustering and subsequent formation of focal adhesions impaired when single integrin-ligand bonds are separated by more than a few tens of nanometres. It has thus been suggested that a crosslinking ‘adaptor’ protein of this size might connect integrins to the actin cytoskeleton, acting as a molecular ruler that senses ligand spacing directly. Here, we develop gels whose rigidity and nanometre-scale distribution of ECM ligands can be controlled and altered. We find that increasing the spacing between ligands promotes the growth of focal adhesions on low-rigidity substrates, but leads to adhesion collapse on more-rigid substrates. Furthermore, disordering the ligand distribution drastically increases adhesion growth, but reduces the rigidity threshold for adhesion collapse. The growth and collapse of focal adhesions are mirrored by, respectively, the nuclear or cytosolic localization of the transcriptional regulator protein YAP. We explain these findings not through direct sensing of ligand spacing, but by using an expanded computational molecular-clutch model, in which individual integrin-ECM bonds—the molecular clutches—respond to force loading by recruiting extra integrins, up to a maximum value. This generates more clutches, redistributing the overall force among them, and reducing the force loading per clutch. At high rigidity and high ligand spacing, maximum recruitment is reached, preventing further force redistribution and leading to adhesion collapse. Measurements of cellular traction forces and actin flow speeds support our model. Our results provide a general framework for how cells sense spatial and physical information at the nanoscale, precisely tuning the range of conditions at which they form adhesions and activate transcriptional regulation.

X-ray crystallographic and computational studies of the O2-tolerant [NiFe]-hydrogenase 1 from Escherichia coli

PubMed Central

Volbeda, Anne; Amara, Patricia; Darnault, Claudine; Mouesca, Jean-Marie; Parkin, Alison; Roessler, Maxie M.; Armstrong, Fraser A.; Fontecilla-Camps, Juan C.

2012-01-01

The crystal structure of the membrane-bound O2-tolerant [NiFe]-hydrogenase 1 from Escherichia coli (EcHyd-1) has been solved in three different states: as-isolated, H2-reduced, and chemically oxidized. As very recently reported for similar enzymes from Ralstonia eutropha and Hydrogenovibrio marinus, two supernumerary Cys residues coordinate the proximal [FeS] cluster in EcHyd-1, which lacks one of the inorganic sulfide ligands. We find that the as-isolated, aerobically purified species contains a mixture of at least two conformations for one of the cluster iron ions and Glu76. In one of them, Glu76 and the iron occupy positions that are similar to those found in O2-sensitive [NiFe]-hydrogenases. In the other conformation, this iron binds, besides three sulfur ligands, the amide N from Cys20 and one Oϵ of Glu76. Our calculations show that oxidation of this unique iron generates the high-potential form of the proximal cluster. The structural rearrangement caused by oxidation is confirmed by our H2-reduced and oxidized EcHyd-1 structures. Thus, thanks to the peculiar coordination of the unique iron, the proximal cluster can contribute two successive electrons to secure complete reduction of O2 to H2O at the active site. The two observed conformations of Glu76 are consistent with this residue playing the role of a base to deprotonate the amide moiety of Cys20 upon iron binding and transfer the resulting proton away, thus allowing the second oxidation to be electroneutral. The comparison of our structures also shows the existence of a dynamic chain of water molecules, resulting from O2 reduction, located near the active site. PMID:22431599

Solvent-mediated secondary building units (SBUs) diversification in a series of MnII-based metal-organic frameworks (MOFs)

NASA Astrophysics Data System (ADS)

Niu, Yan-Fei; Cui, Li-Ting; Han, Jie; Zhao, Xiao-Li

2016-09-01

The role of auxiliary solvents in the formation of MOFs has been investigated for a series of MnII-based framework systems. Reactions of 4,4‧,4″-nitrilotribenzoic acid (H3L) with MnII through varying auxiliary solvents of the medium resulted in the formation of diversified multinuclear MnII subunits in four new coordination polymers: [Mn3(L)(HCOO)3(DEF)3] (1), [Mn3(L)2(EtOH)2]·DMF (2), [Mn5(L)4(H2O)2]·2(H2NMe2)+·4DMF·2H2O (3), and [Mn3(L)2(py)4(H2O)]·H2O (4) (H3L=4,4‧,4‧-nitrilotribenzoic acid, DMF=dimethylformamide, DEF=N,N-diethylformamide, py=pyridine). These four compounds were fully characterized by single-crystal X-ray diffraction, showing interesting SBUs variations. For compound 1, it displays a (3,6)-connected kgd net with wheel [Mn6] cluster serving as SBU, whereas in 2, the sequence of Mn3(COO)9(EtOH)2 is repeated by inversion centers located between Mn1 and Mn3 to form an infinite Mn-carboxylate chain, which are further interlinked by L3- ligands to form a 3D architecture. In 3, the pentanuclear Mn5(CO2)12 clusters are interlinked to form a layer, which are further pillared by L3- to generate a 3D network. Compound 4 has a (3,6)-connected network in which the SBU is a linear trimeric Mn3(COO)6(py)4(H2O) cluster. In addition, the thermal stabilities, X-ray powder diffraction of all the compounds were studied, photoluminescence behaviors of compounds 1, 3 and 4 are discussed.

Three 3D hybrid networks based on octamolybdates and different Cu{sup I}/Cu{sup II}-bis(triazole) motifs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, Chun-Jing; Pang, Hai-Jun; Tang, Qun

2010-12-15

Three 3D compounds based on octamolybdate clusters and various Cu{sup I}/Cu{sup II}-bis(triazole) motifs, [Cu{sup I}{sub 2}btb][{beta}-Mo{sub 8}O{sub 26}]{sub 0.5} (1), [Cu{sup I}{sub 2}btpe][{beta}-Mo{sub 8}O{sub 26}]{sub 0.5} (2), and [Cu{sup II}(btpe){sub 2}][{beta}-Mo{sub 8}O{sub 26}]{sub 0.5} (3) [btb=1,4-bis(1,2,4-triazol-1-yl)butane, btpe=1,5-bis(1,2,4-triazol-1-yl)pentane], were isolated via tuning flexible ligand spacer length and metal coordination preferences. In 1, the copper(I)-btb motif is a one-dimensional (1D) chain which is further linked by hexadentate {beta}-[Mo{sub 8}O{sub 26}]{sup 4-} clusters via coordinating to Cu{sup I} cations giving a 3D structure. In 2, the copper(I)-btpe motif exhibits a 'stairs'-like [Cu{sup I}{sub 2}btpe]{sup 2+} sheet, and the tetradentate {beta}-[Mo{sub 8}O{sub 26}]{sup 4-}more » clusters interact with two neighboring [Cu{sup I}{sub 2}btpe]{sup 2+} sheets constructing a 3D framework. In 3, the copper(II)-btpe motif possesses a novel (2D{yields}3D) interdigitated structure, which is further connected by the tetradentate {beta}-[Mo{sub 8}O{sub 26}]{sup 4-} clusters forming a 3D framework. The thermal stability and luminescent properties of 1-3 are investigated in the solid state. -- Graphical abstract: Three 3D compounds based on {beta}-[Mo{sub 8}O{sub 26}]{sup 4-} clusters with different Cu{sup I}/Cu{sup II}-bis(triazole) motifs were synthesized by regularly tuning flexible ligand spacer length and metal coordination preferences. Display Omitted« less

Lithium formate ion clusters formation during electrospray ionization: Evidence of magic number clusters by mass spectrometry and ab initio calculations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shukla, Anil, E-mail: Anil.Shukla@pnnl.gov; Bogdanov, Bogdan

2015-02-14

Small cationic and anionic clusters of lithium formate were generated by electrospray ionization and their fragmentations were studied by tandem mass spectrometry (collision-induced dissociation with N{sub 2}). Singly as well as multiply charged clusters were formed in both positive and negative ion modes with the general formulae, (HCOOLi){sub n}Li{sup +}, (HCOOLi){sub n}Li{sub m}{sup m+}, (HCOOLi){sub n}HCOO{sup −}, and (HCOOLi){sub n}(HCOO){sub m}{sup m−}. Several magic number cluster (MNC) ions were observed in both the positive and negative ion modes although more predominant in the positive ion mode with (HCOOLi){sub 3}Li{sup +} being the most abundant and stable cluster ion. Fragmentations ofmore » singly charged positive clusters proceed first by the loss of a dimer unit ((HCOOLi){sub 2}) followed by the loss of monomer units (HCOOLi) although the former remains the dominant dissociation process. In the case of positive cluster ions, all fragmentations lead to the magic cluster (HCOOLi){sub 3}Li{sup +} as the most abundant fragment ion at higher collision energies which then fragments further to dimer and monomer ions at lower abundances. In the negative ion mode, however, singly charged clusters dissociated via sequential loss of monomer units. Multiply charged clusters in both positive and negative ion modes dissociated mainly via Coulomb repulsion. Quantum chemical calculations performed for smaller cluster ions showed that the trimer ion has a closed ring structure similar to the phenalenylium structure with three closed rings connected to the central lithium ion. Further additions of monomer units result in similar symmetric structures for hexamer and nonamer cluster ions. Thermochemical calculations show that trimer cluster ion is relatively more stable than neighboring cluster ions, supporting the experimental observation of a magic number cluster with enhanced stability.« less

Ligand-bridged dinuclear cyclometalated Ir(III) complexes: from metallamacrocycles to discrete dimers.

