Synthesis, structure, computational and in-silico anticancer studies of N,N-diethyl-N‧-palmitoylthiourea

NASA Astrophysics Data System (ADS)

Asegbeloyin, Jonnie Niyi; Oyeka, Ebube Evaristus; Okpareke, Obinna; Ibezim, Akachukwu

2018-02-01

A new potential ONS donor ligand N,N-diethyl-N‧-palmitoylthiourea (PACDEA) with the molecular formular C21H42N2OS has been synthesized and characterized by ESI-MS, UV, FTIR 1H and 13C NMR spectroscopy and single X-ray crystallography. The asymmetric molecules crystallized in the centrosymmetric structure of monoclinic crystal system with space group P21/c. In the crystal structure of the compound, molecules are linked in a continuous chain by intermolecular Nsbnd H⋯Odbnd C hydrogen bonds, which stabilized the crystal structure. The palmitoyl moiety and N (2)-ethyl group lie on a plane, while the thiocarbonyl moiety is twisted and lying othorgonal to the plane. Non-covalent interaction (NCI) analysis on the hydrogen bonded solid state structure of the molecule revealed the presence of a significant number of non-covalent interactions including intermolecular hydrogen bonding interactions, Csbnd Hsbnd -lone pair interactions, weak Van der Waals interactions, and steric/ring closure interactions. The NCI analysis also showed the presence of intramolecular stabilizing Csbnd H⋯Odbnd C and Csbnd H⋯Sdbnd C interactions. Docking simulation revealed that the compound interacted favourably with ten selected validated anticancer drug targets, which is an indication that the compound could possess some anticancer properties.

Non-covalent interactions of the carcinogen (+)-anti-BPDE with exon 1 of the human K-ras proto-oncogene

NASA Astrophysics Data System (ADS)

Rodriguez, Jorge H.; Deligkaris, Christos

2013-03-01

Investigating the complementary, but different, effects of physical (non-covalent) and chemical (covalent) mutagen-DNA and carcinogen-DNA interactions is important for understanding possible mechanisms of development and prevention of mutagenesis and carcinogenesis. A highly mutagenic and carcinogenic metabolite of the polycyclic aromatic hydrocarbon benzo[ α]pyrene, namely (+)-anti-BPDE, is known to undergo both physical and chemical complexation with DNA. The major covalent adduct, a promutagenic, is known to be an external (+)-trans-anti-BPDE-N2-dGuanosine configuration whose origins are not fully understood. Thus, it is desirable to study the mechanisms of external non-covalent BPDE-DNA binding and their possible relationships to external covalent trans adduct formation. We present a detailed codon-by-codon computational study of the non-covalent interactions of (+)-anti-BPDE with DNA which explains and correctly predicts preferential (+)-anti-BPDE binding at minor groove guanosines. Due to its relevance to carcinogenesis, the interaction of (+)-anti-BPDE with exon 1 of the human K-ras gene has been studied in detail. Present address: Department of Physics, Drury University

Exploiting non-covalent π interactions for catalyst design

NASA Astrophysics Data System (ADS)

Neel, Andrew J.; Hilton, Margaret J.; Sigman, Matthew S.; Toste, F. Dean

2017-03-01

Molecular recognition, binding and catalysis are often mediated by non-covalent interactions involving aromatic functional groups. Although the relative complexity of these so-called π interactions has made them challenging to study, theory and modelling have now reached the stage at which we can explain their physical origins and obtain reliable insight into their effects on molecular binding and chemical transformations. This offers opportunities for the rational manipulation of these complex non-covalent interactions and their direct incorporation into the design of small-molecule catalysts and enzymes.

Exploiting non-covalent π interactions for catalyst design

PubMed Central

Neel, Andrew J.; Hilton, Margaret J.; Sigman, Matthew S.; Toste, F. Dean

2018-01-01

Molecular recognition, binding and catalysis are often mediated by non-covalent interactions involving aromatic functional groups. Although the relative complexity of these so-called π interactions has made them challenging to study, theory and modelling have now reached the stage at which we can explain their physical origins and obtain reliable insight into their effects on molecular binding and chemical transformations. This offers opportunities for the rational manipulation of these complex non-covalent interactions and their direct incorporation into the design of small-molecule catalysts and enzymes. PMID:28358089

Nature and consequences of non-covalent interactions between flavonoids and macronutrients in foods.

PubMed

Bordenave, Nicolas; Hamaker, Bruce R; Ferruzzi, Mario G

2014-01-01

Many of the potential health benefits of flavonoids have been associated with their specific chemical and biological properties including their ability to interact and bind non-covalently to macronutrients in foods. While flavonoid-protein interactions and binding have been the subject of intensive study, significantly less is understood about non-covalent interactions with carbohydrates and lipids. These interactions with macronutrients are likely to impact both the flavonoid properties in foods, such as their radical scavenging activity, and the food or beverage matrix itself, including their taste, texture and other sensorial properties. Overall, non-covalent binding of flavonoids with macronutrients is primarily driven by van der Waals interactions. From the flavonoid perspective, these interactions are modulated by characteristics such as degree of polymerization, molecular flexibility, number of external hydroxyl groups, or number of terminal galloyl groups. From the macronutrient standpoint, electrostatic and ionic interactions are generally predominant with carbohydrates, while hydrophobic interactions are generally predominant with lipids and mainly limited to interactions with flavonols. All of these interactions are involved in flavonoid-protein interactions. While primarily associated with undesirable characteristics in foods and beverages, such as astringency, negative impact on macronutrient digestibility and hazing, more recent efforts have attempted to leverage these interactions to develop controlled delivery systems or strategies to enhance flavonoids bioavailability. This paper aims at reviewing the fundamental bases for non-covalent interactions, their occurrence in food and beverage systems and their impact on the physico-chemical, organoleptic and some nutritional properties of food.

Chemically interconnected light-weight 3D-carbon nanotube solid network

DOE PAGES

Ozden, Sehmus; Tsafack, Thierry; Owuor, Peter S.; ...

2017-03-31

Owing to the weak physical interactions such as van der Waals and π-π interactions, which hold nanotubes together in carbon nanotube (CNT) bulk structures, the tubes can easily slide on each other. In creating covalent interconnection between individual carbon nanotube (CNT) structures we saw remarkable improvements in the properties of their three-dimensional (3D) bulk structures. The creation of such nanoengineered 3D solid structures with improved properties and low-density remains one of the fundamental challenges in real-world applications. We also report the scalable synthesis of low-density 3D macroscopic structure made of covalently interconnected nanotubes using free-radical polymerization method after functionalized CNTsmore » with allylamine monomers. The resulted interconnected highly porous solid structure exhibits higher mechanical properties, larger surface area and greater porosity than non-crosslinked nanotube structures. To gain further insights into the deformation mechanisms of nanotubes, fully atomistic reactive molecular dynamics simulations are used. Here we demonstrate one such utility in CO 2 uptake, whose interconnected solid structure performed better than non-interconnected structures.« less

Interaction of free arginine and guanidine with glucose under thermal processing conditions and formation of Amadori-derived imidazolones.

PubMed

Zhu, Yuchen; Yaylayan, Varoujan A

2017-04-01

To investigate the reactivity of free guanidine and arginine in the formation of imidazolinone derivatives, model systems of guanidine or arginine/glucose or 13 [C-6]-glucose were heated in aqueous solutions at110°C for 3h and the residues were analyzed by ESI/qTOF/MS using MS/MS and isotope labeling techniques. The analysis of the data indicated that guanidine and arginine formed both covalent and non-covalent interaction products. Covalent interactions included Amadori rearrangement at the α-nitrogen with glucose and imidazolinone formation with 3-deoxy-glucosone at the guanidine side-chain. Non-covalent interactions, such as self-interaction and interaction with free guanidine or arginine and glucose, were also observed. Guanidine underwent three sequential Amadori rearrangements and the free and mono-glycated guanidine also formed imidazolinone derivatives and their corresponding dehydration products and at the same time exhibiting various non-covalent interactions. On the other hand, arginine formed free Amadori product, free imidazolinone and Amadori-derived imidazolinone derivative in addition to methylglyoxal-derived hydroimidazolones. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preparation and characterization of malonic acid cross-linked chitosan and collagen 3D scaffolds: an approach on non-covalent interactions.

PubMed

Mitra, Tapas; Sailakshmi, G; Gnanamani, A; Mandal, A B

2012-05-01

The present study emphasizes the influence of non-covalent interactions on the mechanical and thermal properties of the scaffolds of chitosan/collagen origin. Malonic acid (MA), a bifuncitonal diacid was chosen to offer non-covalent cross-linking. Three dimensional scaffolds was prepared using chitosan at 1.0% (w/v) and MA at 0.2% (w/v), similarly collagen 0.5% (w/v) and MA 0.2% (w/v) and characterized. Results on FT-IR, TGA, DSC, SEM and mechanical properties (tensile strength, stiffness, Young's modulus, etc.) assessment demonstrated the existence of non-covalent interaction between MA and chitosan/collagen, which offered flexibility and high strength to the scaffolds suitable for tissue engineering research. Studies using NIH 3T3 fibroblast cells suggested biocompatibility nature of the scaffolds. Docking simulation study further supports the intermolecular hydrogen bonding interactions between MA and chitosan/collagen.

Water as a matrix for life

NASA Technical Reports Server (NTRS)

Pohorille, Andrew; Pratt, Lawrence

2006-01-01

"Follow the water" is the canonical strategy in searching for life in the universe. Conventionally, discussion of this topic is focused on how solvent supports organic chemistry sufficiently rich to seed life. Perhaps more importantly, solvent must promote self-organization of organic matter into functional structures capable of responding to environmental changes. This process is based on non-covalent interactions. They are constantly formed and broken in response to internal and external stimuli. This requires that their strength must be properly tuned. If they were too weak, the system would exhibit undesired, uncontrolled response to natural fluctuations of physical and chemical parameters. If they were too strong kinetics of biological processes would be slow and energetics costly. Non-covalent interactions are strongly mediated by the solvent. Specifically, high dielectric solvents for life are needed for solubility of polar species and flexibility of biological structures stabilized by electrostatic interactions. Water exhibits a remarkable trait that it promotes solvophobic interactions between non-polar species, which are responsible for self-organization phenomena such as the formation of cellular boundary structures, and protein folding and aggregation. Unusual temperature dependence of hydrophobic interactions - they often become stronger as temperature increases - is a consequence of the temperature insensitivity of properties of the liquid water. This contributes to the existence of robust life over a wide temperature range. Water is not the only liquid with favorable properties for supporting life. Other pure liquids or their mixtures that have high dielectric constants and simultaneously support some level of self-organization will be discussed.

The Use of Hammett Constants to Understand the Non-Covalent Binding of Aromatics

PubMed Central

Lewis, Michael; Bagwill, Christina; Hardebeck, Laura K. E.; Wireduaah, Selina

2012-01-01

Non-covalent interactions of aromatics are important in a wide range of chemical and biological applications. The past two decades have seen numerous reports of arene-arene binding being understood in terms Hammett substituent constants, and similar analyses have recently been extended to cation-arene and anion-arene binding. It is not immediately clear why electrostatic Hammett parameters should work so well in predicting the binding for all three interactions, given that different intermolecular forces dominate each interaction. This review explores such anomalies, and summarizes how Hammett substituent constants have been employed to understand the non-covalent binding in arene-arene, cation-arene and anion-arene interactions. PMID:24688634

Structural basis for ubiquitin-mediated antiviral signal activation by RIG-I.

PubMed

Peisley, Alys; Wu, Bin; Xu, Hui; Chen, Zhijian J; Hur, Sun

2014-05-01

Ubiquitin (Ub) has important roles in a wide range of intracellular signalling pathways. In the conventional view, ubiquitin alters the signalling activity of the target protein through covalent modification, but accumulating evidence points to the emerging role of non-covalent interaction between ubiquitin and the target. In the innate immune signalling pathway of a viral RNA sensor, RIG-I, both covalent and non-covalent interactions with K63-linked ubiquitin chains (K63-Ubn) were shown to occur in its signalling domain, a tandem caspase activation and recruitment domain (hereafter referred to as 2CARD). Non-covalent binding of K63-Ubn to 2CARD induces its tetramer formation, a requirement for downstream signal activation. Here we report the crystal structure of the tetramer of human RIG-I 2CARD bound by three chains of K63-Ub2. 2CARD assembles into a helical tetramer resembling a 'lock-washer', in which the tetrameric surface serves as a signalling platform for recruitment and activation of the downstream signalling molecule, MAVS. Ubiquitin chains are bound along the outer rim of the helical trajectory, bridging adjacent subunits of 2CARD and stabilizing the 2CARD tetramer. The combination of structural and functional analyses reveals that binding avidity dictates the K63-linkage and chain-length specificity of 2CARD, and that covalent ubiquitin conjugation of 2CARD further stabilizes the Ub-2CARD interaction and thus the 2CARD tetramer. Our work provides unique insights into the novel types of ubiquitin-mediated signal-activation mechanism, and previously unexpected synergism between the covalent and non-covalent ubiquitin interaction modes.

The subtle balance of weak supramolecular interactions: The hierarchy of halogen and hydrogen bonds in haloanilinium and halopyridinium salts.

PubMed

Raatikainen, Kari; Cametti, Massimo; Rissanen, Kari

2010-01-15

THE SERIES OF HALOANILINIUM AND HALOPYRIDINIUM SALTS: 4-IPhNH₃Cl (1), 4-IPhNH₃Br (5), 4-IPhNH₃H₂PO₄ (6), 4-ClPhNH₃H₂PO₄ (8), 3-IPyBnCl (9), 3-IPyHCl (10) and 3-IPyH-5NIPA (3-iodopyridinium 5-nitroisophthalate, 13), where hydrogen or/and halogen bonding represents the most relevant non-covalent interactions, has been prepared and characterized by single crystal X-ray diffraction. This series was further complemented by extracting some relevant crystal structures: 4-BrPhNH₃Cl (2, CCDC ref. code TAWRAL), 4-ClPhNH₃Cl (3, CURGOL), 4-FPhNH₃Cl (4, ANLCLA), 4-BrPhNH₃H₂PO₄, (7, UGISEI), 3-BrPyHCl, (11, CIHBAX) and 3-ClPyHCl, (12, VOQMUJ) from Cambridge Structural Database for sake of comparison. Based on the X-ray data it was possible to highlight the balance between non-covalent forces acting in these systems, where the relative strength of the halogen bonding C-X...A⁻ (X = I, Br or Cl) and the ratio between the halogen and hydrogen bonds [C-X...A⁻ : D-H...A⁻] varied across the series.

Model of early self-replication based on covalent complementarity for a copolymer of glycerate-3-phosphate and glycerol-3-phosphate

NASA Technical Reports Server (NTRS)

Weber, Arthur L.

1989-01-01

Glyceraldehyde-3-phosphate acts as the substrate in a model of early self-replication of a phosphodiester copolymer of glycerate-3-phosphate and glycerol-3-phosphate. This model of self-replication is based on covalent complementarity in which information transfer is mediated by a single covalent bond, in contrast to multiple weak interactions that establish complementarity in nucleic acid replication. This replication model is connected to contemporary biochemistry through its use of glyceraldehyde-3-phosphate, a central metabolite of glycolysis and photosynthesis.

Covalent intermolecular interaction of the nitric oxide dimer (NO)2

NASA Astrophysics Data System (ADS)

Zhang, Hui; Zheng, Gui-Li; Lv, Gang; Geng, Yi-Zhao; Ji, Qing

2015-09-01

Covalent bonds arise from the overlap of the electronic clouds in the internucleus region, which is a pure quantum effect and cannot be obtained in any classical way. If the intermolecular interaction is of covalent character, the result from direct applications of classical simulation methods to the molecular system would be questionable. Here, we analyze the special intermolecular interaction between two NO molecules based on quantum chemical calculation. This weak intermolecular interaction, which is of covalent character, is responsible for the formation of the NO dimer, (NO)2, in its most stable conformation, a cis conformation. The natural bond orbital (NBO) analysis gives an intuitive illustration of the formation of the dimer bonding and antibonding orbitals concomitant with the breaking of the π bonds with bond order 0.5 of the monomers. The dimer bonding is counteracted by partially filling the antibonding dimer orbital and the repulsion between those fully or nearly fully occupied nonbonding dimer orbitals that make the dimer binding rather weak. The direct molecular mechanics (MM) calculation with the UFF force fields predicts a trans conformation as the most stable state, which contradicts the result of quantum mechanics (QM). The lesson from the investigation of this special system is that for the case where intermolecular interaction is of covalent character, a specific modification of the force fields of the molecular simulation method is necessary. Project supported by the National Natural Science Foundation of China (Grant Nos. 90403007 and 10975044), the Key Subject Construction Project of Hebei Provincial Universities, China, the Research Project of Hebei Education Department, China (Grant Nos. Z2012067 and Z2011133), the National Natural Science Foundation of China (Grant No. 11147103), and the Open Project Program of State Key Laboratory of Theoretical Physics, Institute of Theoretical Physics, Chinese Academy of Sciences, China (Grant No. Y5KF211CJ1).

Covalent character and electric field dependence of H2-AgX (X = F - I).

PubMed

Li, Xinying

2018-06-16

Mechanisms of Ag-X and Ag…H 2 interactions and stabilities of T-shaped H 2 -AgX (X = F - I) series were investigated at the CCSD(T) level. The "no-density" bond with smaller positive Laplacian and ELF values in interaction regions, as well as considerable delocalization index values, suggest weak covalent "charge-shift" character for the Ag…H 2 interaction. Structure and stability dependence on the electric field were investigated at the MP2 level. Relative total energy curves show obvious parabolic character, and the plots can be fitted by quadratic polynomials as functions of electric field strength.

Cl⋯N weak interactions. Conformational analysis of imidazol-2-ylum heterocycles bearing N-β-chloroethyl and N-vinyl pendant groups

NASA Astrophysics Data System (ADS)

Rodríguez-López, Germán; Montes-Tolentino, Pedro; Sánchez-Ruiz, Sonia; Villaseñor-Granados, Tayde Osvaldo; Flores-Parra, Angelina

2017-11-01

Enantiomerically pure and racemic mixtures of β-chloroethylamines hydrochlorides with one and two stereogenic centres were used to synthesise 1,4-dialkyl-1,3-diimines, which in turn gave place to a series of imidazolium chlorides and tetraphenylborates bearing pendant N-β-chloroethyl substituents (sbnd CHEt-CH2Cl; sbnd CHMe-CHPhCl). Stereoselective dehydrochlorination of imidazolium compounds afforded in good yield the corresponding heterocycles bearing N-vinyl groups (-CEt=CH2; -CMe=CHPh). The volume of the N-substituents provides a steric screening of the cationic ring. The structure of the new compounds was determined by IR, mass spectra, NMR and X-ray diffraction analyses as well as DFT calculations of the optimized geometries. Uncommon stabilising intramolecular Cl⋯N weak interactions are described, together with H⋯Cl and H···π hydrogen bonds. The existence of the non-covalent weak intramolecular bonds was deduced from the X-ray diffraction analysis and confirmed by calculations of the electrostatic potential, electronic density distributions and the maps of the Laplacian functions of the electronic density.

Improved Composites Using Crosslinked, Surface-Modified Carbon Nanotube Materials

NASA Technical Reports Server (NTRS)

Baker, James Stewart

2014-01-01

Individual carbon nanotubes (CNTs) exhibit exceptional tensile strength and stiffness; however, these properties have not translated well to the macroscopic scale. Premature failure of bulk CNT materials under tensile loading occurs due to the relatively weak frictional forces between adjacent CNTs, leading to poor load transfer through the material. When used in polymer matrix composites (PMCs), the weak nanotube-matrix interaction leads to the CNTs providing less than optimal reinforcement.Our group is examining the use of covalent crosslinking and surface modification as a means to improve the tensile properties of PMCs containing carbon nanotubes. Sheet material comprised of unaligned multi-walled carbon nanotubes (MWCNT) was used as a drop-in replacement for carbon fiber in the composites. A variety of post-processing methods have been examined for covalently crosslinking the CNTs to overcome the weak inter-nanotube shear interactions, resulting in improved tensile strength and modulus for the bulk sheet material. Residual functional groups from the crosslinking chemistry may have the added benefit of improving the nanotube-matrix interaction. Composites prepared using these crosslinked, surface-modified nanotube sheet materials exhibit superior tensile properties to composites using the as received CNT sheet material.

Two supramolecular complexes based on polyoxometalates and Co-EDTA units via covalent connection or non-covalent interaction

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

Teng, Chunlin; Xiao, Hanxi; Cai, Qing

Two new 3D network organic-inorganic hybrid supramolecular complexes ([Na{sub 6}(CoEDTA){sub 2}(H{sub 2}O){sub 13}]·(H{sub 2}SiW{sub 12}O{sub 40})·xH{sub 2}O)n (1) and [CoH{sub 4}EDTA(H{sub 2}O)]{sub 2}(SiW{sub 12}O{sub 40})·15H{sub 2}O (2) (H{sub 4}EDTA=Ethylenediamine tetraacetic acid) have been successfully synthesized by solution method, and characterized by infrared spectrum (IR), thermogravimetric-differential thermal analysis (TG-DTA), cyclic voltammetry (CV) and single{sup −}crystal X-ray diffraction (XRD). Both of the complexes are the supramolecules, but with different liking mode, they are two representative models of supramolecule. complex (1) is a 3D infinite network supramolecular coordination polymer with a rare multi-metal sturcture of sodium-cobalt-containing, which is mainly linked through coordinate-covalent bonds.more » While complex (2) is normal supramolecule, which linked by non-covalent interactions, such as H-bonding interaction, electrostatic interaction and van der waals force. Both of complex (1) and (2) exhibit good catalytic activities for catalytic oxidation of methanol, when the initial concentration of methanol is 3.0 g m{sup −3}, flow rate is 10 mL min{sup −1}, and the quality of catalyst is 0.2 g, for complex (1) and complex (2) the maximum elimination rates of methanol are 85% (150 °C) and 92% (120 °C), respectively. - Graphical abstract: Two new organic-inorganic hybrid supramolecular complexes based on Co-EDTA, and Keggin polyanions have been successfully synthesized with different pH value by solution method. They are attributed to two representative models of supramolecule. Complex(1) is an infinite coordination polymer with a rare multi-metal sturcture of sodium-cobalt-containing, which is mainly linked through covalent bonds. Complex (2) is a normal supramolecule, which linked by non-covalent interactions of H-bonding interaction, electrostatic interaction and van der waals force. - Highlights: • Two supramolecules are linked by covalent or non-covalent interactions. • They are attributed to two representative models of supramolecule. • A rare multi-metal infinite supramolecular coordination polymer was formed. • They exhibit good catalytic activities for catalytic oxidation of methanol.« less

Reduced density gradient as a novel approach for estimating QSAR descriptors, and its application to 1, 4-dihydropyridine derivatives with potential antihypertensive effects.

PubMed

Jardínez, Christiaan; Vela, Alberto; Cruz-Borbolla, Julián; Alvarez-Mendez, Rodrigo J; Alvarado-Rodríguez, José G

2016-12-01

The relationship between the chemical structure and biological activity (log IC 50 ) of 40 derivatives of 1,4-dihydropyridines (DHPs) was studied using density functional theory (DFT) and multiple linear regression analysis methods. With the aim of improving the quantitative structure-activity relationship (QSAR) model, the reduced density gradient s( r) of the optimized equilibrium geometries was used as a descriptor to include weak non-covalent interactions. The QSAR model highlights the correlation between the log IC 50 with highest molecular orbital energy (E HOMO ), molecular volume (V), partition coefficient (log P), non-covalent interactions NCI(H4-G) and the dual descriptor [Δf(r)]. The model yielded values of R 2 =79.57 and Q 2 =69.67 that were validated with the next four internal analytical validations DK=0.076, DQ=-0.006, R P =0.056, and R N =0.000, and the external validation Q 2 boot =64.26. The QSAR model found can be used to estimate biological activity with high reliability in new compounds based on a DHP series. Graphical abstract The good correlation between the log IC 50 with the NCI (H4-G) estimated by the reduced density gradient approach of the DHP derivatives.

Conformational landscape of isolated capped amino acids: on the nature of non-covalent interactions*

NASA Astrophysics Data System (ADS)

González, Jorge; Martínez, Rodrigo; Fernández, José A.; Millan, Judith

2017-08-01

The intramolecular interactions for isolated capped amino acids were investigated computationally by characterizing the conformers for selected amino acids with charged (arginine), polar (asparagine and glutamine), non-polar (alanine, valine and isoleucine), and aromatic (phenylalanine, tryptophan and tyrosine) side chains. The computational method applied combined a molecular mechanics conformational search (with an MMFFs forced field) followed by structural and vibrational density-functional calculations (M06-2X with a triple- ζ Pople's basis set). The intramolecular forces in each amino acid were analyzed with the Non-Covalent Interactions (NCI) analysis. The results for the 15 most stable conformers studied showed that the structure of isolated capped amino acids resembles those found in proteins. In particular, the two most stable conformers of the nine amino acids investigated exhibit γ L and β L conformations with 7- and 5-membered rings, respectively, as a result of the balance between non-covalent interactions (hydrogen bonds and van der Waals).

A Comprehensive Analysis in Terms of Molecule-Intrinsic, Quasi-Atomic Orbitals. III. The Covalent Bonding Structure of Urea.

PubMed

West, Aaron C; Schmidt, Michael W; Gordon, Mark S; Ruedenberg, Klaus

2015-10-15

The analysis of molecular electron density matrices in terms of quasi-atomic orbitals, which was developed in previous investigations, is quantitatively exemplified by a detailed application to the urea molecule. The analysis is found to identify strong and weak covalent bonding interactions as well as intramolecular charge transfers. It yields a qualitative as well as quantitative ab initio description of the bonding structure of this molecule, which raises questions regarding some traditional rationalizations.

Sialic Acid-Responsive Polymeric Interface Material: From Molecular Recognition to Macroscopic Property Switching

NASA Astrophysics Data System (ADS)

Xiong, Yuting; Jiang, Ge; Li, Minmin; Qing, Guangyan; Li, Xiuling; Liang, Xinmiao; Sun, Taolei

2017-01-01

Biological systems that utilize multiple weak non-covalent interactions and hierarchical assemblies to achieve various bio-functions bring much inspiration for the design of artificial biomaterials. However, it remains a big challenge to correlate underlying biomolecule interactions with macroscopic level of materials, for example, recognizing such weak interaction, further transforming it into regulating material’s macroscopic property and contributing to some new bio-applications. Here we designed a novel smart polymer based on polyacrylamide (PAM) grafted with lactose units (PAM-g-lactose0.11), and reported carbohydrate-carbohydrate interaction (CCI)-promoted macroscopic properties switching on this smart polymer surface. Detailed investigations indicated that the binding of sialic acid molecules with the grafted lactose units via the CCIs induced conformational transformation of the polymer chains, further resulted in remarkable and reversible switching in surface topography, wettability and stiffness. With these excellent recognition and response capacities towards sialic acid, the PAM-g-lactose0.11 further facilitated good selectivity, strong anti-interference and high adsorption capacity in the capture of sialylated glycopeptides (important biomarkers for cancers). This work provides some enlightenment for the development of biointerface materials with tunable property, as well as high-performance glycopeptide enrichment materials.

Supramolecular reactivity in the gas phase: investigating the intrinsic properties of non-covalent complexes.

PubMed

Cera, Luca; Schalley, Christoph A

2014-03-21

The high vacuum inside a mass spectrometer offers unique conditions to broaden our view on the reactivity of supramolecules. Because dynamic exchange processes between complexes are efficiently suppressed, the intrinsic and intramolecular reactivity of the complexes of interest is observed. Besides this, the significantly higher strength of non-covalent interactions in the absence of competing solvent allows processes to occur that are unable to compete in solution. The present review highlights a series of examples illustrating different aspects of supramolecular gas-phase reactivity ranging from the dissociation and formation of covalent bonds in non-covalent complexes through the reactivity in the restricted inner phase of container molecules and step-by-step mechanistic studies of organocatalytic reaction cycles to cage contraction reactions, processes induced by electron capture, and finally dynamic molecular motion within non-covalent complexes as unravelled by hydrogen-deuterium exchange processes performed in the gas phase.

Non-covalent pomegranate (Punica granatum) hydrolyzable tannin-protein complexes modulate antigen uptake, processing and presentation by a T-cell hybridoma line co-cultured with murine peritoneal macrophages.

PubMed

Madrigal-Carballo, Sergio; Haas, Linda; Vestling, Martha; Krueger, Christian G; Reed, Jess D

2016-12-01

In this work we characterize the interaction of pomegranate hydrolyzable tannins (HT) with hen egg-white lysozyme (HEL) and determine the effects of non-covalent tannin-protein complexes on macrophage endocytosis, processing and presentation of antigen. We isolated HT from pomegranate and complex to HEL, the resulting non-covalent tannin-protein complex was characterized by gel electrophoresis and MALDI-TOF MS. Finally, cell culture studies and confocal microscopy imaging were conducted on the non-covalent pomegranate HT-HEL protein complexes to evaluate its effect on macrophage antigen uptake, processing and presentation to T-cell hybridomas. Our results indicate that non-covalent pomegranate HT-HEL protein complexes modulate uptake, processing and antigen presentation by mouse peritoneal macrophages. After 4 h of pre-incubation, only trace amounts of IL-2 were detected in the co-cultures treated with HEL alone, whereas a non-covalent pomegranate HT-HEL complex had already reached maximum IL-2 expression. Pomegranate HT may increase rate of endocytose of HEL and subsequent expression of IL-2 by the T-cell hybridomas.

Specificity Rendering ‘Hot-Spots’ for Aurora Kinase Inhibitor Design: The Role of Non-Covalent Interactions and Conformational Transitions

PubMed Central

Badrinarayan, Preethi; Sastry, G. Narahari

2014-01-01

The present study examines the conformational transitions occurring among the major structural motifs of Aurora kinase (AK) concomitant with the DFG-flip and deciphers the role of non-covalent interactions in rendering specificity. Multiple sequence alignment, docking and structural analysis of a repertoire of 56 crystal structures of AK from Protein Data Bank (PDB) has been carried out. The crystal structures were systematically categorized based on the conformational disposition of the DFG-loop [in (DI) 42, out (DO) 5 and out-up (DOU) 9], G-loop [extended (GE) 53 and folded (GF) 3] and αC-helix [in (CI) 42 and out (CO) 14]. The overlapping subsets on categorization show the inter-dependency among structural motifs. Therefore, the four distinct possibilities a) 2W1C (DI, CI, GE) b) 3E5A (DI, CI, GF) c) 3DJ6 (DI, CO, GF) d) 3UNZ (DOU, CO, GF) along with their co-crystals and apo-forms were subjected to molecular dynamics simulations of 40 ns each to evaluate the variations of individual residues and their impact on forming interactions. The non-covalent interactions formed by the 157 AK co-crystals with different regions of the binding site were initially studied with the docked complexes and structure interaction fingerprints. The frequency of the most prominent interactions was gauged in the AK inhibitors from PDB and the four representative conformations during 40 ns. Based on this study, seven major non-covalent interactions and their complementary sites in AK capable of rendering specificity have been prioritized for the design of different classes of inhibitors. PMID:25485544

E2 enzyme inhibition by stabilization of a low affinity interface with ubiquitin

PubMed Central

St-Cyr, Daniel J.; Ziemba, Amy; Garg, Pankaj; Plamondon, Serge; Auer, Manfred; Sidhu, Sachdev; Marinier, Anne; Kleiger, Gary; Tyers, Mike; Sicheri, Frank

2014-01-01

Weak protein interactions between ubiquitin and the ubiquitin-proteasome system (UPS) enzymes that mediate its covalent attachment to substrates serve to position ubiquitin for optimal catalytic transfer. We show that a small molecule inhibitor of the E2 ubiquitin conjugating enzyme Cdc34A, called CC0651, acts by trapping a weak interaction between ubiquitin and the E2 donor ubiquitin binding site. A structure of the ternary CC0651-Cdc34A-ubiquitin complex reveals that the inhibitor engages a composite binding pocket formed from Cdc34A and ubiquitin. CC0651 also suppresses the spontaneous hydrolysis rate of the Cdc34A-ubiquitin thioester, without overtly affecting the interaction between Cdc34A and the RING domain subunit of the E3 enzyme. Stabilization of the numerous other weak interactions between ubiquitin and UPS enzymes by small molecules may be a feasible strategy to selectively inhibit different UPS activities. PMID:24316736

Weak Bond-Based Injectable and Stimuli Responsive Hydrogels for Biomedical Applications

PubMed Central

Ding, Xiaochu; Wang, Yadong

2017-01-01

Here we define hydrogels crosslinked by weak bonds as physical hydrogels. They possess unique features including reversible bonding, shear thinning and stimuli-responsiveness. Unlike covalently crosslinked hydrogels, physical hydrogels do not require triggers to initiate chemical reactions for in situ gelation. The drug can be fully loaded in a pre-formed hydrogel for delivery with minimal cargo leakage during injection. These benefits make physical hydrogels useful as delivery vehicles for applications in biomedical engineering. This review focuses on recent advances of physical hydrogels crosslinked by weak bonds: hydrogen bonds, ionic interactions, host-guest chemistry, hydrophobic interactions, coordination bonds and π-π stacking interactions. Understanding the principles and the state of the art of gels with these dynamic bonds may give rise to breakthroughs in many biomedical research areas including drug delivery and tissue engineering. PMID:29062484

π-π-Induced aggregation and single-crystal fluorescence anisotropy of 5,6,10b-tri-aza-acephenanthrylene.

PubMed

Ostrowska, Katarzyna; Ceresoli, Davide; Stadnicka, Katarzyna; Gryl, Marlena; Cazzaniga, Marco; Soave, Raffaella; Musielak, Bogdan; Witek, Łukasz J; Goszczycki, Piotr; Grolik, Jarosław; Turek, Andrzej M

2018-05-01

The structural origin of absorption and fluorescence anisotropy of the single crystal of the π-conjugated heterocyclic system 5,6,10b-tri-aza-acephenan-thrylene, TAAP, is presented in this study. X-ray analysis shows that the crystal framework in the space group P [Formula: see text] is formed by centrosymmetric dimers of face-to-face mutually oriented TAAP molecules joined by π-π non-covalent interactions. The conformation of the TAAP molecule is stabilized by intramolecular C-H⋯N( sp 2 ), N( sp 2 )H⋯π(CN), and C-H⋯O( sp 2 ) hydrogen bonds. The presence of weak π-π interactions is confirmed by quantum theory of atoms in molecules (QTAIM) and non-covalent interaction (NCI) analysis. The analysis of the optical spectra of TAAP in solution and in the solid state does not allow the specification of the aggregation type. DFT calculations for the dimer in the gas phase indicate that the lowest singlet excitation is forbidden by symmetry, suggesting H-type aggregation, even though the overall absorption spectrum is bathochromically shifted as for the J-type. The experimental determination of the permanent dipole moment of a TAAP molecule in 1,4-dioxane solution indicates the presence of the monomer form. The calculated absorption and emission spectra of the crystal in a simple approximation are consistent with the experimentally determined orientation of the absorption and emission transition dipole moments in TAAP single crystals. The electrostatic interaction between monomers with a permanent dipole moment ( ca 4 D each) could result in the unusual spectroscopic JH-aggregate behaviour of the TAAP dimer.

In-situ Click Reaction Coupled with Quantitative Proteomics for Identifying Protein Targets of Catechol Estrogens.