PubMed

Chandrasekhar, Vadapalli; Hajra, Tanima; Bera, Jitendra K; Rahaman, S M Wahidur; Satumtira, Nisa; Elbjeirami, Oussama; Omary, Mohammad A

2012-02-06

Metallamacrocycles 1, 2, and 3 of the general formula [{Ir(ppy)(2)}(2)(μ-BL)(2)](OTf)(2) (ppyH = 2-phenyl pyridine; BL = 1,2-bis(4-pyridyl)ethane (bpa) (1), 1,3-bis(4-pyridyl)propane (bpp) (2), and trans-1,2-bis(4-pyridyl)ethylene (bpe) (3)) have been synthesized by the reaction of [{(ppy)(2)Ir}(2)(μ-Cl)(2)], first with AgOTf to effect dechlorination and later with various bridging ligands. Open-frame dimers [{Ir(ppy)(2)}(2)(μ-BL)](OTf)(2) were obtained in a similar manner by utilizing N,N'-bis(2-pyridyl)methylene-hydrazine (abp) and N,N'-(bis(2-pyridyl)formylidene)ethane-1,2-diamine (bpfd) (for compounds 4 and 5, respectively) as bridging ligands. Molecular structures of 1, 3, 4, and 5 were established by X-ray crystallography. Cyclic voltammetry experiments reveal weakly interacting "Ir(ppy)(2)" units bridged by ethylene-linked bpe ligand in 3; on the contrary the metal centers are electronically isolated in 1 and 2 where the bridging ligands are based on ethane and propane linkers. The dimer 4 exhibits two accessible reversible reduction couples separated by 570 mV indicating the stability of the one-electron reduced species located on the diimine-based bridge abp. The "Ir(ppy)(2)" units in compound 5 are noninteracting as the electronic conduit is truncated by the ethane spacer in the bpfd bridge. The dinuclear compounds 1-5 show ligand centered (LC) transitions involving ppy ligands and mixed metal to ligand/ligand to ligand charge transfer (MLCT/LLCT) transitions involving both the cyclometalating ppy and bridging ligands (BL) in the UV-vis spectra. For the conjugated bridge bpe in compound 3 and abp in compound 4, the lowest-energy charge-transfer absorptions are red-shifted with enhanced intensity. In accordance with their similar electronic structures, compounds 1 and 2 exhibit identical emissions. The presence of vibronic structures in these compounds indicates a predominantly (3)LC excited states. On the contrary, broad and unstructured phosphorescence bands in compounds 3-5 strongly suggest emissive states of mixed (3)MLCT/(3)LLCT character. Density functional theory (DFT) calculations have been carried out to gain insight on the frontier orbitals, and to rationalize the electrochemical and photophysical properties of the compounds based on their electronic structures.

Structural insights into the light-driven auto-assembly process of the water-oxidizing Mn4CaO5-cluster in photosystem II

PubMed Central

Zhang, Miao; Bommer, Martin; Chatterjee, Ruchira; Hussein, Rana; Yano, Junko; Dau, Holger; Kern, Jan; Dobbek, Holger; Zouni, Athina

2017-01-01

In plants, algae and cyanobacteria, Photosystem II (PSII) catalyzes the light-driven splitting of water at a protein-bound Mn4CaO5-cluster, the water-oxidizing complex (WOC). In the photosynthetic organisms, the light-driven formation of the WOC from dissolved metal ions is a key process because it is essential in both initial activation and continuous repair of PSII. Structural information is required for understanding of this chaperone-free metal-cluster assembly. For the first time, we obtained a structure of PSII from Thermosynechococcus elongatus without the Mn4CaO5-cluster. Surprisingly, cluster-removal leaves the positions of all coordinating amino acid residues and most nearby water molecules largely unaffected, resulting in a pre-organized ligand shell for kinetically competent and error-free photo-assembly of the Mn4CaO5-cluster. First experiments initiating (i) partial disassembly and (ii) partial re-assembly after complete depletion of the Mn4CaO5-cluster agree with a specific bi-manganese cluster, likely a di-µ-oxo bridged pair of Mn(III) ions, as an assembly intermediate. DOI: http://dx.doi.org/10.7554/eLife.26933.001 PMID:28718766

Crystal structures of three lead(II) acetate-bridged di-amino-benzene coordination polymers.

PubMed

Geiger, David K; Parsons, Dylan E; Zick, Patricia L

2014-12-01

Poly[tris-(acetato-κ(2) O,O')(μ2-acetato-κ(3) O,O':O)tetra-kis-(μ3-acetato-κ(4) O,O':O:O')bis-(benzene-1,2-di-amine-κN)tetra-lead(II)], [Pb4(CH3COO)8(C6H8N2)2] n , (I), poly[(acetato-κ(2) O,O')(μ3-acetato-κ(4) O,O':O:O')(4-chloro-benzene-1,2-diamine-κN)lead(II)], [Pb(CH3COO)2(C6H7ClN2)] n , (II), and poly[(κ(2) O,O')(μ3-acetato-κ(4) O,O':O:O')(3,4-di-amino-benzo-nitrile-κN)lead(II)], [Pb(CH3COO)2(C7H7N3)] n , (III), have polymeric structures in which monomeric units are joined by bridging acetate ligands. All of the Pb(II) ions exhibit hemidirected coordination. The repeating unit in (I) is composed of four Pb(II) ions having O6, O6N, O7 and O6N coordination spheres, respectively, where N represents a monodentate benzene-1,2-di-amine ligand and O acetate O atoms. Chains along [010] are joined by bridging acetate ligands to form planes parallel to (10-1). (II) and (III) are isotypic and have one Pb(II) ion in the asymmetric unit that has an O6N coordination sphere. Pb2O2 units result from a symmetry-imposed inversion center. Polymeric chains parallel to [100] exhibit hydrogen bonding between the amine and acetate ligands. In (III), additional hydrogen bonds between cyano groups and non-coordinating amines join the chains by forming R 2 (2)(14) rings.

Topological identification of the first uninodal 8-connected lsz MOF built from 2,2'-difluorobiphenyl-4,4'-dicarboxylate pillars and cadmium(II)-triazolate layers.

PubMed

Zhang, Yuchi; Wu, Yuanhua; He, Xin; Ma, Junhan; Shen, Xuan; Zhu, Dunru

2018-03-01

Using polynuclear metal clusters as nodes, many high-symmetry high-connectivity nets, like 8-connnected bcu and 12-connected fcu, have been attained in metal-organic frameworks (MOFs). However, construction of low-symmetry high-connected MOFs with a novel topology still remains a big challenge. For example, a uninodal 8-connected lsz network, observed in inorganic ZrSiO 4 , has not been topologically identified in MOFs. Using 2,2'-difluorobiphenyl-4,4'-dicarboxylic acid (H 2 L) as a new linker and 1,2,4-triazole (Htrz) as a coligand, a novel three-dimensional Cd II -MOF, namely poly[tetrakis(μ 4 -2,2'-difluorobiphenyl-4,4'-dicarboxylato-κ 5 O 1 ,O 1' :O 1' :O 4 :O 4' )tetrakis(N,N-dimethylformamide-κO)tetrakis(μ 3 -1,2,4-triazolato-κ 3 N 1 :N 2 :N 4 )hexacadmium(II)], [Cd 6 (C 14 H 6 F 2 O 4 ) 4 (C 2 H 2 N 3 ) 4 (C 3 H 7 NO) 4 ] n , (I), has been prepared. Single-crystal structure analysis indicates that six different Cd II ions co-exist in (I) and each Cd II ion displays a distorted [CdO 4 N 2 ] octahedral geometry with four equatorial O atoms and two axial N atoms. Three Cd II ions are connected by four carboxylate groups and four trz - ligands to form a linear trinuclear [Cd 3 (COO) 4 (trz) 4 ] cluster, as do the other three Cd II ions. Two Cd 3 clusters are linked by trz - ligands in a μ 1,2,4 -bridging mode to produce a two-dimensional Cd II -triazolate layer with (6,3) topology in the ab plane. These two-dimensional layers are further pillared by the L 2- ligands along the c axis to generate a complicated three-dimensional framework. Topologically, regarding the Cd 3 cluster as an 8-connected node, the whole architecture of (I) is a uninodal 8-connected lsz framework with the Schläfli symbol (4 22 ·6 6 ). Complex (I) was further characterized by elemental analysis, IR spectroscopy, powder X-ray diffraction, thermogravimetric analysis and a photoluminescence study. MOF (I) has a high thermal and water stability.