PubMed

Liang, Huei-Chen; Liu, Yi-Chen; Chen, Hsin; Ku, Ming Chun; Do, Quynh-Trang; Wang, Chih-Yen; Tzeng, Shun-Fen; Chen, Shu-Hui

2018-06-13

Catechol estrogens (CEs) are metabolic electrophiles that actively undergo covalent interaction with cellular proteins, influencing molecular function. There is no feasible method to identify their binders in a living system. Herein, we developed a click chemistry-based approach using ethinylestradiol (EE2) as the precursor probe coupled with quantitative proteomics to identify protein targets of CEs and classify their binding strengths. Using in-situ metabolic conversion and click reaction in liver microsomes, CEs-protein complex was captured by the probe, digested by trypsin, stable isotope labeled via reductive amination, and analyzed by liquid chromatography-mass spectrometry (LC-MS). A total of 334 liver proteins were repeatedly identified (n  2); 274 identified proteins were classified as strong binders based on precursor mass mapping. The binding strength was further scaled by D/H ratio (activity probe/solvent): 259 strong binders had D/H > 5.25; 46 weak binders had 5.25 > D/H > 1; 5 non-specific binders (keratins) had D/H < 1. These results were confirmed using spiked covalent control (strong binder) and noncovalent control (weak binder), as well as in vitro testing of cytochrome c (D/H = 5.9) which showed covalent conjugation with CEs. Many identified strong binders, such as glutathione transferase, catechol-O-methyl transferase, superoxide dismutase, catalase, glutathione peroxidase, and cytochrome c, are involved in cellular redox processes or detoxification activities. CE conjugation was shown to suppress the superoxide oxidase activity of cytochrome c, suggesting that CEs modification may alter the redox action of cellular proteins. Due to structural similarity and inert alkyne group, EE2 probe is very likely to capture protein targets of CEs in general. Thus, this strategy can be adopted to explore the biological impact of CEs modification in living systems.

Probing the molecular forces involved in binding of selected volatile flavour compounds to salt-extracted pea proteins.

PubMed

Wang, Kun; Arntfield, Susan D

2016-11-15

Molecular interactions between heterologous classes of flavour compounds with salt-extracted pea protein isolates (PPIs) were determined using various bond disrupting agents followed by GC/MS analysis. Flavour bound by proteins decreased in the order: dibutyl disulfide>octanal>hexyl acetate>2-octanone=benzaldehyde. Benzaldehyde, 2-octanone and hexyl acetate interacted non-covalently with PPIs, whereas octanal bound PPIs via covalent and non-covalent forces. Dibutyl disulfide reacted with PPIs covalently, as its retention was not diminished by urea and guanidine hydrochloride. Using propylene glycol, H-bonding and ionic interactions were implicated for hexyl acetate, benzaldehyde, and 2-octanone. A protein-destabilising salt (Cl3CCOONa) reduced bindings for 2-octanone, hexyl acetate, and benzaldehyde; however, retention for octanal and dibutyl disulfide increased. Conversely, a protein-stabilising salt (Na2SO4) enhanced retention for benzaldehyde, 2-octanone, hexyl acetate and octanal. Formation of a volatile flavour by-product, 1-butanethiol, from dibutyl disulfide when PPIs were treated with dithiothreitol indicated occurrence of sulfhydryl-disulfide interchange reactions. Copyright © 2016 Elsevier Ltd. All rights reserved.

DNA Detection by Flow Cytometry using PNA-Modified Metal-Organic Framework Particles.

PubMed

Mejia-Ariza, Raquel; Rosselli, Jessica; Breukers, Christian; Manicardi, Alex; Terstappen, Leon W M M; Corradini, Roberto; Huskens, Jurriaan

2017-03-23

A DNA-sensing platform is developed by exploiting the easy surface functionalization of metal-organic framework (MOF) particles and their highly parallelized fluorescence detection by flow cytometry. Two strategies were employed to functionalize the surface of MIL-88A, using either covalent or non-covalent interactions, resulting in alkyne-modified and biotin-modified MIL-88A, respectively. Covalent surface coupling of an azide-dye and the alkyne-MIL-88A was achieved by means of a click reaction. Non-covalent streptavidin-biotin interactions were employed to link biotin-PNA to biotin-MIL-88A particles mediated by streptavidin. Characterization by confocal imaging and flow cytometry demonstrated that DNA can be bound selectively to the MOF surface. Flow cytometry provided quantitative data of the interaction with DNA. Making use of the large numbers of particles that can be simultaneously processed by flow cytometry, this MOF platform was able to discriminate between fully complementary, single-base mismatched, and randomized DNA targets. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

NASA Astrophysics Data System (ADS)

Amor, B. R. C.; Schaub, M. T.; Yaliraki, S. N.; Barahona, M.

2016-08-01

Allostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph-theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites.

Prediction of allosteric sites and mediating interactions through bond-to-bond propensities

PubMed Central

Amor, B. R. C.; Schaub, M. T.; Yaliraki, S. N.; Barahona, M.

2016-01-01

Allostery is a fundamental mechanism of biological regulation, in which binding of a molecule at a distant location affects the active site of a protein. Allosteric sites provide targets to fine-tune protein activity, yet we lack computational methodologies to predict them. Here we present an efficient graph-theoretical framework to reveal allosteric interactions (atoms and communication pathways strongly coupled to the active site) without a priori information of their location. Using an atomistic graph with energy-weighted covalent and weak bonds, we define a bond-to-bond propensity quantifying the non-local effect of instantaneous bond fluctuations propagating through the protein. Significant interactions are then identified using quantile regression. We exemplify our method with three biologically important proteins: caspase-1, CheY, and h-Ras, correctly predicting key allosteric interactions, whose significance is additionally confirmed against a reference set of 100 proteins. The almost-linear scaling of our method renders it suitable for high-throughput searches for candidate allosteric sites. PMID:27561351

Hirshfeld surface analyses and crystal structures of supramolecular self-assembly thiourea derivatives directed by non-covalent interactions

NASA Astrophysics Data System (ADS)

Gumus, Ilkay; Solmaz, Ummuhan; Binzet, Gun; Keskin, Ebru; Arslan, Birdal; Arslan, Hakan

2018-04-01

The novel N-(bis(3,5-dimethoxybenzyl)carbamothioyl)-4-R-benzamide (R: H, Cl, CH3 and OCH3) compounds have been synthesized and characterized by FT-IR, 1H NMR and 13C NMR spectroscopy. Their crystal structures were also determined by single-crystal X-ray diffraction studies. Hirshfeld surfaces analysis and their associated two dimensional fingerprint plots of compounds were used as theoretical approach to assess driving force for crystal structure formation via the intermolecular interactions in the crystal lattices of synthesized compounds. The study of X-ray single crystal diffraction and Hirshfeld surfaces analysis of the prepared compounds shows that hydrogen bonding and other weaker interactions such as Nsbnd H⋯S, weak Csbnd H⋯S, Csbnd H⋯O, Csbnd H⋯N and Csbnd H···π intermolecular interactions and π-π stacking, among molecules of synthesized compounds participate in a cooperative way to stabilize the supramolecular structures.

Note: The performance of new density functionals for a recent blind test of non-covalent interactions

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

Mardirossian, Narbe; Head-Gordon, Martin

Benchmark datasets of non-covalent interactions are essential for assessing the performance of density functionals and other quantum chemistry approaches. In a recent blind test, Taylor et al. benchmarked 14 methods on a new dataset consisting of 10 dimer potential energy curves calculated using coupled cluster with singles, doubles, and perturbative triples (CCSD(T)) at the complete basis set (CBS) limit (80 data points in total). Finally, the dataset is particularly interesting because compressed, near-equilibrium, and stretched regions of the potential energy surface are extensively sampled.

Note: The performance of new density functionals for a recent blind test of non-covalent interactions

DOE PAGES

Mardirossian, Narbe; Head-Gordon, Martin

2016-11-09

Benchmark datasets of non-covalent interactions are essential for assessing the performance of density functionals and other quantum chemistry approaches. In a recent blind test, Taylor et al. benchmarked 14 methods on a new dataset consisting of 10 dimer potential energy curves calculated using coupled cluster with singles, doubles, and perturbative triples (CCSD(T)) at the complete basis set (CBS) limit (80 data points in total). Finally, the dataset is particularly interesting because compressed, near-equilibrium, and stretched regions of the potential energy surface are extensively sampled.

Non-covalent interaction between Cu-phthalocyanine and methanato borondifluoride derivatives in two different medium

NASA Astrophysics Data System (ADS)

Pal, Chiranjit; Chaudhuri, Tandrima; Chattopdhyay, Subrata; Banerjee, Manas

2017-04-01

This study sort out chemical physics of non-covalent interaction between Copper phthalocyanine (CuPC) with Methanato borondifluoride derivatives (MBDF) in chloroform and ethanol. Formation of isosbestic points indicated stable ground state equilibrium between CuPC and MBDF, association ability were more pronounced in less polar chloroform. Interesting overall parallel orientation of MBDF over CuPC in gas phase geometries indicated that fluorine centre of MBDF lying just above the Cu-centre of CuPC. Thus strong interaction between Cu(II)- and F- centre could not be overruled and was also established by NBO calculation. TDDFT along with FMO features and heat of reaction values clearly designated the existence of π-π interaction and effect of solvent polarity on that interaction.

Spectroscopic and molecular modelling studies of binding mechanism of metformin with bovine serum albumin

NASA Astrophysics Data System (ADS)

Sharma, Deepti; Ojha, Himanshu; Pathak, Mallika; Singh, Bhawna; Sharma, Navneet; Singh, Anju; Kakkar, Rita; Sharma, Rakesh K.

2016-08-01

Metformin is a biguanide class of drug used for the treatment of diabetes mellitus. It is well known that serum protein-ligand binding interaction significantly influence the biodistribution of a drug. Current study was performed to characterize the binding mechanism of metformin with serum albumin. The binding interaction of the metformin with bovine serum albumin (BSA) was examined using UV-Vis absorption spectroscopy, fluorescence, circular dichroism, density functional theory and molecular docking studies. Absorption spectra and fluorescence emission spectra pointed out the weak binding of metformin with BSA as was apparent from the slight change in absorbance and fluorescence intensity of BSA in presence of metformin. Circular dichroism study implied the significant change in the conformation of BSA upon binding with metformin. Density functional theory calculations showed that metformin has non-planar geometry and has two energy states. The docking studies evidently signified that metformin could bind significantly to the three binding sites in BSA via hydrophobic, hydrogen bonding and electrostatic interactions. The data suggested the existence of non-covalent specific binding interaction in the complexation of metformin with BSA. The present study will certainly contribute to the development of metformin as a therapeutic molecule.

Identification of non-classical C-H···M interactions in early and late transition metal complexes containing the CH(ArO)3 ligand.

PubMed

Lein, Matthias; Harrison, John A; Nielson, Alastair J

2013-08-14

The fully optimised DFT structure of the d(0) complex [{CH(ArO)3}Ti(NEt2)] (2) at the B3LYP level compares well with the distorted tetrahedral geometry shown by the X-ray crystal structure. QTAIM analysis of the electron density associated with the C-H···Ti interaction shows a well defined bond critical point, a bond path between the hydrogen and titanium centres and a negative value for the energy density indicative of covalency. A natural bond orbital (NBO) picture of the interaction shows that the C-H σ bond electron density donates to a d hybrid orbital on the metal in a linear fashion. Calculated IR and NMR data for the components of the interaction are consistent with experiment. The computed structures for [{CH(ArO)3}Ti(OPh)] (3), [{CH(ArO)3}Zr(NEt2)] (4), [{CH(ArO)3}Hf(NEt2)] (5), show tetrahedral geometries and QTAIM and NBO properties similar to (2). [{CH(ArO)3}Mo(NEt2)] (6) shows distortion of the tripodal ligand and a reduced C-H···M bond angle with properties more consistent with a C-H···M side-on donor interaction. In [{CH(ArO)3}Fe(NEt2)] (7) the C-H···M bond angle is linear and involves a donor interaction. An energy minimised structure maintaining the three fold coordination to the tripodal ligand was not obtained for [{CH(ArO)3}Ni(NEt2)](2-) but changing from a diethyl amide ligand to phenolato gave energy minimised [{CH(ArO)3}Ni(OPh)](2-) (8). This structure shows a distorted square planar geometry with a substantially bent phenoxo ligand and a near linear C-H···M covalent interaction with donor and back bonding properties. The work shows that linear C-H···M interactions can have both agostic and weak hydrogen bond-like covalency.

Cooperativity of anion⋯π and π⋯π interactions regulates the self-assembly of a series of carbene proligands: Towards quantitative analysis of intermolecular interactions with Hirshfeld surface

NASA Astrophysics Data System (ADS)

Samanta, Tapastaru; Dey, Lingaraj; Dinda, Joydev; Chattopadhyay, Shyamal Kumar; Seth, Saikat Kumar

2014-06-01

The cooperative effect of weak non-covalent forces between anions and electron deficient aromatics by π⋯π stacking of a series of carbene proligands (1-3) have been thoroughly explored by crystallographic studies. Structural analysis revealed that the anion⋯π and π⋯π interactions along with intermolecular hydrogen bonding mutually cooperate to facilitate the assembling of the supramolecular framework. The π⋯π and corresponding anion⋯π interactions have been investigated in the title carbene proligands despite their association with counter ions. The presence of the anion in the vicinity of the π-system leads to the formation of anion⋯π/π⋯π/π⋯anion network for an inductive stabilization of the assemblies. To assess the dimensionality of the supramolecular framework consolidated by cooperative anion⋯π/π⋯π interactions and hydrogen bonding, different substituent effects in the carbene backbone have been considered to tune these interactions. These facts show that the supramolecular framework based on these cooperative weak forces may be robust enough for application in molecular recognition. The investigation of close intermolecular interactions between the molecules via Hirshfeld surface analyses is presented in order to reveal subtle differences and similarities in the crystal structures. The decomposition of the fingerprint plot area provides a percentage of each intermolecular interaction, allowing for a quantified analysis of close contacts within each crystal.

Deciphering the Dynamics of Non-Covalent Interactions Affecting Thermal Stability of a Protein: Molecular Dynamics Study on Point Mutant of Thermus thermophilus Isopropylmalate Dehydrogenase.

PubMed

Sharma, Reetu; Sastry, G Narahari

2015-01-01

Thermus thermophilius isopropylmalate dehydrogenase catalyzes oxidative decarboxylation and dehydrogenation of isopropylmalate. Substitution of leucine to alanine at position 172 enhances the thermal stability among the known point mutants. Exploring the dynamic properties of non-covalent interactions such as saltbridges, hydrogen bonds and hydrophobic interactions to explain thermal stability of a protein is interesting in its own right. In this study dynamic changes in the non-covalent interactions are studied to decipher the deterministic features of thermal stability of a protein considering a case study of a point mutant in Thermus thermophilus isopropylmalate dehydrogenase. A total of four molecular dynamic simulations of 0.2 μs were carried out on wild type and mutant's functional dimers at 300 K and 337 K. Higher thermal stability of the mutant as compared to wild type is revealed by root mean square deviation, root mean square fluctuations and Cα-Cα distance with an increase in temperature from 300 K to 337 K. Most of the regions of wild type fluctuate higher than the corresponding regions of mutant with an increase in temperature. Cα-Cα distance analysis suggests that long distance networks are significantly affected in wild type as compared to the mutant. Short lived contacts are higher in wild type, while long lived contacts are lost at 337 K. The mutant forms less hydrogen bonds with water as compared to wild type at 337 K. In contrast to wild type, the mutant shows significant increase in unique saltbridges, hydrogen bonds and hydrophobic contacts at 337 K. The current study indicates that there is a strong inter-dependence of thermal stability on the way in which non-covalent interactions reorganize, and it is rewarding to explore this connection in single mutant studies.

Easy methods to study the smart energetic TNT/CL-20 co-crystal.

PubMed

Li, Huarong; Shu, Yuanjie; Gao, Shijie; Chen, Ling; Ma, Qing; Ju, Xuehai

2013-11-01

2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) is a high-energy nitramine explosive with high mechanical sensitivity. 2,4,6-trinitrotoluene (TNT) is insensitive but by no means a high performance explosive. To reveal the significant importance and smart-material functionality of the energetic-energetic co-crystals, the stability, mechanical and explosive properties TNT/CL-20 co-crystal, TNT crystal and CL-20 crystal were studied. Non-hydrogen bonded non-covalent interactions govern the structures of energetic-energetic co-crystals. However, it is very difficult to accurately calculate the non-covalent intermolecular interaction energies. In this paper, the local conformation and the intricate non-covalent interactions were effectively mapped and analyzed from the electron density (ρ) and its derivatives. The results show that the two components TNT and CL-20 are connected mainly by nitro-aromatic interactions, and nitro-nitro interactions. The steric interactions in TNT/CL-20 could not be confronted with the attractive interactions. Moreover, the scatter graph of TNT crystal reveals the reason why TNT is brittle. The detailed electrostatic potential analysis predicted that the detonation velocities (D) and impact sensitivity for the compounds both increase in the sequence of CL-20 > TNT/CL-20 co-crystal > TNT. Additionally, TNT/CL-20 co-crystal has better malleability than its pure components. This demonstrates the capacity and the feasibility of realizing explosive smart materials by co-crystallization, even if strong hydrogen bonding schemes are generally lacking in energetic materials.

Decoupled electron and phonon transports in hexagonal boron nitride-silicene bilayer heterostructure

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

Cai, Yongqing; Pei, Qing-Xiang, E-mail: peiqx@ihpc.a-star.edu.sg, E-mail: zhangg@ihpc.a-star.edu.sg; Zhang, Gang, E-mail: peiqx@ihpc.a-star.edu.sg, E-mail: zhangg@ihpc.a-star.edu.sg

2016-02-14

Calculations based on the density functional theory and empirical molecular dynamics are performed to investigate interlayer interaction, electronic structure and thermal transport of a bilayer heterostructure consisting of silicene and hexagonal boron nitride (h-BN). In this heterostructure, the two layers are found to interact weakly via a non-covalent binding. As a result, the Dirac cone of silicene is preserved with the Dirac cone point being located exactly at the Fermi level, and only a small amount of electrons are transferred from h-BN to silicene, suggesting that silicene dominates the electronic transport. Molecular dynamics calculation results demonstrate that the heat currentmore » along h-BN is six times of that along silicene, suggesting that h-BN dominates the thermal transport. This decoupled role of h-BN and silicene in thermal and electronic transport suggests that the BN-silicene bilayer heterostructure is promising for thermoelectric applications.« less

Inactivation by omeprazole of the carnitine transporter (OCTN2) reconstituted in liposomes.

PubMed

Pochini, Lorena; Scalise, Mariafrancesca; Indiveri, Cesare

2009-05-15

The effect of omeprazole on the carnitine (OCTN2) transporter reconstituted in liposomes has been studied. Omeprazole externally added to the proteoliposomes, inhibited the carnitine/carnitine antiport catalysed by the reconstituted transporter. The inhibition was partially reversed by DTE indicating that it was caused by the covalent reaction of omeprazole with Cys residue(s) of the transporter. Similar results were found with intact brush border vesicles. The residual inhibition of the transport in the presence of DTE, indicated the occurrence of an alternative inhibition mechanism of non-covalent nature. The IC(50) of the two inhibition modes derived from dose-response curves, were 5.7 microM and 20.4 microM, respectively. Kinetic studies of the inhibition showed that in the absence of DTE omeprazole behaved as non-competitive inhibitor. On the contrary, in the presence of DTE competitive inhibition was found. The K(i) of the transporter for the inhibitor was 5.2 microM or 14.6 microM in the absence or presence of DTE, i.e., under condition of covalent (non-competitive) or non-covalent (competitive) interaction of the inhibitor with the transporter. The presence of the substrate during the incubation of the omeprazole (in the absence of DTE) with the proteoliposomes facilitated the covalent reaction of the pharmacological compound with the transporter. Omeprazole did not inhibit when present in the internal proteoliposomal compartment, indicating that the inhibition was specifically due to interaction with external site(s) of the protein. The pharmacological compound was not transported by the reconstituted transporter. The possible in vivo implications of the interaction of omeprazole with the transporter are discussed.

Effective empirical corrections for basis set superposition error in the def2-SVPD basis: gCP and DFT-C

NASA Astrophysics Data System (ADS)

Witte, Jonathon; Neaton, Jeffrey B.; Head-Gordon, Martin

2017-06-01

With the aim of mitigating the basis set error in density functional theory (DFT) calculations employing local basis sets, we herein develop two empirical corrections for basis set superposition error (BSSE) in the def2-SVPD basis, a basis which—when stripped of BSSE—is capable of providing near-complete-basis DFT results for non-covalent interactions. Specifically, we adapt the existing pairwise geometrical counterpoise (gCP) approach to the def2-SVPD basis, and we develop a beyond-pairwise approach, DFT-C, which we parameterize across a small set of intermolecular interactions. Both gCP and DFT-C are evaluated against the traditional Boys-Bernardi counterpoise correction across a set of 3402 non-covalent binding energies and isomerization energies. We find that the DFT-C method represents a significant improvement over gCP, particularly for non-covalently-interacting molecular clusters. Moreover, DFT-C is transferable among density functionals and can be combined with existing functionals—such as B97M-V—to recover large-basis results at a fraction of the cost.

Rotational Spectrum and Conformational Analysis of N-methyl-2-aminoethanol: Insights into the Shape of Adrenergic Neurotransmitters

NASA Astrophysics Data System (ADS)

Calabrese, Camilla; Maris, Assimo; Evangelisti, Luca; Piras, Anna; Parravicini, Valentina; Melandri, Sonia

2018-02-01

Abstract We describe an experimental and quantum chemical study for the accurate determination of the conformational space of small molecular systems governed by intramolecular non-covalent interactions. The model systems investigated belong to the biological relevant aminoalcohol’s family, and include 2-aminophenylethanol, 2-methylaminophenylethanol, noradrenaline, adrenaline 2-aminoethanol and N-methyl-2-aminoethanol. For the latter molecule, the rotational spectrum in the 6-18 and 59.6-74.4 GHz ranges was recorded in the isolated conditions of a free jet expansion. Based on the analysis of the rotational spectra, two different conformational species and 11 isotopologues were observed and their spectroscopic constants, including 14N-nuclear hyperfine coupling constants and methyl internal rotation barriers, were determined. From the experimental data a structural determination was obtained, which was also used to benchmark accurate quantum chemical calculations on the whole conformational space. Atom in molecules and non-covalent interactions theories allowed the characterization of the position of the intramolecular non-covalent interactions and the energies involved, highlighting the subtle balance responsible of the stabilization of all the molecular systems.

Non-covalent synthesis of supermicelles with complex architectures using spatially confined hydrogen-bonding interactions

PubMed Central

Li, Xiaoyu; Gao, Yang; Boott, Charlotte E.; Winnik, Mitchell A.; Manners, Ian

2015-01-01

Nature uses orthogonal interactions over different length scales to construct structures with hierarchical levels of order and provides an important source of inspiration for the creation of synthetic functional materials. Here, we report the programmed assembly of monodisperse cylindrical block comicelle building blocks with crystalline cores to create supermicelles using spatially confined hydrogen-bonding interactions. We also demonstrate that it is possible to further program the self-assembly of these synthetic building blocks into structures of increased complexity by combining hydrogen-bonding interactions with segment solvophobicity. The overall approach offers an efficient, non-covalent synthesis method for the solution-phase fabrication of a range of complex and potentially functional supermicelle architectures in which the crystallization, hydrogen-bonding and solvophobic interactions are combined in an orthogonal manner. PMID:26337527

Experimental and density functional theory studies on benzalkonium ibuprofenate, a double active pharmaceutical ingredient.

PubMed

Safna Hussan, K P; Thayyil, M Shahin; Rajan, Vijisha K; Muraleedharan, K

2018-02-01

Molecular aspects of a double active pharmaceutical ingredient in ionic liquid form, benzalkonium ibuprofenate (BaIb), were studied using density functional theory (DFT/B3LYP/6-31+G (d, p)). A detailed discussion on optimized geometry, energy, heat and the enthalpy of BaIb was carried out. The computed vibrational results agree well with the experimental results. The stability and biological activity were compared to the parent drugs on the basis of global descriptive parameters. The electrophilic and nucleophilic sites were pointed out in the MESP structures well evidently. NBO analysis was also done to predict the relative aromaticity, delocalization effects and the contribution towards stabilization energy of the title compound. The information about non-covalent, non-ionic weak interaction between the cation and anion was obtained from the list of Mulliken charges and NBO analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

An internal thioester in a pathogen surface protein mediates covalent host binding

PubMed Central

Walden, Miriam; Edwards, John M; Dziewulska, Aleksandra M; Bergmann, Rene; Saalbach, Gerhard; Kan, Su-Yin; Miller, Ona K; Weckener, Miriam; Jackson, Rosemary J; Shirran, Sally L; Botting, Catherine H; Florence, Gordon J; Rohde, Manfred; Banfield, Mark J; Schwarz-Linek, Ulrich

2015-01-01

To cause disease and persist in a host, pathogenic and commensal microbes must adhere to tissues. Colonization and infection depend on specific molecular interactions at the host-microbe interface that involve microbial surface proteins, or adhesins. To date, adhesins are only known to bind to host receptors non-covalently. Here we show that the streptococcal surface protein SfbI mediates covalent interaction with the host protein fibrinogen using an unusual internal thioester bond as a ‘chemical harpoon’. This cross-linking reaction allows bacterial attachment to fibrin and SfbI binding to human cells in a model of inflammation. Thioester-containing domains are unexpectedly prevalent in Gram-positive bacteria, including many clinically relevant pathogens. Our findings support bacterial-encoded covalent binding as a new molecular principle in host-microbe interactions. This represents an as yet unexploited target to treat bacterial infection and may also offer novel opportunities for engineering beneficial interactions. DOI: http://dx.doi.org/10.7554/eLife.06638.001 PMID:26032562

Chirality of weakly bound complexes: The potential energy surfaces for the hydrogen-peroxide−noble-gas interactions

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

Roncaratti, L. F., E-mail: lz@fis.unb.br; Leal, L. A.; Silva, G. M. de

2014-10-07

We consider the analytical representation of the potential energy surfaces of relevance for the intermolecular dynamics of weakly bound complexes of chiral molecules. In this paper we study the H{sub 2}O{sub 2}−Ng (Ng=He, Ne, Ar, Kr, and Xe) systems providing the radial and the angular dependence of the potential energy surface on the relative position of the Ng atom. We accomplish this by introducing an analytical representation which is able to fit the ab initio energies of these complexes in a wide range of geometries. Our analysis sheds light on the role that the enantiomeric forms and the symmetry ofmore » the H{sub 2}O{sub 2} molecule play on the resulting barriers and equilibrium geometries. The proposed theoretical framework is useful to study the dynamics of the H{sub 2}O{sub 2} molecule, or other systems involving O–O and S–S bonds, interacting by non-covalent forces with atoms or molecules and to understand how the relative orientation of the O–H bonds changes along collisional events that may lead to a hydrogen bond formation or even to selectivity in chemical reactions.« less

Prediction of Carbohydrate Binding Sites on Protein Surfaces with 3-Dimensional Probability Density Distributions of Interacting Atoms

PubMed Central

Tsai, Keng-Chang; Jian, Jhih-Wei; Yang, Ei-Wen; Hsu, Po-Chiang; Peng, Hung-Pin; Chen, Ching-Tai; Chen, Jun-Bo; Chang, Jeng-Yih; Hsu, Wen-Lian; Yang, An-Suei

2012-01-01

Non-covalent protein-carbohydrate interactions mediate molecular targeting in many biological processes. Prediction of non-covalent carbohydrate binding sites on protein surfaces not only provides insights into the functions of the query proteins; information on key carbohydrate-binding residues could suggest site-directed mutagenesis experiments, design therapeutics targeting carbohydrate-binding proteins, and provide guidance in engineering protein-carbohydrate interactions. In this work, we show that non-covalent carbohydrate binding sites on protein surfaces can be predicted with relatively high accuracy when the query protein structures are known. The prediction capabilities were based on a novel encoding scheme of the three-dimensional probability density maps describing the distributions of 36 non-covalent interacting atom types around protein surfaces. One machine learning model was trained for each of the 30 protein atom types. The machine learning algorithms predicted tentative carbohydrate binding sites on query proteins by recognizing the characteristic interacting atom distribution patterns specific for carbohydrate binding sites from known protein structures. The prediction results for all protein atom types were integrated into surface patches as tentative carbohydrate binding sites based on normalized prediction confidence level. The prediction capabilities of the predictors were benchmarked by a 10-fold cross validation on 497 non-redundant proteins with known carbohydrate binding sites. The predictors were further tested on an independent test set with 108 proteins. The residue-based Matthews correlation coefficient (MCC) for the independent test was 0.45, with prediction precision and sensitivity (or recall) of 0.45 and 0.49 respectively. In addition, 111 unbound carbohydrate-binding protein structures for which the structures were determined in the absence of the carbohydrate ligands were predicted with the trained predictors. The overall prediction MCC was 0.49. Independent tests on anti-carbohydrate antibodies showed that the carbohydrate antigen binding sites were predicted with comparable accuracy. These results demonstrate that the predictors are among the best in carbohydrate binding site predictions to date. PMID:22848404

Enhancement of Thermodynamic Gas-Phase Acidity and Basicity of Water by Means of Secondary Interactions.

PubMed

Montero-Campillo, M Merced; Alkorta, Ibon; Elguero, Jose

2018-06-26

A series of A···water, B···water complexes (A = acid, B =base) are studied at the G4 level of theory to show that water acidity or basicity can be modulated by non-covalent interactions. Protic and non-protic acids interacting with water form hydrogen bonds or other kind of non-covalent interactions, respectively, that may dramatically change the acidity of water up to almost 360 kJ·mol-1 in terms of enthalpy. Similarly, hydrogen bonds responsible for the interaction between typical small nitrogen-containing Lewis bases and water can enhance the proton affinity of water by almost 300 kJ·mol-1. Our results reveal that these large enhancements are linearly related with the binding energy of the charged complexes, and are determined by the Lewis acid-base properties of the molecule involved in the interaction, allowing a quite precise modulation of the corresponding acid-base properties of water. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Molecular Interactions between (−)-Epigallocatechin Gallate Analogs and Pancreatic Lipase

PubMed Central

Wang, Shihui; Sun, Zeya; Dong, Shengzhao; Liu, Yang; Liu, Yun

2014-01-01

The molecular interactions between pancreatic lipase (PL) and four tea polyphenols (EGCG analogs), like (−)-epigallocatechin gallate (EGCG), (−)-gallocatechin gallate (GCG), (−)-epicatechin gallate (ECG), and (−)-epigallocatechin (EC), were studied from PL activity, conformation, kinetics and thermodynamics. It was observed that EGCG analogs inhibited PL activity, and their inhibitory rates decreased by the order of EGCG>GCG>ECG>EC. PL activity at first decreased rapidly and then slowly with the increase of EGCG analogs concentrations. α-Helix content of PL secondary structure decreased dependent on EGCG analogs concentration by the order of EGCG>GCG>ECG>EC. EGCG, ECG, and EC could quench PL fluorescence both dynamically and statically, while GCG only quenched statically. EGCG analogs would induce PL self-assembly into complexes and the hydrodynamic radii of the complexes possessed a close relationship with the inhibitory rates. Kinetics analysis showed that EGCG analogs non-competitively inhibited PL activity and did not bind to PL catalytic site. DSC measurement revealed that EGCG analogs decreased the transition midpoint temperature of PL enzyme, suggesting that these compounds reduced PL enzyme thermostability. In vitro renaturation through urea solution indicated that interactions between PL and EGCG analogs were weak and non-covalent. PMID:25365042

Behavior of the E-E' Bonds (E, E' = S and Se) in Glutathione Disulfide and Derivatives Elucidated by Quantum Chemical Calculations with the Quantum Theory of Atoms-in-Molecules Approach.

PubMed

Hayashi, Satoko; Tsubomoto, Yutaka; Nakanishi, Waro

2018-02-17

The nature of the E-E' bonds (E, E' = S and Se) in glutathione disulfide ( 1 ) and derivatives 2 - 3 , respectively, was elucidated by applying quantum theory of atoms-in-molecules (QTAIM) dual functional analysis (QTAIM-DFA), to clarify the basic contribution of E-E' in the biological redox process, such as the glutathione peroxidase process. Five most stable conformers a - e were obtained, after applying the Monte-Carlo method then structural optimizations. In QTAIM-DFA, total electron energy densities H b ( r c ) are plotted versus H b ( r c ) - V b ( r c )/2 at bond critical points (BCPs), where V b ( r c ) are potential energy densities at BCPs. Data from the fully optimized structures correspond to the static nature. Those containing perturbed structures around the fully optimized one in the plot represent the dynamic nature of interactions. The behavior of E-E' was examined carefully. Whereas E-E' in 1a - 3e were all predicted to have the weak covalent nature of the shared shell interactions, two different types of S-S were detected in 1 , depending on the conformational properties. Contributions from the intramolecular non-covalent interactions to stabilize the conformers were evaluated. An inverse relationship was observed between the stability of a conformer and the strength of E-E' in the conformer, of which reason was discussed.

Non-covalent interactions between thio-caffeine derivatives and water-soluble porphyrin in ethanol-water environment

NASA Astrophysics Data System (ADS)

Lipke, Agnieszka; Makarska-Bialokoz, Magdalena; Sierakowska, Arleta; Jasiewicz, Beata

2018-03-01

To determine the binding interactions and ability to form the non-covalent systems, the association process between 5,10,15,20-tetrakis[4-(trimethylammonio)phenyl]-21H,23H-porphine tetra-p-tosylate (H2TTMePP) and a series of five structurally diverse thio-caffeine analogues has been studied in ethanol and ethanol-water solutions, analyzing its absorption and steady-state fluorescence spectra. The porphyrin fluorescence lifetimes in the systems studied were established as well. During the titration with thio-caffeine compounds the slight bathochromic effect and considerable hypochromicity of the porphyrin Soret band maximum can be noted. The fluorescence quenching effect observed for interactions in H2TTMePP - thio-caffeine derivative systems, as well as the order of binding and fluorescence quenching constants (of 105-103 mol- 1) suggest the existence of the mechanism of static quenching due to the formation of non-covalent and non-fluorescent stacking complexes. In all the systems studied the phenomenon of the fractional accessibility of the fluorophore for the quencher was observed as well. Additionally, the specific binding interactions, due to the changes in reaction environment polarity, can be observed. It was found that thio-caffeine compounds can quench the porphyrin fluorescence according to the structure of thio-substituent in caffeine molecule. The obtained results can be potentially useful from scientific, therapeutic or environmental points of view.

Scaled MP3 non-covalent interaction energies agree closely with accurate CCSD(T) benchmark data.

PubMed

Pitonák, Michal; Neogrády, Pavel; Cerný, Jirí; Grimme, Stefan; Hobza, Pavel

2009-01-12

Scaled MP3 interaction energies calculated as a sum of MP2/CBS (complete basis set limit) interaction energies and scaled third-order energy contributions obtained in small or medium size basis sets agree very closely with the estimated CCSD(T)/CBS interaction energies for the 22 H-bonded, dispersion-controlled and mixed non-covalent complexes from the S22 data set. Performance of this so-called MP2.5 (third-order scaling factor of 0.5) method has also been tested for 33 nucleic acid base pairs and two stacked conformers of porphine dimer. In all the test cases, performance of the MP2.5 method was shown to be superior to the scaled spin-component MP2 based methods, e.g. SCS-MP2, SCSN-MP2 and SCS(MI)-MP2. In particular, a very balanced treatment of hydrogen-bonded compared to stacked complexes is achieved with MP2.5. The main advantage of the approach is that it employs only a single empirical parameter and is thus biased by two rigorously defined, asymptotically correct ab-initio methods, MP2 and MP3. The method is proposed as an accurate but computationally feasible alternative to CCSD(T) for the computation of the properties of various kinds of non-covalently bound systems.

Molecular gels in the gas phase? Gelator-gelator and gelator-solvent interactions probed by vibrational spectroscopy.

PubMed

Lozada-Garcia, Rolando; Mu, Dan; Plazanet, Marie; Çarçabal, Pierre

2016-08-10

Benzylidene glucose (BzGlc) is a member of the benzylidene glycoside family. These molecules have the ability to form molecular physical gels. These materials are formed when gelator molecules create a non-covalently bound frame where solvent molecules are trapped. Since the gel formation process and its properties are determined by the subtle balance between non-covalent forces, it is difficult to anticipate them. Quantitative and qualitative understanding of the gelator-gelator and gelator-solvent interactions is needed to better control these materials for important potential applications. We have used gas phase vibrational spectroscopy and theoretical chemistry to study the conformational choices of BzGlc, its dimer and the complexes it forms with water or toluene. To interpret the vibrational spectra we have used the dispersion corrected functional B97D which we have calibrated for the calculation of OH stretching frequencies. Even at the most basic molecular level, it is possible to interrogate a large range of non-covalent interactions ranging from OH → OH hydrogen bonding, to OH → π, and CH → π, all being at the center of gel properties at the macroscopic level.

Amorphous chalcogenides as random octahedrally bonded solids: I. Implications for the first sharp diffraction peak, photodarkening, and Boson peak

NASA Astrophysics Data System (ADS)

Lukyanov, Alexey; Lubchenko, Vassiliy

2017-09-01

We develop a computationally efficient algorithm for generating high-quality structures for amorphous materials exhibiting distorted octahedral coordination. The computationally costly step of equilibrating the simulated melt is relegated to a much more efficient procedure, viz., generation of a random close-packed structure, which is subsequently used to generate parent structures for octahedrally bonded amorphous solids. The sites of the so-obtained lattice are populated by atoms and vacancies according to the desired stoichiometry while allowing one to control the number of homo-nuclear and hetero-nuclear bonds and, hence, effects of the mixing entropy. The resulting parent structure is geometrically optimized using quantum-chemical force fields; by varying the extent of geometric optimization of the parent structure, one can partially control the degree of octahedrality in local coordination and the strength of secondary bonding. The present methodology is applied to the archetypal chalcogenide alloys AsxSe1-x. We find that local coordination in these alloys interpolates between octahedral and tetrahedral bonding but in a non-obvious way; it exhibits bonding motifs that are not characteristic of either extreme. We consistently recover the first sharp diffraction peak (FSDP) in our structures and argue that the corresponding mid-range order stems from the charge density wave formed by regions housing covalent and weak, secondary interactions. The number of secondary interactions is determined by a delicate interplay between octahedrality and tetrahedrality in the covalent bonding; many of these interactions are homonuclear. The present results are consistent with the experimentally observed dependence of the FSDP on arsenic content, pressure, and temperature and its correlation with photodarkening and the Boson peak. They also suggest that the position of the FSDP can be used to infer the effective particle size relevant for the configurational equilibration in covalently bonded glassy liquids, where the identification of the effective rigid molecular unit is ambiguous.

Atomic-Resolution Structure of an N(5) Flavin Adduct in D-Arginine Dehydrogenase

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

Fu, Guoxing; Yuan, Hongling; Wang, Siming

2011-09-06

D-Arginine dehydrogenase (DADH) catalyzes the flavin-dependent oxidative deamination of D-arginine and other D-amino acids to the corresponding imino acids. The 1.07 {angstrom} atomic-resolution structure of DADH crystallized with D-leucine unexpectedly revealed a covalent N(5) flavin adduct, instead of the expected iminoleucine product in the active site. This acyl adduct has been successfully reproduced by photoreduction of DADH in the presence of 4-methyl-2-oxopentanoic acid (ketoleucine). The iminoleucine may be released readily because of weak interactions in the binding site, in contrast to iminoarginine, converted to ketoleucine, which reacts with activated FAD to form the covalently linked acyl adduct.

Design and synthesis of (aza)indolyl maleimide-based covalent inhibitors of glycogen synthase kinase 3β.

PubMed

Yang, Zhimin; Liu, Hui; Pan, Botao; He, Fengli; Pan, Zhengying

2018-05-21

As an important kinase in multiple signal transduction pathways, GSK-3β has been an attractive target for chemical probe discovery and drug development. Compared to numerous reversible inhibitors that have been developed, covalent inhibitors of GSK-3β are noticeably lacking. Here, we report the discovery of a series of covalent GSK-3β inhibitors by optimizing both non-covalent interactions and reactive groups. Among these covalent inhibitors, compound 38b with a mild α-fluoromethyl amide reactive group emerges as a selective and covalent inhibitor against GSK-3β, effectively inhibits the phosphorylation of glycogen synthase and tau protein, and increases β-catenin's levels in living cells. In addition, compound 38b is highly permeable and not a substrate of P-glycoprotein.

X-ray electron density investigation of chemical bonding in van der Waals materials

NASA Astrophysics Data System (ADS)

Kasai, Hidetaka; Tolborg, Kasper; Sist, Mattia; Zhang, Jiawei; Hathwar, Venkatesha R.; Filsø, Mette Ø.; Cenedese, Simone; Sugimoto, Kunihisa; Overgaard, Jacob; Nishibori, Eiji; Iversen, Bo B.

2018-03-01

Van der Waals (vdW) solids have attracted great attention ever since the discovery of graphene, with the essential feature being the weak chemical bonding across the vdW gap. The nature of these weak interactions is decisive for many extraordinary properties, but it is a strong challenge for current theory to accurately model long-range electron correlations. Here we use synchrotron X-ray diffraction data to precisely determine the electron density in the archetypal vdW solid, TiS2, and compare the results with density functional theory calculations. Quantitative agreement is observed for the chemical bonding description in the covalent TiS2 slabs, but significant differences are identified for the interactions across the gap, with experiment revealing more electron deformation than theory. The present data provide an experimental benchmark for testing theoretical models of weak chemical bonding.

Interaction of In(I) and Tl(I) cations with 2,6-diaryl pyridine ligands: cation encapsulation within a very weakly interacting N/arene host environment.

PubMed

Mansaray, Hassanatu B; Tang, Christina Y; Vidovic, Dragoslav; Thompson, Amber L; Aldridge, Simon

2012-12-03

The interaction of 2,6-dimesitylpyridine with Tl(I) and In(I) cations has been investigated with a view to developing tractable molecular M(I) compounds which are soluble in organic media. In stark contrast to isosteric and isoelectronic terphenyl systems, complexes featuring the [(2,6-Mes(2)py)M](+) fragment feature very weak metal-ligand interactions in the solid state, as revealed by M-N distances of the order of 2.45 Å (M = In) and 2.64 Å (M = Tl). While additional weak π interactions are observed with arene solvate molecules in these systems, the related 2:1 complex [(2,6-Mes(2)py)(2)In][BAr(f)(4)] features an In(I) center wholly encapsulated by the bulky Mes(2)py donors, and even longer In-N distances [2.586(6) and 2.662(5) Å]. These contacts are about 0.5 Å greater than the sum of the respective covalent radii (2.13 Å) and provide evidence for an effectively "naked" In(I) cation stabilized to a minor extent by orbital interactions.

Surface Immobilization of Molecular Electrocatalysts for Energy Conversion

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

Bullock, R. Morris; Das, Atanu K.; Appel, Aaron M.

2017-03-22

Electrocatalysts are critically important for a secure energy future, as they facilitate the conversion between electrical energy and chemical energy. Molecular catalysts offer precise control of their structure, and the ability to modify the substituents to understand structure-reactivity relationships that are more difficult to achieve with heterogeneous catalysts. Molecular electrocatalysts can be immobilized on surfaces by covalent bonds or through non-covalent interactions. Advantages of surface immobilization include the need for less catalyst, avoidance of bimolecular decomposition pathways, and easier determination of catalyst lifetime. Copper-catalyzed click reactions are often used to form covalent bonds to surfaces, and pi-pi stacking of pyrenemore » substituents appended to the ligand of a molecular complex is a frequently used method to achieve non-covalent surface immobilization. This mini-review highlights surface confinement of molecular electrocatalysts for reduction of O2, oxidation of H2O, production of H2, and reduction of CO2.« less

Mechanism of Amido-Thiourea Catalyzed Enantioselective Imine Hydrocyanation: Transition State Stabilization via Multiple Non-Covalent Interactions

PubMed Central

Zuend, Stephan J.

2009-01-01

An experimental and computational investigation of amido-thiourea promoted imine hydrocyanation has revealed a new and unexpected mechanism of catalysis. Rather than direct activation of the imine by the thiourea, as had been proposed previously in related systems, the data are consistent with a mechanism involving catalyst-promoted proton transfer from hydrogen isocyanide to imine to generate diastereomeric iminium/cyanide ion pairs that are bound to catalyst through multiple non-covalent interactions; these ion pairs collapse to form the enantiomeric α-aminonitrile products. This mechanistic proposal is supported by the observation of a statistically significant correlation between experimental and calculated enantioselectivities induced by eight different catalysts (P ≪ 0.01). The computed models reveal a basis for enantioselectivity that involves multiple stabilizing and destabilizing interactions between substrate and catalyst, including thiourea-cyanide and amide-iminium interactions. PMID:19778044

Ab initio study on electronically excited states of lithium isocyanide, LiNC

NASA Astrophysics Data System (ADS)

Yasumatsu, Hisato; Jeung, Gwang-Hi

2014-01-01

The electronically excited states of the lithium isocyanide molecule, LiNC, were studied by means of ab initio calculations. The bonding nature of LiNC up to ∼10 eV is discussed on the basis of the potential energy surfaces according to the interaction between the ion-pair and covalent states. The ion-pair states are described by Coulomb attractive interaction in the long distance range, while the covalent ones are almost repulsive or bound with a very shallow potential dent. These two states interact each other to form adiabatic potential energy surfaces with non-monotonic change in the potential energy with the internuclear distance.

The Janus Kinase (JAK) FERM and SH2 Domains: Bringing Specificity to JAK-Receptor Interactions.

PubMed

Ferrao, Ryan; Lupardus, Patrick J

2017-01-01

The Janus kinases (JAKs) are non-receptor tyrosine kinases essential for signaling in response to cytokines and interferons and thereby control many essential functions in growth, development, and immune regulation. JAKs are unique among tyrosine kinases for their constitutive yet non-covalent association with class I and II cytokine receptors, which upon cytokine binding bring together two JAKs to create an active signaling complex. JAK association with cytokine receptors is facilitated by N-terminal FERM and SH2 domains, both of which are classical mediators of peptide interactions. Together, the JAK FERM and SH2 domains mediate a bipartite interaction with two distinct receptor peptide motifs, the proline-rich "Box1" and hydrophobic "Box2," which are present in the intracellular domain of cytokine receptors. While the general sidechain chemistry of Box1 and Box2 peptides is conserved between receptors, they share very weak primary sequence homology, making it impossible to posit why certain JAKs preferentially interact with and signal through specific subsets of cytokine receptors. Here, we review the structure and function of the JAK FERM and SH2 domains in light of several recent studies that reveal their atomic structure and elucidate interaction mechanisms with both the Box1 and Box2 receptor motifs. These crystal structures demonstrate how evolution has repurposed the JAK FERM and SH2 domains into a receptor-binding module that facilitates interactions with multiple receptors possessing diverse primary sequences.

Insight into the mechanism of action and selectivity of caspase-3 reversible inhibitors through in silico studies

NASA Astrophysics Data System (ADS)

Minini, Lucía; Ferraro, Florencia; Cancela, Saira; Merlino, Alicia

2017-11-01

Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder worldwide for which there is currently no cure. Recently, caspase-3 has been proposed as a potential therapeutic target for treating AD. Since this enzyme is overexpressed in brains from AD patients its selective modulation by non-covalent inhibitors becomes an interesting strategy in the search of potential drugs against this neuropathology. With this in mind, we have combined molecular docking, molecular dynamics simulations and QM calculations of unliganded caspase-3 and caspase-7 and in complex with a series of known inhibitors of caspase-3 described in the literature in order to assess the structural features responsible for good inhibitory activity and selectivity against this potential target. This work has allowed us to identify hotspots for drug binding as well as the importance of shape and charge distribution for interacting into the substrate binding cleft or into the dimer interface in each enzyme. Our results showed that most selective compounds against caspsase-3 bind into the substrate binding cleft acting as competitive inhibitors whereas in caspase-7 they bind close to an allosteric site at the dimer interface but since they are weakly bound their presence would not be affecting enzyme dynamics or function. In addition, for both enzymes we have found evidence indicating that differences in shape and accessibility exist between the substrate binding site of each monomer which could be modulating the binding affinity of non-covalent molecules.

Electrophoretic mobility patterns of collagen following laser welding

NASA Astrophysics Data System (ADS)

Bass, Lawrence S.; Moazami, Nader; Pocsidio, Joanne O.; Oz, Mehmet C.; LoGerfo, Paul; Treat, Michael R.

1991-06-01

Clinical application of laser vascular anastomosis in inhibited by a lack of understanding of its mechanism. Whether tissue fusion results from covalent or non-covalent bonding of collagen and other structural proteins is unknown. We compared electrophoretic mobility of collagen in laser treated and untreated specimens of rat tail tendon (>90% type I collagen) and rabbit aorta. Welding was performed, using tissue shrinkage as the clinical endpoint, using the 808 nm diode laser (power density 14 watts/cm2) and topical indocyanine green dye (max absorption 805 nm). Collagen was extracted with 8 M urea (denaturing), 0.5 M acetic acid (non-denaturing) and acetic acid/pepsin (cleaves non- helical protein). Mobility patterns on gel electrophoresis (SDS-PAGE) after urea or acetic acid extraction were identical in the lasered and control tendon and vessel (confirmed by optical densitometry), revealing no evidence of formation of novel covalent bonds. Alpha and beta band intensity was diminished in pepsin incubated lasered specimens compared with controls (optical density ratio 0.00 +/- 9 tendon, 0.65 +/- 0.12 aorta), indicating the presence of denatured collagen. With the laser parameters used, collagen is denatured without formation of covalent bonds, suggesting that non-covalent interaction between denatured collagen molecules may be responsible for the weld. Based on this mechanism, welding parameters can be chosen which produce collagen denaturation without cell death.

Targeting breast cancer with sugar-coated carbon nanotubes

PubMed Central

Fahrenholtz, Cale D; Hadimani, Mallinath; King, S Bruce; Torti, Suzy V; Singh, Ravi

2015-01-01

Aims To evaluate the use of glucosamine functionalized multiwalled carbon nanotubes (glyco-MWCNTs) for breast cancer targeting. Materials & methods Two types of glucosamine functionalized MWCNTs were developed (covalently linked glucosamine and non-covalently phospholipid-glucosamine coated) and evaluated for their potential to bind and target breast cancer cells in vitro and in vivo. Results & conclusion Binding of glyco-MWCNTs in breast cancer cells is mediated by specific interaction with glucose transporters. Glyco-MWCNTs prepared by non-covalent coating with phospholipid-glucosamine displayed an extended blood circulation time, delayed urinary clearance, low tissue retention and increased breast cancer tumor accumulation in vivo. These studies lay the foundation for development of a cancer diagnostic agent based upon glyco-MWCNTs with the potential for superior accuracy over current radiopharmaceuticals. PMID:26296098

Preparation of non-aggregated fluorescent nanodiamonds (FNDs) by non-covalent coating with a block copolymer and proteins for enhancement of intracellular uptake.

PubMed

Lee, Jong Woo; Lee, Seonju; Jang, Sangmok; Han, Kyu Young; Kim, Younggyu; Hyun, Jaekyung; Kim, Seong Keun; Lee, Yan

2013-05-01

Fluorescent nanodiamonds (FNDs) are very promising fluorophores for use in biosystems due to their high biocompatibility and photostability. To overcome their tendency to aggregate in physiological solutions, which severely limits the biological applications of FNDs, we developed a new non-covalent coating method using a block copolymer, PEG-b-P(DMAEMA-co-BMA), or proteins such as BSA and HSA. By simple mixing of the block copolymer with FNDs, the cationic DMAEMA and hydrophobic BMA moieties can strongly interact with the anionic and hydrophobic moieties on the FND surface, while the PEG block can form a shell to prevent the direct contact between FNDs. The polymer-coated FNDs, along with BSA- and HSA-coated FNDs, showed non-aggregation characteristics and maintained their size at the physiological salt concentration. The well-dispersed, polymer- or protein-coated FNDs in physiological solutions showed enhanced intracellular uptake, which was confirmed by CLSM. In addition, the biocompatibility of the coated FNDs was expressly supported by a cytotoxicity assay. Our simple non-covalent coating with the block copolymer, which can be easily modified by various chemical methods, projects a very promising outlook for future biomedical applications, especially in comparison with covalent coating or protein-based coating.

Phytochemical, spectroscopic and density functional theory study of Diospyrin, and non-bonding interactions of Diospyrin with atmospheric gases

NASA Astrophysics Data System (ADS)

Fazl-i-Sattar; Ullah, Zakir; Ata-ur-Rahman; Rauf, Abdur; Tariq, Muhammad; Tahir, Asif Ali; Ayub, Khurshid; Ullah, Habib

2015-04-01

Density functional theory (DFT) and phytochemical study of a natural product, Diospyrin (DO) have been carried out. A suitable level of theory was developed, based on correlating the experimental and theoretical data. Hybrid DFT method at B3LYP/6-31G (d,p) level of theory is employed for obtaining the electronic, spectroscopic, inter-molecular interaction and thermodynamic properties of DO. The exact structure of DO is confirmed from the nice validation of the theory and experiment. Non-covalent interactions of DO with different atmospheric gases such as NH3, CO2, CO, and H2O were studied to find out its electroactive nature. The experimental and predicted geometrical parameters, IR and UV-vis spectra (B3LYP/6-31+G (d,p) level of theory) show excellent correlation. Inter-molecular non-bonding interaction of DO with atmospheric gases is investigated through geometrical parameters, electronic properties, charge analysis, and thermodynamic parameters. Electronic properties include, ionization potential (I.P.), electron affinities (E.A.), electrostatic potential (ESP), density of states (DOS), HOMO, LUMO, and band gap. All these characterizations have corroborated each other and confirmed the presence of non-covalent nature in DO with the mentioned gases.

Investigation of non-covalent and hydrogen bonding interactions on the formation of crystalline networks and supramolecular synthons of a series of α-aminophosphonates: Crystallography and DFT studies

NASA Astrophysics Data System (ADS)

Mirzaei, Masoud; Eshghi, Hossein; Akhlaghi Bagherjeri, Fateme; Mirzaei, Mahdi; Farhadipour, Abolghasem

2018-07-01

α-Aminophosphonates have been rarely explored in the field of crystal engineering. These organic molecules are capable of forming reliable and reproducible supramolecular synthons through non-covalent interactions that can be employed for designing high dimensional supramolecular architectures. Here, we systematically study the influence of conventional and unconventional hydrogen bonding interactions on the formation of these synthons and stability of the crystal packing. The theoretical studies were employed to further confirm the presence of these synthons by comparing the stabilization energies of the dimers and monomers. The dependence of the stability of NH⋯O hydrogen bonds to the aromatic substituents were investigated using NBO analysis. The most stable compound was determined by comparing the HOMO-LUMO energy gap of all compounds and compared with NBO analysis.

Extent of Fock-exchange mixing for a hybrid van der Waals density functional?

NASA Astrophysics Data System (ADS)

Jiao, Yang; Schröder, Elsebeth; Hyldgaard, Per

2018-05-01

The vdW-DF-cx0 exchange-correlation hybrid design [K. Berland et al., J. Chem. Phys. 146, 234106 (2017)] has a truly nonlocal correlation component and aims to facilitate concurrent descriptions of both covalent and non-covalent molecular interactions. The vdW-DF-cx0 design mixes a fixed ratio, a, of the Fock exchange into the consistent-exchange van der Waals density functional, vdW-DF-cx [K. Berland and P. Hyldgaard, Phys. Rev. B 89, 035412 (2014)]. The mixing value a is sometimes taken as a semi-empirical parameter in hybrid formulations. Here, instead, we assert a plausible optimum average a value for the vdW-DF-cx0 design from a formal analysis; A new, independent determination of the mixing a is necessary since the Becke fit [A. D. Becke, J. Chem. Phys. 98, 5648 (1993)], yielding a' = 0.2, is restricted to semilocal correlation and does not reflect non-covalent interactions. To proceed, we adapt the so-called two-legged hybrid construction [K. Burke et al., Chem. Phys. Lett. 265, 115 (1997)] to a starting point in the vdW-DF-cx functional. For our approach, termed vdW-DF-tlh, we estimate the properties of the adiabatic-connection specification of the exact exchange-correlation functional, by combining calculations of the Fock exchange and of the coupling-constant variation in vdW-DF-cx. We find that such vdW-DF-tlh hybrid constructions yield accurate characterizations of molecular interactions (even if they lack self-consistency). The accuracy motivates trust in the vdW-DF-tlh determination of system-specific values of the Fock-exchange mixing. We find that an average value a' = 0.2 best characterizes the vdW-DF-tlh description of covalent and non-covalent interactions, although there exists some scatter. This finding suggests that the original Becke value, a' = 0.2, also represents an optimal average Fock-exchange mixing for the new, truly nonlocal-correlation hybrids. To enable self-consistent calculations, we furthermore define and test a zero-parameter hybrid functional vdW-DF-cx0p (having fixed mixing a' = 0.2) and document that this truly nonlocal correlation hybrid works for general molecular interactions (at reference and at relaxed geometries). It is encouraging that the vdW-DF-cx0p functional remains useful also for descriptions of some extended systems.

Identification of a Novel Class of Covalent Modifiers of Hemoglobin as Potential Antisickling Agents

PubMed Central

Omar, A. M.; Mahran, M. A.; Ghatge, M. S.; Chowdhury, N.; Bamane, F. H. A.; El-Araby, M. E.; Abdulmalik, O.; Safo, M. K.

2015-01-01

Aromatic aldehydes and ethacrynic acid (ECA) exhibit antipolymerization properties that are beneficial for sickle cell disease therapy. Based on ECA pharmacophore and its atomic interaction with hemoglobin, we designed and synthesized several compounds--designated as KAUS (imidazolylacryloyl derivatives)--that we hypothesized would bind covalently to βCys93 of hemoglobin and inhibit sickling. The compounds surprisingly showed weak allosteric and antisickling properties. X-ray studies of hemoglobin in complex with representative KAUS compounds revealed an unanticipated mode of Michael addition reaction between the β-unsaturated carbon and the N-terminal αVal1 nitrogen at the α-cleft of hemoglobin, with no observable interaction with βCys93. Interestingly, the compounds exhibited almost no reactivity with the free amino acids, L-Val, L-His and L-Lys, however showed some reactivity with both glutathione and L-Cys. Our findings provide a molecular level explanation to the compounds biological activities and an important framework for targeted modifications that would yield novel potent antisickling agents. PMID:25974708

Investigation of Natural Bombyx mori Silk Fibroin Proteins Using INS

NASA Astrophysics Data System (ADS)

Crain, Christopher; Strange, Nicholas; Larese, J. Z.

The mechanical properties of many protein comprised biomaterials are a direct reflection of non-covalent (i.e. weak) interacting ions such as F-actin in muscles, tubulin in the cytoskeleton of cells, viral capsids, and silk. Porter and Vollrath underscored the two main factors that are critical for understanding the high mechanical strength of silks: the nanoscale semi-crystalline folding structure, which gives it exceptional toughness and strength, and the degree of hydration of the disordered fraction, which acts to modify these properties. Understanding and controlling these two principal factors are the key to the functionality of protein elastomers, and render silk an ideal model protein for (bio)material design. We will describe our investigation of electrospun silk of the Bombyx mori (silk worm), using Inelastic Neutron Scattering (INS). These techniques were used to investigate the microscopic dynamics of the dry and hydrated protein.

Interactions of praseodymium and neodymium with nucleosides and nucleotides: absorption difference and comparative absorption spectral study.

PubMed

Misra, S N; Anjaiah, K; Joseph, G; Abdi, S H

1992-02-01

The interactions of praseodymium(III) and neodymium(III) with nucleosides and nucleotides have been studied in different stoichiometry in water and water-DMF mixtures by employing absorption difference and comparative absorption spectrophotometry. The 4f-4f bands were analysed by linear curve analysis followed by gaussian curve analysis, and various spectral parameters were computed, using partial and multiple regression method. The magnitude of changes in both energy interaction and intensity were used to explore the degree of outer and inner sphere coordination, incidence of covalency and the extent of metal 4f-orbital involvement in chemical bonding. Crystalline complexes of the type [Ln(nucleotide)2(H2O)2]- (where nucleotide--GMP or IMP) were characterized by IR, 1H NMR, 31P NMR data. These studies indicated that the binding of the nucleotide is through phosphate oxygen in a bidentate manner and the complexes undergo substantial ionisation in aqueous medium, thereby supporting the observed weak 4f-4f bands and lower values for nephelauxetic effect (1-beta), bonding (b) and covalency (delta) parameters derived from coulombic and spin orbit interaction parameters.

Computational investigation of non-covalent interactions in 1-butyl 3-methylimidazolium/bis(trifluoromethylsulfonyl)imide [bmim][Tf2N] in EMD and NEMD

NASA Astrophysics Data System (ADS)

Blanco-Díaz, Edgar G.; Vázquez-Montelongo, Erik A.; Cisneros, G. Andrés; Castrejón-González, Edgar Omar

2018-02-01

Non-covalent interactions (NCIs) play a crucial role in the behavior and properties of ionic liquids (ILs). These interactions are particularly important for non-equilibrium properties such as the change in viscosity due to shearing forces (shear viscosity). Therefore, a detailed understanding of these interactions can improve our understanding of these important classes of liquids. Here, we have employed quantum mechanical energy decomposition analysis (EDA) and NCI analysis to investigate a series of representative 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([bmim][Tf2N]) ion pairs extracted from classical equilibrium and non-equilibrium molecular dynamics simulations. EDA based on symmetry-adapted perturbation theory (SAPT) for the complete monomers, as well as fragment SAPT (FSAPT), for the functional fragments has been carried out. In general, the electrostatic component comprises ≈80% of the intermolecular interaction, and significant contributions from other components (induction and dispersion) are also observed, especially for interactions involving bifurcated hydrogen bonds. The FSAPT analysis suggests that caution is warranted when employing simplified assumptions for non-bonded interactions, e.g., focusing only on hydrogen bonds between functional fragments, since this view may not provide a complete picture of the complicated interactions between the ions. In non-equilibrium molecular dynamics, the total interaction energies of some fragments have a significant qualitative change as the shear rate increases. Our results indicate that the inter-fragment interactions play a fundamental role in the viscous behavior of ILs, suggesting that the exclusive use of geometric criteria to analyze inter-molecular interactions in these systems is not sufficient to investigate shear-thinning effects.

Interrogating heterobimetallic co-catalytic responses for the electrocatalytic reduction of CO2 using supramolecular assembly.

PubMed

Machan, Charles W; Kubiak, Clifford P

2016-10-12

The use of hydrogen-bonding interactions to direct the non-covalent assembly of a heterobimetallic supramolecular system with Re and Mn bipyridine-based electrocatalysts is reported. Under catalytic conditions, the formation of hydrogen bonds generates a catalyst system which passes ∼10% more current than the individual current responses of the respective Re and Mn complexes for the reduction of CO 2 to CO and H 2 O. Infrared spectroelectrochemical studies indicate that the Re and Mn metal centers interact during the reduction mechanism, even forming heterobimetallic bonds under reducing conditions in the absence of substrate. These findings demonstrate that non-covalent assembly is a powerful method for generating new co-catalyst systems with greater reactivity and efficiency for transformations of interest.

Two-dimensional honeycomb network through sequence-controlled self-assembly of oligopeptides.

PubMed

Abb, Sabine; Harnau, Ludger; Gutzler, Rico; Rauschenbach, Stephan; Kern, Klaus

2016-01-12

The sequence of a peptide programs its self-assembly and hence the expression of specific properties through non-covalent interactions. A large variety of peptide nanostructures has been designed employing different aspects of these non-covalent interactions, such as dispersive interactions, hydrogen bonding or ionic interactions. Here we demonstrate the sequence-controlled fabrication of molecular nanostructures using peptides as bio-organic building blocks for two-dimensional (2D) self-assembly. Scanning tunnelling microscopy reveals changes from compact or linear assemblies (angiotensin I) to long-range ordered, chiral honeycomb networks (angiotensin II) as a result of removal of steric hindrance by sequence modification. Guided by our observations, molecular dynamic simulations yield atomistic models for the elucidation of interpeptide-binding motifs. This new approach to 2D self-assembly on surfaces grants insight at the atomic level that will enable the use of oligo- and polypeptides as large, multi-functional bio-organic building blocks, and opens a new route towards rationally designed, bio-inspired surfaces.

Cholera Toxin Inhibitors Studied with High-Performance Liquid Affinity Chromatography: A Robust Method to Evaluate Receptor–Ligand Interactions

PubMed Central

Bergström, Maria; Liu, Shuang; Kiick, Kristi L.; Ohlson, Sten

2009-01-01

Anti-adhesion drugs may be an alternative to antibiotics to control infection of micro-organisms. The well-characterized interaction between cholera toxin and the cellular glycolipid GM1 makes it an attractive model for inhibition studies in general. In this report, we demonstrate a high-performance liquid affinity chromatography approach called weak affinity chromatography to evaluate cholera toxin inhibitors. The cholera toxin B-subunit was covalently coupled to porous silica and a (weak) affinity column was produced. The KD values of galactose and meta-nitrophenyl α-D-galactoside were determined with weak affinity chromatography to be 52 and 1 mM, respectively, which agree well with IC50 values previously reported. To increase inhibition potency multivalent inhibitors have been developed and the interaction with multivalent glycopolypeptides was also evaluated. The affinity of these compounds was found to correlate with the galactoside content but KD values were not obtained because of the inhomogeneous response and slow off-rate from multivalent interactions. Despite the limitations in obtaining direct KD values of the multivalent galactopolypeptides, weak affinity chromatography represents an additional and valuable tool in the evaluation of monovalent as well as multivalent cholera toxin inhibitors. It offers multiple advantages, such as a low sample consumption, high reproducibility and short analysis time, which are often not observed in other methods of analysis. PMID:19152642

New insights into the mechanism of interaction between CO2 and polymers from thermodynamic parameters obtained by in situ ATR-FTIR spectroscopy.

PubMed

Gabrienko, Anton A; Ewing, Andrew V; Chibiryaev, Andrey M; Agafontsev, Alexander M; Dubkov, Konstantin A; Kazarian, Sergei G

2016-03-07

This work reports new physical insights of the thermodynamic parameters and mechanisms of possible interactions occurring in polymers subjected to high-pressure CO2. ATR-FTIR spectroscopy has been used in situ to determine the thermodynamic parameters of the intermolecular interactions between CO2 and different functional groups of the polymers capable of specific interactions with sorbed CO2 molecules. Based on the measured ATR-FTIR spectra of the polymer samples subjected to high-pressure CO2 (30 bar) at different temperatures (300-340 K), it was possible to characterize polymer-polymer and CO2-polymer interactions. Particularly, the enthalpy and entropy of the formation of the specific non-covalent complexes between CO2 and the hydroxy (-OH), carbonyl (C[double bond, length as m-dash]O) and hydroxyimino ([double bond, length as m-dash]N-OH) functional groups of the polymer samples have been measured. Furthermore, the obtained spectroscopic results have provided an opportunity for the structure of these complexes to be proposed. An interesting phenomenon regarding the behavior of CO2/polymer systems has also been observed. It has been found that only for the polyketone, the value of enthalpy was negative indicating an exothermic process during the formation of the CO2-polymer non-covalent complexes. Conversely, for the polyoxime and polyalcohol samples there is a positive enthalpy determined. This is a result of the initial polymer-polymer interactions requiring more energy to break than is released during the formation of the CO2-polymer complex. The effect of increasing temperature to facilitate the breaking of the polymer-polymer interactions has also been observed. Hence, a mechanism for the formation of CO2-polymer complexes was suggested based on these results, which occurs via a two-step process: (1) the breaking of the existing polymer-polymer interactions followed by (2) the formation of new CO2-polymer non-covalent interactions.

Co-assembly of Peptide Amphiphiles and Lipids into Supramolecular Nanostructures Driven by Anion-π Interactions

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

Yu, Zhilin; Erbas, Aykut; Tantakitti, Faifan

Co-assembly of binary systems driven by specific non-covalent interactions can greatly expand the structural and functional space of supramolecular nanostructures. We report here on the self-assembly of peptide amphiphiles and fatty acids driven primarily by anion-π interactions. The peptide sequences investigated were functionalized with a perfluorinated phenylalanine residue to promote anion-π interactions with carboxylate headgroups in fatty acids. These interactions were verified here by NMR and circular dichroism experiments as well as investigated using atomistic simulations. Positioning the aromatic units close to the N-terminus of the peptide backbone near the hydrophobic core of cylindrical nanofibers leads to strong anion-π interactionsmore » between both components. With a low content of dodecanoic acid in this position, the cylindrical morphology is preserved. However, as the aromatic units are moved along the peptide backbone away from the hydrophobic core, the interactions with dodecanoic acid transform the cylindrical supramolecular morphology into ribbon-like structures. Increasing the ratio of dodecanoic acid to PA leads to either the formation of large vesicles in the binary systems where the anion-π interactions are strong, or a heterogeneous mixture of assemblies when the peptide amphiphiles associate weakly with dodecanoic acid. Our findings reveal how co-assembly involving designed specific interactions can drastically change supramolecular morphology and even cross from nano to micro scales.« less

Investigation of Non-Covalent Interactions of Aflatoxins (B1, B2, G1, G2, and M1) with Serum Albumin

PubMed Central

Poór, Miklós; Bálint, Mónika; Hetényi, Csaba; Gődér, Beatrix; Kunsági-Máté, Sándor; Lemli, Beáta

2017-01-01

Aflatoxins are widely spread mycotoxins produced mainly by Aspergillus species. Consumption of aflatoxin-contaminated foods and drinks causes serious health risks for people worldwide. It is well-known that the reactive epoxide metabolite of aflatoxin B1 (AFB1) forms covalent adducts with serum albumin. However, non-covalent interactions of aflatoxins with human serum albumin (HSA) are poorly characterized. Thus, in this study the complex formation of aflatoxins was examined with HSA applying spectroscopic and molecular modelling studies. Our results demonstrate that aflatoxins form stable complexes with HSA as reflected by binding constants between 2.1 × 104 and 4.5 × 104 dm3/mol. A binding free energy value of −26.90 kJ mol−1 suggests a spontaneous binding process between AFB1 and HSA at room-temperature, while the positive entropy change of 55.1 JK−1 mol−1 indicates a partial decomposition of the solvation shells of the interacting molecules. Modeling studies and investigations with site markers suggest that Sudlow’s Site I of subdomain IIA is the high affinity binding site of aflatoxins on HSA. Interaction of AFB1 with bovine, porcine, and rat serum albumins was also investigated. Similar stabilities of the examined AFB1-albumin complexes were observed suggesting the low species differences of the albumin-binding of aflatoxins. PMID:29068381

Structural and Functional Investigations of the N-Terminal Ubiquitin Binding Region of Usp25.