Using novel descriptor accounting for ligand-receptor interactions to define and visually explore biologically relevant chemical space.

PubMed

Rabal, Obdulia; Oyarzabal, Julen

2012-05-25

The definition and pragmatic implementation of biologically relevant chemical space is critical in addressing navigation strategies in the overlapping regions where chemistry and therapeutically relevant targets reside and, therefore, also key to performing an efficient drug discovery project. Here, we describe the development and implementation of a simple and robust method for representing biologically relevant chemical space as a general reference according to current knowledge, independently of any reference space, and analyzing chemical structures accordingly. Underlying our method is the generation of a novel descriptor (LiRIf) that converts structural information into a one-dimensional string accounting for the plausible ligand-receptor interactions as well as for topological information. Capitalizing on ligand-receptor interactions as a descriptor enables the clustering, profiling, and comparison of libraries of compounds from a chemical biology and medicinal chemistry perspective. In addition, as a case study, R-groups analysis is performed to identify the most populated ligand-receptor interactions according to different target families (GPCR, kinases, etc.), as well as to evaluate the coverage of biologically relevant chemical space by structures annotated in different databases (ChEMBL, Glida, etc.).

Four transition metal complexes with a semicarbazone ligand bearing pyrazine unit

NASA Astrophysics Data System (ADS)

Chen, Hong; Ma, Xiu-qin; Lv, Yan-yun; Jia, Lei; Xu, Jun; Wang, Yuan; Ge, Zhi-jun

2016-04-01

Four new complexes based on L (where L = 3-ethyl-2-acetylpyrazine semicarbazone), namely [CoL2]Cl2·0.5H2O (1), [CoL2](NO3)2 (2), [CdL(H2O)2(NO3)](NO3)·H2O (3) and [CuL(CH3OH)Cl2]·[CuLCl2] (4) have been synthesized and characterized by X-ray diffraction analyses. The results show that the semicarbazone acts as a tridentate neutral ligand in all complexes. Each of complex 1 and 2 reveals a distorted octahedral geometry around the metal ion provided by two units of the ligand, while the ratio of the ligand and metal is 1:1 in complexes 3 and 4. The effect of complexes 1-4 on cell proliferation, apoptosis of human pancreatic cancer (Patu8988), human gastric cancer (SGC7901) and human hepatic cancer (SMMC7721) cell lines have been detected by MTT assay, Annexin V/PI double staining flow cytometry and TUNEL assay. The results show that complexes 1-4 can inhibit cell proliferation of Patu8988, SGC7901 and SMMC7721 cells, significantly higher than the effect of the ligand. However, the complex 4 reveals higher apoptosis rate, and displays up-regulated expression level of caspase 3, detected by western blotting, which also indicates the complex 4 can induce caspase-dependent cell apoptosis in SMMC7721.

Probing the importance of the hemilabile site of bis(phosphine) monoxide ligands in the copper-catalyzed addition of diethylzinc to N-phosphinoylimines: discovery of new effective chiral ligands.

PubMed

Bonnaventure, Isabelle; Charette, André B

2008-08-15

The hemilabile ligand Me-DuPHOS(O) 2 has proven to be a successful ligand for the copper-catalyzed addition of diethylzinc to N-phosphinoylimines. The corresponding alpha-chiral amines were obtained in high yields (80-98%) and enantiomeric ratios (19.0:1 to 99.0:1 er). Furthermore, this Cu* 2 catalytic system has been shown to be effective in the addition of diethylzinc to nitroalkenes and in the reduction of beta,beta-disubstituted vinyl phenyl sulfones. This paper describes a general structure/selectivity study in which the three ligand subunits (chiral phospholane-linker-labile coordinating group (Z)) are systematically modified and tested in the copper-catalyzed addition of diethylzinc to the N-phosphinoylimine 1 derived from benzaldehyde. This study led to the discovery of a new class of effective chiral ligands that combine a chiral phospholane unit and an achiral phosphine oxide.

Zn and Fe complexes containing a redox active macrocyclic biquinazoline ligand.

PubMed

Banerjee, Priyabrata; Company, Anna; Weyhermüller, Thomas; Bill, Eckhard; Hess, Corinna R

2009-04-06

A series of iron and zinc complexes has been synthesized, coordinated by the macrocyclic biquinazoline ligand, 2-4:6-8-bis(3,3,4,4-tetramethyldihydropyrrolo)-10-15-(2,2'-biquinazolino)-[15]-1,3,5,8,10,14-hexaene-1,3,7,9,11,14-N(6) (Mabiq). The Mabiq ligand consists of a bipyrimidine moiety and two dihydropyrrole units. The electronic structures of the metal-Mabiq complexes have been characterized using spectroscopic and density-functional theory (DFT) computational methods. The parent zinc complex exhibits a ligand-centered reduction to generate the metal-coordinated Mabiq radical dianion, establishing the redox non-innocence of this ligand. Iron-Mabiq complexes have been isolated in three oxidation states. This redox series includes low-spin ferric and low-spin ferrous species, as well as an intermediate-spin Fe(II) compound. In the latter complex, the iron ion is antiferromagnetically coupled to a Mabiq-centered pi-radical. The results demonstrate the rich redox chemistry and electronic properties of metal complexes coordinated by the Mabiq ligand.

Geographic Clustering of Cardiometabolic Risk Factors in Metropolitan Centres in France and Australia

PubMed Central

Paquet, Catherine; Chaix, Basile; Howard, Natasha J.; Coffee, Neil T.; Adams, Robert J.; Taylor, Anne W.; Thomas, Frédérique; Daniel, Mark

2016-01-01

Understanding how health outcomes are spatially distributed represents a first step in investigating the scale and nature of environmental influences on health and has important implications for statistical power and analytic efficiency. Using Australian and French cohort data, this study aimed to describe and compare the extent of geographic variation, and the implications for analytic efficiency, across geographic units, countries and a range of cardiometabolic parameters (Body Mass Index (BMI) waist circumference, blood pressure, resting heart rate, triglycerides, cholesterol, glucose, HbA1c). Geographic clustering was assessed using Intra-Class Correlation (ICC) coefficients in biomedical cohorts from Adelaide (Australia, n = 3893) and Paris (France, n = 6430) for eight geographic administrative units. The median ICC was 0.01 suggesting 1% of risk factor variance attributable to variation between geographic units. Clustering differed by cardiometabolic parameters, administrative units and countries and was greatest for BMI and resting heart rate in the French sample, HbA1c in the Australian sample, and for smaller geographic units. Analytic inefficiency due to clustering was greatest for geographic units in which participants were nested in fewer, larger geographic units. Differences observed in geographic clustering across risk factors have implications for choice of geographic unit in sampling and analysis, and highlight potential cross-country differences in the distribution, or role, of environmental features related to cardiometabolic health. PMID:27213423

Career Orientation Curriculum Guide: 7-8.

ERIC Educational Resources Information Center

Willoughby-Eastlake School District, Willoughby, OH.

The Ohio Career Development Model at the 7th and 8th grade level, the career orientation segment, states that students are to be exposed or oriented to the 15 USOE occupational clusters. Units are outlined relating each subject area to a specific cluster or clusters. Each unit includes a developmental objective, related behavioral objectives, and…

Transportation: Grade 8. Cluster IV.

ERIC Educational Resources Information Center

Calhoun, Olivia H.

A curriculum guide for grade 8, the document is devoted to the occupational cluster "Transportation." It is divided into five units: surface transportation, interstate transportation, air transportation, water transportation, and subterranean transportation (the Metro). Each unit is introduced by a statement of the topic, the unit's…

Propensity score matching with clustered data. An application to the estimation of the impact of caesarean section on the Apgar score.