PubMed

Yang, Yuanyuan; Shi, Li; Ding, Yiluan; Shi, Yanhong; Hu, Hong-Yu; Wen, Yi; Zhang, Naixia

2017-05-23

Ubiquitin-specific protease 25 (Usp25) is a deubiquitinase that is involved in multiple biological processes. The N-terminal ubiquitin-binding region (UBR) of Usp25 contains one ubiquitin-associated domain, one small ubiquitin-like modifier (SUMO)-interacting motif and two ubiquitin-interacting motifs. Previous studies suggest that the covalent sumoylation in the UBR of Usp25 impairs its enzymatic activity. Here, we raise the hypothesis that non-covalent binding of SUMO, a prerequisite for efficient sumoylation, will impair Usp25's catalytic activity as well. To test our hypothesis and elucidate the underlying molecular mechanism, we investigated the structure and function of the Usp25 N-terminal UBR. The solution structure of Usp25 1-146 is obtained, and the key residues responsible for recognition of ubiquitin and SUMO2 are identified. Our data suggest inhibition of Usp25's catalytic activity upon the non-covalent binding of SUMO2 to the Usp25 SUMO-interacting motif. We also find that SUMO2 can competitively block the interaction between the Usp25 UBR and its ubiquitin substrates. Based on our findings, we have proposed a working model to depict the regulatory role of the Usp25 UBR in the functional display of the enzyme. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

A comprehensive theoretical investigation about the bio-functionalization capability of single walled CNT, BNNT and SiCNT using DNA/RNA nucleobases

NASA Astrophysics Data System (ADS)

Alinezhad, Heshmatollah; Ganji, Masoud Darvish; Soleymani, Elham; Tajbakhsh, Mahmood

2017-11-01

By means of Density Functional Theory (DFT) based calculations, we have elucidated the interactions between five nucleobases and three nanotubes, namely: CNT, BNNT and SiCNT. The energetics and equilibrium geometries have been calculated within the framework of revPBE method in combination with third version of Grimme's atom pair-wise dispersion corrections with Becke-Johnson damping (D3BJ). The obtained results in terms of adsorption energy values and geometrical parameters suggest that the overall interactions are divided into two parts: non-covalently and covalently bonded systems as the nucleobases are physisorbed onto the surface of CNT and BNNT (Eads ranges from -0.57 to -0.76 eV and -0.54 to -0.78 eV for CNT and BNNT complexes, respectively) while the type of interactions between nucleobase molecules and SiCNT has been found to be of covalent type with the Eads ranging from -0.61 to -1.8 eV. Moreover, the empirical dispersion corrections have been found to play crucial roles in obtaining reliable geometries and adsorption energy values for the non-covalently bonded systems. The role of solvation on the overall interactions has also been explored using the COSMO model within a media with dielectric constant of 78.39 which resembles the water environment and the results revealed that the interaction strength showed a decreasing trend with increasing the polarity of the system. Considering the adsorption energy differences between each nucleobase and the nanotubes, the SiCNT showed promising performance in differentiating between the nucleobase molecules and exhibited the highest affinity to be biofunctionalized in comparison to other nanotubes. The findings of the present work would be very useful for understanding the underlying phenomena behind the interface interactions and would aid future experimental investigations in the fields of biotechnology and materials science.

Silver(I) complexes of the weakly coordinating solvents SO(2) and CH(2)Cl(2): crystal structures, bonding, and energetics of [Ag(OSO)][Al{OC(CF(3))(3)}(4)], [Ag(OSO)(2/2)][SbF(6)], and [Ag(CH(2)Cl(2))(2)][SbF(6)].

PubMed

Decken, Andreas; Knapp, Carsten; Nikiforov, Grigori B; Passmore, Jack; Rautiainen, J Mikko; Wang, Xinping; Zeng, Xiaoqing

2009-06-22

Pushing the limits of coordination chemistry: The most weakly coordinated silver complexes of the very weakly coordinating solvents dichloromethane and liquid sulfur dioxide were prepared. Special techniques at low temperatures and the use of weakly coordinating anions allowed structural characterization of [Ag(OSO)][Al{OC(CF(3))(3)}(4)], [Ag(OSO)(2/2)][SbF(6)], and [Ag(Cl(2)CH(2))(2)][SbF(6)] (see figure). An investigation of the bonding shows that these complexes are mainly stabilized by electrostatic monopole-dipole interactions.The synthetically useful solvent-free silver(I) salt Ag[Al(pftb)(4)] (pftb=--OC(CF(3))(3)) was prepared by metathesis reaction of Li[Al(pftb)(4)] with Ag[SbF(6)] in liquid SO(2). The solvated complexes [Ag(OSO)][Al(pftb)(4)], [Ag(OSO)(2/2)][SbF(6)], and [Ag(CH(2)Cl(2))(2)][SbF(6)] were prepared and isolated by special techniques at low temperatures and structurally characterized by single-crystal X-ray diffraction. The SO(2) complexes provide the first examples of coordination of the very weak Lewis base SO(2) to silver(I). The SO(2) molecule in [Ag(OSO)][Al(pftb)(4)] is eta(1)-O coordinated to Ag(+), while the SO(2) ligands in [Ag(OSO)(2/2)][SbF(6)] bridge two Ag(+) ions in an eta(2)-O,O' (trans,trans) manner. [Ag(CH(2)Cl(2))(2)][SbF(6)] contains [Ag(CH(2)Cl(2))(2)](+) ions linked through [SbF(6)](-) ions to give a polymeric structure. The solid-state silver(I) ion affinities (SIA) of SO(2) and CH(2)Cl(2), based on bond lengths and corresponding valence units in the corresponding complexes and tensimetric titrations of Ag[Al(pftb)(4)] and Ag[SbF(6)] with SO(2) vapor, show that SO(2) is a weaker ligand to Ag(+) than the commonly used weakly coordinating solvent CH(2)Cl(2) and indicated that binding strength of SO(2) to silver(I) in the silver(I) salts increases with increasing size of the corresponding counteranion ([Al(pftb)(4)](-)>[SbF(6)](-)). The experimental findings are in good agreement with theoretical gas-phase ligand-binding energies of [Ag(L)(n)](+) (L=SO(2), CH(2)Cl(2); n=1, 2) and solid-state enthalpies obtained from Born-Fajans-Haber cycles by using the volume-based thermodynamics (VBT) approach. Bonding analysis (VB, NBO, MO) of [Ag(L)(n)](+) suggests that these complexes are almost completely stabilized by electrostatic interaction, that is, monopole-dipole interaction, with almost no covalent contribution by electron donation from the ligand orbitals into the vacant 5s orbital of Ag(+). All experimental findings and theoretical considerations demonstrate that SO(2) is less covalently bound to Ag(+) than CH(2)Cl(2) and support the thesis that SO(2) is a polar but non-coordinating solvent towards Ag(+).

Non-covalent Small-Molecule Kelch-like ECH-Associated Protein 1-Nuclear Factor Erythroid 2-Related Factor 2 (Keap1-Nrf2) Inhibitors and Their Potential for Targeting Central Nervous System Diseases.

PubMed

Pallesen, Jakob S; Tran, Kim T; Bach, Anders

2018-05-29

The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) has a protective effect against oxidative stress and plays a major role in inflammation and central nervous system (CNS) diseases. Inhibition of the protein-protein interaction (PPI) between Nrf2 and its repressor protein, Kelch-like ECH-associated protein 1 (Keap1), leads to translocation of Nrf2 from the cytosol to the nucleus and expression of detoxifying antioxidant enzymes. To date, several non-covalent small-molecule Keap1-Nrf2 inhibitors have been identified; however, many of them contain carboxylic acids and are rather large in size, which likely prevents or decreases CNS permeability. This Perspective describes current small-molecule Keap1-Nrf2 inhibitors with experimental evidence for the ability to inhibit the Keap1-Nrf2 interaction by binding to Keap1 in a non-covalent manner. Binding data, biostructural studies, and biological activity are summarized for the inhibitors, and their potential as CNS tool compounds is discussed by analyzing physicochemical properties, including CNS multiparameter optimization (MPO) scoring algorithms. Finally, several strategies for identifying CNS-targeting Keap1 inhibitors are described.

Probing hydrogen and halogen-oxo interactions in uranyl coordination polymers: a combined crystallographic and computational study

DOE PAGES

Carter, Korey P.; Kalaj, Mark; Kerridge, Andrew; ...

2018-01-01

Four uranyl compounds containing either benzoic acid ( 1 ), m -chlorobenzoic acid ( 2 ), m -bromobenzoic acid ( 3 ), or m -iodobenzoic acid ( 4 ) are described, and the latter two compounds are used to probe non-covalent interaction strengths via structural, vibrational, and computational means.

Non-Covalent Functionalization of Carbon Nanovectors with an Antibody Enables Targeted Drug Delivery

PubMed Central

Berlin, Jacob M.; Pham, Tam T.; Sano, Daisuke; Mohamedali, Khalid A.; Marcano, Daniela C.; Myers, Jeffrey N.; Tour, James M.

2011-01-01

Current chemotherapeutics are characterized by efficient tumor cell-killing and severe side effects mostly derived from off target toxicity. Hence targeted delivery of these drugs to tumor cells is actively sought. We previously demonstrated that poly(ethylene glycol)-functionalized carbon nanovectors are able to sequester paclitaxel, a widely used hydrophobic cancer drug, by simple physisorption and deliver the drug for killing of cancer cells. The cell-killing when these drug-loaded carbon nanoparticles were used was equivalent to when a commercial formulation of paclitaxel was used. Here we show that by further mixing the drug-loaded nanoparticles with Cetuximab, a monoclonal antibody that recognizes the epidermal growth factor receptor (EGFR), paclitaxel is preferentially targeted to EGFR+ tumor cells in vitro. This supports progressing to in vivo studies. Moreover, the construct is unusual in that all three components are assembled through non-covalent interactions. Such non-covalent assembly could enable high-throughput screening of drug/antibody combinations. PMID:21736358

Electronic cooling via interlayer Coulomb coupling in multilayer epitaxial graphene

PubMed Central

Mihnev, Momchil T.; Tolsma, John R.; Divin, Charles J.; Sun, Dong; Asgari, Reza; Polini, Marco; Berger, Claire; de Heer, Walt A.; MacDonald, Allan H.; Norris, Theodore B.

2015-01-01

In van der Waals bonded or rotationally disordered multilayer stacks of two-dimensional (2D) materials, the electronic states remain tightly confined within individual 2D layers. As a result, electron–phonon interactions occur primarily within layers and interlayer electrical conductivities are low. In addition, strong covalent in-plane intralayer bonding combined with weak van der Waals interlayer bonding results in weak phonon-mediated thermal coupling between the layers. We demonstrate here, however, that Coulomb interactions between electrons in different layers of multilayer epitaxial graphene provide an important mechanism for interlayer thermal transport, even though all electronic states are strongly confined within individual 2D layers. This effect is manifested in the relaxation dynamics of hot carriers in ultrafast time-resolved terahertz spectroscopy. We develop a theory of interlayer Coulomb coupling containing no free parameters that accounts for the experimentally observed trends in hot-carrier dynamics as temperature and the number of layers is varied. PMID:26399955

Smart Polymers with Special Wettability.

PubMed

Chang, Baisong; Zhang, Bei; Sun, Taolei

2017-01-01

Surface wettability plays a key role in addressing issues ranging from basic life activities to our daily life, and thus being able to control it is an attractive goal. Learning from nature, both of its structure and function, brings us much inspiration in designing smart polymers to tackle this major challenge. Life functions particularly depend on biomolecular recognition-induced interfacial properties from the aqueous phase onto either "soft" cell and tissue or "hard" inorganic bone and tooth surfaces. The driving force is noncovalent weak interactions rather than strong covalent combinations. An overview is provided of the weak interactions that perform vital actions in mediating biological processes, which serve as a basis for elaborating multi-component polymers with special wettabilities. The role of smart polymers from molecular recognitions to macroscopic properties are highlighted. The rationale is that highly selective weak interactions are capable of creating a dynamic synergetic communication in the building components of polymers. Biomolecules could selectively induce conformational transitions of polymer chains, and then drive a switching of physicochemical properties, e.g., roughness, stiffness and compositions, which are an integrated embodiment of macroscopic surface wettabilities. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photophysical characterization of a cytidine-guanosine tethered phthalocyanine-fullerene dyad.

PubMed

Torres, Tomas; Gouloumis, Andreas; Sanchez-Garcia, David; Jayawickramarajah, Janarthanan; Seitz, Wolfgang; Guldi, Dirk M; Sessler, Jonathan L

2007-01-21

A new non-covalent electron transfer model system, based on the use of cytidine-guanosine hydrogen bonding interactions, is described that incorporates a phthalocyanine photodonor and a C60 fullerene acceptor.

Phytochemical, spectroscopic and density functional theory study of Diospyrin, and non-bonding interactions of Diospyrin with atmospheric gases.

PubMed

Fazl-i-Sattar; Ullah, Zakir; Ata-ur-Rahman; Rauf, Abdur; Tariq, Muhammad; Tahir, Asif Ali; Ayub, Khurshid; Ullah, Habib

2015-04-15

Density functional theory (DFT) and phytochemical study of a natural product, Diospyrin (DO) have been carried out. A suitable level of theory was developed, based on correlating the experimental and theoretical data. Hybrid DFT method at B3LYP/6-31G (d,p) level of theory is employed for obtaining the electronic, spectroscopic, inter-molecular interaction and thermodynamic properties of DO. The exact structure of DO is confirmed from the nice validation of the theory and experiment. Non-covalent interactions of DO with different atmospheric gases such as NH3, CO2, CO, and H2O were studied to find out its electroactive nature. The experimental and predicted geometrical parameters, IR and UV-vis spectra (B3LYP/6-31+G (d,p) level of theory) show excellent correlation. Inter-molecular non-bonding interaction of DO with atmospheric gases is investigated through geometrical parameters, electronic properties, charge analysis, and thermodynamic parameters. Electronic properties include, ionization potential (I.P.), electron affinities (E.A.), electrostatic potential (ESP), density of states (DOS), HOMO, LUMO, and band gap. All these characterizations have corroborated each other and confirmed the presence of non-covalent nature in DO with the mentioned gases. Copyright © 2015 Elsevier B.V. All rights reserved.

Non-covalent conjugation of cutinase from Fusarium sp. ICT SAC1 with pectin for enhanced stability: Process minutiae, kinetics, thermodynamics and structural study.

PubMed

Muley, Abhijeet B; Chaudhari, Sandeep A; Singhal, Rekha S

2017-09-01

Cutinase, a member of α/β-fold hydrolase family possess potentially diverse applications in several industrial processes and products. The present work aims towards thermo-stabilization of cutinase from novel source Fusarium sp. ICT SAC1 via non-covalent interaction with polysaccharides. Although all six polysaccharides chosen for study enhanced the thermal stability, pectin was found to be most promising. The interaction protocol for cutinase with pectin was optimized sequentially with respect to the ratio of enzyme to pectin, solution pH, and buffer strength. Cutinase-pectin conjugate under optimized conditions (1:12, pH-6.5, 50mM) showed enhanced thermal stability as evident from lower inactivation rate constant, higher half-life and D-value within the 40-55°C. A slender rise in K m and V max values and enhanced thermodynamic parameters of cutinase-pectin conjugate were observed after non-covalent interaction. Entropy values were 1.5-fold higher for cutinase-pectin conjugate at each temperature suggesting an upsurge in number of protein molecules in a transition activated state. Positive values of entropy for both forms of cutinase suggested a rise in disordered conformation. Noticeable conformational changes in cutinase after conjugation with pectin were confirmed by FTIR as well as fluorescence emission spectra. An increment in helix to turn conversion was observed in complexed cutinase vis-à-vis free cutinase. Copyright © 2017 Elsevier B.V. All rights reserved.

Fibrinogen, Riboflavin, and UVA to Immobilize a Corneal Flap—Conditions for Tissue Adhesion

PubMed Central

Littlechild, Stacy L.; Brummer, Gage; Zhang, Yuntao; Conrad, Gary W.

2012-01-01

Purpose. Laser-assisted in situ keratomileus (LASIK) creates a permanent flap that remains non-attached to the underlying laser-modified stroma. This lack of permanent adhesion is a liability. To immobilize a corneal flap, a protocol using fibrinogen (FIB), riboflavin (RF), and ultraviolet (UVA) light (FIB+RF+UVA) was devised to re-adhere the flap to the stroma. Methods. A model flap was created using rabbit (Oryctolagus cuniculus) and shark (Squalus acanthias) corneas. Solutions containing FIB and RF were applied between corneal strips as glue. Experimental corneas were irradiated with long wavelength (365 nm) UVA. To quantify adhesive strength between corneal strips, the glue-tissue interface was subjected to a constant force while a digital force gauge recorded peak tension. Results. In the presence of FIB, substantive non-covalent interactions occurred between rabbit corneal strips. Adhesiveness was augmented if RF and UVA also were applied, suggesting formation of covalent bonds. Additionally, exposing both sides of rabbit corneas to UVA generated more adhesion than exposure from one side, suggesting that RF in the FIB solution catalyzes formation of covalent bonds at only the interface between stromal molecules and FIB closest to the UVA. In contrast, in the presence of FIB, shark corneal strips interacted non-covalently more substantively than those of rabbits, and adhesion was not augmented by applying RF+UVA, from either or both sides. Residual RF could be rinsed away within 1 hour. Conclusions. Glue solution containing FIB and RF, together with UVA treatment, may aid immobilization of a corneal flap, potentially reducing risk of flap dislodgement. PMID:22589434

Implications of non-covalent interactions in zein-starch dough and bread quality

USDA-ARS?s Scientific Manuscript database

Breads made from non-wheat flours are made from thick batters and are lower quality than wheat bread. The development of visco-elastic doughs from non-wheat proteins would allow a wider range of gluten-free products and would improve the quality of such foods. Only recently has the mechanism of zei...

Rapid, High Affinity Binding by a Fluorescein Templated Copolymer Combining Covalent, Hydrophobic, and Acid–Base Noncovalent Crosslinks

PubMed Central

Timberman, Anthony; Yang, Rongfang; Papantones, Alex; Seitz, W. Rudolf

2018-01-01

A new type of biomimetic templated copolymer has been prepared by reverse addition fragmentation chain transfer polymerization (RAFT) in dioxane. The initial formulation includes the template fluorescein, N-isopropylacrylamide (NIPAM, 84 mol %), methacrylic acid (MAA, 5-mol %), 4-vinylpyridine (4-VP, 9 mmol %), and N,N′-methylenebis(acrylamide) (MBA, 2 mol %). PolyNIPAM is a thermosensitive polymer that comes out of aqueous solution above its lower critical solution temperature forming hydrophobic ‘crosslinks’. MAA and 4-VP interact in dioxane forming acid–base crosslinks. The excess 4-VP serves as a recognition monomer organizing around the template fluorescein to form a binding site that is held in place by the noncovalent and covalent crosslinks. The MBA is a covalent crosslinker. The RAFT agent in the resulting copolylmer was reduced to a thiol and attached to gold nanoparticles. The gold nanoparticle bound copolymer binds fluorescein completely in less than two seconds with an affinity constant greater than 108 M−1. A reference copolymer prepared with the same monomers by the same procedure binds fluorescein much more weakly. PMID:29693601

Covalent surface modification of gallium arsenide photocathodes for water splitting in highly acidic electrolyte

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

Garner, Logan E.; Steirer, K. Xerxes; Young, James L.

Efficient water splitting using light as the only energy input requires stable semiconductor electrodes with favorable energetics for the water-oxidation and proton-reduction reactions. Strategies to tune electrode potentials using molecular dipoles adsorbed to the semiconductor surface have been pursued for decades but are often based on weak interactions and quickly react to desorb the molecule under conditions relevant to sustained photoelectrolysis. Here, we show that covalent attachment of fluorinated, aromatic molecules to p-GaAs(1 0 0) surfaces can be employed to tune the photocurrent onset potentials of p-GaAs(1 0 0) photocathodes and reduce the external energy required for water splitting. Resultsmore » indicate that initial photocurrent onset potentials can be shifted by nearly 150 mV in pH -0.5 electrolyte under 1 Sun (1000 W m -2) illumination resulting from the covalently bound surface dipole. Furthermore, X-ray photoelectron spectroscopy analysis reveals that the covalent molecular dipole attachment is not robust under extended 50 h photoelectrolysis, the modified surface delays arsenic oxide formation that results in a p-GaAs(1 0 0) photoelectrode operating at a sustained photocurrent density of -20.5 mA cm -2 within -0.5 V of the reversible hydrogen electrode.« less

Covalent surface modification of gallium arsenide photocathodes for water splitting in highly acidic electrolyte

DOE PAGES

Garner, Logan E.; Steirer, K. Xerxes; Young, James L.; ...

2016-12-12

Efficient water splitting using light as the only energy input requires stable semiconductor electrodes with favorable energetics for the water-oxidation and proton-reduction reactions. Strategies to tune electrode potentials using molecular dipoles adsorbed to the semiconductor surface have been pursued for decades but are often based on weak interactions and quickly react to desorb the molecule under conditions relevant to sustained photoelectrolysis. Here, we show that covalent attachment of fluorinated, aromatic molecules to p-GaAs(1 0 0) surfaces can be employed to tune the photocurrent onset potentials of p-GaAs(1 0 0) photocathodes and reduce the external energy required for water splitting. Resultsmore » indicate that initial photocurrent onset potentials can be shifted by nearly 150 mV in pH -0.5 electrolyte under 1 Sun (1000 W m -2) illumination resulting from the covalently bound surface dipole. Furthermore, X-ray photoelectron spectroscopy analysis reveals that the covalent molecular dipole attachment is not robust under extended 50 h photoelectrolysis, the modified surface delays arsenic oxide formation that results in a p-GaAs(1 0 0) photoelectrode operating at a sustained photocurrent density of -20.5 mA cm -2 within -0.5 V of the reversible hydrogen electrode.« less

Supramolecular chemistry and chemical warfare agents: from fundamentals of recognition to catalysis and sensing.

PubMed

Sambrook, M R; Notman, S

2013-12-21

Supramolecular chemistry presents many possible avenues for the mitigation of the effects of chemical warfare agents (CWAs), including sensing, catalysis and sequestration. To-date, efforts in this field both to study fundamental interactions between CWAs and to design and exploit host systems remain sporadic. In this tutorial review the non-covalent recognition of CWAs is considered from first principles, including taking inspiration from enzymatic systems, and gaps in fundamental knowledge are indicated. Examples of synthetic systems developed for the recognition of CWAs are discussed with a focus on the supramolecular complexation behaviour and non-covalent approaches rather than on the proposed applications.

Microfluidic free-flow electrophoresis for the discovery and characterisation of calmodulin binding partners

NASA Astrophysics Data System (ADS)

Herling, Therese; Linse, Sara; Knowles, Tuomas

2015-03-01

Non-covalent and transient protein-ligand interactions are integral to cellular function and malfunction. Key steps in signalling and regulatory pathways rely on reversible non-covalent protein-protein binding or ion chelation. Here we present a microfluidic free-flow electrophoresis method for detecting and characterising protein-ligand interactions in solution. We apply this method to probe the binding equilibria of calmodulin, a central protein to calcium signalling pathways. In this study we characterise the specific binding of calmodulin to phosphorylase kinase, a known target, and creatine kinase, which we identify as a putative binding partner through a protein array screen and surface plasmon resonance experiments. We verify the interaction between calmodulin and creatine kinase in solution using free-flow electrophoresis and investigate the effect of calcium and sodium chloride on the calmodulin-ligand binding affinity in free solution without the presence of a potentially interfering surface. Our results demonstrate the general applicability of quantitative microfluidic electrophoresis to characterise binding equilibria between biomolecules in solution.

Non-covalent biofunctionalization of single-walled carbon nanotubes via biotin attachment by π-stacking interactions and pyrrole polymerization.

PubMed

Haddad, R; Cosnier, S; Maaref, A; Holzinger, M

2009-12-01

Single-walled carbon nanotubes were functionalized with biotin using either electropolymerization or formation of pi-stacking interactions for the construction of biosensors. Thanks to the high affinity of the avidin-biotin interactions, a biotinylated glucose oxidase (B-GOX) as a biomolecule model was immobilized on the biotinylated nanotubes. The influence of the biosensor configuration on their amperometric performances was investigated by changing the amount of nanotubes and the numbers of avidin/B-GOX layers. By increasing the amount of nanotube and avidin/B-GOX layers, both sensor setups show a perfect linear increase of immobilized enzymes reflecting a high reproducibility of our systems. The highest sensitivities (up to 5.2 mA M(-1) cm(-2)) and maximum current densities (up to 55 microA cm(-2)) were obtained using nanotube deposits modified by electrochemical coatings. In contrast, non-covalently functionalized biotin-nanotubes show a better permeability for the enzymatically generated hydrogen peroxide.

Microwave plasma induced surface modification of diamond-like carbon films

NASA Astrophysics Data System (ADS)

Rao Polaki, Shyamala; Kumar, Niranjan; Gopala Krishna, Nanda; Madapu, Kishore; Kamruddin, Mohamed; Dash, Sitaram; Tyagi, Ashok Kumar

2017-12-01

Tailoring the surface of diamond-like carbon (DLC) film is technically relevant for altering the physical and chemical properties, desirable for useful applications. A physically smooth and sp3 dominated DLC film with tetrahedral coordination was prepared by plasma-enhanced chemical vapor deposition technique. The surface of the DLC film was exposed to hydrogen, oxygen and nitrogen plasma for physical and chemical modifications. The surface modification was based on the concept of adsorption-desorption of plasma species and surface entities of films. Energetic chemical species of microwave plasma are adsorbed, leading to desorbtion of the surface carbon atoms due to energy and momentum exchange. The interaction of such reactive species with DLC films enhanced the roughness, surface defects and dangling bonds of carbon atoms. Adsorbed hydrogen, oxygen and nitrogen formed a covalent network while saturating the dangling carbon bonds around the tetrahedral sp3 valency. The modified surface chemical affinity depends upon the charge carriers and electron covalency of the adsorbed atoms. The contact angle of chemically reconstructed surface increases when a water droplet interacts either through hydrogen or van dear Waals bonding. These weak interactions influenced the wetting property of the DLC surface to a great extent.

Quantitative analysis of intermolecular interactions in orthorhombic rubrene

DOE PAGES

Hathwar, Venkatesha R.; Sist, Mattia; Jørgensen, Mads R. V.; ...

2015-08-14

Rubrene is one of the most studied organic semiconductors to date due to its high charge carrier mobility which makes it a potentially applicable compound in modern electronic devices. Previous electronic device characterizations and first principles theoretical calculations assigned the semiconducting properties of rubrene to the presence of a large overlap of the extended π-conjugated core between molecules. We present here the electron density distribution in rubrene at 20 K and at 100 K obtained using a combination of high-resolution X-ray and neutron diffraction data. The topology of the electron density and energies of intermolecular interactions are studied quantitatively. Specifically,more » the presence of C π...C πinteractions between neighbouring tetracene backbones of the rubrene molecules is experimentally confirmed from a topological analysis of the electron density, Non-Covalent Interaction (NCI) analysis and the calculated interaction energy of molecular dimers. A significant contribution to the lattice energy of the crystal is provided by H—H interactions. The electron density features of H—H bonding, and the interaction energy of molecular dimers connected by H—H interaction clearly demonstrate an importance of these weak interactions in the stabilization of the crystal structure. Finally, the quantitative nature of the intermolecular interactions is virtually unchanged between 20 K and 100 K suggesting that any changes in carrier transport at these low temperatures would have a different origin. The obtained experimental results are further supported by theoretical calculations.« less

The effect of dimensionality of nanostructured carbon on the architecture of organic-inorganic hybrid materials.

PubMed

Misra, R D K; Depan, D; Shah, J

2013-08-21

The natural tendency of carbon nanotubes (CNTs) to agglomerate is an underlying reason that prevents the realization of their full potential. On the other hand, covalent functionalization of CNTs to control dispersion leads to disruption of π-conjugation in CNTs and the non-covalent functionalization leads to a weak CNT-polymer interface. To overcome these challenges, we describe the characteristics of fostering of direct nucleation of polymers on nanostructured carbon (CNTs of diameters (~2-200 nm), carbon nanofibers (~200-300 nm), and graphene), which culminates in interfacial adhesion, resulting from electrostatic and van der Waals interaction in the hybrid nanostructured carbon-polymer architecture. Furthermore, the structure is tunable through a change in undercooling. High density polyethylene and polypropylene were selected as two model polymers and two sets of experiments were carried out. The first set of experiments was carried out using CNTs of diameter ~2-5 nm to explore the effect of undercooling and polymer concentration. The second set of experiments was focused on studying the effect of dimensionality on geometrical confinements. The periodic crystallization of polyethylene on small diameter CNTs is demonstrated to be a consequence of the geometrical confinement effect, rather than epitaxy, such that petal-like disks nucleate on large diameter CNTs, carbon nanofibers, and graphene. The application of the process is illustrated in terms of fabricating a system for cellular uptake and bioimaging.

The bright future of unconventional σ/π-hole interactions.

PubMed

Bauzá, Antonio; Mooibroek, Tiddo J; Frontera, Antonio

2015-08-24

Non-covalent interactions play a crucial role in (supramolecular) chemistry and much of biology. Supramolecular forces can indeed determine the structure and function of a host-guest system. Many sensors, for example, rely on reversible bonding with the analyte. Natural machineries also often have a significant non-covalent component (e.g. protein folding, recognition) and rational interference in such 'living' devices can have pharmacological implications. For the rational design/tweaking of supramolecular systems it is helpful to know what supramolecular synthons are available and to understand the forces that make these synthons stick to one another. In this review we focus on σ-hole and π-hole interactions. A σ- or π-hole can be seen as positive electrostatic potential on unpopulated σ* or π(() *()) orbitals, which are thus capable of interacting with some electron dense region. A σ-hole is typically located along the vector of a covalent bond such as XH or XHlg (X=any atom, Hlg=halogen), which are respectively known as hydrogen and halogen bond donors. Only recently it has become clear that σ-holes can also be found along a covalent bond with chalcogen (XCh), pnictogen (XPn) and tetrel (XTr) atoms. Interactions with these synthons are named chalcogen, pnigtogen and tetrel interactions. A π-hole is typically located perpendicular to the molecular framework of diatomic π-systems such as carbonyls, or conjugated π-systems such as hexafluorobenzene. Anion-π and lone-pair-π interactions are examples of named π-hole interactions between conjugated π-systems and anions or lone-pair electrons respectively. While the above nomenclature indicates the distinct chemical identity of the supramolecular synthon acting as Lewis acid, it is worth stressing that the underlying physics is very similar. This implies that interactions that are now not so well-established might turn out to be equally useful as conventional hydrogen and halogen bonds. In summary, we describe the physical nature of σ- and π-hole interactions, present a selection of inquiries that utilise σ- and π-holes, and give an overview of analyses of structural databases (CSD/PDB) that demonstrate how prevalent these interactions already are in solid-state structures. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Non-covalent nanodiamond-polymer dispersions and electrostatic immobilization of bovine serum albumin protein

NASA Astrophysics Data System (ADS)

Skaltsas, T.; Pispas, S.; Tagmatarchis, N.

2015-11-01

Nanodiamonds (NDs) lack efficient dispersion, not only in solvents but also in aqueous media. The latter is of great importance, considering the inherent biocompatibility of NDs and the plethora of suitable strategies for immobilizing functional biomolecules. In this work, a series of polymers was non-covalently interacted with NDs, forming ND-polymer ensembles, and their dispersibility and stability was examined. Dynamic light scattering gave valuable information regarding the size of the ensembles in liquid phase, while their morphology was further examined by high-resolution transmission electron microscopy imaging. In addition, thermal analysis measurements were applied to collect information on the thermal behavior of NDs and their ensembles and to calculate the amount of polymer interacting with the NDs, as well as the dispersibility values of the ND-polymer ensembles. Finally, the bovine serum albumin protein was electrostatically bound to a ND-polymer ensemble in which the polymeric moiety was carrying quaternized pyridine units.

A strategy to synthesize graphene-incorporated lignin polymer composite materials with uniform graphene dispersion and covalently bonded interface engineering

NASA Astrophysics Data System (ADS)

Wang, Mei; Duong, Le Dai; Ma, Yifei; Sun, Yan; Hong, Sung Yong; Kim, Ye Chan; Suhr, Jonghwan; Nam, Jae-Do

2017-08-01

Graphene-incorporated polymer composites have been demonstrated to have excellent mechanical and electrical properties. In the field of graphene-incorporated composite material synthesis, there are two main obstacles: Non-uniform dispersion of graphene filler in the matrix and weak interface bonding between the graphene filler and polymer matrix. To overcome these problems, we develop an in-situ polymerization strategy to synthesize uniformly dispersed and covalently bonded graphene/lignin composites. Graphene oxide (GO) was chemically modified by 4,4'-methylene diphenyl diisocyanate (MDI) to introduce isocyanate groups and form the urethane bonds with lignin macromonomers. Subsequential polycondensation reactions of lignin groups with caprolactone and sebacoyl chloride bring about a covalent network of modified GO and lignin-based polymers. The flexible and robust lignin polycaprolactone polycondensate/modified GO (Lig-GOm) composite membranes are achieved after vacuum filtration, which have tunable hydrophilicity and electrical resistance according to the contents of GOm. This research transforms lignin from an abundant biomass into film-state composite materials, paving a new way for the utilization of biomass wastes.

Functional Importance of Covalent Homodimer of Reelin Protein Linked via Its Central Region*

PubMed Central

Yasui, Norihisa; Kitago, Yu; Beppu, Ayako; Kohno, Takao; Morishita, Shunsuke; Gomi, Hiroki; Nagae, Masamichi; Hattori, Mitsuharu; Takagi, Junichi

2011-01-01

Reelin is a 3461-residue secreted glycoprotein that plays a critical role in brain development through its action on target neurons. Although it is known that functional reelin protein exists as multimer formed by interchain disulfide bond(s) as well as through non-covalent interactions, the chemical nature of the multimer assembly has been elusive. In the present study, we identified, among 122 cysteines present in full-length reelin, the single critical cysteine residue (Cys2101) responsible for the covalent multimerization. C2101A mutant reelin failed to assemble into disulfide-bonded multimers, whereas it still exhibited non-covalently associated high molecular weight oligomeric states in solution. Detailed analysis of tryptic fragments produced from the purified reelin proteins revealed that the minimum unit of the multimer is a homodimeric reelin linked via Cys2101 present in the central region and that this cysteine does not connect to the N-terminal region of reelin, which had been postulated as the primary oligomerization domain. A surface plasmon resonance binding assay confirmed that C2101A mutant reelin retained binding capability toward two neuronal receptors apolipoprotein E receptor 2 and very low density lipoprotein receptor. However, it failed to show signaling activity in the assay using the cultured neurons. These results indicate that an intact higher order architecture of reelin multimer maintained by both Cys2101-mediated homodimerization and other non-covalent association present elsewhere in the reelin primary structure are essential for exerting its full biological activity. PMID:21844191

Superglue from bacteria: unbreakable bridges for protein nanotechnology.

PubMed

Veggiani, Gianluca; Zakeri, Bijan; Howarth, Mark

2014-10-01

Biotechnology is often limited by weak interactions. We suggest that an ideal interaction between proteins would be covalent, specific, require addition of only a peptide tag to the protein of interest, and form under a wide range of conditions. Here we summarize peptide tags that are able to form spontaneous amide bonds, based on harnessing reactions of adhesion proteins from the bacterium Streptococcus pyogenes. These include the irreversible peptide-protein interaction of SpyTag with SpyCatcher, as well as irreversible peptide-peptide interactions via SpyLigase. We describe existing applications, including polymerization to enhance cancer cell capture, assembly of living biomaterial, access to diverse protein shapes, and improved enzyme resilience. We also indicate future opportunities for resisting biological force and extending the scope of protein nanotechnology. Copyright © 2014 Elsevier Ltd. All rights reserved.

Weak hydrogen bonds in complexes pairing monohalomethanes with neutral formic acid

NASA Astrophysics Data System (ADS)

Solimannejad, Mohammad; Scheiner, Steve

2006-06-01

Ab initio calculations are used to analyze the interaction between formic acid and CH 3X, for X equal to each of F, Cl, and Br. All minima are cyclic in that they contain more than one H-bond. The most strongly bound contain a OH⋯X bond, along with CH⋯O, and the others contain CH⋯X and CH⋯O interactions. Alterations of the covalent bond lengths within each subunit, and vibrational frequency shifts, coupled with electronic charge shifts, reveal fundamental features of these complexes, and the nature of the interactions. The OH⋯X bond is the strongest of those examined here, followed by CH⋯X and CH⋯O.

Spectroscopic and DFT Studies of Second Sphere Variants of the Type 1 Copper Site in Azurin: Covalent and Non-Local Electrostatic Contributions to Reduction Potentials

PubMed Central

Hadt, Ryan G.; Sun, Ning; Marshall, Nicholas M.; Hodgson, Keith O.; Hedman, Britt; Lu, Yi; Solomon, Edward I.

2012-01-01

The reduction potentials (E0) of type 1 (T1) or blue copper (BC) sites in proteins and enzymes with identical first coordination spheres around the redox active copper ion can vary by ~400 mV. Here, we use a combination of low temperature electronic absorption and magnetic circular dichroism, electron paramagnetic resonance, resonance Raman, and S K-edge X-ray absorption spectroscopies to investigate a series of second sphere variants—F114P, N47S, and F114N in Pseudomonas aeruginosa azurin (Az)—which modulate hydrogen bonding to and protein derived dipoles nearby the Cu-S(Cys) bond. Density functional theory (DFT) calculations correlated to the experimental data allow for the fractionation of the contributions to tuning E0 into covalent and non-local electrostatic components. These are found to be significant, comparable in magnitude, and additive for active H-bonds, while passive H-bonds are mostly non-local electrostatic in nature. For dipoles, these terms can be additive to or oppose one another. This study provides a methodology for uncoupling covalency from non-local electrostatics, which, when coupled to X-ray crystallographic data, distinguishes specific local interactions from more long range protein/active interactions, while affording further insight into the second sphere mechanisms available to the protein to tune the E0 of electron transfer sites in biology. PMID:22985400

Covalent Polymers Containing Discrete Heterocyclic Anion Receptors

PubMed Central

Rambo, Brett M.; Silver, Eric S.; Bielawski, Christopher W.; Sessler, Jonathan L.

2010-01-01

This chapter covers recent advances in the development of polymeric materials containing discrete heterocyclic anion receptors, and focuses on advances in anion binding and chemosensor chemistry. The development of polymers specific for anionic species is a relatively new and flourishing area of materials chemistry. The incorporation of heterocyclic receptors capable of complexing anions through non-covalent interactions (e.g., hydrogen bonding and electrostatic interactions) provides a route to not only sensitive but also selective polymer materials. Furthermore, these systems have been utilized in the development of polymers capable of extracting anionic species from aqueous environments. These latter materials may lead to advances in water purification and treatment of diseases resulting from surplus ions. PMID:20871791

[Noncovalent cation-π interactions--their role in nature].

PubMed

Fink, Krzysztof; Boratyński, Janusz

2014-11-07

Non-covalent interactions play an extremely important role in organisms. The main non-covalent interactions in nature are: ion-ion interactions, dipole-dipole interactions, hydrogen bonds, and van der Waals interactions. A new kind of intermolecular interactions--cation-π interactions--is gaining increasing attention. These interactions occur between a cation and a π system. The main contributors to cation-π interactions are electrostatic, polarization and, to a lesser extent, dispersion interactions. At first, cation-π interactions were studied in a gas phase, with metal cation-aromatic system complexes. The characteristics of these complexes are as follows: an increase of cation atomic number leads to a decrease of interaction energy, and an increase of cation charge leads to an increase of interaction energy. Aromatic amino acids bind with metal cations mainly through interactions with their main chain. Nevertheless, cation-π interaction with a hydrophobic side chain significantly enhances binding energy. In water solutions most cations preferentially interact with water molecules rather than aromatic systems. Cation-π interactions occur in environments with lower accessibility to a polar solvent. Cation-π interactions can have a stabilizing role on the secondary, tertiary and quaternary structure of proteins. These interactions play an important role in substrate or ligand binding sites in many proteins, which should be taken into consideration when the screening of effective inhibitors for these proteins is carried out. Cation-π interactions are abundant and play an important role in many biological processes.

Water as a matrix for life

NASA Technical Reports Server (NTRS)

Pohorille, Andrew

2005-01-01

Life is based on non-covalent interactions. They might be either specific (enzyme-substrate interactions, selective ion transport) or nonspecific (lipid-lipid and lipid-protein interactions needed for membrane integrity, fusion and division). Their strength needs to be properly tuned, and this is mediated by the solvent. If interactions are too weak, there might be undesired response to natural fluctuations of physical and chemical parameters. If they are too strong it could impede kinetics and energetics of cellular processes. Thus, the solvent must allow for balancing these interactions. Physical and chemical properties of solvent provide strong constraints for life. Water exhibits a remarkable trait that it promotes both solvophobic and solvophilic interactions. Solvophobic interactions; related to high dielectric constant of the solvent) are necessary for self-organization of matter whereas solvophilic interactions are needed to ensure solubility of polar species. Water offers a large temperature domain of stable liquid and the characteristics hydrophobic effects are a consequence of the temperature in sensitivity of essential properties of its liquid state. Water, however, is not the only liquid with these favorable properties. I will compare in detail properties of water and other pure liquids or their mixtures that have a high dielectric constant and simultaneously support self-organization. I will also discuss properties of water that are unfavorable to life (e.g. its chemical activity against polymerization reactions) and close with summarizing what are alternatives to water as a matrix of life in space.

Non-covalent bonding interaction of surfactants with functionalized carbon nanotubes in proton exchange membranes for fuel cell applications.

PubMed

Sayeed, M Abu; Kim, Young Ho; Park, Younjin; Gopalan, A I; Lee, Kwang-Pill; Choi, Sang-June

2013-11-01

Dispersion of functionalized multiwalled carbon nanotubes (MWCNTs) in proton exchange membranes (PEMs) was conducted via non-covalent bonding between benzene rings of various surfactants and functionalized MWCNTs. In the solution casting method, dispersion of functionalized MWCNTs in PEMs such as Nafion membranes is a critical issue. In this study, 1 wt.% pristine MWCNTs (p-MWCNTs) and oxidized MWCNTs (ox-MWCNTs) were reinforced in Nafion membranes by adding 0.1-0.5 wt.% of a surfactant such as benzalkonium chloride (BKC) as a cationic surfactant with a benzene ring, Tween-80 as a nonanionic surfactant without a benzene ring, sodium dodecylsulfonate (SDS) as an anionic surfactant without a benzene ring, or sodium dodecylben-zenesulfonate (SDBS) as an anionic surfactant with a benzene ring and their effects on the dispersion of nanocomposites were then observed. Among these surfactants, those with benzene rings such as BKC and SDBS produced enhanced dispersion via non-covalent bonding interaction between CNTs and surfactants. Specifically, the surfactants were adsorbed onto the surface of functionalized MWCNTs, where they prevented re-aggregation of MWCNTs in the nanocomposites. Furthermore, the prepared CNTs reinforced nanocomposite membranes showed reduced methanol uptake values while the ion exchange capacity values were maintained. The enhanced properties, including thermal property of the CNTs reinforced PEMs with surfactants, could be applicable to fuel cell applications.

Non-covalent Interactions with SUMO and Ubiquitin Orchestrate Distinct Functions of the SLX4 Complex in Genome Maintenance

PubMed Central

Ouyang, Jian; Garner, Elizabeth; Hallet, Alexander; Nguyen, Hai Dang; Rickman, Kimberly A.; Gill, Grace; Smogorzewska, Agata; Zou, Lee

2014-01-01

SLX4, a coordinator of multiple DNA structure-specific endonucleases, is important for several DNA repair pathways. Non-covalent interactions of SLX4 with ubiquitin are required for localizing SLX4 to DNA-interstrand crosslinks (ICLs), yet how SLX4 is targeted to other functional contexts remains unclear. Here, we show that SLX4 binds SUMO-2/3 chains via SUMO-interacting motifs (SIMs). The SIMs of SLX4 are dispensable for ICL repair, but important for processing CPT-induced replication intermediates, suppressing fragile site instability, and localizing SLX4 to ALT telomeres. The localization of SLX4 to laser-induced DNA damage also requires the SIMs, as well as DNA-end resection, UBC9 and MDC1. Furthermore, the SUMO binding of SLX4 enhances its interaction with specific DNA-damage sensors or telomere-binding proteins, including RPA, MRE11-RAD50-NBS1 and TRF2. Thus, the interactions of SLX4 with SUMO and ubiquitin increase its affinity for factors recognizing different DNA lesions or telomeres, helping to direct the SLX4 complex in distinct functional contexts. PMID:25533185

Bioorganometallic chemistry. 8. The molecular recognition of aromatic and aliphatic amino acids and substituted aromatic and aliphatic carboxylic acid guests with supramolecular ({eta}{sup 5}-pentamethylcyclopentadienyl)rhodium - nucleobase, nucleoside, and nucleotide cyclic trimer hosts via non-covalent {pi}-{pi} and hydrophobic interactions in water: Steric, electronic, and conformational parameters

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

Chen, H.; Ogo, Seiji; Fish, R.H.

Molecular recognition, via non-covalent processes such as hydrogen bonding, {pi}-{pi}, and hydrophobic interactions, is an important biological phenomenon for guests, such as drugs, proteins, and other important biological molecules with, for example, host DNA/RNA. We have studied a novel molecular recognition process using guests that encompass aromatic and aliphatic amino acids [L-alanine, L-glutamine (L-Gln), L-histidine, L-isoleucine(L-Ile), L-leucine(L-Leu), L-phenylalanine(L-Phe), L-proline, L-tryptophan(L-Trp), L-valine(L-Val)], substituted aromatic carboxylic acids o-, m-, p-aminobenzoic acids (G1-3), benzoic acid (G4), phenylacetic acid (G5), p-methoxyphenylacetic acid (G6), o-methyoxybenozoic acid (G9), o-nitrobenzoic acid (G10), and aliphatic carboxylic acids [cyclohexylacetic acid (G7), 1-adamantanecarboxylic acid (G8)] with supramolecular, bioorganometallic hosts, ({eta}{supmore » 5}-pentamethylcyclopentadienyl)rhodium (Cp{sup *}Rh)-nucleobase, nucleoside, and nucleotide cyclic trimer complexes in aqueous solution at pH 7, utilizing {sup 1}H NMR, NOE, and molecular modeling techniques, and, as well, determining association constants (K{sub a}) and free energies of complexation ({Delta}{degree}G). The host-guest complexation occurs predominantly via non-covalent {pi}-{pi}, hydrophobic, and possible subtle H-bonding interactions, with steric, electronic, and molecular conformational parameters as important criteria. 8 refs., 6 figs., 3 tabs.« less

Substituent effects that control conjugated oligomer conformation through non-covalent interactions

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

Sharber, Seth A.; Baral, Rom Nath; Frausto, Fanny

Although understanding the conformations and arrangements of conjugated materials as solids is key to their prospective applications, predictive power over these structural factors remains elusive. In this work, substituent effects tune non-covalent interactions between side-chain fluorinated benzyl esters and main-chain terminal arenes, in turn controlling the conformations and interchromophore aggregation of three-ring phenylene-ethynylenes (PEs). Cofacial fluoroarene–arene (ArF–ArH) interactions cause twisting in the PE backbone, interrupting intramolecular conjugation as well as blocking chromophore aggregation, both of which prevent the typically observed bathochromic shift observed upon transitioning PEs from solution to solid. This work highlights two structural factors that determine whether themore » ArF–ArH interactions, and the resulting twisted, unaggregated chromophores, occur in these solids: (i) the electron-releasing characteristic of substituents on ArH, with more electron-releasing character favoring ArF–ArH interactions, and (ii) the fluorination pattern of the ArF ring, with 2,3,4,5,6-pentafluorophenyl favoring ArF–ArH interactions over 2,4,6-trifluorophenyl. Furthermore, these trends indicate that considerations of electrostatic complementarity, whether through a polar-π or substituent–substituent mechanism, can serve as an effective design principle in controlling the interaction strengths, and therefore the optoelectronic properties, of these molecules as solids.« less

Substituent effects that control conjugated oligomer conformation through non-covalent interactions

DOE PAGES

Sharber, Seth A.; Baral, Rom Nath; Frausto, Fanny; ...

2017-03-31

Although understanding the conformations and arrangements of conjugated materials as solids is key to their prospective applications, predictive power over these structural factors remains elusive. In this work, substituent effects tune non-covalent interactions between side-chain fluorinated benzyl esters and main-chain terminal arenes, in turn controlling the conformations and interchromophore aggregation of three-ring phenylene-ethynylenes (PEs). Cofacial fluoroarene–arene (ArF–ArH) interactions cause twisting in the PE backbone, interrupting intramolecular conjugation as well as blocking chromophore aggregation, both of which prevent the typically observed bathochromic shift observed upon transitioning PEs from solution to solid. This work highlights two structural factors that determine whether themore » ArF–ArH interactions, and the resulting twisted, unaggregated chromophores, occur in these solids: (i) the electron-releasing characteristic of substituents on ArH, with more electron-releasing character favoring ArF–ArH interactions, and (ii) the fluorination pattern of the ArF ring, with 2,3,4,5,6-pentafluorophenyl favoring ArF–ArH interactions over 2,4,6-trifluorophenyl. Furthermore, these trends indicate that considerations of electrostatic complementarity, whether through a polar-π or substituent–substituent mechanism, can serve as an effective design principle in controlling the interaction strengths, and therefore the optoelectronic properties, of these molecules as solids.« less

Ionic Liquids as a Basis Context for Developing High school Chemistry Teaching Materials

NASA Astrophysics Data System (ADS)

Hernani; Mudzakir, A.; Sumarna, O.

2017-02-01

This research aims to produce a map of connectedness highschool chemical content with the context of the modern chemical materials applications based on ionic liquids. The research method is content analysis of journal articles related to the ionic liquid materials and the textbooks of high school chemistry and textbooks of general chemistry at the university. The instrument used is the development format of basic text that connect and combine content and context. The results showed the connectedness between: (1) the context lubricants ionic liquid with the content of ionic bonding, covalent bonding, metal bonding, interaction between the particles of matter, the elements of main group, the elements of transition group, and the classification of macromolecules; (2) the context of fuel cell electrolite with the content of ionic bonding, covalent bonding, metal bonding, interaction between the particles of matter, Volta cell, and electrolysis cell; (3) the contect of nanocellulose with the content of ionic bonding, covalent bonding, metal bonding, interaction between the particles of matter, colloid, carbon compound, and the classification of macromolecules; and (4) the context of artificial muscle system with the content of ionic bond, covalent bond, metal bonding, interaction between the particles of matter, hydrocarbons, electrolytes and non-electrolytes, and the classification of macromolecules. Based on the result of this content analysis, the context of ionic liquid is predicted can be utilized for the enrichment of high school chemistry and has the potential to become teaching material’s context of high school chemistry in the future.

Consistent structures and interactions by density functional theory with small atomic orbital basis sets.

PubMed

Grimme, Stefan; Brandenburg, Jan Gerit; Bannwarth, Christoph; Hansen, Andreas

2015-08-07

A density functional theory (DFT) based composite electronic structure approach is proposed to efficiently compute structures and interaction energies in large chemical systems. It is based on the well-known and numerically robust Perdew-Burke-Ernzerhoff (PBE) generalized-gradient-approximation in a modified global hybrid functional with a relatively large amount of non-local Fock-exchange. The orbitals are expanded in Ahlrichs-type valence-double zeta atomic orbital (AO) Gaussian basis sets, which are available for many elements. In order to correct for the basis set superposition error (BSSE) and to account for the important long-range London dispersion effects, our well-established atom-pairwise potentials are used. In the design of the new method, particular attention has been paid to an accurate description of structural parameters in various covalent and non-covalent bonding situations as well as in periodic systems. Together with the recently proposed three-fold corrected (3c) Hartree-Fock method, the new composite scheme (termed PBEh-3c) represents the next member in a hierarchy of "low-cost" electronic structure approaches. They are mainly free of BSSE and account for most interactions in a physically sound and asymptotically correct manner. PBEh-3c yields good results for thermochemical properties in the huge GMTKN30 energy database. Furthermore, the method shows excellent performance for non-covalent interaction energies in small and large complexes. For evaluating its performance on equilibrium structures, a new compilation of standard test sets is suggested. These consist of small (light) molecules, partially flexible, medium-sized organic molecules, molecules comprising heavy main group elements, larger systems with long bonds, 3d-transition metal systems, non-covalently bound complexes (S22 and S66×8 sets), and peptide conformations. For these sets, overall deviations from accurate reference data are smaller than for various other tested DFT methods and reach that of triple-zeta AO basis set second-order perturbation theory (MP2/TZ) level at a tiny fraction of computational effort. Periodic calculations conducted for molecular crystals to test structures (including cell volumes) and sublimation enthalpies indicate very good accuracy competitive to computationally more involved plane-wave based calculations. PBEh-3c can be applied routinely to several hundreds of atoms on a single processor and it is suggested as a robust "high-speed" computational tool in theoretical chemistry and physics.

Topological analysis (BCP) of vibrational spectroscopic studies, docking, RDG, DSSC, Fukui functions and chemical reactivity of 2-methylphenylacetic acid

NASA Astrophysics Data System (ADS)

Kavimani, M.; Balachandran, V.; Narayana, B.; Vanasundari, K.; Revathi, B.

2018-02-01

Experimental FT-IR and FT-Raman spectra of 2-methylphenylacetic acid (MPA) were recorded and theoretical values are also analyzed. The non-linear optical (NLO) properties were evaluated by determination of first (5.5053 × 10- 30 e.s.u.) and second hyper-polarizabilities (7.6833 × 10- 36 e.s.u.) of the title compound. The Multiwfn package is used to find the weak non-covalent interaction (Van der Wall interaction) and strong repulsion (steric effect) of the molecule and examined by reduced density gradient. The molecular electrostatic potential (MEP) analysis used to find the most reactive sites for the electrophilic and nucleophilic attack. The chemical activity (electronegativity, hardness, chemical softness and chemical potential) of the title compound was predicted with the help of HOMO-LUMO energy values. The natural bond orbital (NBO) has been analyzed the stability of the molecule arising from the hyper-conjugative interaction. DSSCs were discussed in structural modifications that improve the electron injection efficiency of the title compound (MPA). The Fukui functions are calculated in order to get information associated with the local reactivity properties of the title compound. The binding sites of the two receptors were reported by molecular docking field and active site bond distance is same 1.9 Å. The inhibitor of the title compound forms a stable complex with 1QYV and 2H1K proteins at the binding energies are - 5.38 and - 5.85 (Δ G in kcal/mol).

Strategies to balance covalent and non-covalent biomolecule attachment within collagen-GAG biomaterials.

PubMed

Pence, Jacquelyn C; Gonnerman, Emily A; Bailey, Ryan C; Harley, Brendan A C

2014-09-01

Strategies to integrate instructive biomolecular signals into a biomaterial are becoming increasingly complex and bioinspired. While a large majority of reports still use repeated treatments with soluble factors, this approach can be prohibitively costly and difficult to translate in vivo for applications where spatial control over signal presentation is necessary. Recent efforts have explored the use of covalent immobilization of biomolecules to the biomaterial, via both bulk (ubiquitous) as well as spatially-selective light-based crosslinking, as a means to both enhance stability and bioactivity. However, little is known about how processing conditions during immobilization impact the degree of unintended non-covalent interactions, or fouling, that takes place between the biomaterial and the biomolecule of interest. Here we demonstrate the impact of processing conditions for bulk carbodiimide (EDC) and photolithography-based benzophenone (BP) crosslinking on specific attachment vs. fouling of a model protein (Concanavalin A, ConA) within collagen-glycosaminoglycan (CG) scaffolds. Collagen source significantly impacts the selectivity of biomolecule immobilization. EDC crosslinking intensity and ligand concentration significantly impacted selective immobilization. For benzophenone photoimmobilization we observed that increased UV exposure time leads to increased ConA immobilization. Immobilization efficiency for both EDC and BP strategies was maximal at physiological pH. Increasing ligand concentration during immobilization process led to enhanced immobilization for EDC chemistry, no impact on BP immobilization, but significant increases in non-specific fouling. Given recent efforts to covalently immobilize biomolecules to a biomaterial surface to enhance bioactivity, improved understanding of the impact of crosslinking conditions on selective attachment versus non-specific fouling will inform the design of instructive biomaterials for applications across tissue engineering.

Formation of Polymer Particles by Direct Polymerization on the Surface of a Supramolecular Template.

PubMed

Schmuck, Carsten; Li, Mao; Zellermann, Elio

2018-04-06

Formation of polymeric materials on the surface of supramolecular assemblies is rather challenging due to the often weak non-covalent interactions between the self-assembled template and the monomers before polymerization. We herein describe that the introduction of a supramolecular anion recognition motif, the guanidiniocarbonyl pyrrole cation (GCP), into a short Fmoc-dipeptide 1 leads to self-assembled spherical nanoparticles in aqueous solution. Onto the surface of these nanoparticles negatively charged diacetylene monomers can be attached which after UV polymerization lead to the formation of a polymer shell around the self-assembled template. The hybrid supramolecular and polymeric nanoparticles demonstrated intriguing thermal hysteresis phenomenon. The template nanoparticle could be disassembled through the treatment with organic base which cleaved the Fmoc moiety on 1. This strategy thus showed that a supramolecular anion recognition motif allows the post-assembly formation of polymeric nanomaterials from anionic monomers around a cationic self-assembled template. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Covalent Surface Modification of Gallium Arsenide Photocathodes for Water Splitting in Highly Acidic Electrolyte.

PubMed

Garner, Logan E; Steirer, K Xerxes; Young, James L; Anderson, Nicholas C; Miller, Elisa M; Tinkham, Jonathan S; Deutsch, Todd G; Sellinger, Alan; Turner, John A; Neale, Nathan R

2017-02-22

Efficient water splitting using light as the only energy input requires stable semiconductor electrodes with favorable energetics for the water-oxidation and proton-reduction reactions. Strategies to tune electrode potentials using molecular dipoles adsorbed to the semiconductor surface have been pursued for decades but are often based on weak interactions and quickly react to desorb the molecule under conditions relevant to sustained photoelectrolysis. Here, we show that covalent attachment of fluorinated, aromatic molecules to p-GaAs(1 0 0) surfaces can be employed to tune the photocurrent onset potentials of p-GaAs(1 0 0) photocathodes and reduce the external energy required for water splitting. Results indicate that initial photocurrent onset potentials can be shifted by nearly 150 mV in pH -0.5 electrolyte under 1 Sun (1000 W m -2 ) illumination resulting from the covalently bound surface dipole. Though X-ray photoelectron spectroscopy analysis reveals that the covalent molecular dipole attachment is not robust under extended 50 h photoelectrolysis, the modified surface delays arsenic oxide formation that results in a p-GaAs(1 0 0) photoelectrode operating at a sustained photocurrent density of -20.5 mA cm -2 within -0.5 V of the reversible hydrogen electrode. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Size-Dependent Affinity of Glycine and Its Short Oligomers to Pyrite Surface: A Model for Prebiotic Accumulation of Amino Acid Oligomers on a Mineral Surface

PubMed Central

Afrin, Rehana; Ganbaatar, Narangerel; Aono, Masashi; Cleaves, H. James; Yano, Taka-aki; Hara, Masahiko

2018-01-01

The interaction strength of progressively longer oligomers of glycine, (Gly), di-Gly, tri-Gly, and penta-Gly, with a natural pyrite surface was directly measured using the force mode of an atomic force microscope (AFM). In recent years, selective activation of abiotically formed amino acids on mineral surfaces, especially that of pyrite, has been proposed as an important step in many origins of life scenarios. To investigate such notions, we used AFM-based force measurements to probe possible non-covalent interactions between pyrite and amino acids, starting from the simplest amino acid, Gly. Although Gly itself interacted with the pyrite surface only weakly, progressively larger unbinding forces and binding frequencies were obtained using oligomers from di-Gly to penta-Gly. In addition to an expected increase of the configurational entropy and size-dependent van der Waals force, the increasing number of polar peptide bonds, among others, may be responsible for this observation. The effect of chain length was also investigated by performing similar experiments using l-lysine vs. poly-l-lysine (PLL), and l-glutamic acid vs. poly-l-glutamic acid. The results suggest that longer oligomers/polymers of amino acids can be preferentially adsorbed on pyrite surfaces. PMID:29370126

Painting proteins with covalent labels: what's in the picture?

PubMed

Fitzgerald, Michael C; West, Graham M

2009-06-01

Knowledge about the structural and biophysical properties of proteins when they are free in solution and/or in complexes with other molecules is essential for understanding the biological processes that proteins regulate. Such knowledge is also important to drug discovery efforts, particularly those focused on the development of therapeutic agents with protein targets. In the last decade a variety of different covalent labeling techniques have been used in combination with mass spectrometry to probe the solution-phase structures and biophysical properties of proteins and protein-ligand complexes. Highlighted here are five different mass spectrometry-based covalent labeling strategies including: continuous hydrogen/deuterium (H/D) exchange labeling, hydroxyl radical-mediated footprinting, SUPREX (stability of unpurified proteins from rates of H/D exchange), PLIMSTEX (protein-ligand interaction by mass spectrometry, titration, and H/D exchange), and SPROX (stability of proteins from rates of oxidation). The basic experimental protocols used in each of the above-cited methods are summarized along with the kind of biophysical information they generate. Also discussed are the relative strengths and weaknesses of the different methods for probing the wide range of conformational states that proteins and protein-ligand complexes can adopt when they are in solution.

Selectivity and direct visualization of carbon dioxide and sulfur dioxide in a decorated porous host.

PubMed

Yang, Sihai; Sun, Junliang; Ramirez-Cuesta, Anibal J; Callear, Samantha K; David, William I F; Anderson, Daniel P; Newby, Ruth; Blake, Alexander J; Parker, Julia E; Tang, Chiu C; Schröder, Martin

2012-11-01

Understanding the mechanism by which porous solids trap harmful gases such as CO(2) and SO(2) is essential for the design of new materials for their selective removal. Materials functionalized with amine groups dominate this field, largely because of their potential to form carbamates through H(2)N(δ(-))···C(δ(+))O(2) interactions, thereby trapping CO(2) covalently. However, the use of these materials is energy-intensive, with significant environmental impact. Here, we report a non-amine-containing porous solid (NOTT-300) in which hydroxyl groups within pores bind CO(2) and SO(2) selectively. In situ powder X-ray diffraction and inelastic neutron scattering studies, combined with modelling, reveal that hydroxyl groups bind CO(2) and SO(2) through the formation of O=C(S)=O(δ(-))···H(δ(+))-O hydrogen bonds, which are reinforced by weak supramolecular interactions with C-H atoms on the aromatic rings of the framework. This offers the potential for the application of new 'easy-on/easy-off' capture systems for CO(2) and SO(2) that carry fewer economic and environmental penalties.

Selectivity and direct visualization of carbon dioxide and sulfur dioxide in a decorated porous host

NASA Astrophysics Data System (ADS)

Yang, Sihai; Sun, Junliang; Ramirez-Cuesta, Anibal J.; Callear, Samantha K.; David, William I. F.; Anderson, Daniel P.; Newby, Ruth; Blake, Alexander J.; Parker, Julia E.; Tang, Chiu C.; Schröder, Martin

2012-11-01

Understanding the mechanism by which porous solids trap harmful gases such as CO2 and SO2 is essential for the design of new materials for their selective removal. Materials functionalized with amine groups dominate this field, largely because of their potential to form carbamates through H2N(δ-)···C(δ+)O2 interactions, thereby trapping CO2 covalently. However, the use of these materials is energy-intensive, with significant environmental impact. Here, we report a non-amine-containing porous solid (NOTT-300) in which hydroxyl groups within pores bind CO2 and SO2 selectively. In situ powder X-ray diffraction and inelastic neutron scattering studies, combined with modelling, reveal that hydroxyl groups bind CO2 and SO2 through the formation of O=C(S)=O(δ-)···H(δ+)-O hydrogen bonds, which are reinforced by weak supramolecular interactions with C-H atoms on the aromatic rings of the framework. This offers the potential for the application of new ‘easy-on/easy-off’ capture systems for CO2 and SO2 that carry fewer economic and environmental penalties.

Structural characterization, surface characteristics and non covalent interactions of a heterocyclic Schiff base: Evaluation of antioxidant potential by UV-visible spectroscopy and DFT

NASA Astrophysics Data System (ADS)

Chithiraikumar, S.; Gandhimathi, S.; Neelakantan, M. A.

2017-06-01

A heterocyclic Schiff base, (E)-4-(1-((pyridin-2-ylmethyl)imino)ethyl)benzene-1,3-diol (L) was synthesized and isolated as single crystals. Its structure was characterized by FT-IR, UV, 1H and 13C NMR, and further confirmed by X-ray crystallography. Qualitatively and quantitatively the various interactions in the crystal structure of L has been analyzed by Hirshfeld surfaces and 2D fingerprint plots. Non covalent interactions have been studied by electron localization function (ELF) and mapped with reduced density gradient (RDG) analysis. The molecular structure was studied computationally by DFT-B3LYP/6-311G(d,p) calculations. HOMO-LUMO energy levels, chemical reactivity descriptors and thermodynamic parameters have been investigated at the same level of theory. The antioxidant potential of L was evaluated experimentally by measuring DPPH free radical scavenging effect using UV-visible spectroscopy and theoretically by DFT. Theoretical parameters, such as bond dissociation enthalpy (BDE) and spin density calculated suggests that antioxidant potential of L is due to H atom abstraction from the sbnd OH group.

Recognition of anions using urea and thiourea substituted calixarenes: A density functional theory study of non-covalent interactions

NASA Astrophysics Data System (ADS)

Athar, Mohd; Lone, Mohsin Y.; Jha, Prakash C.

2018-02-01

Designing of new calixarene receptors for the selective binding of anions is an age-old concept; even though expected outcomes from this field are at premature stage. Herein, we have performed quantum chemical calculations to provide structural basis of anion binding with urea and thiourea substituted calixarenes (1, 2, and 3). In particular, spherical halides (F-, Cl-, Br-) and linear anions (CN-, N3-, SCN-) were modelled for calculating binding energies with receptor 1, 2 and 3 followed by their marked IR vibrations; taking the available experimental information into account. We found that the thiourea substitutions have better capability to stabilize the anions. Results have suggested that the structural behaviour of macrocyclic motifs were responsible for displaying the anion binding potentials. Moreover, second order "charge transfer" interactions of n-σ∗NH and n-σ∗OH type along the H-bond axis played critical role in developing hydrogen bonds. The present work also examines the role of non-covalent interactions (NCI) and their effects on thermodynamic and chemical-reactivity descriptors.

Is Water a Universal Solvent for Life?

NASA Technical Reports Server (NTRS)

Pohorill, Andrew

2012-01-01

There are strong reasons to believe that the laws, principles and constraints of physics and chemistry are universal. It is much less clear how this universality translates into our understanding of the origins of life. Conventionally, discussions of this topic focus on chemistry that must be sufficiently rich to seed life. Although this is clearly a prerequisite for the emergence of living systems, I propose to focus instead on self-organization of matter into functional structures capable of reproduction, evolution and responding to environmental changes. In biology, most essential functions are largely mediated by noncovalent interactions (interactions that do not involve making or breaking chemical bonds). Forming chemical bonds is only a small part of what living systems do. There are specific implications of this point of view for universality. I will concentrate on one of these implications. Strength of non-covalent interactions must be properly tuned. If they were too weak, the system would exhibit undesired, uncontrolled response to natural fluctuations of physical and chemical parameters. If they were too strong kinetics of biological processes would be slow and energetics costly. This balance, however, is not a natural property of complex chemical systems. Instead, it has to be achieved with the aid of an appropriate solvent for life. In particular, potential solvents for life must be characterized by a high dielectric constant to ensure solubility of polar species and sufficient flexibility of biological structures stabilized by electrostatic interactions. Among these solvents, water exhibits a remarkable trait that it also promotes solvophobic (hydrophobic) interactions between non-polar species, typically manifested by a tendency of these species to aggregate and minimize their contacts with the aqueous solvent. Hydrophobic interactions are responsible, at least in part, for many self-organization phenomena in biological systems, such as the formation of cellular boundary structures or protein folding. Strengths of electrostatic and hydrophobic interactions are similar and can be balanced over a wide range of temperatures, which considerably increases the repertoire of interactions that can be used to modulate biological functions. Some properties of water, e.g. its chemical activity against polymerization reactions, are considered as unfavorable to life. In actuality, this might be a favorable trait because life requires a balance between constructive and destructive processes. For example, molecules synthesized in response to specific conditions must be degraded once these conditions change. Otherwise regulation of biological processes would be virtually impossible. Water might not be the only liquid with favorable properties for supporting life. It has been proposed that formamide, which might be present elsewhere in the universe in sufficient quantities to warrant interest, could be a potential alternative to water for the origin of life. However, this will remain highly hypothetical until it is demonstrated in further studies on its physical, chemical and biological properties it is capable of mediating self-organization of matter and providing proper balance between different types of non-covalent interactions.

Magnetically Separable Fe3O4@DOPA-Pd: A Heterogeneous Catalyst for Aqueous Heck Reaction

EPA Science Inventory

Magnetically separable Fe3O4@DOPA-Pd catalyst has been synthesized via anchoring of palladium over dopamine-coated magnetite via non-covalent interaction and the catalyst is utilized for expeditious Heck coupling in aqueous media.

Transuranic Hybrid Materials: Crystallographic and Computational Metrics of Supramolecular Assembly

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

Surbella, Robert G.; Ducati, Lucas C.; Pellegrini, Kristi L.

A family of twelve supramolecular [AnO2Cl4]2- (An = U, Np, Pu) containing compounds assembled via hydrogen and halogen bonds donated by substituted 4-X-pyridinium cations (X = H, Cl, Br, I) is reported. These materials were prepared from a room-temperature synthesis wherein crystallization of unhydrolyzed and valence pure [An(VI)O2Cl4]2- (An = U, Np, Pu) tectons are the norm. We present a hierarchy of assembly criteria based on crystallographic observations, and subsequently quantify the strengths of the non-covalent interactions using Kohn-Sham density functional calculations. We provide, for the first time, a detailed description of the electrostatic potentials (ESPs) of the actinyl tetrahalidemore » dianions and reconcile crystallographically observed structural motifs and non-covalent interaction (NCI) acceptor-donor pairings. Our findings indicate that the average electrostatic potential across the halogen ligands (the acceptors) changes by only ~2 kJ mol-1 across the AnO22+ series, indicating the magnitude of the potential is independent of the metal center. The role of the cation is therefore critical in directing structural motifs and dictating the resulting hydrogen and halogen bond strengths, the former being stronger due to the positive charge centralized on the pyridyl nitrogen N-H+. Subsequent analyses using the Quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) approaches support this conclusion and highlight the structure directing role of the cations. Whereas one can infer that the 2 Columbic attraction is the driver for assembly, the contribution of the non-covalent interaction is to direct the molecular-level arrangement (or disposition) of the tectons.« less

Using an innovative multiple regression procedure in a cancer population (Part II): fever, depressive affect, and mobility problems clarify an influential symptom pair (pain-fatigue/weakness) and cluster (pain-fatigue/weakness-sleep problems).