PubMed

Arpino, Bruno; Cannas, Massimo

2016-05-30

This article focuses on the implementation of propensity score matching for clustered data. Different approaches to reduce bias due to cluster-level confounders are considered and compared using Monte Carlo simulations. We investigated methods that exploit the clustered structure of the data in two ways: in the estimation of the propensity score model (through the inclusion of fixed or random effects) or in the implementation of the matching algorithm. In addition to a pure within-cluster matching, we also assessed the performance of a new approach, 'preferential' within-cluster matching. This approach first searches for control units to be matched to treated units within the same cluster. If matching is not possible within-cluster, then the algorithm searches in other clusters. All considered approaches successfully reduced the bias due to the omission of a cluster-level confounder. The preferential within-cluster matching approach, combining the advantages of within-cluster and between-cluster matching, showed a relatively good performance both in the presence of big and small clusters, and it was often the best method. An important advantage of this approach is that it reduces the number of unmatched units as compared with a pure within-cluster matching. We applied these methods to the estimation of the effect of caesarean section on the Apgar score using birth register data. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Carbonate Complexation of Mn2+ in Aqueous Phase

PubMed Central

Dasgupta, Jyotishman; Tyryshkin, Alexei M.; Kozlov, Yuri N.; Klimov, Vyacheslav V.; Dismukes, G. Charles

2008-01-01

The chemical speciation of Mn2+ within cells is critical for its transport, availability and redox properties. Herein we investigate the redox behavior and complexation equilibria of Mn2+ in aqueous solutions of bicarbonate by voltametry and electron paramagnetic resonance (EPR) spectroscopy, and discuss the implications for the uptake of Mn2+ by mangano-cluster enzymes like photosystem II (PSII). Both the electrochemical reduction of Mn2+ to Mn0 at an Hg electrode and EPR (in the absence of a polarizing electrode), revealed formation of 1:1 and 1:2 Mn-(bi)carbonate complexes as a function of Mn2+ and bicarbonate concentrations. Pulsed EPR spectroscopy, including ENDOR, ESEEM and 2D-HYSCORE, were used to probe the hyperfine couplings to 1H and 13C nuclei of the ligand(s) bound to Mn2+. For the 1:2 complex the complete 13C hyperfine tensor for one of the (bi)carbonate ligands was determined and it was established that this ligand coordinates to Mn2+ in bidentate mode with 13C-Mn distance of 2.85 ± 0.1 Å. The second (bi)carbonate ligand in the 1:2 complex coordinates possibly in monodentate mode, which is structurally less defined, and its 13C signal is broad and unobservable. 1H ENDOR reveals that 1-2 water ligands are lost upon binding of one bicarbonate ion in the 1:1 complex while 3-4 water ligands are lost upon forming the 1:2 complex. Thus, we deduce that the dominant species above 0.1 M bicarbonate concentration is the 1:2 complex, [Mn(CO3)(HCO3)(OH2)3]-. PMID:16526753

Poly[bis­[μ2-1,4-bis­(1H-imidazol-1-yl)butane]­dichloridonickel(II)

PubMed Central

Zhang, Jia; Song, Jiang-Feng

2011-01-01

The asymmetric unit of the title compound, [NiCl2(C10H14N4)2]n, consists of one Ni2+ ion which is located on an inversion center, one 1,4-bis­(imidazol-1-yl)butane (bimb) and one chloride ion. The Ni2+ ion exhibits a distorted octa­hedral coordination environment defined by four N atoms from four bimb ligands in the equatorial plane and two chloride ions in axial positions. The bridging coordination mode of the bimb ligands leads to the formation of inter­penetrating square Ni4(bimb)4 units that are arranged parallel to (001). The separation between the Ni atoms in these units is 13.740 (3) Å. PMID:22219855

Poly[tetra­aqua­(μ6-9,10-dioxo-9,10-dihydro­anthracene-1,4,5,8-tetra­carboxyl­ato)dimanganese(II)

PubMed Central

Xu, Rui; Liu, Jian-Lan

2012-01-01

The title complex, [Mn2(C18H4O10)(H2O)4]n, was synthesized from manganese(II) chloride tetra­hydrate and 9,10-dioxo-9,10-dihydro­anthracene-1,4,5,8-tetra­carb­oxy­lic acid (H4AQTC) in water. The anthraquinone unit is located about a crystallographic center of inversion. Each asymmetric unit therefore contains one MnII atom, two water ligands and one half AQTC4− anion. The MnII atom is coordinated in a distorted octa­hedral geometry by four O atoms from three AQTC4− ligands and two water O atoms. Two of the carboxyl­ate groups coordinate one MnII atom in a chelating mode, whereas the others each coordinate two MnII atoms. Each AQTC4− tetra-anion therefore coordinates six different MnII ions and, as a result, a three-dimensional coordination polymer is formed. O—H⋯O hydrogen bonds, some of them bifurcated, between water ligands and neighboring water or anthraquinone ligands are observed in the crystal structure. PMID:22807779

Expression, purification, crystallization and preliminary X-ray analysis of the ligand-binding domain of metabotropic glutamate receptor 7

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muto, Takanori; Tsuchiya, Daisuke; Morikawa, Kosuke, E-mail: morikako@protein.osaka-u.ac.jp

2007-07-01

The ligand-binding domain of metabotropic glutamate receptor 7 has been overexpressed, purified, and crystallized by the hanging-drop vapour-diffusion method. A complete data set has been collected to 3.30 Å. Glutamate is the major excitatory neurotransmitter and its metabotropic glutamate receptor (mGluR) plays an important role in the central nervous system. The ligand-binding domain (LBD) of mGluR subtype 7 (mGluR7) was produced using the baculovirus expression system and purified from the culture medium. The purified protein was characterized by gel-filtration chromatography, SDS–PAGE and a ligand-binding assay. Crystals of mGluR7 LBD were grown at 293 K by the hanging-drop vapour-diffusion method. Themore » crystals diffracted X-rays to 3.30 Å resolution using synchrotron radiation and belong to the trigonal space group P3{sub 1}21, with unit-cell parameters a = b = 92.4, c = 114.3 Å. Assuming the presence of one protomer per crystallographic asymmetric unit, the Matthews coefficient V{sub M} was calculated to be 2.5 Å{sup 3} Da{sup −1} and the solvent content was 51%.« less

Using inositol as a biocompatible ligand for efficient transgene expression

PubMed Central

Zhang, Lei; Bellis, Susan L; Fan, Yiwen; Wu, Yunkun

2015-01-01

Transgene transfection techniques using cationic polymers such as polyethylenimines (PEIs) and PEI derivatives as gene vectors have shown efficacy, although they also have shortcomings. PEIs have decent DNA-binding capability and good cell internalization performance, but they cannot deliver gene payloads very efficiently to cell nuclei. In this study, three hyperbranched polyglycerol-polyethylenimine (PG6-PEI) polymers conjugated with myo-inositol (INO) molecules were developed. The three resulting PG6-PEI-INO polymers have an increased number of INO ligands per molecule. PG6-PEI-INO 1 had only 14 carboxymethyl INO (CMINO) units per molecule. PG6-PEI-INO 2 had approximately 130 CMINO units per molecule. PG6-PEI-INO 3 had as high as 415 CMINO units approximately. Mixing PG6-PEI-INO polymers with DNA produced compact nanocomposites. We then performed localization studies using fluorescent microscopy. As the number of conjugated inositol ligands increased in PG6-PEI-INO polymers, there was a corresponding increase in accumulation of the polymers within 293T cell nuclei. Transfection performed with spherical 293T cells yielded 82% of EGFP-positive cells when using PG6-PEI-INO 3 as the vehicle. Studies further revealed that extracellular adenosine triphosphate (eATP) can inhibit the transgene efficiency of PG6-PEI-INO polymers, as compared with PEI and PG6-PEI that were not conjugated with inositol. Our work unveiled the possibility of using inositol as an effective ligand for transgene expression. PMID:25926732

Characterization of the ligand-binding site of the transferrin receptor in Trypanosoma brucei demonstrates a structural relationship with the N-terminal domain of the variant surface glycoprotein.

PubMed

Salmon, D; Hanocq-Quertier, J; Paturiaux-Hanocq, F; Pays, A; Tebabi, P; Nolan, D P; Michel, A; Pays, E

1997-12-15

The Trypanosoma brucei transferrin (Tf) receptor is a heterodimer encoded by ESAG7 and ESAG6, two genes contained in the different polycistronic transcription units of the variant surface glycoprotein (VSG) gene. The sequence of ESAG7/6 differs slightly between different units, so that receptors with different affinities for Tf are expressed alternatively following transcriptional switching of VSG expression sites during antigenic variation of the parasite. Based on the sequence homology between pESAG7/6 and the N-terminal domain of VSGs, it can be predicted that the four blocks containing the major sequence differences between pESAG7 and pESAG6 form surface-exposed loops and generate the ligand-binding site. The exchange of a few amino acids in this region between pESAG6s encoded by different VSG units greatly increased the affinity for bovine Tf. Similar changes in other regions were ineffective, while mutations predicted to alter the VSG-like structure abolished the binding. Chimeric proteins containing the N-terminal dimerization domain of VSG and the C-terminal half of either pESAG7 or pESAG6, which contains the ligand-binding domain, can form heterodimers that bind Tf. Taken together, these data provided evidence that the T.brucei Tf receptor is structurally related to the N-terminal domain of the VSG and that the ligand-binding site corresponds to the exposed surface loops of the protein.

Growth of in situ functionalized luminescent silver nanoclusters by direct reduction and size focusing.