PubMed

Francoeur, Richard B

2015-01-01

Most patients with advanced cancer experience symptom pairs or clusters among pain, fatigue, and insomnia. However, only combinations where symptoms are mutually influential hold potential for identifying patient subgroups at greater risk, and in some contexts, interventions with "cross-over" (multisymptom) effects. Improved methods to detect and interpret interactions among symptoms, signs, or biomarkers are needed to reveal these influential pairs and clusters. I recently created sequential residual centering (SRC) to reduce multicollinearity in moderated regression, which enhances sensitivity to detect these interactions. I applied SRC to moderated regressions of single-item symptoms that interact to predict outcomes from 268 palliative radiation outpatients. I investigated: 1) the hypothesis that the interaction, pain × fatigue/weakness × sleep problems, predicts depressive affect only when fever presents, and 2) an exploratory analysis, when fever is absent, that the interaction, pain × fatigue/weakness × sleep problems × depressive affect, predicts mobility problems. In the fever context, three-way interactions (and derivative terms) of the four symptoms (pain, fatigue/weakness, fever, sleep problems) are tested individually and simultaneously; in the non-fever context, a single four-way interaction (and derivative terms) is tested. Fever interacts separately with fatigue/weakness and sleep problems; these comoderators each magnify the pain-depressive affect relationship along the upper or full range of pain values. In non-fever contexts, fatigue/weakness, sleep problems, and depressive affect comagnify the relationship between pain and mobility problems. Different mechanisms contribute to the pain × fatigue/weakness × sleep problems interaction, but all depend on the presence of fever, a sign/biomarker/symptom of proinflammatory sickness behavior. In non-fever contexts, depressive affect is no longer an outcome representing malaise from the physical symptoms of sickness, but becomes a fourth symptom of the interaction. In outpatient subgroups at heightened risk, single interventions could potentially relieve multiple symptoms when fever accompanies sickness malaise and in non-fever contexts with mobility problems. SRC strengthens insights into symptom pairs/clusters.

Photodissociative Cross-Linking of Non-covalent Peptide-Peptide Ion Complexes in the Gas Phase

NASA Astrophysics Data System (ADS)

Nguyen, Huong T. H.; Andrikopoulos, Prokopis C.; Rulíšek, Lubomír; Shaffer, Christopher J.; Tureček, František

2018-05-01

We report a gas-phase UV photodissociation study investigating non-covalent interactions between neutral hydrophobic pentapeptides and peptide ions incorporating a diazirine-tagged photoleucine residue. Phenylalanine (Phe) and proline (Pro) were chosen as the conformation-affecting residues that were incorporated into a small library of neutral pentapeptides. Gas-phase ion-molecule complexes of these peptides with photo-labeled pentapeptides were subjected to photodissociation. Selective photocleavage of the diazirine ring at 355 nm formed short-lived carbene intermediates that underwent cross-linking by insertion into H-X bonds of the target peptide. The cross-link positions were established from collision-induced dissociation tandem mass spectra (CID-MS3) providing sequence information on the covalent adducts. Effects of the amino acid residue (Pro or Phe) and its position in the target peptide sequence were evaluated. For proline-containing peptides, interactions resulting in covalent cross-links in these complexes became more prominent as proline was moved towards the C-terminus of the target peptide sequence. The photocross-linking yields of phenylalanine-containing peptides depended on the position of both phenylalanine and photoleucine. Density functional theory calculations were used to assign structures of low-energy conformers of the (GLPMG + GLL*LK + H)+ complex. Born-Oppenheimer molecular dynamics trajectory calculations were used to capture the thermal motion in the complexes within 100 ps and determine close contacts between the incipient carbene and the H-X bonds in the target peptide. This provided atomic-level resolution of potential cross-links that aided spectra interpretation and was in agreement with experimental data. [Figure not available: see fulltext.

Non-covalently functionalized carbon nanostructures for synthesizing carbon-based hybrid nanomaterials.

PubMed

Li, Haiqing; Song, Sing I; Song, Ga Young; Kim, Il

2014-02-01

Carbon nanostructures (CNSs) such as carbon nanotubes, graphene sheets, and nanodiamonds provide an important type of substrate for constructing a variety of hybrid nanomaterials. However, their intrinsic chemistry-inert surfaces make it indispensable to pre-functionalize them prior to immobilizing additional components onto their surfaces. Currently developed strategies for functionalizing CNSs include covalent and non-covalent approaches. Conventional covalent treatments often damage the structure integrity of carbon surfaces and adversely affect their physical properties. In contrast, the non-covalent approach offers a non-destructive way to modify CNSs with desired functional surfaces, while reserving their intrinsic properties. Thus far, a number of surface modifiers including aromatic compounds, small-molecular surfactants, amphiphilic polymers, and biomacromolecules have been developed to non-covalently functionalize CNS surfaces. Mediated by these surface modifiers, various functional components such as organic species and inorganic nanoparticles were further decorated onto their surfaces, resulting in versatile carbon-based hybrid nanomaterials with broad applications in chemical engineering and biomedical areas. In this review, the recent advances in the generation of such hybrid nanostructures based on non-covalently functionalized CNSs will be reviewed.

Crystal engineering of versatile Hg(II) halides complexes of N,N,N‧,N‧-tetraalkyl substituted 3,5 pyridinedicarboxamides

NASA Astrophysics Data System (ADS)

Rana, Love Karan; Sharma, Sanyog; Hundal, Geeta

2018-02-01

Two new ligands N,N,N‧,N‧-tetraisopropyl/butyl-3,5-pyridinedicarboxamide (L3-L4) and six of their Hg(II)X2 complexes (where X = Cl-, Br- and I-), have been synthesized and characterized using single crystal X-ray diffraction and spectroscopic techniques. Complexes of L3 (1-3) with HgCl2/Br2/I2, have dimeric structure, with the ligand behaving as a 2-C linker. Complexes 4-6 are 1D coordination polymers with either 3- or 2-C, L4 linker and bridging halides. A delicate balance of anion, solvent, denticity and conformation of the ligands on the ensuing molecular and crystal structures has been delineated. Various non-covalent interactions, extending the dimensionality of the complexes are calculated, analyzed and discussed. A significant role of semi-localized LP···π non-covalent interactions in stabilizing the basic dimeric unit in the complexes, has been discerned.

New coordination features; A bridging pyridine and the forced shortest non-covalent distance between two CO 3 2- species

DOE PAGES

Velasco, V.; Aguilà, D.; Barrios, L. A.; ...

2014-09-29

The aerobic reaction of the multidentate ligand 2,6-bis-(3-oxo-3-(2-hydroxyphenyl)-propionyl)-pyridine, H 4L, with Co (II) salts in strong basic conditions produces the clusters [Co 4(L) 2(OH)(py) 7]NO 3 (1) and [Co 8Na 4(L) 4(OH) 2(CO 3) 2(py) 10](BF 4) 2 (2). Analysis of their structure unveils unusual coordination features including a very rare bridging pyridine ligand or two trapped carbonate anions within one coordination cage, forced to stay at an extremely close distance (d O···O = 1.946 Å). This unprecedented non-bonding proximity represents a meeting point between long covalent interactions and “intermolecular” contacts. These original motifs have been analysed here through DFTmore » calculations, which have yielded interaction energies and the reduced repulsion energy experimented by both CO 3 2- anions when located in close proximity inside the coordination cage.« less

Configuration and energy landscape of the benzonitrile anion

NASA Astrophysics Data System (ADS)

Kirnosov, Nikita; Adamowicz, Ludwik

2017-05-01

Quantum chemical calculations are employed to study the configurational isomers of the anion formed by benzene substituted with a cyano group. It is found that an excess electron can form dipole-bound (DB) states with benzonitrile and phenyl-isocyanide isomers. It can also attach to the cyano group, if this group is separated from the benzene ring by some distance, forming a covalent CN- anion. There are four positions at peripherals of the benzene ring where this anion can localize and form stable complexes with the benzene radical. In these complexes CN- is connected to the benzene radical via non-covalent interactions.

Guest-Release Control in Enzyme-Sensitive, Amphiphilic-Dendrimer-Based Nanoparticles through Photochemical Crosslinking

PubMed Central

Raghupathi, Krishna R.; Azagarsamy, Malar A.; Thayumanavan, S.

2012-01-01

Stimuli sensitive, facially amphiphilic dendrimers have been synthesized and their enzyme-responsive nature has been determined with dual fluorescence responses of both covalently conjugated and non-covalently bound reporter units. These dual responses are correlated to ascertain the effect of enzymatic action on micellar aggregates and the consequential guest release. The release of the guest molecule is conveniently tuned by stabilizing the micellar aggregates through photochemical crosslinking of hydrophobic coumarin units. This photo-crosslinking is also utilized as a tool to investigate the mode of enzyme-substrate interaction in the context of aggregate-monomer equilibrium. PMID:21887830

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

Grimme, Stefan, E-mail: grimme@thch.uni-bonn.de; Brandenburg, Jan Gerit; Bannwarth, Christoph

A density functional theory (DFT) based composite electronic structure approach is proposed to efficiently compute structures and interaction energies in large chemical systems. It is based on the well-known and numerically robust Perdew-Burke-Ernzerhoff (PBE) generalized-gradient-approximation in a modified global hybrid functional with a relatively large amount of non-local Fock-exchange. The orbitals are expanded in Ahlrichs-type valence-double zeta atomic orbital (AO) Gaussian basis sets, which are available for many elements. In order to correct for the basis set superposition error (BSSE) and to account for the important long-range London dispersion effects, our well-established atom-pairwise potentials are used. In the design ofmore » the new method, particular attention has been paid to an accurate description of structural parameters in various covalent and non-covalent bonding situations as well as in periodic systems. Together with the recently proposed three-fold corrected (3c) Hartree-Fock method, the new composite scheme (termed PBEh-3c) represents the next member in a hierarchy of “low-cost” electronic structure approaches. They are mainly free of BSSE and account for most interactions in a physically sound and asymptotically correct manner. PBEh-3c yields good results for thermochemical properties in the huge GMTKN30 energy database. Furthermore, the method shows excellent performance for non-covalent interaction energies in small and large complexes. For evaluating its performance on equilibrium structures, a new compilation of standard test sets is suggested. These consist of small (light) molecules, partially flexible, medium-sized organic molecules, molecules comprising heavy main group elements, larger systems with long bonds, 3d-transition metal systems, non-covalently bound complexes (S22 and S66×8 sets), and peptide conformations. For these sets, overall deviations from accurate reference data are smaller than for various other tested DFT methods and reach that of triple-zeta AO basis set second-order perturbation theory (MP2/TZ) level at a tiny fraction of computational effort. Periodic calculations conducted for molecular crystals to test structures (including cell volumes) and sublimation enthalpies indicate very good accuracy competitive to computationally more involved plane-wave based calculations. PBEh-3c can be applied routinely to several hundreds of atoms on a single processor and it is suggested as a robust “high-speed” computational tool in theoretical chemistry and physics.« less

Chemical trend of superconducting transition temperature in hole-doped delafossite of CuAlO2, AgAlO2 and AuAlO2

NASA Astrophysics Data System (ADS)

Nakanishi, Akitaka; Katayama-Yoshida, Hiroshi

2012-12-01

We have performed the first-principles calculations about the superconducting transition temperature Tc of hole-doped delafossite CuAlO2, AgAlO2 and AuAlO2. Calculated Tc are about 50 K (CuAlO2), 40 K (AgAlO2) and 3 K(AuAlO2) at maximum in the optimum hole-doping concentration. The low Tc of AuAlO2 is attributed to the weak electron-phonon interaction caused by the low covalency and heavy atomic mass.

Adsorption mechanisms of metal ions on the potassium dihydrogen phosphate (1 0 0) surface: A density functional theory-based investigation.

PubMed

Wu, Yulin; Zhang, Lei; Liu, Yao; Qu, Yunpeng

2018-07-15

The adsorption of metal ions (K + , Na + , Ca 2+ , Cu 2+ , Al 3+ , Cr 3+ ) on the (1 0 0) surface of potassium dihydrogen phosphate (KDP) has been studied using density functional theory (DFT). Calculation results show that all the investigated metal ions can be spontaneously adsorbed on the surface with negative adsorption energies. The adsorption stability increases in the order of Na +  < K +  < Cu 2+  < Ca 2+  < Al 3+  < Cr 3+ , and shows a consistent trend as the adsorbed metal ion valence (monovalent < divalent < trivalent). Three types of stable adsorption configurations are observed, corresponding to three different bonding mechanisms. Na + , K + and Ca 2+ ions with a large radius can form two ionic bonds and one weak covalent bond with the O and H atoms respectively. In addition, the medium-sized ion of Cu 2+ forms two covalent bonds with the O and H atoms. Furthermore, Al 3+ and Cr 3+ ions with the smallest radius form two metal-oxygen and one metal-hydrogen covalent bonds with the surface, making one H-O bond broken. Compared with other metal ions, Al 3+ and Cr 3+ have the strongest interactions with the surface, which can be explained by the significant electron transfer and more stable covalent bond formations between these two ions and the surface. Copyright © 2018 Elsevier Inc. All rights reserved.

Electronic structures of Al-Si clusters and the magic number structure Al8Si4

NASA Astrophysics Data System (ADS)

Du, Ning; Su, Mingzhi; Chen, Hongshan

2018-02-01

The low-energy structures of Al8Sim (m = 1-6) have been determined by using the genetic algorithm combined with density functional theory and the Second-order Moller-Plesset perturbation theory (MP2) models. The results show that the close-packed structures are preferable in energy for Al-Si clusters and in most cases there exist a few isomers with close energies. The valence molecular orbitals, the orbital level structures and the electron localisation function (ELF) consistently demonstrate that the electronic structures of Al-Si clusters can be described by the jellium model. Al8Si4 corresponds to a magic number structure with pronounced stability and large energy gap; the 40 valence electrons form closed 1S21P61D102S21F142P6 shells. The ELF attractors also suggest weak covalent Si-Si, Si-Al and Al-Al bonding, and doping Si in aluminium clusters promotes the covalent interaction between Al atoms.

An In Vivo Photo-Cross-Linking Approach Reveals a Homodimerization Domain of Aha1 in S. cerevisiae

PubMed Central

Berg, Michael; Michalowski, Annette; Palzer, Silke; Rupp, Steffen; Sohn, Kai

2014-01-01

Protein-protein interactions play an essential role in almost any biological processes. Therefore, there is a particular need for methods which describe the interactions of a defined target protein in its physiological context. Here we report a method to photo-cross-link interacting proteins in S. cerevisiae by using the non-canonical amino acid p-azido-L-phenylalanine (pAzpa). Based on the expanded genetic code the photoreactive non-canonical amino acid pAzpa was site-specifically incorporated at eight positions into a domain of Aha1 that was previously described to bind Hsp90 in vitro to function as a cochaperone of Hsp90 and activates its ATPase activity. In vivo photo-cross-linking to the cognate binding partner of Aha1 was carried out by irradiation of mutant strains with UV light (365 nm) to induce covalent intermolecular bonds. Surprisingly, an interaction between Aha1 and Hsp90 was not detected, although, we could confirm binding of suppressed pAzpa containing Aha1 to Hsp90 by native co-immunoprecipitation. However, a homodimer consisting of two covalently crosslinked Aha1 monomers was identified by mass spectrometry. This homodimer could also be confirmed using p-benzoyl-L-phenylalanine, another photoreactive non-canonical amino acid. Crosslinking was highly specific as it was dependent on irradiation using UV light, the exact position of the non-canonical amino acid in the protein sequence as well as on the addition of the non-canonical amino acid to the growth medium. Therefore it seems possible that an interaction of Aha1 with Hsp90 takes place at different positions than previously described in vitro highlighting the importance of in vivo techniques to study protein-protein interactions. Accordingly, the expanded genetic code can easily be applied to other S. cerevisiae proteins to study their interaction under physiological relevant conditions in vivo. PMID:24614167

Magnetic graphitic carbon nitride: its application in the C–H activation of amines

EPA Science Inventory

Magnetic graphitic carbon nitride, Fe@g-C3N4, has been synthesized by adorning graphitic carbon nitride (g-C3N4) support with iron oxide via non-covalent interaction. The magnetically recyclable catalyst showed excellent reactivity for expeditious C-H activation and cyanation of ...

The effect of ligand substituent on crystal packing: Structural and theoretical studies of two Ga(III) supramolecular compounds

NASA Astrophysics Data System (ADS)

Soleimannejad, Janet; Nazarnia, Esfandiar

2016-07-01

A new Ga(III) supramolecular compound (4,4‧-bipyH2)[Ga(hpydc)2]2·7H2O (2) (where H2hpydc = 4-hydroxy-pyridine-2,6-dicarboxylic acid and 4,4‧-bipy = 4,4‧-bipyridine) was synthesized using the proton transfer reaction. Compound 2 was structurally characterized using single crystal X-ray diffraction, and it was shown that its asymmetric unit consists of two independent anionic Ga(III) complexes, one fully protonated 4,4‧-bipyridine and seven uncoordinated water molecules. In order to understand the effect of pyridine OH substituent on supramolecular interactions and crystal packing, compound 2 was compared with (bipyH2)[Ga(pydc)2]·(H2pydc)·4H2O (1) (where H2pydc = pyridine-2,6-dicarboxylic acid), that does not have an OH group on the pyridine ligand. The Density Functional Theory (DFT) and Natural Bond Orbital (NBO) calculations and also Atoms in Molecules (AIM) analysis were used to analyze the non-covalent interactions in both complexes. The calculation of non-covalent interactions' energy provides a useful means to investigate their effects in the crystal packing.

Density functional theory calculations on transition metal atoms adsorbed on graphene monolayers

NASA Astrophysics Data System (ADS)

Dimakis, Nicholas; Flor, Fernando Antonio; Salgado, Andres; Adjibi, Kolade; Vargas, Sarah; Saenz, Justin

2017-11-01

Transition metal atom adsorption on graphene monolayers has been elucidated using periodic density functional theory under hybrid and generalized gradient approximation functionals. More specifically, we examined the adsorption of Cu, Fe, Zn, Ru, and Os on graphene monolayers by calculating, among others, the electronic density-of-states spectra of the adatom-graphene system and the overlap populations of the adatom with the nearest adsorbing graphene carbon atoms. These calculations reveal that Cu form primarily covalent bonds with graphene atoms via strong hybridization between the adatom orbitals and the sp band of the graphene substrate, whereas the interaction of the Ru and Os with graphene also contain ionic parts. Although the interaction of Fe with graphene atoms is mostly covalent, some charge transfer to graphene is also observed. The interaction of Zn with graphene is weak. Mulliken population analysis and charge contour maps are used to elucidate charge transfers between the adatom and the substrate. The adsorption strength is correlated with the metal adsorption energy and the height of the metal adatom from the graphene plane for the geometrically optimized adatom-graphene system. Our analysis shows that show that metal adsorption strength follows the adatom trend Ru ≈ Os > Fe > Cu > Zn, as verified by corresponding changes in the adsorption energies. The increased metal-carbon orbital overlap for the Ru relative to Os adatom is attributed to hybridization defects.

Benchmarking lithium amide versus amine bonding by charge density and energy decomposition analysis arguments.

PubMed

Engelhardt, Felix; Maaß, Christian; Andrada, Diego M; Herbst-Irmer, Regine; Stalke, Dietmar

2018-03-28

Lithium amides are versatile C-H metallation reagents with vast industrial demand because of their high basicity combined with their weak nucleophilicity, and they are applied in kilotons worldwide annually. The nuclearity of lithium amides, however, modifies and steers reactivity, region- and stereo-selectivity and product diversification in organic syntheses. In this regard, it is vital to understand Li-N bonding as it causes the aggregation of lithium amides to form cubes or ladders from the polar Li-N covalent metal amide bond along the ring stacking and laddering principle. Deaggregation, however, is more governed by the Li←N donor bond to form amine adducts. The geometry of the solid state structures already suggests that there is σ- and π-contribution to the covalent bond. To quantify the mutual influence, we investigated [{(Me 2 NCH 2 ) 2 (C 4 H 2 N)}Li] 2 ( 1 ) by means of experimental charge density calculations based on the quantum theory of atoms in molecules (QTAIM) and DFT calculations using energy decomposition analysis (EDA). This new approach allows for the grading of electrostatic Li + N - , covalent Li-N and donating Li←N bonding, and provides a way to modify traditional widely-used heuristic concepts such as the -I and +I inductive effects. The electron density ρ ( r ) and its second derivative, the Laplacian ∇ 2 ρ ( r ), mirror the various types of bonding. Most remarkably, from the topological descriptors, there is no clear separation of the lithium amide bonds from the lithium amine donor bonds. The computed natural partial charges for lithium are only +0.58, indicating an optimal density supply from the four nitrogen atoms, while the Wiberg bond orders of about 0.14 au suggest very weak bonding. The interaction energy between the two pincer molecules, (C 4 H 2 N) 2 2- , with the Li 2 2+ moiety is very strong ( ca. -628 kcal mol -1 ), followed by the bond dissociation energy (-420.9 kcal mol -1 ). Partitioning the interaction energy into the Pauli (Δ E Pauli ), dispersion (Δ E disp ), electrostatic (Δ E elstat ) and orbital (Δ E orb ) terms gives a 71-72% ionic and 25-26% covalent character of the Li-N bond, different to the old dichotomy of 95 to 5%. In this regard, there is much more potential to steer the reactivity with various substituents and donor solvents than has been anticipated so far.

The use of native chemical functional groups presented by wound beds for the covalent attachment of polymeric microcarriers of bioactive factors

PubMed Central

Jain, Rishabh; Agarwal, Ankit; Kierski, Patricia R.; Schurr, Michael J.; Murphy, Christopher J.; McAnulty, Jonathan F.; Abbott, Nicholas L.

2012-01-01

The development of versatile methods that provide spatial and temporal control over the presentation of physical and biochemical cues on wound beds can lead to new therapeutic approaches that expedite wound healing by favorably influencing cellular behaviors. Towards that goal, we report that native chemical functional groups presented by wound beds can be utilized for direct covalent attachment of polymeric microbeads. Specifically, we demonstrated the covalent attachment of maleimide-functionalized and catechol-functionalized microbeads, made of either polystyrene (non-degradable) or poly(lactic-co-glycolic acid) ((PLGA), degradable), to sulfhydryl and amine groups present on porcine dermis used here as an ex vivo model wound bed. A pronounced increase (10–70 fold) in the density and persistence of the covalently reactive microbeads was observed relative to microbeads that adsorb via non-covalent interactions. Complementary characterization of the surface chemistry of the ex vivo wound beds using Raman microspectroscopy provides support for our conclusion that the increased adherence of the maleimide-functionalized beads results from their covalent bond formation with sulfhydryl groups on the wound bed. The attachment of maleimide-functionalized microbeads to wounds created in live wild-type and diabetic mice led to observations of differential immobilization of microbeads on them and were consistent with anticipated differences in the presentation of sulfhydryl groups on the two different wound types. Finally, the incorporation of maleimide-functionalized microbeads in wounds created in wild-type mice did not impair the rate of wound closure relative to an untreated wound. Overall, the results presented in this paper enable a general and facile approach to the engineering of wound beds in which microbeads are covalently immobilized to wound beds. Such immobilized microbeads could be used in future studies to release bioactive factors (e.g., antimicrobial agents or growth factors) and/or introduce topographical cues that promote cell behaviors underlying healing and wound closure. PMID:23088838

Approximations to complete basis set-extrapolated, highly correlated non-covalent interaction energies.

PubMed

Mackie, Iain D; DiLabio, Gino A

2011-10-07

The first-principles calculation of non-covalent (particularly dispersion) interactions between molecules is a considerable challenge. In this work we studied the binding energies for ten small non-covalently bonded dimers with several combinations of correlation methods (MP2, coupled-cluster single double, coupled-cluster single double (triple) (CCSD(T))), correlation-consistent basis sets (aug-cc-pVXZ, X = D, T, Q), two-point complete basis set energy extrapolations, and counterpoise corrections. For this work, complete basis set results were estimated from averaged counterpoise and non-counterpoise-corrected CCSD(T) binding energies obtained from extrapolations with aug-cc-pVQZ and aug-cc-pVTZ basis sets. It is demonstrated that, in almost all cases, binding energies converge more rapidly to the basis set limit by averaging the counterpoise and non-counterpoise corrected values than by using either counterpoise or non-counterpoise methods alone. Examination of the effect of basis set size and electron correlation shows that the triples contribution to the CCSD(T) binding energies is fairly constant with the basis set size, with a slight underestimation with CCSD(T)∕aug-cc-pVDZ compared to the value at the (estimated) complete basis set limit, and that contributions to the binding energies obtained by MP2 generally overestimate the analogous CCSD(T) contributions. Taking these factors together, we conclude that the binding energies for non-covalently bonded systems can be accurately determined using a composite method that combines CCSD(T)∕aug-cc-pVDZ with energy corrections obtained using basis set extrapolated MP2 (utilizing aug-cc-pVQZ and aug-cc-pVTZ basis sets), if all of the components are obtained by averaging the counterpoise and non-counterpoise energies. With such an approach, binding energies for the set of ten dimers are predicted with a mean absolute deviation of 0.02 kcal/mol, a maximum absolute deviation of 0.05 kcal/mol, and a mean percent absolute deviation of only 1.7%, relative to the (estimated) complete basis set CCSD(T) results. Use of this composite approach to an additional set of eight dimers gave binding energies to within 1% of previously published high-level data. It is also shown that binding within parallel and parallel-crossed conformations of naphthalene dimer is predicted by the composite approach to be 9% greater than that previously reported in the literature. The ability of some recently developed dispersion-corrected density-functional theory methods to predict the binding energies of the set of ten small dimers was also examined. © 2011 American Institute of Physics

Asymmetric Michael Addition Mediated by Chiral Ionic Liquids.

PubMed

Suzuki, Yumiko

2018-06-01

Chiral ionic liquids with a focus on their applications in asymmetric Michael additions and related reactions were reviewed. The examples were classified on the basis of the mode of asymmetric induction (e.g., external induction/non-covalent interaction or internal induction/covalent bond formation), the roles in reactions (as a solvent or catalyst), and their structural features (e.g., imidazolium-based chiral cations, other chiral oniums; proline derivatives). Most of the reactions with high chiral induction are Michael addition of ketones or aldehydes to chalcones or nitrostyrenes where proline-derived chiral ionic liquids catalyze the reaction through enamine/ iminium formation. Many reports demonstrate the recyclability of ionic liquid-tagged pyrrolidines.

pH-controlled doxorubicin anticancer loading and release from carbon nanotube noncovalently modified by chitosan: MD simulations.

PubMed

Rungnim, Chompoonut; Rungrotmongkol, Thanyada; Poo-Arporn, Rungtiva P

2016-11-01

In the present study, we describe here the pH condition activating doxorubicin (DOX) anticancer drugs loading and release over single-wall carbon nanotube (SWNT) non-covalently wrapped with chitosan (CS). The possibility of drug displacement on DOX/CS/SWNT nanocarrier was investigated using molecular dynamics simulations. The drug loading and release were monitored via displacement analysis and binding energy calculations. The simulated results clearly showed that the drugs well interacted with the CS/SWNT at physiological pH (pH 7.4), where CS was in the deprotonated form. Contrastingly, in weakly acidic environments (pH 5.0-6.5) which is a pH characteristics of certain cancer environments, the protonated CS became loosen wrapped around the SWNT and triggered drugs release as a result of charge-charge repulsion between CS and drug molecules. The obtained data fulfil the understanding at atomic level of drug loading and release controlled by pH-sensitive polymer, which might be useful for further cancer therapy researches. Copyright © 2016 Elsevier Inc. All rights reserved.

Self-assembly of coordination polymers of Pr(III), Nd(III), Tb(III), Dy(III) and Ho(III) with 5-hydroxyisophthalic acid and adipic acid: Syntheses, structures, porosity, luminescence and magnetic properties

NASA Astrophysics Data System (ADS)

Kariem, Mukaddus; Yawer, Mohd; Kumar, Manesh; Nawaz Sheikh, Haq; Sood, Puneet; Kolekar, Sanjay S.

2017-11-01

Five novel coordination polymers (CPs) with the formula [Ln (hip) (adip)0.5(H2O)2]n. nH2O [Ln = Pr (1), Nd (2), Tb (3), Dy (4) and Ho (5)] were synthesized by self-organization of lanthanide salts with rigid [5-hydroxyisophthalic acid (H2hip)] and flexible [adipic acid (H2adip)] linkers under solvothermal condition. X-ray diffraction revealed data that all five CPs 1-5 are isostructural and crystallizes in monoclinic C2/c space group. Coordination polymers 1-5 exhibit 1D linear ladder shaped extension with the linkage of lanthanide carboxylate chains having the backbone of H2hip and H2adip ligands. The 1D linear ladder chains get transformed into three dimensional (3D) supramolecular network via non-covalent interactions (π-π and H - bonding). The porosity study showed that 20.34 mL of N2 gets adsorbed per 1.0 g of sample at 1 atm pressure. The CP 3 (Tb) and 4 (Dy) emit strong ligand sensitized characteristic f-f luminescence emission. The CPs 3 and 4 exhibit weak ferromagnetic interactions at lower temperatures.

Photobleaching effect in azo-dye containing epoxy resin films: the potentiality of carbon nanotubes as azo-dye dispensers

NASA Astrophysics Data System (ADS)

Díaz Costanzo, Guadalupe; Goyanes, Silvia; Ledesma, Silvia

2015-04-01

Azo-dye molecules may suffer from bleaching under certain illumination conditions. When this photoinduced process occurs, it generates an irreversible effect that is characterized by the loss of absorption of the dye molecule. Moreover, the well-known isomerization of azodye molecules does not occur anymore. In this work it is shown how the addition of a small amount of multi-walled carbon nanotubes (MWCNTs) helps to decrease the bleaching effect in a photosensitive guest-host azo-polymer film. Two different systems were fabricated using an epoxy resin as polymer matrix. An azo-dye, Disperse Orange 3, was used as photosensitive material in both systems and MWCNTs were added into one of them. The optical response of the polymeric systems was studied considering the degree of photoinduced birefringence. Photobleaching of the azo-dye was observed in all cases however, the effect is lower for the composite material containing 0.2 wt % MWCNTs. The weak interaction between MWCNTs and dye molecules is less favorable when the material is heated. The optical behavior of the heated composite material suggests that carbon nanotubes can be potentially used as azo dye dispensers. The results are interpreted in terms of the non-covalent interaction between azo-dye molecules and MWCNTs.

Syntheses, crystal structures and Hirshfeld surface analysis of a coordination polymer of Cu(II) chlorido and a tris-octahedral complex of Ni(II) containing isonicotinoylhydrazone blockers

NASA Astrophysics Data System (ADS)

Mahmoudi, Ghodrat; Chowdhury, Habibar; Ghosh, Barindra K.; Lofland, Samuel E.; Maniukiewicz, Waldemar

2018-05-01

One-pot reactions of pre-assigned molar ratios of appropriate metal (II) salts and HL1 (2-acetylpyridine nicotinoylhydrazone) or HL2 (2-acetylpyridine isonicotinoylhydrazone) in MeOH solutions at room temperature afford 1D coordination polymeric chain [Cu(μ-L1) (Cl)]n (1) and a mononuclear complex [Ni(L2)2] (2). The compounds (1) and (2) were characterized using elemental analyses, spectral and other physicochemical methods. Single crystal X-ray diffraction measurements for (1) and (2) have been made to define the molecular aggregates and crystalline architectures. In (1), each copper (II) center adopts a distorted square pyramidal geometry with a CuN3OCl chromophore linked through μ-L1 to form the 1D polymeric chain. While in (2) each Ni(II) cation is six-coordinate with octahedral structure having NiN4O2 chromophore containing two L2 units each functioning as a classical tridentate (N,N,O) chelator. Different weak non-covalent interactions promote dimensionalities in the compounds. A Hirshfeld surface analysis was employed to gain additional insight into interactions responsible for packing of (1) and (2). Magnetic susceptibility measurement of (1) in the 4-300 K range reveals simple paramagnetism.

Trelagliptin (SYR-472, Zafatek), novel once-weekly treatment for type 2 diabetes, inhibits dipeptidyl peptidase-4 (DPP-4) via a non-covalent mechanism

DOE PAGES

Grimshaw, Charles E.; Jennings, Andy; Kamran, Ruhi; ...

2016-06-21

Trelagliptin (SYR-472), a novel dipeptidyl peptidase-4 inhibitor, shows sustained efficacy by once-weekly dosing in type 2 diabetes patients. In this study, we characterized in vitro properties of trelagliptin, which exhibited approximately 4-and 12-fold more potent inhibition against human dipeptidyl peptidase-4 than alogliptin and sitagliptin, respectively, and >10,000-fold selectivity over related proteases including dipeptidyl peptidase-8 and dipeptidyl peptidase-9. Kinetic analysis revealed reversible, competitive and slow-binding inhibition of dipeptidyl peptidase-4 by trelagliptin (t 1/2 for dissociation ≈ 30 minutes). X-ray diffraction data indicated a non-covalent interaction between dipeptidyl peptidase and trelagliptin. Altogether, potent dipeptidyl peptidase inhibitionmay partially contribute to sustained efficacy ofmore » trelagliptin.« less

Trelagliptin (SYR-472, Zafatek), novel once-weekly treatment for type 2 diabetes, inhibits dipeptidyl peptidase-4 (DPP-4) via a non-covalent mechanism

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

Grimshaw, Charles E.; Jennings, Andy; Kamran, Ruhi

Trelagliptin (SYR-472), a novel dipeptidyl peptidase-4 inhibitor, shows sustained efficacy by once-weekly dosing in type 2 diabetes patients. In this study, we characterized in vitro properties of trelagliptin, which exhibited approximately 4-and 12-fold more potent inhibition against human dipeptidyl peptidase-4 than alogliptin and sitagliptin, respectively, and >10,000-fold selectivity over related proteases including dipeptidyl peptidase-8 and dipeptidyl peptidase-9. Kinetic analysis revealed reversible, competitive and slow-binding inhibition of dipeptidyl peptidase-4 by trelagliptin (t 1/2 for dissociation ≈ 30 minutes). X-ray diffraction data indicated a non-covalent interaction between dipeptidyl peptidase and trelagliptin. Altogether, potent dipeptidyl peptidase inhibitionmay partially contribute to sustained efficacy ofmore » trelagliptin.« less

Non-covalent interactions of a drug molecule encapsulated in a hybrid silica gel.

PubMed

Paul, Geo; Steuernagel, Stefan; Koller, Hubert

2007-12-28

The drug molecule Propranolol has been encapsulated by a sol-gel process in an organic-inorganic hybrid matrix by in-situ self-assembly; the 2D HETCOR solid state NMR spectroscopy provides direct proof of the intimate spatial relationship between the host matrix and guest drug molecules.

An in vitro FRET-based assay for the analysis of SUMO conjugation and isopeptidase cleavage.

PubMed

Stankovic-Valentin, Nicolas; Kozaczkiewicz, Lukasz; Curth, Katja; Melchior, Frauke

2009-01-01

To measure rates of sumoylation and isopeptidase cleavage in vitro, we developed an enzyme assay that is based on fluorescence resonance energy transfer (FRET). FRET is a process by which the excited state energy of a fluorescent donor molecule is transferred to an acceptor molecule. Efficient energy transfer requires very close proximity, and can therefore be used as a read-out for covalent and non-covalent protein interactions. The assay described here uses bacterially expressed and purified YFP-SUMO-1 and CFP-RanGAP1 as model substrates that are covalently coupled in the presence of recombinant SUMO E1 and E2 enzymes and ATP. Reactions of 25 microl volume, set up in 384-wells plates, give sufficient signal for analysis. Consequently, this assay requires very low amounts of recombinant proteins and allows measurement of time courses in high-throughput format.

Supramolecular gating of ion transport in nanochannels.

PubMed

Kumar, B V V S Pavan; Rao, K Venkata; Sampath, S; George, Subi J; Eswaramoorthy, Muthusamy

2014-11-24

Several covalent strategies towards surface charge-reversal in nanochannels have been reported with the purpose of manipulating ion transport. However, covalent routes lack dynamism, modularity and post-synthetic flexibility, and hence restrict their applicability in different environments. Here, we introduce a facile non-covalent approach towards charge-reversal in nanochannels (<10 nm) using strong charge-transfer interactions between dicationic viologen (acceptor) and trianionic pyranine (donor). The polarity of ion transport was switched from anion selective to ambipolar to cation selective by controlling the extent of viologen bound to the pyranine. We could also regulate the ion transport with respect to pH by selecting a donor with pH-responsive functional groups. The modularity of this approach further allows facile integration of various functional groups capable of responding to stimuli such as light and temperature to modulate the transport of ions as well as molecules. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Covalent Bonding of Pyrrolobenzodiazepines (PBDs) to Terminal Guanine Residues within Duplex and Hairpin DNA Fragments

PubMed Central

Mantaj, Julia; Jackson, Paul J. M.; Karu, Kersti; Rahman, Khondaker M.; Thurston, David E.

2016-01-01

Pyrrolobenzodiazepines (PBDs) are covalent-binding DNA-interactive agents with growing importance as payloads in Antibody Drug Conjugates (ADCs). Until now, PBDs were thought to covalently bond to C2-NH2 groups of guanines in the DNA-minor groove across a three-base-pair recognition sequence. Using HPLC/MS methodology with designed hairpin and duplex oligonucleotides, we have now demonstrated that the PBD Dimer SJG-136 and the C8-conjugated PBD Monomer GWL-78 can covalently bond to a terminal guanine of DNA, with the PBD skeleton spanning only two base pairs. Control experiments with the non-C8-conjugated anthramycin along with molecular dynamics simulations suggest that the C8-substituent of a PBD Monomer, or one-half of a PBD Dimer, may provide stability for the adduct. This observation highlights the importance of PBD C8-substituents, and also suggests that PBDs may bind to terminal guanines within stretches of DNA in cells, thus representing a potentially novel mechanism of action at the end of DNA strand breaks. PMID:27055050

Molecular recognition of organic ammonium ions in solution using synthetic receptors

PubMed Central

Späth, Andreas

2010-01-01

Summary Ammonium ions are ubiquitous in chemistry and molecular biology. Considerable efforts have been undertaken to develop synthetic receptors for their selective molecular recognition. The type of host compounds for organic ammonium ion binding span a wide range from crown ethers to calixarenes to metal complexes. Typical intermolecular interactions are hydrogen bonds, electrostatic and cation–π interactions, hydrophobic interactions or reversible covalent bond formation. In this review we discuss the different classes of synthetic receptors for organic ammonium ion recognition and illustrate the scope and limitations of each class with selected examples from the recent literature. The molecular recognition of ammonium ions in amino acids is included and the enantioselective binding of chiral ammonium ions by synthetic receptors is also covered. In our conclusion we compare the strengths and weaknesses of the different types of ammonium ion receptors which may help to select the best approach for specific applications. PMID:20502608

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

Peng, Hua; College of Physics and Optoelectronics, Taiyuan University of Technology, Taiyuan 030024; Kioussis, Nicholas, E-mail: nick.kioussis@csun.edu

Using ab initio based calculations, we have calculated the intrinsic lattice thermal conductivity of chiral tellurium. We show that the interplay between the strong covalent intrachain and weak van der Waals interchain interactions gives rise to the phonon band gap between the lower and higher optical phonon branches. The underlying mechanism of the large anisotropy of the thermal conductivity is the anisotropy of the phonon group velocities and of the anharmonic interatomic force constants (IFCs), where large interchain anharmonic IFCs are associated with the lone electron pairs. We predict that tellurium has a large three-phonon scattering phase space that resultsmore » in low thermal conductivity. The thermal conductivity anisotropy decreases under applied hydrostatic pressure.« less

Ga(+) Basicity and Affinity Scales Based on High-Level Ab Initio Calculations.

PubMed

Brea, Oriana; Mó, Otilia; Yáñez, Manuel

2015-10-26

The structure, relative stability and bonding of complexes formed by the interaction between Ga(+) and a large set of compounds, including hydrocarbons, aromatic systems, and oxygen-, nitrogen-, fluorine and sulfur-containing Lewis bases have been investigated through the use of the high-level composite ab initio Gaussian-4 theory. This allowed us to establish rather accurate Ga(+) cation affinity (GaCA) and Ga(+) cation basicity (GaCB) scales. The bonding analysis of the complexes under scrutiny shows that, even though one of the main ingredients of the Ga(+) -base interaction is electrostatic, it exhibits a non-negligible covalent character triggered by the presence of the low-lying empty 4p orbital of Ga(+) , which favors a charge donation from occupied orbitals of the base to the metal ion. This partial covalent character, also observed in AlCA scales, is behind the dissimilarities observed when GaCA are compared with Li(+) cation affinities, where these covalent contributions are practically nonexistent. Quite unexpectedly, there are some dissimilarities between several Ga(+) -complexes and the corresponding Al(+) -analogues, mainly affecting the relative stability of π-complexes involving aromatic compounds. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantum chemical investigation of attractive non-covalent interactions between halomethanes and rare gases.

PubMed

McAllister, Linda J; Bruce, Duncan W; Karadakov, Peter B

2012-11-01

The interaction between rare gas atoms and trifluoromethylhalides and iodomethane is investigated using ab initio and density functional theory (DFT) methods: MP2, CCSD, B3LYP, M06, M06-L, M06-2X, M06-HF, X3LYP, PBE, B97-D, B3LYP-D3, and M06-L-D3, in combination with the aug-cc-pVTZ and aug-cc-pVTZ-PP basis sets. A weakly attractive interaction is observed for all complexes, whose strength increases as the rare gas and halogen bond donor become more polarizable, and as the group bound to the halogen bond donor becomes more electron-withdrawing. The separation between iodine and krypton in the complex CF(3)I···Kr, calculated at the MP2 and B3LYP-D3 levels of theory, agrees very well with recent experimental results (Stephens, S. L.; Walker, N. R.; Legon, A. C. J. Chem. Phys. 2011, 135, 224309). Analysis of the ability of theoretical methods to account for the dispersion interaction present in these complexes leads to the conclusion that MP2 and B3LYP-D3, which produce very similar results, are the better performing methods, followed by B97-D and the M06 suite of functionals; the popular B3LYP as well as X3LYP perform poorly and significantly underestimate the interaction strength. The orbitals responsible for the interaction are identified through Edmiston-Ruedenberg localization; it is shown that, by combining the key orbitals, it is possible to observe a molecular orbital picture of a σ-hole interaction.

Energy and fuels from electrochemical interfaces

NASA Astrophysics Data System (ADS)

Stamenkovic, Vojislav R.; Strmcnik, Dusan; Lopes, Pietro P.; Markovic, Nenad M.

2017-01-01

Advances in electrocatalysis at solid-liquid interfaces are vital for driving the technological innovations that are needed to deliver reliable, affordable and environmentally friendly energy. Here, we highlight the key achievements in the development of new materials for efficient hydrogen and oxygen production in electrolysers and, in reverse, their use in fuel cells. A key issue addressed here is the degree to which the fundamental understanding of the synergy between covalent and non-covalent interactions can form the basis for any predictive ability in tailor-making real-world catalysts. Common descriptors such as the substrate-hydroxide binding energy and the interactions in the double layer between hydroxide-oxides and H---OH are found to control individual parts of the hydrogen and oxygen electrochemistry that govern the efficiency of water-based energy conversion and storage systems. Links between aqueous- and organic-based environments are also established, encouraging the 'fuel cell' and 'battery' communities to move forward together.

The emerging role of native mass spectrometry in characterizing the structure and dynamics of macromolecular complexes

PubMed Central

Boeri Erba, Elisabetta; Petosa, Carlo

2015-01-01

Mass spectrometry (MS) is a powerful tool for determining the mass of biomolecules with high accuracy and sensitivity. MS performed under so-called “native conditions” (native MS) can be used to determine the mass of biomolecules that associate noncovalently. Here we review the application of native MS to the study of protein−ligand interactions and its emerging role in elucidating the structure of macromolecular assemblies, including soluble and membrane protein complexes. Moreover, we discuss strategies aimed at determining the stoichiometry and topology of subunits by inducing partial dissociation of the holo-complex. We also survey recent developments in "native top-down MS", an approach based on Fourier Transform MS, whereby covalent bonds are broken without disrupting non-covalent interactions. Given recent progress, native MS is anticipated to play an increasingly important role for researchers interested in the structure of macromolecular complexes. PMID:25676284

Chromatin immunoprecipitation (ChIP) method for non-model fruit flies (Diptera: Tephritidae) and evidence of histone modifications.

PubMed

Nagalingam, Kumaran; Lorenc, Michał T; Manoli, Sahana; Cameron, Stephen L; Clarke, Anthony R; Dudley, Kevin J

2018-01-01

Interactions between DNA and proteins located in the cell nucleus play an important role in controlling physiological processes by specifying, augmenting and regulating context-specific transcription events. Chromatin immunoprecipitation (ChIP) is a widely used methodology to study DNA-protein interactions and has been successfully used in various cell types for over three decades. More recently, by combining ChIP with genomic screening technologies and Next Generation Sequencing (e.g. ChIP-seq), it has become possible to profile DNA-protein interactions (including covalent histone modifications) across entire genomes. However, the applicability of ChIP-chip and ChIP-seq has rarely been extended to non-model species because of a number of technical challenges. Here we report a method that can be used to identify genome wide covalent histone modifications in a group of non-model fruit fly species (Diptera: Tephritidae). The method was developed by testing and refining protocols that have been used in model organisms, including Drosophila melanogaster. We demonstrate that this method is suitable for a group of economically important pest fruit fly species, viz., Bactrocera dorsalis, Ceratitis capitata, Zeugodacus cucurbitae and Bactrocera tryoni. We also report an example ChIP-seq dataset for B. tryoni, providing evidence for histone modifications in the genome of a tephritid fruit fly for the first time. Since tephritids are major agricultural pests globally, this methodology will be a valuable resource to study taxa-specific evolutionary questions and to assist with pest management. It also provides a basis for researchers working with other non-model species to undertake genome wide DNA-protein interaction studies.

How Y-Family DNA polymerase IV is more accurate than Dpo4 at dCTP insertion opposite an N2-dG adduct of benzo[a]pyrene.

PubMed

Sholder, Gabriel; Creech, Amanda; Loechler, Edward L

2015-11-01

To bypass DNA damage, cells have Y-Family DNA polymerases (DNAPs). One Y-Family-class includes DNAP κ and DNAP IV, which accurately insert dCTP opposite N(2)-dG adducts, including from the carcinogen benzo[a]pyrene (BP). Another class includes DNAP η and DNAP V, which insert accurately opposite UV-damage, but inaccurately opposite BP-N(2)-dG. To investigate structural differences between Y-Family-classes, regions are swapped between DNAP IV (a κ/IV-class-member) and Dpo4 (a η/V-class-member); the kinetic consequences are evaluated via primer-extension studies with a BP-N(2)-dG-containing template. Four key structural elements are revealed. (1) Y-Family DNAPs have discreet non-covalent contacts between their little finger-domain (LF-Domain) and their catalytic core-domain (CC-Domain), which we call "non-covalent bridges" (NCBs). Arg37 and Arg38 in DNAP IV's CC-Domain near the active site form a non-covalent bridge (AS-NCB) by interacting with Glu251 and Asp252, respectively, in DNAP IV's LF-Domain. Without these interactions dATP/dGTP/dTTP misinsertions increase. DNAP IV's AS-NCB suppresses misinsertions better than Dpo4's equivalent AS-NCB. (2) DNAP IV also suppresses dATP/dGTP/dTTP misinsertions via a second non-covalent bridge, which is ∼8Å from the active site (Distal-NCB). Dpo4 has no Distal-NCB, rendering it inferior at dATP/dGTP/dTTP suppression. (3) dCTP insertion is facilitated by the larger minor groove opening near the active site in DNAP IV versus Dpo4, which is sensible given that Watson/Crick-like [dCTP:BP-N(2)-dG] pairing requires the BP-moiety to be in the minor groove. (4) Compared to Dpo4, DNAP IV has a smaller major groove opening, which suppresses dGTP misinsertion, implying BP-N(2)-dG bulk in the major groove during Hoogsteen syn-adduct-dG:dGTP pairing. In summary, DNAP IV has a large minor groove opening to enhance dCTP insertion, a plugged major groove opening to suppress dGTP misinsertion, and two non-covalent bridges (near and distal to the active site) to suppress dATP/dGTP/dTTP misinsertions; collectively these four structural features enhance DNAP IV's dNTP insertion fidelity opposite a BP-N(2)-dG adduct compared to Dpo4. Copyright © 2015 Elsevier B.V. All rights reserved.

Meaning and consequence of the coexistence of competitive hydrogen bond/salt forms on the dissociation orientation of non-covalent complexes.

PubMed

Darii, Ekaterina; Alves, Sandra; Gimbert, Yves; Perret, Alain; Tabet, Jean-Claude

2017-03-15

Non-covalent complexes (NCC) between hexose monophosphates (HexP) and arginine (R) were analyzed using ESI MS and MS/MS in negative mode under different (hard, HC and soft, SC) desolvation conditions. High resolution mass spectrometry (HRMS) revealed the presence of different ionic species, namely, homo- and heteromultimers of R and HexP. Deprotonated heterodimers and corresponding sodiated species were enhanced under HC likely due to a decrease in available charge number associated with the reduction of H + /Na + exchange. The quantum calculations showed that the formation of covalent systems is very little exothermic, therefore, such systems are disfavored. Desolvation dependent CID spectra of deprotonated [(HexP+R)‒H] - complexes demonstrated that they can exist within the hydrogen bond (HB) and salt bridge (SB) forms, yielding either NCC separation or covalent bond cleavages, respectively. Although HB forms are the main species, they cannot survive under HC; therefore, the minor SB forms became detectable. Energy-resolved mass spectrometry (ERMS) experiments revealed diagnostic fragment ions from both SB and HB forms, providing evidence that these isomeric forms are inconvertible. SB formation should result from the ionic interactions of highly acidic group of HexP with strongly basic guanidine group of arginine and thus requires an arginine zwitterion (ZW) form. This was confirmed by quantum calculations. Ion-ion interactions are significantly affected by the presence of sodium cation as demonstrated by the fragmentation patterns of sodiated complex species. Regarding CID data, only SB between protonated amino group of R and deprotonated phosphate group of HexP could be suggested, but the primary amine is not enough basic then, the SB must be fleeting. Nevertheless, the observation of the covalent bond cleavages suggests the presence of structures with a free negative charge able to induce fragmentations. Indeed, according to quantum calculations, solvated salt (SS) systems involving Na + /COO - salt solvated by neutral phosphate and negative charge on sugar ring are preferentially formed. Copyright © 2016 Elsevier B.V. All rights reserved.

Density functional theory and phytochemical study of 8-hydroxyisodiospyrin

NASA Astrophysics Data System (ADS)

Ullah, Zakir; Ata-ur-Rahman; Fazl-i-Sattar; Rauf, Abdur; Yaseen, Muhammad; Hassan, Waseem; Tariq, Muhammad; Ayub, Khurshid; Tahir, Asif Ali; Ullah, Habib

2015-09-01

Comprehensive theoretical and experimental studies of a natural product, 8-hydroxyisodiospyrin (HDO) have been carried out. Based on the correlation of experimental and theoretical data, an appropriate computational model was developed for obtaining the electronic, spectroscopic, and thermodynamic parameters of HDO. First of all, the exact structure of HDO is confirmed from the nice correlation of theory and experiment, prior to determination of its electroactive nature. Hybrid density functional theory (DFT) is employed for all theoretical simulations. The experimental and predicted IR and UV-vis spectra [B3LYP/6-31+G(d,p) level of theory] have excellent correlation. Inter-molecular non-covalent interaction of HDO with different gases such as NH3, CO2, CO, H2O is investigated through geometrical counterpoise (gCP) i.e., B3LYP-gCP-D3/6-31G∗ method. Furthermore, the inter-molecular interaction is also supported by geometrical parameters, electronic properties, thermodynamic parameters and charge analysis. All these characterizations have corroborated each other and confirmed the electroactive nature (non-covalent interaction ability) of HDO for the studied gases. Electronic properties such as Ionization Potential (IP), Electron Affinities (EA), electrostatic potential (ESP), density of states (DOS), HOMO, LUMO, and band gap of HDO have been estimated for the first time theoretically.

Electronic excitations in long polyenes revisited

NASA Astrophysics Data System (ADS)

Schmidt, Maximilian; Tavan, Paul

2012-03-01

We apply the valence shell model OM2 [W. Weber and W. Thiel, Theor. Chem. Acc. 103, 495, (2000), 10.1007/s002149900083] combined with multireference configuration interaction (MRCI) to compute the vertical excitation energies and transition dipole moments of the low-energy singlet excitations in the polyenes with 4 ⩽ N ⩽ 22π-electrons. We find that the OM2/MRCI descriptions closely resemble those of Pariser-Parr-Pople (PPP) π-electron models [P. Tavan and K. Schulten, Phys. Rev. B 36, 4337, (1987)], if equivalent MRCI procedures and regularly alternating model geometries are used. OM2/MRCI optimized geometries are shown to entail improved descriptions particularly for smaller polyenes (N ⩽ 12), for which sizeable deviations from the regular model geometries are found. With configuration interaction active spaces covering also the σ- in addition to the π-electrons, OM2/MRCI excitation energies turn out to become smaller by at most 0.35 eV for the ionic and 0.15 eV for the covalent excitations. The particle-hole (ph) symmetry, which in Pariser-Parr-Pople models arises from the zero-differential overlap approximation, is demonstrated to be only weakly broken in OM2 such that the oscillator strengths of the covalent 1B_u^- states, which artificially vanish in ph-symmetric models, are predicted to be very small. According to OM2/MRCI and experimental data the 1B_u^- state is the third excited singlet state for N < 12 and becomes the second for N ⩾ 14. By comparisons with results of other theoretical approaches and experimental evidence we argue that deficiencies of the particular MRCI method employed by us, which show up in a poor size consistency of the covalent excitations for N > 12, are caused by its restriction to at most doubly excited references.

Direct covalent attachment of small peptide antigens to enzyme-linked immunosorbent assay plates using radiation and carbodiimide activation.

PubMed

Dagenais, P; Desprez, B; Albert, J; Escher, E

1994-10-01

Direct adsorption of small peptide antigens to unaltered, commercially available polystyrene surfaces may be too weak to permit suitable assay by ELISA. We therefore developed a simple method for the covalent attachment of small, potentially single epitope antigens to polystyrene surfaces. Chemical activation of polystyrene plates with carbodiimide considerably improves the total and covalent attachment of radioactive octapeptides. The covalent attachment was demonstrated by washing with hot detergent. A 3.5 Mrad gamma-irradiation of plates also increases total binding, particularly in combination with chemical activation. The covalent attachment presumably occurs through formation and chemical activation of carboxylate functions on the polystyrene surface which form amide bonds with peptides. ELISA test was performed with CGRP and successive smaller CGRP fragments. Covalent attachment of C-terminal peptide fragments as detection antigens allows optimal recognition and sensitivity even for hexapeptides, while decapeptide antigens were already poorly recognized using a conventional antigen plating technique. Repetitive detergent washes and/or prolonged storage of plates with covalently bound antigens did not reduce their ELISA sensitivity. The method with storage and reutilization capacities that we present here will be useful for the development of preplated antibody screening test.

Cellular Interactions and Immune Response of Spherical Nucleic Acid (SNA) Nanoconjugates

NASA Astrophysics Data System (ADS)

Massich, Matthew David

Spherical nucleic acid (SNA) nanoconjugates consist of a densely packed monolayer shell of highly-oriented oligonucleotides covalently bound to a gold nanoparticle core. The nanoconjugates exhibit several important qualities, which make them useful for various biological applications, such as antisense gene regulation strategies and the intracellular detection of biomolecules. The focus of this thesis was to characterize the nanoconjugates interaction with cultured cells and specifically the immune response to their intracellular presence. The immune response of macrophage cells to internalized nanoconjugates was studied, and due to the dense functionalization of oligonucleotides on the surface of the nanoparticle and the resulting high localized salt concentration the innate immune response to the nanoconjugates is ˜25-fold less when compared to a lipoplex carrying the same sequence. Additionally, genome-wide expression profiling was used to study the biological response of cultured cells to the nanoconjugates. The biological response of HeLa cells to gold nanoparticles stabilized by weakly bound ligands was significant, yet when these same nanoparticles were stably functionalized with covalently attached oligonucleotides the cells showed no measurable response. In human keratinocytes, the oligonucleotide sequences caused 427 genes to be differentially expressed when complexed with Dharmafect, but when the oligonucleotides were conjugated to nanoparticles only 7 genes were differentially expressed. Beyond characterizing the cellular interactions and immune response of the nanoconjugates, the optimal length of siRNA (from 19--34 base pairs) that induces the most gene knockdown while maintaining limited immune activation was determined to be 24 base pairs. Further, the SNAs were shown to be useful as a potential antiviral gene therapy by demonstrating approximately 50% knockdown of the Ebola VP35 gene. Lastly, a scanning probe-enabled method was used to rapidly create nanoscale fibronectin patterns over large areas with a range of feature sizes, thereby opening the field of nanocombinatorics. This allowed the investigation of the relationship between fibronectin feature size and stem cell fate. MSCs cultured on nanoscale fibronectin features directed differentiation toward osteogenesis to a greater extent than cells grown on both microscale features and cells grown on non-patterned fibronectin substrates with osteogenic inducing media, demonstrating a new method for controlling stem cell fate.

Role of non-covalent interactions in the production of visco-elastic material from zein

USDA-ARS?s Scientific Manuscript database

Zein has been used in the production of a wide variety of materials during the last century. One of the more intriguing developments in zein utilization has been the discovery that zein can be made to form a visco-elastic dough for bread production. Although significant research has been conducted t...

Asymmetric Michael Addition Mediated by Chiral Ionic Liquids

PubMed Central

Suzuki, Yumiko

2018-01-01

Chiral ionic liquids with a focus on their applications in asymmetric Michael additions and related reactions were reviewed. The examples were classified on the basis of the mode of asymmetric induction (e.g., external induction/non-covalent interaction or internal induction/covalent bond formation), the roles in reactions (as a solvent or catalyst), and their structural features (e.g., imidazolium-based chiral cations, other chiral oniums; proline derivatives). Most of the reactions with high chiral induction are Michael addition of ketones or aldehydes to chalcones or nitrostyrenes where proline-derived chiral ionic liquids catalyze the reaction through enamine/ iminium formation. Many reports demonstrate the recyclability of ionic liquid-tagged pyrrolidines. PMID:29861702

Engaging the Terminal: Promoting Halogen Bonding Interactions with Uranyl Oxo Atoms.

PubMed

Carter, Korey P; Kalaj, Mark; Surbella, Robert G; Ducati, Lucas C; Autschbach, Jochen; Cahill, Christopher L

2017-11-02

Engaging the nominally terminal oxo atoms of the linear uranyl (UO 2 2+ ) cation in non-covalent interactions represents both a significant challenge and opportunity within the field of actinide hybrid materials. An approach has been developed for promoting oxo atom participation in a range of non-covalent interactions, through judicious choice of electron donating equatorial ligands and appropriately polarizable halogen-donor atoms. As such, a family of uranyl hybrid materials was generated based on a combination of 2,5-dihalobenzoic acid and aromatic, chelating N-donor ligands. Delineation of criteria for oxo participation in halogen bonding interactions has been achieved by preparing materials containing 2,5-dichloro- (25diClBA) and 2,5-dibromobenzoic acid (25diBrBA) coupled with 2,2'-bipyridine (bipy) (1 and 2), 1,10-phenanthroline (phen) (3-5), 2,2':6',2''-terpyridine (terpy) (6-8), or 4'-chloro-2,2':6',2''-terpyridine (Cl-terpy) (9-10), which have been characterized through single crystal X-ray diffraction, Raman, Infrared (IR), and luminescence spectroscopy, as well as through density functional calculations of electrostatic potentials. Looking comprehensively, these results are compared with recently published analogues featuring 2,5-diiodobenzoic acid which indicate that although inclusion of a capping ligand in the uranyl first coordination sphere is important, it is the polarizability of the selected halogen atom that ultimately drives halogen bonding interactions with the uranyl oxo atoms. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Halogen bonding from a hard and soft acids and bases perspective: investigation by using density functional theory reactivity indices.

PubMed

Pinter, Balazs; Nagels, Nick; Herrebout, Wouter A; De Proft, Frank

2013-01-07

Halogen bonds between the trifluoromethyl halides CF(3)Cl, CF(3)Br and CF(3)I, and dimethyl ether, dimethyl sulfide, trimethylamine and trimethyl phosphine were investigated using Pearson's hard and soft acids and bases (HSAB) concept with conceptual DFT reactivity indices, the Ziegler-Rauk-type energy-decomposition analysis, the natural orbital for chemical valence (NOCV) framework and the non-covalent interaction (NCI) index. It is found that the relative importance of electrostatic and orbital (charge transfer) interactions varies as a function of both the donor and acceptor molecules. Hard and soft interactions were distinguished and characterised by atomic charges, electrophilicity and local softness indices. Dual-descriptor plots indicate an orbital σ hole on the halogen similar to the electrostatic σ hole manifested in the molecular electrostatic potential. The predicted high halogen-bond-acceptor affinity of N-heterocyclic carbenes was evidenced in the highest complexation energy for the hitherto unknown CF(3) I·NHC complex. The dominant NOCV orbital represents an electron-density deformation according to a n→σ*-type interaction. The characteristic signal found in the reduced density gradient versus electron-density diagram corresponds to the non-covalent interaction between contact atoms in the NCI plots, which is the manifestation of halogen bonding within the NCI theory. The unexpected C-X bond strengthening observed in several cases was rationalised within the molecular orbital framework. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Non-Covalent Assembly of Targeted Carbon Nanovectors Enables Synergistic Drug and Radiation Cancer Therapy In Vivo

PubMed Central

Sano, Daisuke; Berlin, Jacob M.; Pham, Tam T.; Marcano, Daniela C.; Valdecanas, David R.; Zhou, Ge; Milas, Luka; Myers, Jeffrey N.; Tour, James M.

2012-01-01

Current chemotherapeutics are characterized by efficient tumor cell-killing and severe side effects mostly derived from off target toxicity. Hence targeted delivery of these drugs to tumor cells is actively sought. In an in vitro system, we previously demonstrated that targeted drug delivery to cancer cells overexpressing epidermal growth factor receptor (EGFR+) can be achieved by poly(ethylene glycol)-functionalized carbon nanovectors simply mixed with a drug, paclitaxel, and an antibody that binds to the epidermal growth factor receptor, Cetuximab. This construct is unusual in that all three components are assembled through non-covalent interactions. Here we show that this same construct is effective in vivo, enhancing radiotherapy of EGFR+ tumors. This targeted nanovector system has the potential to be a new therapy for head and neck squamous cell carcinomas, deserving of further preclinical development. PMID:22316245

Investigation of the adsorption of polymer chains on amine-functionalized double-walled carbon nanotubes.

PubMed

Ansari, R; Ajori, S; Rouhi, S

2015-12-01

Molecular dynamics (MD) simulations were used to study the adsorption of different polymer chains on functionalized double-walled carbon nanotubes (DWCNTs). The nanotubes were functionalized with two different amines: NH2 (a small amine) and CH2-NH2 (a large amine). Considering three different polymer chains, all with the same number of atoms, the effect of polymer type on the polymer-nanotube interaction was studied. In general, it was found that covalent functionalization considerably improved the polymer-DWCNT interaction. By comparing the results obtained with different polymer chains, it was observed that, unlike polyethylene and polyketone, poly(styrene sulfonate) only weakly interacts with the functionalized DWCNTs. Accordingly, the smallest radius of gyration was obtained with adsorbed poly(styrene sulfonate). It was also observed that the DWCNTs functionalized with the large amine presented more stable interactions with polyketone and poly(styrene sulfonate) than with polyethylene, whereas the DWCNTs functionalized with the small amine showed better interfacial noncovalent bonding with polyethylene.

Single molecular dynamic interactions between glycophorin A and lectin as probed by atomic force microscopy.

PubMed

Yan, Chao; Yersin, Alexandre; Afrin, Rehana; Sekiguchi, Hiroshi; Ikai, Atsushi

2009-09-01

Glycophorin A (GpA) is one of the most abundant transmembrane proteins in human erythrocytes and its interaction with lectins has been studied as model systems for erythrocyte related biological processes. We performed a force measurement study using the force mode of atomic force microscopy (AFM) to investigate the single molecular level biophysical mechanisms involved in GpA-lectin interactions. GpA was mounted on a mica surface or natively presented on the erythrocyte membrane and probed with an AFM tip coated with the monomeric but multivalent Psathyrella velutina lectin (PVL) through covalent crosslinkers. A dynamic force spectroscopy study revealed similar interaction properties in both cases, with the unbinding force centering around 60 pN with a weak loading rate dependence. Hence we identified the presence of one energy barrier in the unbinding process. Force profile analysis showed that more than 70% of GpAs are free of cytoskeletal associations in agreement with previous reports.

Relaxations of fluorouracil tautomers by decorations of fullerene-like SiCs: DFT studies

NASA Astrophysics Data System (ADS)

Kouchaki, Alireza; Gülseren, Oğuz; Hadipour, Nasser; Mirzaei, Mahmoud

2016-06-01

Decorations of silicon carbide (SiC) fullerene-like nanoparticles by fluorouracil (FU) and its tautomers are investigated through density functional theory (DFT) calculations. Two models of fullerene-like particles including Si12C8 and Si8C12 are constructed to be counterparts of decorated hybrid structures, FU@Si12C8 and FU@Si8C12, respectively. The initial models including original FU and tautomeric structures and SiC nanoparticles are individually optimized and then combined for further optimizations in the hybrid forms. Covalent bonds are observed for FU@Si12C8 hybrids, whereas non-covalent interactions are seen for FU@Si8C12 ones. The obtained properties indicated that Si12C8 model could be considered as a better counterpart for interactions with FU structures than Si8C12 model. The results also showed significant effects of interactions on the properties of atoms close to the interacting regions in nanoparticles. Finally, the tautomeric structures show different behaviors in interactions with SiC nanoparticles, in which the SiC nanoparticles could be employed to detect the situations of tautomeric processes for FU structures.

Determination and Quantification of Molecular Interactions in Protein Films: A Review.

PubMed

Hammann, Felicia; Schmid, Markus

2014-12-10

Protein based films are nowadays also prepared with the aim of replacing expensive, crude oil-based polymers as environmentally friendly and renewable alternatives. The protein structure determines the ability of protein chains to form intra- and intermolecular bonds, whereas the degree of cross-linking depends on the amino acid composition and molecular weight of the protein, besides the conditions used in film preparation and processing. The functionality varies significantly depending on the type of protein and affects the resulting film quality and properties. This paper reviews the methods used in examination of molecular interactions in protein films and discusses how these intermolecular interactions can be quantified. The qualitative determination methods can be distinguished by structural analysis of solutions (electrophoretic analysis, size exclusion chromatography) and analysis of solid films (spectroscopy techniques, X-ray scattering methods). To quantify molecular interactions involved, two methods were found to be the most suitable: protein film swelling and solubility. The importance of non-covalent and covalent interactions in protein films can be investigated using different solvents. The research was focused on whey protein, whereas soy protein and wheat gluten were included as further examples of proteins.

Determination Quantification of Molecular Interactions in Protein Films: A Review

PubMed Central

Hammann, Felicia; Schmid, Markus

2014-01-01

Protein based films are nowadays also prepared with the aim of replacing expensive, crude oil-based polymers as environmentally friendly and renewable alternatives. The protein structure determines the ability of protein chains to form intra- and intermolecular bonds, whereas the degree of cross-linking depends on the amino acid composition and molecular weight of the protein, besides the conditions used in film preparation and processing. The functionality varies significantly depending on the type of protein and affects the resulting film quality and properties. This paper reviews the methods used in examination of molecular interactions in protein films and discusses how these intermolecular interactions can be quantified. The qualitative determination methods can be distinguished by structural analysis of solutions (electrophoretic analysis, size exclusion chromatography) and analysis of solid films (spectroscopy techniques, X-ray scattering methods). To quantify molecular interactions involved, two methods were found to be the most suitable: protein film swelling and solubility. The importance of non-covalent and covalent interactions in protein films can be investigated using different solvents. The research was focused on whey protein, whereas soy protein and wheat gluten were included as further examples of proteins. PMID:28788285

Synthetic Covalent and Non-Covalent 2D Materials.

PubMed

Boott, Charlotte E; Nazemi, Ali; Manners, Ian

2015-11-16

The creation of synthetic 2D materials represents an attractive challenge that is ultimately driven by their prospective uses in, for example, electronics, biomedicine, catalysis, sensing, and as membranes for separation and filtration. This Review illustrates some recent advances in this diverse field with a focus on covalent and non-covalent 2D polymers and frameworks, and self-assembled 2D materials derived from nanoparticles, homopolymers, and block copolymers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interaction between dimer interface residues of native and mutated SOD1 protein: a theoretical study.

PubMed

Keerthana, S P; Kolandaivel, P

2015-04-01

Cu-Zn superoxide dismutase 1 (SOD1) is a highly conserved bimetallic protein enzyme, used for the scavenging the superoxide radicals (O2 (-)) produced due to aerobic metabolism in the mitochondrial respiratory chain. Over 100 mutations have been identified and found to be in the homodimeric structure of SOD1. The enzyme has to be maintained in its dimeric state for the structural stability and enzymatic activity. From our investigation, we found that the mutations apart from the dimer interface residues are found to affect the dimer stability of protein and hence enhancing the aggregation and misfolding tendency of mutated protein. The homodimeric state of SOD1 is found to be held together by the non-covalent interactions. The molecular dynamics simulation has been used to study the hydrogen bond interactions between the dimer interface residues of the monomers in native and mutated forms of SOD1 in apo- and holo-states. The results obtained by this analysis reveal the fact that the loss of hydrogen bond interactions between the monomers of the dimer is responsible for the reduced stability of the apo- and holo-mutant forms of SOD1. The conformers with dimer interface residues in native and mutated protein obtained by the molecular dynamics simulation is subjected to quantum mechanical study using M052X/6-31G(d) level of theory. The charge transfer between N-H···O interactions in the dimer interface residues were studied. The weak interaction between the monomers of the dimer accounts for the reduced dimerization and enhanced deformation energy in the mutated SOD1 protein.