PubMed

Muhammed, Madathumpady Abubaker Habeeb; Aldeek, Fadi; Palui, Goutam; Trapiella-Alfonso, Laura; Mattoussi, Hedi

2012-10-23

We have used one phase growth reaction to prepare a series of silver nanoparticles (NPs) and luminescent nanoclusters (NCs) using sodium borohydride (NaBH(4)) reduction of silver nitrate in the presence of molecular scale ligands made of polyethylene glycol (PEG) appended with lipoic acid (LA) groups at one end and reactive (-COOH/-NH(2)) or inert (-OCH(3)) functional groups at the other end. The PEG segment in the ligand promotes solubility in a variety of solvents including water, while LAs provide multidentate coordinating groups that promote Ag-ligand complex formation and strong anchoring onto the NP/NC surface. The particle size and properties were primarily controlled by varying the Ag-to-ligand (Ag:L) molar ratios and the molar amount of NaBH(4) used. We found that while higher Ag:L ratios produced NPs, luminescent NCs were formed at lower ratios. We also found that nonluminescent NPs can be converted into luminescent clusters, via a process referred to as "size focusing", in the presence of added excess ligands and reducing agent. The nanoclusters emit in the far red region of the optical spectrum with a quantum yield of ~12%. They can be redispersed in a number of solvents with varying polarity while maintaining their optical and spectroscopic properties. Our synthetic protocol also allowed control over the number and type of reactive functional groups per nanocluster.

Structural variation in transition-metal bispidine compounds.

PubMed

Comba, Peter; Kerscher, Marion; Merz, Michael; Müller, Vera; Pritzkow, Hans; Remenyi, Rainer; Schiek, Wolfgang; Xiong, Yun

2002-12-16

The experimentally determined molecular structures of 40 transition metal complexes with the tetradentate bispyridine-substituted bispidone ligand, 2,4-bis(2-pyridine)-3,7-diazabicyclo[3.3.1]nonane-9-one [M(bisp)XYZ]n+; M = CrIII, MnII, FeII, CoII, CuII, CuI, ZnII; X, Y, Z = mono- or bidentate co-ligands; penta-, hexa- or heptacoordinate complexes) are characterized in detail, supported by force-field and DFT calculations. While the bispidine ligand is very rigid (N3...N7 distance = 2.933 +/- 0.025 A), it tolerates a large range of metal-donor bond lengths (2.07 A < sigma(M-N)/4 < 2.35 A). Of particular interest is the ratio of the bond lengths between the metal center and the two tertiary amine donors (0.84 A < M-N3/M-N7 < 1.05 A) and the fact that, in terms of this ratio there seem to be two clusters with M-N3 < M-N7 and M-N3 > or = M-N7. Calculations indicate that the two structural types are close to degenerate, and the structural form therefore depends on the metal ion, the number and type of co-ligands, as well as structural variations of the bispidine ligand backbone. Tuning of the structures is of importance since the structurally differing complexes have very different stabilities and reactivities.

Chemistry in acetone complexes of metal dications: a remarkable ethylene production pathway.

PubMed

Wu, Jianhua; Liu, Dan; Zhou, Jian-Ge; Hagelberg, Frank; Park, Sung Soo; Shvartsburg, Alexandre A

2007-06-07

Electrospray ionization can generate microsolvated multiply charged metal ions for various metals and ligands, allowing exploration of chemistry within such clusters. The finite size of these systems permits comparing experimental results with accurate calculations, creating a natural laboratory to research ion solvation. Mass spectrometry has provided much insight into the stability and dissociation of ligated metal cations. While solvated singly charged ions tend to shrink by ligand evaporation, solvated polycations below a certain size exhibit charge reduction and/or ligand fragmentation due to organometallic reactions. Here we investigate the acetone complexes of representative divalent metals (Ca, Mn, Co, Ni, and Cu), comparing the results of collision-induced dissociation with the predictions of density functional theory. As for other solvated dications, channels involving proton or electron transfer compete with ligand loss and become dominant for smaller complexes. The heterolytic C-C bond cleavage is common, like in DMSO and acetonitrile complexes. Of primary interest is the unanticipated neutral ethylene loss, found for all metals studied except Cu and particularly intense for Ca and Mn. We focus on understanding that process in the context of competing dissociation pathways, as a function of metal identity and number of ligands. According to first-principles modeling, ethylene elimination proceeds along a complex path involving two intermediates. These results suggest that chemistry in microsolvated multiply charged ions may still hold major surprises.

Ligand-Enhanced Optical Response of Gold Nanomolecules and Its Fragment Projection Analysis: The Case of Au 30 (SR) 18

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sementa, Luca; Barcaro, Giovanni; Baseggio, Oscar

Here we investigate via first-principles simulations the optical absorption spectra of three different Au30(SR)18 monolayer-protected clusters (MPC): Au30(StBu)18, which is known in the literature and whose crystal structure is available, and two species – Au30(SPh)18 and Au30(SPh-pNO2)18 – which have been designed by replacing the tert-butyl organic residues with aromatic ones so as to investigate the effects of ligand replacement on the optical response of Au nanomolecules. In analogy with previously studied but rather different Au23(SR)16- anionic species, a substantial ligand-enhancement of the absorption intensity in the optical region is obtained for the Au30(SPhpNO2)18 neutral MPC. This demonstrates that usingmore » conjugated aromatic ligands with properly chosen electron withdrawal substituents and exhibiting steric hindrance so as to also achieve charge decompression at the surface is a general approach to enhance MPC photo-absorption intensity in the optical region. Moreover, the ligand-enhancement phenomenon is subjected to a detailed analysis based on fragment projection of electronic excited states and on induced transition densities, leading to a better understanding of its physical origin, thus opening avenues to its more precise control and exploitation.« less

Reversible Self-Assembly of Glutathione-Coated Gold Nanoparticle Clusters via pH-Tunable Interactions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moaseri, Ehsan; Bollinger, Jonathan A.; Changalvaie, Behzad

In this study, nanoparticle (NP) clusters with diameters ranging from 20 to 100 nm are reversibly assembled from 5 nm gold (Au) primary particles coated with glutathione (GSH) in aqueous solution as a function of pH in the range of 5.4 to 3.8. As the pH is lowered, the GSH surface ligands become partially zwitterionic and form interparticle hydrogen bonds that drive the self-limited assembly of metastable clusters in <1 min. Whereas clusters up to 20 nm in size are stable against cluster–cluster aggregation for up to 1 day, clusters up to 80 nm in size can be stabilized overmore » this period via the addition of citrate to the solution in equal molarity with GSH molecules. The cluster diameter may be cycled reversibly by tuning pH to manipulate the colloidal interactions; however, modest background cluster–cluster aggregation occurs during cycling. Cluster sizes can be stabilized for at least 1 month via the addition of PEG-thiol as a grafted steric stabilizer, where PEG-grafted clusters dissociate back to starting primary NPs at pH 7 in fewer than 3 days. Whereas the presence of excess citrate has little effect on the initial size of the metastable clusters, it is necessary for both the cycling and dissociation to mediate the GSH–GSH hydrogen bonds. In conclusion, these metastable clusters exhibit significant characteristics of equilibrium self-limited assembly between primary particles and clusters on time scales where cluster–cluster aggregation is not present.« less

Reversible Self-Assembly of Glutathione-Coated Gold Nanoparticle Clusters via pH-Tunable Interactions

DOE PAGES

Moaseri, Ehsan; Bollinger, Jonathan A.; Changalvaie, Behzad; ...

2017-10-06

In this study, nanoparticle (NP) clusters with diameters ranging from 20 to 100 nm are reversibly assembled from 5 nm gold (Au) primary particles coated with glutathione (GSH) in aqueous solution as a function of pH in the range of 5.4 to 3.8. As the pH is lowered, the GSH surface ligands become partially zwitterionic and form interparticle hydrogen bonds that drive the self-limited assembly of metastable clusters in <1 min. Whereas clusters up to 20 nm in size are stable against cluster–cluster aggregation for up to 1 day, clusters up to 80 nm in size can be stabilized overmore » this period via the addition of citrate to the solution in equal molarity with GSH molecules. The cluster diameter may be cycled reversibly by tuning pH to manipulate the colloidal interactions; however, modest background cluster–cluster aggregation occurs during cycling. Cluster sizes can be stabilized for at least 1 month via the addition of PEG-thiol as a grafted steric stabilizer, where PEG-grafted clusters dissociate back to starting primary NPs at pH 7 in fewer than 3 days. Whereas the presence of excess citrate has little effect on the initial size of the metastable clusters, it is necessary for both the cycling and dissociation to mediate the GSH–GSH hydrogen bonds. In conclusion, these metastable clusters exhibit significant characteristics of equilibrium self-limited assembly between primary particles and clusters on time scales where cluster–cluster aggregation is not present.« less

Efficient electrocatalytic conversion of CO.sub.2 to CO using ligand-protected Au.sub.25 clusters

DOEpatents

Kauffman, Douglas; Matranga, Christopher; Qian, Huifeng; Jin, Rongchao; Alfonso, Dominic R.

2015-09-22

An apparatus and method for CO.sub.2 reduction using an Au.sub.25 electrode. The Au.sub.25 electrode is comprised of ligand-protected Au.sub.25 having a structure comprising an icosahedral core of 13 atoms surrounded by a shell of six semi-ring structures bonded to the core of 13 atoms, where each semi-ring structure is typically --SR--Au--SR--Au--SR or --SeR--Au--SeR--Au--SeR. The 12 semi-ring gold atoms within the six semi-ring structures are stellated on 12 of the 20 faces of the icosahedron of the Au.sub.13 core, and organic ligand --SR or --SeR groups are bonded to the Au.sub.13 core with sulfur or selenium atoms. The Au.sub.25 electrode and a counter-electrode are in contact with an electrolyte comprising CO.sub.2 and H+, and a potential of at least -0.1 volts is applied from the Au.sub.25 electrode to the counter-electrode.

Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Salaita, Khalid; Nair, Pradeep M; Petit, Rebecca S

2009-09-09

Activation of the EphA2 receptor tyrosine kinase by ephrin-A1 ligands presented on apposed cell surfaces plays important roles in development and exhibits poorly understood functional alterations in cancer. We reconstituted this intermembrane signaling geometry between live EphA2-expressing human breast cancer cells and supported membranes displaying laterally mobile ephrin-A1. Receptor-ligand binding, clustering, and subsequent lateral transport within this junction were observed. EphA2 transport can be blocked by physical barriers nanofabricated onto the underlying substrate. This physical reorganization of EphA2 alters the cellular response to ephrin-A1, as observed by changes in cytoskeleton morphology and recruitment of a disintegrin and metalloprotease 10. Quantitativemore » analysis of receptor-ligand spatial organization across a library of 26 mammary epithelial cell lines reveals characteristic differences that strongly correlate with invasion potential. These observations reveal a mechanism for spatio-mechanical regulation of EphA2 signaling pathways.« less

High-Throughput Screening based Identification of Small Molecule Antagonists of Integrin CD11b/CD18 Ligand Binding

PubMed Central

Faridi, Mohd Hafeez; Maiguel, Dony; Brown, Brock T.; Suyama, Eigo; Barth, Constantinos J.; Hedrick, Michael; Vasile, Stefan; Sergienko, Eduard; Schürer, Stephan; Gupta, Vineet

2010-01-01

Binding of leukocyte specific integrin CD11b/CD18 to its physiologic ligands is important for the development of normal immune response in vivo. Integrin CD11b/CD18 is also a key cellular effector of various inflammatory and autoimmune diseases. However, small molecules selectively inhibiting the function of integrin CD11b/CD18 are currently lacking. We used a newly described cell-based high throughput screening assay to identify a number of highly potent antagonists of integrin CD11b/CD18 from chemical libraries containing >100,000 unique compounds. Computational analyses suggest that the identified compounds cluster into several different chemical classes. A number of the newly identified compounds blocked adhesion of wild-type mouse neutrophils to CD11b/CD18 ligand fibrinogen. Mapping the most active compounds against chemical fingerprints of known antagonists of related integrin CD11a/CD18 shows little structural similarity, suggesting that the newly identified compounds are novel and unique. PMID:20188705

Hydrogels with tunable stress relaxation regulate stem cell fate and activity

PubMed Central

Chaudhuri, Ovijit; Gu, Luo; Klumpers, Darinka; Darnell, Max; Bencherif, Sidi A.; Weaver, James C.; Huebsch, Nathaniel; Lee, Hong-pyo; Lippens, Evi; Duda, Georg N.; Mooney, David J.

2015-01-01

Natural extracellular matrices (ECMs) are viscoelastic and exhibit stress relaxation. However, hydrogels used as synthetic ECMs for three-dimensional (3D) culture are typically elastic. Here, we report a materials approach to tune the rate of stress relaxation of hydrogels for 3D culture, independently of the hydrogel’s initial elastic modulus, cell-adhesion-ligand density and degradation. We find that cell spreading, proliferation, and osteogenic differentiation of mesenchymal stem cells (MSCs) are all enhanced in cells cultured in gels with faster relaxation. Strikingly, MSCs form a mineralized, collagen-1-rich matrix similar to bone in rapidly relaxing hydrogels with an initial elastic modulus of 17 kPa. We also show that the effects of stress relaxation are mediated by adhesion-ligand binding, actomyosin contractility and mechanical clustering of adhesion ligands. Our findings highlight stress relaxation as a key characteristic of cell-ECM interactions and as an important design parameter of biomaterials for cell culture. PMID:26618884

Determination of the equilibrium constant of C60 fullerene binding with drug molecules.

PubMed

Mosunov, Andrei A; Pashkova, Irina S; Sidorova, Maria; Pronozin, Artem; Lantushenko, Anastasia O; Prylutskyy, Yuriy I; Parkinson, John A; Evstigneev, Maxim P

2017-03-01

We report a new analytical method that allows the determination of the magnitude of the equilibrium constant of complexation, K h , of small molecules to C 60 fullerene in aqueous solution. The developed method is based on the up-scaled model of C 60 fullerene-ligand complexation and contains the full set of equations needed to fit titration datasets arising from different experimental methods (UV-Vis spectroscopy, 1 H NMR spectroscopy, diffusion ordered NMR spectroscopy, DLS). The up-scaled model takes into consideration the specificity of C 60 fullerene aggregation in aqueous solution and allows the highly dispersed nature of C 60 fullerene cluster distribution to be accounted for. It also takes into consideration the complexity of fullerene-ligand dynamic equilibrium in solution, formed by various types of self- and hetero-complexes. These features make the suggested method superior to standard Langmuir-type analysis, the approach used to date for obtaining quantitative information on ligand binding with different nanoparticles.

A microporous lanthanum metal-organic framework as a bi-functional chemosensor for the detection of picric acid and Fe(3+) ions.

PubMed

Zhang, Chuanqi; Yan, Yan; Pan, Qinhe; Sun, Libo; He, Hongming; Liu, Yunling; Liang, Zhiqiang; Li, Jiyang

2015-08-07

A microporous lanthanum metal-organic framework [La(TPT)(DMSO)2]·H2O (La-MOF ()), has been synthesized using a rigid unsymmetrical tricarboxylate ligand of p-terphenyl-3,4'',5-tricarboxylic acid (H3TPT). The structure of is constructed by bi-nuclear lanthanum clusters and fully deprotonated TPT(3-) ligands, which can be simplified into a 3,6-connected flu-3,6-C2/c topology with a point symbol of (4(4)·6)2(4·6(2)·8(7)·10(2)). The π-electron rich ligand H3TPT enables to have blue luminescence when excited at 342 nm at ambient temperature. Meanwhile, exhibits the selective detection of picric acid (PA) and Fe(3+) ions in ethanol solution over other nitroaromatic compounds and metal ions. The high quenching efficiency and selectivity of makes it a potential bi-functional chemosensor for both PA and Fe(3+) ions.

Polymeric Cd(II), trinuclear and mononuclear Ni(II) complexes of 5-methyl-4-phenyl-1,2,4-triazole-3-thione: Synthesis, structural characterization, thermal behaviour, fluorescence properties and antibacterial activity

NASA Astrophysics Data System (ADS)

Bharty, M. K.; Paswan, S.; Dani, R. K.; Singh, N. K.; Sharma, V. K.; Kharwar, R. N.; Butcher, R. J.

2017-02-01

Syntheses of a polymeric Cd(II) complex, [Cd(mptt)2]n (1), a trinuclear Ni(II) complex, [Ni3(μ-mptt)4(μ-H2O)2(H2O)2(ttfa)2]·3H2O (2) and a mononuclear Ni(II) complex [Ni(mptt)2(en)2] (3) have been performed using the ligand 5-methyl-4-phenyl-1,2,4-triazole-3-thione (Hmptt) and nickel(II)/cadmium(II) salts {ttfa = thenoyltrifluroacetonate). The ligand and the complexes have been characterized by various physicochemical methods in addition to their single crystal X-ray structure. The Cd centre in complex 1 adopts a distorted tetrahedral geometry with one sulfur atom and two mptt ligands provide three nitrogen atoms from three triazole units. The sulfur atom of the ligand binds covalently and overall the ligand acts as uninigative N,S/N,N bidentate moiety. The polymeric structure of complex 1 results from the N atoms of the neighboring triazole units coordinating with the Cd(II) centre. The three Ni(II) centres in the trinuclear Ni(II) complex 2 form a linear arrangement and all have six coordinated arrangements. The middle Ni(II) binds with four deprotonated triazole ring nitrogens and two water molecules form two bridges. The terminal Ni(II) centres bind through two thenoyl oxygens, two triazole nitrogens and water molecules that formed bridges with the middle Ni centre. In complex 3, the nickel(II) centre is covalently bonded through two deprotonated triazole ring nitrogens from two ligand moieties and other four sites are occupied by four nitrogens from two bidentate en ligands. Thermogravimetric analyses (TGA) of the complexes indicated for NiO as the final residue. The bioefficacy of the ligand and complexes 2 and 3 have been examined against the growth of bacteria to evaluate their anti-microbial potential. Complex 2 showed high antibacterial activity as compared to the ligand and complex 3. Complexes 1, 2 and 3 are fluorescent materials with maximum emissions at 425, 421 and 396 nm at an excitation wavelength of 323, 348 and 322 nm, respectively.

Capping Ligand Vortices as “Atomic Orbitals” in Nanocrystal Self-Assembly

DOE PAGES

Waltmann, Curt; Horst, Nathan; Travesset, Alex

2017-10-27

In this work, we present a detailed analysis of the interaction between two nanocrystals capped with ligands consisting of hydrocarbon chains by united atom molecular dynamics simulations. We show that the bonding of two nanocrystals is characterized by ligand textures in the form of vortices. These results are generalized to nanocrystals of different types (differing core and ligand sizes) where the structure of the vortices depends on the softness asymmetry. We provide rigorous calculations for the binding free energy, show that these energies are independent of the chemical composition of the cores, and derive analytical formulas for the equilibrium separation.more » We discuss the implications of our results for the self-assembly of single-component and binary nanoparticle superlattices. Overall, our results show that the structure of the ligands completely determines the bonding of nanocrystals, fully supporting the predictions of the recently proposed Orbifold topological model.« less

Capping Ligand Vortices as "Atomic Orbitals" in Nanocrystal Self-Assembly.

PubMed

Waltmann, Curt; Horst, Nathan; Travesset, Alex

2017-11-28

We present a detailed analysis of the interaction between two nanocrystals capped with ligands consisting of hydrocarbon chains by united atom molecular dynamics simulations. We show that the bonding of two nanocrystals is characterized by ligand textures in the form of vortices. These results are generalized to nanocrystals of different types (differing core and ligand sizes) where the structure of the vortices depends on the softness asymmetry. We provide rigorous calculations for the binding free energy, show that these energies are independent of the chemical composition of the cores, and derive analytical formulas for the equilibrium separation. We discuss the implications of our results for the self-assembly of single-component and binary nanoparticle superlattices. Overall, our results show that the structure of the ligands completely determines the bonding of nanocrystals, fully supporting the predictions of the recently proposed Orbifold topological model.

Protein-ligand complex structure from serial femtosecond crystallography using soaked thermolysin microcrystals and comparison with structures from synchrotron radiation.

PubMed

Naitow, Hisashi; Matsuura, Yoshinori; Tono, Kensuke; Joti, Yasumasa; Kameshima, Takashi; Hatsui, Takaki; Yabashi, Makina; Tanaka, Rie; Tanaka, Tomoyuki; Sugahara, Michihiro; Kobayashi, Jun; Nango, Eriko; Iwata, So; Kunishima, Naoki

2017-08-01

Serial femtosecond crystallography (SFX) with an X-ray free-electron laser is used for the structural determination of proteins from a large number of microcrystals at room temperature. To examine the feasibility of pharmaceutical applications of SFX, a ligand-soaking experiment using thermolysin microcrystals has been performed using SFX. The results were compared with those from a conventional experiment with synchrotron radiation (SR) at 100 K. A protein-ligand complex structure was successfully obtained from an SFX experiment using microcrystals soaked with a small-molecule ligand; both oil-based and water-based crystal carriers gave essentially the same results. In a comparison of the SFX and SR structures, clear differences were observed in the unit-cell parameters, in the alternate conformation of side chains, in the degree of water coordination and in the ligand-binding mode.

Highly efficient bioinspired molecular Ru water oxidation catalysts with negatively charged backbone ligands.

PubMed

Duan, Lele; Wang, Lei; Li, Fusheng; Li, Fei; Sun, Licheng

2015-07-21

The oxygen evolving complex (OEC) of the natural photosynthesis system II (PSII) oxidizes water to produce oxygen and reducing equivalents (protons and electrons). The oxygen released from PSII provides the oxygen source of our atmosphere; the reducing equivalents are used to reduce carbon dioxide to organic products, which support almost all organisms on the Earth planet. The first photosynthetic organisms able to split water were proposed to be cyanobacteria-like ones appearing ca. 2.5 billion years ago. Since then, nature has chosen a sustainable way by using solar energy to develop itself. Inspired by nature, human beings started to mimic the functions of the natural photosynthesis system and proposed the concept of artificial photosynthesis (AP) with the view to creating energy-sustainable societies and reducing the impact on the Earth environments. Water oxidation is a highly energy demanding reaction and essential to produce reducing equivalents for fuel production, and thereby effective water oxidation catalysts (WOCs) are required to catalyze water oxidation and reduce the energy loss. X-ray crystallographic studies on PSII have revealed that the OEC consists of a Mn4CaO5 cluster surrounded by oxygen rich ligands, such as oxyl, oxo, and carboxylate ligands. These negatively charged, oxygen rich ligands strongly stabilize the high valent states of the Mn cluster and play vital roles in effective water oxidation catalysis with low overpotential. This Account describes our endeavors to design effective Ru WOCs with low overpotential, large turnover number, and high turnover frequency by introducing negatively charged ligands, such as carboxylate. Negatively charged ligands stabilized the high valent states of Ru catalysts, as evidenced by the low oxidation potentials. Meanwhile, the oxygen production rates of our Ru catalysts were improved dramatically as well. Thanks to the strong electron donation ability of carboxylate containing ligands, a seven-coordinate Ru(IV) species was isolated as a reaction intermediate, shedding light on the reaction mechanisms of Ru-catalyzed water oxidation chemistry. Auxiliary ligands have dramatic effects on the water oxidation catalysis in terms of the reactivity and the reaction mechanism. For instance, Ru-bda (H2bda = 2,2'-bipyridine-6,6'-dicarboxylic acid) water oxidation catalysts catalyze Ce(IV)-driven water oxidation extremely fast via the radical coupling of two Ru(V)═O species, while Ru-pda (H2pda = 1,10-phenanthroline-2,9-dicarboxylic acid) water oxidation catalysts catalyze the same reaction slowly via water nucleophilic attack on a Ru(V)═O species. With a number of active Ru catalysts in hands, light driven water oxidation was accomplished using catalysts with low catalytic onset potentials. The structures of molecular catalysts could be readily tailored to introduce additional functional groups, which favors the fabrication of state-of-the-art Ru-based water oxidation devices, such as electrochemical water oxidation anodes and photo-electrochemical anodes. The development of efficient water oxidation catalysts has led to a step forward in the sustainable energy system.

A flexible docking scheme to explore the binding selectivity of PDZ domains

PubMed Central

Gerek, Z Nevin; Ozkan, S Banu

2010-01-01

Modeling of protein binding site flexibility in molecular docking is still a challenging problem due to the large conformational space that needs sampling. Here, we propose a flexible receptor docking scheme: A dihedral restrained replica exchange molecular dynamics (REMD), where we incorporate the normal modes obtained by the Elastic Network Model (ENM) as dihedral restraints to speed up the search towards correct binding site conformations. To our knowledge, this is the first approach that uses ENM modes to bias REMD simulations towards binding induced fluctuations in docking studies. In our docking scheme, we first obtain the deformed structures of the unbound protein as initial conformations by moving along the binding fluctuation mode, and perform REMD using the ENM modes as dihedral restraints. Then, we generate an ensemble of multiple receptor conformations (MRCs) by clustering the lowest replica trajectory. Using RosettaLigand, we dock ligands to the clustered conformations to predict the binding pose and affinity. We apply this method to postsynaptic density-95/Dlg/ZO-1 (PDZ) domains; whose dynamics govern their binding specificity. Our approach produces the lowest energy bound complexes with an average ligand root mean square deviation of 0.36 Å. We further test our method on (i) homologs and (ii) mutant structures of PDZ where mutations alter the binding selectivity. In both cases, our approach succeeds to predict the correct pose and the affinity of binding peptides. Overall, with this approach, we generate an ensemble of MRCs that leads to predict the binding poses and specificities of a protein complex accurately. PMID:20196074

Formation, Fragmentation, and Structures of YxOy(+) (x = 1, 2, y = 1 - 13) Clusters: Collision-Induced Dissociation Experiments and Density Functional Theory Calculations.

PubMed

Glodić, Pavle; Mihesan, Claudia; Klontzas, Emmanouel; Velegrakis, Michalis

2016-02-25

Yttrium oxide cluster cations have been experimentally and theoretically studied. We produced small, oxygen-rich yttrium oxide clusters, YxOy+ (x = 1, 2, y = 1–13), by mixing the laser-produced yttrium plasma with a molecular oxygen jet. Mass spectrometry measurements showed that the most stable clusters are those consisting of one yttrium and an odd number of oxygen atoms of the form YO(+)(2k+1) (k = 0–6). Additionally, we performed collision induced dissociation experiments, which indicated that the loss of pairs of oxygen atoms down to a YO+ core is the preferred fragmentation channel for all clusters investigated. Furthermore, we conduct DFT calculations and we obtained two types of low-energy structures: one containing an yttrium cation core and the other composed of YO+ core and O2 ligands, being in agreement with the observed fragmentation pattern. Finally, from the fragmentation studies, total collision cross sections are obtained and these are compared with geometrical cross sections of the calculated structures.

75 FR 44937 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-30

... is a block cluster, which consists of one or more contiguous census blocks. The P sample is a sample of housing units and persons obtained independently from the census for a sample of block clusters. The E sample is a sample of census housing units and enumerations in the same block of clusters as the...

Construction and Environment: Grade 7. Cluster IV.

ERIC Educational Resources Information Center

Calhoun, Olivia H.

A curriculum guide for grade 7, the document is devoted to the occupational cluster "Construction and Environment." It is divided into four units: urban renewal and development, urban and suburban construction and planning, megalopolis, and demography. Each unit is introduced by a statement of the topic, the unit's purpose, main ideas,…

Many Mg-Mg bonds form the core of the Mg16Cp*8Br4K cluster anion: the key to a reassessment of the Grignard reagent (GR) formation process?

PubMed

Kruczyński, T; Henke, F; Neumaier, M; Bowen, K H; Schnöckel, H

2016-02-01

It caused a sensation eight years ago, when the first room temperature stable molecular compound with a Mg-Mg bond (LMgMgL, L = chelating ligand) containing magnesium in the oxidation state +1 was prepared. Here, we report the preparation of a [Mg 16 Cp*8Br 4 K] - cluster anion (Cp* = pentamethylcyclopentadiene) with 27 Mg-Mg bonds. It has been obtained through the reaction of KCp* with a metastable solution of MgBr in toluene. A highly-resolved Fourier transform mass spectrum (FT-MS) of this cluster anion, brought into vacuum by electrospraying its solution in THF, provides the title cluster's stoichiometry. This Mg 16 cluster together with experiments on the metastable solution of MgBr show that: during the formation process of GRs (Grignard reagents) which are involved in most of sophisticated syntheses of organic products, not the highly reactive MgBr radical as often presumed, but instead the metalloid Mg 16 Cp*8Br 4 cluster anion and its related cousins that are the operative intermediates along the pathway from Mg metal to GRs ( e.g. Cp*MgBr).

Synthesis, Characterization, and Reactivity of Functionalized Trinuclear Iron–Sulfur Clusters – A New Class of Bioinspired Hydrogenase Models

PubMed Central

Kaiser, Manuel; Knör, Günther

2015-01-01

The air- and moisture-stable iron–sulfur carbonyl clusters Fe3S2(CO)7(dppm) (1) and Fe3S2(CO)7(dppf) (2) carrying the bisphosphine ligands bis(diphenylphosphanyl)methane (dppm) and 1,1′-bis(diphenylphosphanyl)ferrocene (dppf) were prepared and fully characterized. Two alternative synthetic routes based on different thionation reactions of triiron dodecacarbonyl were tested. The molecular structures of the methylene-bridged compound 1 and the ferrocene-functionalized derivative 2 were determined by single-crystal X-ray diffraction. The catalytic reactivity of the trinuclear iron–sulfur cluster core for proton reduction in solution at low overpotential was demonstrated. These deeply colored bisphosphine-bridged sulfur-capped iron carbonyl systems are discussed as promising candidates for the development of new bioinspired model compounds of iron-based hydrogenases. PMID:26512211

Characteristics Of Bridging Oxo And Sulfido Groups In Multinuclear Iron Proteins

NASA Astrophysics Data System (ADS)

Loehr, Thomas M.

1989-07-01

The presence of oxo-bridged dinuclear iron clusters has been established in the respiratory protein, hemerythrin (Hr), and in the DNA-biosynthesis regulatory enzyme, ribonucleotide reductase (Rr). For the iron proteins uteroferrin and purple acid phosphatase (PAP) evidence for μ-oxo-bridged centers is less clear. Resonance Raman (RR) spectra obtained by excitation into an 0(2-) --> Fe(III) CT band may show strong symmetric and weak antisymmetric Fe-0-Fe vibrational modes. We have investigated the spectra of a variety of μ-oxo-bridged Fe(III) complexes to establish the dependence of Raman scattering intensities upon structural parameters. Intensities were found to relate to the nature of the ligand trans to the oxo group: nitrogen ligands with unsaturation (e.g., pyrazole and imidazole) lead to strong scattering, whereas saturated ligands provide only poor scattering. The Fe-0 bonds in Hr and Rr are strong scatterers; the former is known from x-ray crystallography to have a histidyl ligand trans to the μ-oxo group. On this basis, a similar ligand structure is likely in the reductase. In contrast, PAP shows no oxo-bridge with UV and near-UV excitation. We propose that a different structural framework is necessary to account for this result. Hydrogen bonding of protein side chains to oxo and sulfido ligands is proposed to explain changes in frequencies for samples dissolved in water vs. D20. Differences in hydrogen-bond strengths between 0...(D) and S...(D) systems are transferred to the observed Fe-0 and Fe-S bond vibrations.

Nanosized (mu12-Pt)Pd164-xPtx(CO)72(PPh3)20 (x approximately 7) containing Pt-centered four-shell 165-atom Pd-Pt core with unprecedented intershell bridging carbonyl ligands: comparative analysis of icosahedral shell-growth patterns with geometrically related Pd145(CO)x(PEt3)30 (x approximately 60) containing capped three-shell Pd145 core.

PubMed

Mednikov, Evgueni G; Jewell, Matthew C; Dahl, Lawrence F

2007-09-19

Presented herein are the preparation and crystallographic/microanalytical/magnetic/spectroscopic characterization of the Pt-centered four-shell 165-atom Pd-Pt cluster, (mu(12)-Pt)Pd(164-x)Pt(x)(CO)(72)(PPh(3))(20) (x approximately 7), 1, that replaces the geometrically related capped three-shell icosahedral Pd(145) cluster, Pd(145)(CO)(x)(PEt(3))(30) (x approximately 60), 2, as the largest crystallographically determined discrete transition metal cluster with direct metal-metal bonding. A detailed comparison of their shell-growth patterns gives rise to important stereochemical implications concerning completely unexpected structural dissimilarities as well as similarities and provides new insight concerning possible synthetic approaches for generation of multi-shell metal clusters. 1 was reproducibly prepared in small yields (<10%) from the reaction of Pd(10)(CO)(12)(PPh(3))(6) with Pt(CO)(2)(PPh(3))(2). Its 165-atom metal-core geometry and 20 PPh(3) and 72 CO ligands were established from a low-temperature (100 K) CCD X-ray diffraction study. The well-determined crystal structure is attributed largely to 1 possessing cubic T(h) (2/m3) site symmetry, which is the highest crystallographic subgroup of the noncrystallographic pseudo-icosahedral I(h) (2/m35) symmetry. The "full" four-shell Pd-Pt anatomy of 1 consists of: (a) shell 1 with the centered (mu(12)-Pt) atom encapsulated by the 12-atom icosahedral Pt(x)Pd(12-x) cage, x = 1.2(3); (b) shell 2 with the 42-atom nu(2) icosahedral Pt(x)Pd(42-x) cage, x = 3.5(5); (c) shell 3 with the anti-Mackay 60-atom semi-regular rhombicosidodecahedral Pt(x)Pd(60-x) cage, x = 2.2(6); (d) shell 4 with the 50-atom nu(2) pentagonal dodecahedral Pd(50) cage. The total number of crystallographically estimated Pt atoms, 8 +/- 3, which was obtained from least-squares (Pt(x)/Pd(1-x))-occupancy analysis of the X-ray data that conclusively revealed the central atom to be pure Pt (occupancy factor, x = 1.00(3)), is fortuitously in agreement with that of 7.6(7) found from an X-ray Pt/Pd microanalysis (WDS spectrometer) on three crystals of 1. Our utilization of this site-occupancy (Pt(x)Pd(1-x))-analysis for shells 1-3 originated from the microanalytical results; otherwise, the presumed metal-core composition would have been (mu(12)-Pt)Pd(164). [Alternatively, the (mu(12)-Pt)M(164) core-geometry of 1 may be viewed as a pseudo-Ih Pt-centered six-shell successive nu(1) polyhedral system, each with radially equivalent vertex atoms: Pt@M(12)(icosahedron)@M(30)(icosidodecahedron)@M(12)(icosahedron)@M(60)(rhombicosidodecahedron)@M(30)(icosidodecahedron)@M(20)(pentagonal dodecahedron)]. Completely surprising structural dissimilarities between 1 and 2 are: (1) to date 1 is only reproducibly isolated as a heterometallic Pd-Pt cluster with a central Pt instead of Pd atom; (2) the 50 atoms comprising the outer fourth nu(2) pentagonal dodecahedral shell in 1 are less than the 60 atoms of the inner third shell in 1, in contradistinction to shell-by-shell growth processes in all other known shell-based structures; (3) the 10 fewer PR3 ligands in 1 necessitate larger bulky PPh(3) ligands to protect the Pd-Pt core-geometry; (4) the 72 CO ligands consist of six bridging COs within each of the 12 pentagons in shell 4 that are coordinated to intershell metal atoms. SQUID magnetometry measurements showed a single-crystal sample of 1 to be diamagnetic over the entire temperature range of 10-300 K.