Investigation of phonon transport and thermal boundary conductance at the interface of functionalized SWCNT and poly (ether-ketone)

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

Huang, Haoxiang; Kumar, Satish, E-mail: satish.kumar@me.gatech.edu; Chen, Liang

2016-09-07

Carbon nanostructures such as carbon nanotube (CNT), graphene, and carbon fibers can be used as fillers in amorphous polymers to improve their thermal properties. In this study, the effect of covalent bonding of CNT with poly(ether ketone) (PEK) on interfacial thermal interactions is investigated using non-equilibrium molecular dynamics simulations. The number of covalent bonds between (20, 20) CNT and PEK is varied in the range of 0–80 (0%–6.25%), and the thermal boundary conductance is computed. The analysis reveals that covalent functionalization of CNT atoms can enhance the thermal boundary conductance by an order of magnitude compared to the non-functionalized CNT-PEKmore » interface at a high degree of CNT functionalization. Besides strengthening the thermal coupling, covalent functionalization is also shown to modify the phonon spectra of CNT. The transient spectral energy analysis shows that the crosslinks cause faster energy exchange from CNT to PEK in different frequency bands. The oxygen atom of hydroxyl group of PEK contributes energy transfer in the low frequency band, while aromatic and carbonyl carbon atoms play a more significant role in high frequency bands. In addition, by analyzing the relaxation time of the spectral temperature of different frequency bands of CNT, it is revealed that with increasing number of bonds, both lower frequency vibrational modes and higher frequency modes efficiently couple across the CNT-PEK interface and contribute in thermal energy transfer from CNT to the matrix.« less

Approximate solution of coupled cluster equations: application to the coupled cluster doubles method and non-covalent interacting systems.

PubMed

Smiga, Szymon; Fabiano, Eduardo

2017-11-15

We have developed a simplified coupled cluster (SCC) methodology, using the basic idea of scaled MP2 methods. The scheme has been applied to the coupled cluster double equations and implemented in three different non-iterative variants. This new method (especially the SCCD[3] variant, which utilizes a spin-resolved formalism) has been found to be very efficient and to yield an accurate approximation of the reference CCD results for both total and interaction energies of different atoms and molecules. Furthermore, we demonstrate that the equations determining the scaling coefficients for the SCCD[3] approach can generate non-empirical SCS-MP2 scaling coefficients which are in good agreement with previous theoretical investigations.

Tuning the mesomorphic properties of phenoxy-terminated smectic liquid crystals: the effect of fluoro substitution.

PubMed

Thompson, Matthew; Carkner, Carolyn; Mosey, Nicholas J; Kapernaum, Nadia; Lemieux, Robert P

2015-05-21

The mesomorphic properties of phenoxy-terminated 5-alkoxy-2-(4-alkoxyphenyl)pyrimidine liquid crystals can be tuned in a predictable fashion with fluoro substituents on the phenoxy end-group. We show that an ortho-fluoro substituent promotes the formation of a tilted smectic C (SmC) phase whereas a para-fluoro substituent promotes the formation of an orthogonal smectic A (SmA) phase. The balance between SmA and SmC phases may be understood in terms of the energetic preference of the phenoxy end-groups to self-assemble via arene-arene interactions in a parallel or antiparallel geometry, and how these non-covalent interactions may cause either a suppression or enhancement of out-of-layer fluctuations at the interface of smectic layers. Calculations of changes in the potential energy of association ΔE for non-covalent dimers of fluoro-substituted n-butyloxybenzene molecules in parallel and antiparallel geometries support this hypothesis. We also show how mesomorphic properties can be further tuned by difluoro and perfluoro substitution, including difluoro substitution at the ortho positions, which uniquely promotes the formation of a SmC-nematic phase sequence.

A new topology of the HK97-like fold revealed in Bordetella bacteriophage by cryoEM at 3.5 Å resolution

PubMed Central

Zhang, Xing; Guo, Huatao; Jin, Lei; Czornyj, Elizabeth; Hodes, Asher; Hui, Wong H; Nieh, Angela W; Miller, Jeff F; Zhou, Z Hong

2013-01-01

Bacteriophage BPP-1 infects and kills Bordetella species that cause whooping cough. Its diversity-generating retroelement (DGR) provides a naturally occurring phage-display system, but engineering efforts are hampered without atomic structures. Here, we report a cryo electron microscopy structure of the BPP-1 head at 3.5 Å resolution. Our atomic model shows two of the three protein folds representing major viral lineages: jellyroll for its cement protein (CP) and HK97-like (‘Johnson’) for its major capsid protein (MCP). Strikingly, the fold topology of MCP is permuted non-circularly from the Johnson fold topology previously seen in viral and cellular proteins. We illustrate that the new topology is likely the only feasible alternative of the old topology. β-sheet augmentation and electrostatic interactions contribute to the formation of non-covalent chainmail in BPP-1, unlike covalent inter-protein linkages of the HK97 chainmail. Despite these complex interactions, the termini of both CP and MCP are ideally positioned for DGR-based phage-display engineering. DOI: http://dx.doi.org/10.7554/eLife.01299.001 PMID:24347545

The RING 2.0 web server for high quality residue interaction networks.

PubMed

Piovesan, Damiano; Minervini, Giovanni; Tosatto, Silvio C E

2016-07-08

Residue interaction networks (RINs) are an alternative way of representing protein structures where nodes are residues and arcs physico-chemical interactions. RINs have been extensively and successfully used for analysing mutation effects, protein folding, domain-domain communication and catalytic activity. Here we present RING 2.0, a new version of the RING software for the identification of covalent and non-covalent bonds in protein structures, including π-π stacking and π-cation interactions. RING 2.0 is extremely fast and generates both intra and inter-chain interactions including solvent and ligand atoms. The generated networks are very accurate and reliable thanks to a complex empirical re-parameterization of distance thresholds performed on the entire Protein Data Bank. By default, RING output is generated with optimal parameters but the web server provides an exhaustive interface to customize the calculation. The network can be visualized directly in the browser or in Cytoscape. Alternatively, the RING-Viz script for Pymol allows visualizing the interactions at atomic level in the structure. The web server and RING-Viz, together with an extensive help and tutorial, are available from URL: http://protein.bio.unipd.it/ring. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Detection of free and covalently bound microcystins in animal tissues by liquid chromatography-tandem mass spectrometry.

PubMed

Neffling, Milla-Riina; Lance, Emilie; Meriluoto, Jussi

2010-03-01

Microcystins are cyanobacterial hepatotoxins capable of accumulation into animal tissues. The toxins act by inhibiting specific protein phosphatases and both non-covalent and covalent interactions occur. The 2-methyl-3-methoxy-4-phenylbutyric acid (MMPB) method determines the total, i.e. the sum of free and protein-bound microcystin in tissues. The aim of the method development in this paper was to tackle the problems with the MMPB methodology: the rather laborious workflow and the loss of material during different steps of the method. In the optimised workflow the oxidation recovery was of acceptable level (29-40%), the extraction efficiency good (62-97%), but the signal suppression effect from the matrix remained severe in our system (16-37% signal left). The extraction efficiency for the determination of the free, extractable microcystins, was found to be good, 52-100%, depending on the sample and the toxin variant and concentration. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Cu+ association to some Ph-X (X = OH, NH2, CHO, COOH, CF3) phenyl derivatives.: A comparison with Li+ complexes

NASA Astrophysics Data System (ADS)

Corral, Ines; Mo, Otilia; Yanez, Manuel

2006-09-01

The complexes of Cu+ with phenol, aniline, benzaldehyde, benzoic acid, and trifluromethyl-benzene were investigated through the use of MP2 and density functional theory (DFT) methods. Both harmonic vibrational frequencies and optimized geometries were obtained at the B3LYP/6-311G(d,p) and MP2(full)/6-311G(d,p) levels of theory. Final energies were obtained through single point B3LYP/6-311+G(3df,2p)//B3LYP/6-311G(d,p) calculations. The interactions of Cu+ with these aromatic compounds have a non-negligible covalent character, which clearly differentiate Cu+-complexes from the corresponding Li+-complexes. These dissimilarities are reflected in the geometries, binding energies and infrared spectra of the most stable adducts. For Li+ only conventional [pi]-complexes should be expected when interacting with aniline, while Cu+ attaches preferentially to the para carbon atom. For phenol, besides the conventional [pi]-complexes, a 12% of oxygen attached species are expected to be found upon Li+ association. Conversely, no oxygen attached species should be formed in reactions of phenol with Cu+. For benzoic acid and benzaldehyde, Li+ aligns with the dipole moment of the base, interacting exclusively with the carbonyl oxygen in the plane of the molecule. This is also the case in Cu+-benzoic acid complex, while in the Cu+-benzaldehyde complex the metal ion also interacts with the aromatic [pi]-system. Cu+ binding enthalpies (BEs) are systematically larger (about 1.3 times) than Li+ BEs. The covalent character of Cu+ interactions is associated with electron donations from bonding ([pi]) orbitals or lone-pairs of the base toward the 4s empty orbital of the metal and with back-donations from the occupied d orbitals of the metal toward antibonding ([pi]*) empty orbitals of the base. This non-negligible covalent character is also reflected in a rough correlation between the calculated Cu+ BEs and the available experimental proton affinities that does not exist for Li+ BEs.

Characterising non-covalent interactions with the Cambridge Structural Database.

PubMed

Lommerse, J P; Taylor, R

1997-02-01

This review describes how the CSD can be used to study non-covalent interactions. Several different types of information may be obtained. First, the relative frequencies of various interactions can be studied; for example, we have shown that the terminal oxygen atoms of phosphate groups accept hydrogen bonds far more often than the linkage oxygens. Secondly, information can be obtained about the geometries of nonbonded contacts; for example, hydrogen bonds to P-O groups rarely form along the extension of the P-O bond, whereas short contacts between oxygen and carbon-bound iodine show a strong preference for linear C-I ... O angles. Thirdly, the CSD can be searched for novel interactions which may be exploited in inhibitor design; for example, the I ... O contacts just mentioned, and N-H ... pi hydrogen bonds. Finally, the CSD can suggest synthetic targets for medicinal chemistry; for example, molecules containing delocalised electron deficient groups such as trimethylammonium, pyridinium, thaizolium and dinitrophenyl have a good chance of binding to an active-site tryptophan. Although the CSD contains small-molecule crystal structures, not protein-ligand complexes, there is considerable evidence that the contacts seen in the two types of structures are similar. We have illustrated this a number of times in the present review and additional evidence has been given previously by Klebe. The major advantages of the CSD are its size, diversity and experimental accuracy. For these reasons, it is a useful tool for modellers engaged in rational inhibitor design.

Elevated nitrogen allows the weak invasive plant Galinsoga quadriradiata to become more vigorous with respect to inter-specific competition.

PubMed

Liu, Gang; Yang, Ying-Bo; Zhu, Zhi-Hong

2018-02-16

Elevated nitrogen associated with global change is believed to promote the invasion of many vigorous exotic plants. However, it is unclear how a weak exotic plant will respond to elevated nitrogen in the future. In this study, the competitive outcome of a weak invasive plant (Galinsoga quadriradiata) and two non-invasive plants was detected. The plants were subjected to 3 types of culture (mixed, monoculture or one-plant), 2 levels of nitrogen (ambient or elevated at a rate of 2 g m -2 yr -1 ) and 2 levels of light (65% shade or full sunlight). The results showed that elevated nitrogen significantly promoted the growth of both the weak invader and the non-invasive plants in one-plant pots; however, growth promotion was not observed for the non-invasive species in the mixed culture pots. The presence of G. quadriradiata significantly inhibited the growth of the non-invasive plants, and a decreased negative species interaction was detected as a result of elevated nitrogen. Our results suggest that competitive interactions between G. quadriradiata and the non-invasive plants were altered by elevated nitrogen. It provides exceptional evidence that an initially weak invasive plant can become an aggressive invader through elevated nitrogen deposition.

On the nature of interactions in the F2 OXe(…) NCCH3 complex: Is there the Xe(IV)N bond?

PubMed

Makarewicz, Emilia; Lundell, Jan; Gordon, Agnieszka J; Berski, Slawomir

2016-07-01

Nature of the bonding in isolated XeOF2 molecule and F2 OXe(…) NCCH3 complexes have been studied in the gas phase (0 K) using Quantum Chemical Topology methods. The wave functions have been approximated at the MP2 and DFT levels of calculations, using the APFD, B3LYP, M062X, and B2PLYP functionals with the GD3 dispersion correction. The nature of the formal XeO bond in the XeOF2 monomer depends on the basis set used (all-electron vs. the ecp-28 approximation for Xe). Within the all-electron basis set approach the bond is represented by two bonding attractors, Vi = 1,2 (Xe,O), with total population of about 1.06e and highly delocalized electron density in both bonding basins. No bonding basins are observed using the ecp-28 approximation. These results shows that the nature of xenon-oxygen is complicated and may be described with mesomeric equilibrium of the Lewis representations: Xe((+)) O((-)) and Xe((-)) O((+)) . For both the xenon-oxygen and xenon-fluorine interactions the charge-shift model can be applied. The F2 OXe(…) NCCH3 complex exists in two structures: "parallel," stabilized by non-covalent C(…) O and Xe(…) N interactions and "linear" stabilized by the Xe(…) N interaction. Topological analysis of ELF shows that the F2 OXe(…) NCCH3 molecule appears as a weakly bound intermolecular complex. Intermolecular interaction energy components have also been studied using Symmetry Adapted Perturbation Theory. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Charge-mediated Fab-Fc interactions in an IgG1 antibody induce reversible self-association, cluster formation, and elevated viscosity.

PubMed

Arora, Jayant; Hu, Yue; Esfandiary, Reza; Sathish, Hasige A; Bishop, Steven M; Joshi, Sangeeta B; Middaugh, C Russell; Volkin, David B; Weis, David D

Concentration-dependent reversible self-association (RSA) of monoclonal antibodies (mAbs) poses a challenge to their pharmaceutical development as viable candidates for subcutaneous delivery. While the role of the antigen-binding fragment (Fab) in initiating RSA is well-established, little evidence supports the involvement of the crystallizable fragment (Fc). In this report, a variety of biophysical tools, including hydrogen exchange mass spectrometry, are used to elucidate the protein interface of such non-covalent protein-protein interactions. Using dynamic and static light scattering combined with viscosity measurements, we find that an IgG1 mAb (mAb-J) undergoes RSA primarily through electrostatic interactions and forms a monomer-dimer-tetramer equilibrium. We provide the first direct experimental mapping of the interface formed between the Fab and Fc domains of an antibody at high protein concentrations. Charge distribution heterogeneity between the positively charged interface spanning complementarity-determining regions CDR3H and CDR2L in the Fab and a negatively charged region in C H 3/Fc domain mediates the RSA of mAb-J. When arginine and NaCl are added, they disrupt RSA of mAb-J and decrease the solution viscosity. Fab-Fc domain interactions between mAb monomers may promote the formation of large transient antibody complexes that ultimately cause increases in solution viscosity. Our findings illustrate how limited specific arrangements of amino-acid residues can cause mAbs to undergo RSA at high protein concentrations and how conserved regions in the Fc portion of the antibody can also play an important role in initiating weak and transient protein-protein interactions.

Analysis of Structural Features Contributing to Weak Affinities of Ubiquitin/Protein Interactions.

PubMed

Cohen, Ariel; Rosenthal, Eran; Shifman, Julia M

2017-11-10

Ubiquitin is a small protein that enables one of the most common post-translational modifications, where the whole ubiquitin molecule is attached to various target proteins, forming mono- or polyubiquitin conjugations. As a prototypical multispecific protein, ubiquitin interacts non-covalently with a variety of proteins in the cell, including ubiquitin-modifying enzymes and ubiquitin receptors that recognize signals from ubiquitin-conjugated substrates. To enable recognition of multiple targets and to support fast dissociation from the ubiquitin modifying enzymes, ubiquitin/protein interactions are characterized with low affinities, frequently in the higher μM and lower mM range. To determine how structure encodes low binding affinity of ubiquitin/protein complexes, we analyzed structures of more than a hundred such complexes compiled in the Ubiquitin Structural Relational Database. We calculated various structure-based features of ubiquitin/protein binding interfaces and compared them to the same features of general protein-protein interactions (PPIs) with various functions and generally higher affinities. Our analysis shows that ubiquitin/protein binding interfaces on average do not differ in size and shape complementarity from interfaces of higher-affinity PPIs. However, they contain fewer favorable hydrogen bonds and more unfavorable hydrophobic/charge interactions. We further analyzed how binding interfaces change upon affinity maturation of ubiquitin toward its target proteins. We demonstrate that while different features are improved in different experiments, the majority of the evolved complexes exhibit better shape complementarity and hydrogen bond pattern compared to wild-type complexes. Our analysis helps to understand how low-affinity PPIs have evolved and how they could be converted into high-affinity PPIs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Unconventional Magnetism and Band Gap Formation in LiFePO4: Consequence of Polyanion Induced Non-planarity.

PubMed

Jena, Ajit; Nanda, B R K

2016-01-21

Oxygen plays a critical role in strongly correlated transition metal oxides as crystal field effect is one of the key factors that determine the degree of localization of the valence d/f states. Based on the localization, a set of conventional mechanisms such as Mott-Hubbard, Charge-transfer and Slater were formulated to explain the antiferromagnetic and insulating (AFI) phenomena in many of these correlated systems. From the case study on LiFePO4, through density-functional calculations, we demonstrate that none of these mechanisms are strictly applicable to explain the AFI behavior when the transition metal oxides have polyanions such as (PO4)(3-). The symmetry-lowering of the metal-oxygen complex, to stabilize the polyanion, creates an asymmetric crystal field for d/f states. In LiFePO4 this field creates completely non-degenerate Fe-d states which, with negligible p-d and d-d covalent interactions, become atomically localized to ensure a gap at the Fermi level. Due to large exchange splitting, high spin state is favored and an antiferromagnetic configuration is stabilized. For the prototype LiFePO4, independent electron approximation is good enough to obtain the AFI ground state. Inclusion of additional correlation measures like Hubbard U simply amplifies the gap and therefore LiFePO4 can be preferably called as weakly coupled Mott insulator.

Unconventional Magnetism and Band Gap Formation in LiFePO4: Consequence of Polyanion Induced Non-planarity

PubMed Central

Jena, Ajit; Nanda, B. R. K.

2016-01-01

Oxygen plays a critical role in strongly correlated transition metal oxides as crystal field effect is one of the key factors that determine the degree of localization of the valence d/f states. Based on the localization, a set of conventional mechanisms such as Mott-Hubbard, Charge-transfer and Slater were formulated to explain the antiferromagnetic and insulating (AFI) phenomena in many of these correlated systems. From the case study on LiFePO4, through density-functional calculations, we demonstrate that none of these mechanisms are strictly applicable to explain the AFI behavior when the transition metal oxides have polyanions such as (PO4)3−. The symmetry-lowering of the metal-oxygen complex, to stabilize the polyanion, creates an asymmetric crystal field for d/f states. In LiFePO4 this field creates completely non-degenerate Fe-d states which, with negligible p-d and d-d covalent interactions, become atomically localized to ensure a gap at the Fermi level. Due to large exchange splitting, high spin state is favored and an antiferromagnetic configuration is stabilized. For the prototype LiFePO4, independent electron approximation is good enough to obtain the AFI ground state. Inclusion of additional correlation measures like Hubbard U simply amplifies the gap and therefore LiFePO4 can be preferably called as weakly coupled Mott insulator. PMID:26791249

CRITIC2: A program for real-space analysis of quantum chemical interactions in solids

NASA Astrophysics Data System (ADS)

Otero-de-la-Roza, A.; Johnson, Erin R.; Luaña, Víctor

2014-03-01

We present CRITIC2, a program for the analysis of quantum-mechanical atomic and molecular interactions in periodic solids. This code, a greatly improved version of the previous CRITIC program (Otero-de-la Roza et al., 2009), can: (i) find critical points of the electron density and related scalar fields such as the electron localization function (ELF), Laplacian, … (ii) integrate atomic properties in the framework of Bader’s Atoms-in-Molecules theory (QTAIM), (iii) visualize non-covalent interactions in crystals using the non-covalent interactions (NCI) index, (iv) generate relevant graphical representations including lines, planes, gradient paths, contour plots, atomic basins, … and (v) perform transformations between file formats describing scalar fields and crystal structures. CRITIC2 can interface with the output produced by a variety of electronic structure programs including WIEN2k, elk, PI, abinit, Quantum ESPRESSO, VASP, Gaussian, and, in general, any other code capable of writing the scalar field under study to a three-dimensional grid. CRITIC2 is parallelized, completely documented (including illustrative test cases) and publicly available under the GNU General Public License. Catalogue identifier: AECB_v2_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AECB_v2_0.html Program obtainable from: CPC Program Library, Queen’s University, Belfast, N. Ireland Licensing provisions: yes No. of lines in distributed program, including test data, etc.: 11686949 No. of bytes in distributed program, including test data, etc.: 337020731 Distribution format: tar.gz Programming language: Fortran 77 and 90. Computer: Workstations. Operating system: Unix, GNU/Linux. Has the code been vectorized or parallelized?: Shared-memory parallelization can be used for most tasks. Classification: 7.3. Catalogue identifier of previous version: AECB_v1_0 Journal reference of previous version: Comput. Phys. Comm. 180 (2009) 157 Nature of problem: Analysis of quantum-chemical interactions in periodic solids by means of atoms-in-molecules and related formalisms. Solution method: Critical point search using Newton’s algorithm, atomic basin integration using bisection, qtree and grid-based algorithms, diverse graphical representations and computation of the non-covalent interactions index on a three-dimensional grid. Additional comments: !!!!! The distribution file for this program is over 330 Mbytes and therefore is not delivered directly when download or Email is requested. Instead a html file giving details of how the program can be obtained is sent. !!!!! Running time: Variable, depending on the crystal and the source of the underlying scalar field.

Chemomechanical Polymers as Sensors and Actuators for Biological and Medicinal Applications

PubMed Central

Schneider, Hans-Jörg; Kato, Kazuaki; Strongin, Robert M.

2007-01-01

Changes in the chemical environment can trigger large motions in chemomechanical polymers. The unique feature of such intelligent materials, mostly in the form of hydrogels, is therefore, that they serve as sensors and actuators at the same time, and do not require any measuring devices, transducers or power supplies. Until recently the most often used of these materials responded to changes in pH. Chemists are now increasingly using supramolecular recognition sites in materials, which are covalently bound to the polymer backbone. This allows one to use a nearly unlimited variety of guest (or effector) compounds in the environment for a selective response by automatically triggered size changes. This is illustrated with non-covalent interactions of effectors comprising of metal ions, isomeric organic compounds, including enantiomers, nucleotides, aminoacids, and peptides. Two different effector molecules can induce motions as functions of their concentration, thus representing a logical AND gate. This concept is particularly fruitful with effector compounds such as peptides, which only trigger size changes if, e.g. copper ions are present in the surroundings. Another principle relies on the fast formation of covalent bonds between an effector and the chemomechanical polymer. The most promising application is the selective interaction of covalently fixed boronic acid residues with glucose, which renders itself not only for sensing, but eventually also for delivery of drugs such as insulin. The speed of the responses can significantly increase by increasing the surface to volume ratio of the polymer particles. Of particular interest is the sensitivity increase which can be reached by downsizing the particle volume. PMID:19606275

Double and Triple Si-H-M Bridge Bonds: Matrix Infrared Spectra and Theoretical Calculations for Reaction Products of Silane with Ti, Zr, and Hf Atoms.

PubMed

Xu, Bing; Shi, Peipei; Huang, Tengfei; Wang, Xuefeng; Andrews, Lester

2017-05-25

Infrared spectra of matrix isolated dibridged Si(μ-H) 2 MH 2 and tribridged Si(μ-H) 3 MH molecules (M = Zr and Hf) were observed following the laser-ablated metal atom reactions with SiH 4 during condensation in excess argon and neon, but only the latter species was observed with titanium. Assignments of the major vibrational modes, which included terminal MH, MH 2 and hydrogen bridge Si-H-M stretching modes, were confirmed by the appropriate SiD 4 isotopic shifts and density functional vibrational frequency calculations (B3LYP and BPW91). The Si-H-M hydrogen bridge bond is calculated as weak covalent interaction and compared with the C-H···M agostic interaction in terms of electron localization function (ELF) analysis and noncovalent interaction index (NCI) calculations. Furthermore, the different products of Ti, Zr, and Hf reactions with SiH 4 are discussed in detail.

Analysis of the binding interaction in uric acid - Human hemoglobin system by spectroscopic techniques

NASA Astrophysics Data System (ADS)

Makarska-Bialokoz, Magdalena

2017-05-01

The binding interaction between human hemoglobin and uric acid has been studied for the first time, by UV-vis absorption and steady-state, synchronous and three-dimensional fluorescence techniques. Characteristic effects observed for human hemoglobin intrinsic fluorescence during interaction with uric acid at neutral pH point at the formation of stacking non-covalent and non-fluorescent complexes. All the calculated parameters, the binding, fluorescence quenching and bimolecular quenching rate constants, as well as Förster resonance energy transfer parameters confirm the existence of static quenching. The results of synchronous fluorescence measurements indicate that the fluorescence quenching of human hemoglobin originates both from Trp and Tyr residues and that the addition of uric acid could significantly hinder the physiological functions of human hemoglobin.

Design, synthesis and DNA interactions of a chimera between a platinum complex and an IHF mimicking peptide.

PubMed

Rao, Harita; Damian, Mariana S; Alshiekh, Alak; Elmroth, Sofi K C; Diederichsen, Ulf

2015-12-28

Conjugation of metal complexes with peptide scaffolds possessing high DNA binding affinity has shown to modulate their biological activities and to enhance their interaction with DNA. In this work, a platinum complex/peptide chimera was synthesized based on a model of the Integration Host Factor (IHF), an architectural protein possessing sequence specific DNA binding and bending abilities through its interaction with a minor groove. The model peptide consists of a cyclic unit resembling the minor grove binding subdomain of IHF, a positively charged lysine dendrimer for electrostatic interactions with the DNA phosphate backbone and a flexible glycine linker tethering the two units. A norvaline derived artificial amino acid was designed to contain a dimethylethylenediamine as a bidentate platinum chelating unit, and introduced into the IHF mimicking peptides. The interaction of the chimeric peptides with various DNA sequences was studied by utilizing the following experiments: thermal melting studies, agarose gel electrophoresis for plasmid DNA unwinding experiments, and native and denaturing gel electrophoresis to visualize non-covalent and covalent peptide-DNA adducts, respectively. By incorporation of the platinum metal center within the model peptide mimicking IHF we have attempted to improve its specificity and DNA targeting ability, particularly towards those sequences containing adjacent guanine residues.

Energy and fuels from electrochemical interfaces

DOE PAGES

Stamenkovic, Vojislav R.; Strmcnik, Dusan; Lopes, Pietro P.; ...

2016-12-20

Advances in electrocatalysis at solid–liquid interfaces are vital for driving the technological innovations that are needed to deliver reliable, affordable and environmentally friendly energy. Here, in this paper, we highlight the key achievements in the development of new materials for efficient hydrogen and oxygen production in electrolysers and, in reverse, their use in fuel cells. A key issue addressed here is the degree to which the fundamental understanding of the synergy between covalent and non-covalent interactions can form the basis for any predictive ability in tailor-making real-world catalysts. Common descriptors such as the substrate–hydroxide binding energy and the interactions inmore » the double layer between hydroxide-oxides and H---OH are found to control individual parts of the hydrogen and oxygen electrochemistry that govern the efficiency of water-based energy conversion and storage systems. Lastly, links between aqueous- and organic-based environments are also established, encouraging the 'fuel cell' and 'battery' communities to move forward together.« less

Metal Based Synthetic Strategies and the Examination of Structure Determining Factors in Alkaline Earth Metal Compounds

NASA Astrophysics Data System (ADS)

Takahashi, Yuriko

Last decades have witnessed a large expansion of the organometallic heavier alkaline earth metal species. However, continued growth of this promising area of chemistry has been slowed by severe restrictions and limitations in viable synthetic methodologies leading to difficulties in preparing and characterizing the target compounds. There is clearly a need for the further development of synthetic methodologies and detailed structure function analysis that will promote the further advancement of organoalkaline earth metal chemistry in applications as diverse as materials chemistry and catalysis. This thesis work greatly extends the synthetic options currently available towards organoalkaline earth metal species by introducing redox transmetallation protolysis (RTP), a reaction based on the readily available Ph3Bi as a non-toxic transmetallation agent. Based on a straightforward one-pot procedure and work-up, Ph3Bi based RTP presents a powerful synthetic alternative for the facile preparation of a large variety of heavy alkaline earth metal compounds. The second part of the thesis explores the effect of secondary non covalent interactions on the coordination chemistry as well as thermal properties of a series of novel alkali, alkaline earth, rare earth as well as heterobimetallic alkali/alkaline earth fluoroalkoxides. These compounds showcase the significance of non-covalent M···F-C and agostic interactions on metal stabilization and structural features, providing critical input on ligand design for the design of advanced metal organic vapor deposition (MOCVD) precursor materials. This work also showcases the impact of M···F-C interactions over M---co-ligand coordination, a critical precursor design element as well.

Crystal Structure of the Dithiol Oxidase DsbA Enzyme from Proteus Mirabilis Bound Non-covalently to an Active Site Peptide Ligand

PubMed Central

Kurth, Fabian; Duprez, Wilko; Premkumar, Lakshmanane; Schembri, Mark A.; Fairlie, David P.; Martin, Jennifer L.

2014-01-01

The disulfide bond forming DsbA enzymes and their DsbB interaction partners are attractive targets for development of antivirulence drugs because both are essential for virulence factor assembly in Gram-negative pathogens. Here we characterize PmDsbA from Proteus mirabilis, a bacterial pathogen increasingly associated with multidrug resistance. PmDsbA exhibits the characteristic properties of a DsbA, including an oxidizing potential, destabilizing disulfide, acidic active site cysteine, and dithiol oxidase catalytic activity. We evaluated a peptide, PWATCDS, derived from the partner protein DsbB and showed by thermal shift and isothermal titration calorimetry that it binds to PmDsbA. The crystal structures of PmDsbA, and the active site variant PmDsbAC30S were determined to high resolution. Analysis of these structures allows categorization of PmDsbA into the DsbA class exemplified by the archetypal Escherichia coli DsbA enzyme. We also present a crystal structure of PmDsbAC30S in complex with the peptide PWATCDS. The structure shows that the peptide binds non-covalently to the active site CXXC motif, the cis-Pro loop, and the hydrophobic groove adjacent to the active site of the enzyme. This high-resolution structural data provides a critical advance for future structure-based design of non-covalent peptidomimetic inhibitors. Such inhibitors would represent an entirely new antibacterial class that work by switching off the DSB virulence assembly machinery. PMID:24831013

Dodecylamine functionalization of carbon nanotubes to improve dispersion, thermal and mechanical properties of polyethylene based nanocomposites

NASA Astrophysics Data System (ADS)

Ferreira, F. V.; Franceschi, W.; Menezes, B. R. C.; Brito, F. S.; Lozano, K.; Coutinho, A. R.; Cividanes, L. S.; Thim, G. P.

2017-07-01

This study presents the effect of dodecylamine (DDA) functionalization of carbon nanotubes (CNTs) on the thermo-physical and mechanical properties of high-density polyethylene (HDPE) based composites. Here, we showed that the functionalization with DDA improved the dispersion of the CNTs as well as the interfacial adhesion with the HDPE matrix via non-covalent interactions. The better dispersion and interaction of CNT in the HDPE matrix as a function of the surface chemistry was correlated with the improved thermo-physical and mechanical properties.

Hydrogels with covalent and noncovalent crosslinks

NASA Technical Reports Server (NTRS)

Kilck, Kristi L. (Inventor); Yamaguchi, Nori (Inventor)

2013-01-01

A method for targeted delivery of therapeutic compounds from hydrogels is presented. The method involves administering to a cell a hydrogel in which a therapeutic compound is noncovalently bound to heparin. The hydrogel may contain covalent and non-covalent crosslinks.

Covalent binding of C3b to tetanus toxin: influence on uptake/internalization of antigen by antigen-specific and non-specific B cells.

PubMed Central

Villiers, M B; Villiers, C L; Jacquier-Sarlin, M R; Gabert, F M; Journet, A M; Colomb, M G

1996-01-01

Antigen opsonization by the C3b fragment of complement is a significant event in the modulation of cell-mediated immune response, but its mechanism is still largely unknown. The structural characteristics of C3b allow it to act as a bifunctional ligand between antigen and cells via their membrane C3b receptors. It was thus of interest to study the influence of the covalent link between C3b and antigen on the fixation and internalization of this antigen by antigen-presenting cells. Tetanus toxin (TT) was used as antigen, either free or covalently linked to C3b (TT-C3b). The antigen-presenting cells were TT-specific (4.2) or non-specific (BL15) Epstein-Barr virus (EBV)-transformed B cells. C3b was found to play an important role in antigen fixation and internalization by both antigen-specific and antigen non-specific cells. Covalent binding of C3b on TT (1) permitted fixation and internalization of this antigen by non-specific cells via their complement receptors; (2) enhanced antigen fixation and resulted in cross-linking between membrane immunoglobulins and complement receptors on antigen-specific cells. The consequences of covalent C3b binding to TT were analysed using antigen-specific and antigen-nonspecific cells. In both cases, a net increase in antigen fixation was observed. At the intracellular level, covalent C3b binding to TT resulted in a large TT incorporation in endosomes of nonspecific cells, similar to that observed in antigen-specific cells. Thus, C3b covalently linked to antigen enlarges the array of B-cell types capable of presenting antigen, including non-specific cells. Images Figure 2 PMID:8958046

Modular assembly of chimeric phi29 packaging RNAs that support DNA packaging.

PubMed

Fang, Yun; Shu, Dan; Xiao, Feng; Guo, Peixuan; Qin, Peter Z

2008-08-08

The bacteriophage phi29 DNA packaging motor is a protein/RNA complex that can produce strong force to condense the linear-double-stranded DNA genome into a pre-formed protein capsid. The RNA component, called the packaging RNA (pRNA), utilizes magnesium-dependent inter-molecular base-pairing interactions to form ring-shaped complexes. The pRNA is a class of non-coding RNA, interacting with phi29 motor proteins to enable DNA packaging. Here, we report a two-piece chimeric pRNA construct that is fully competent in interacting with partner pRNA to form ring-shaped complexes, in packaging DNA via the motor, and in assembling infectious phi29 virions in vitro. This is the first example of a fully functional pRNA assembled using two non-covalently interacting fragments. The results support the notion of modular pRNA architecture in the phi29 packaging motor.

Modular assembly of chimeric phi29 packaging RNAs that support DNA packaging

PubMed Central

Fang, Yun; Shu, Dan; Xiao, Feng; Guo, Peixuan; Qin, Peter Z.

2008-01-01

The bacteriophage phi29 DNA packaging motor is a protein/RNA complex that can produce strong force to condense the linear-double stranded DNA genome into a pre-formed protein capsid. The RNA component, called the packaging RNA (pRNA), utilizes magnesium-dependent intermolecular base-pairing interactions to form ring-shaped complexes. The pRNA is a class of non-coding RNA, interacting with phi29 motor proteins to enable DNA packaging. Here, we report a 2-piece chimeric pRNA construct that is fully competent in interacting with partner pRNA to form ring-shaped complexes, in packaging DNA via the motor, and in assembling infectious phi29 virions in vitro. This is the first example of a fully functional pRNA assembled using two non-covalently interacting fragments. The results support the notion of modular pRNA architecture in the phi29 packaging motor. PMID:18514064

Tough Adhesives for Diverse Wet Surfaces

PubMed Central

Li, J.; Celiz, A. D.; Yang, J.; Yang, Q.; Wamala, I.; Whyte, W.; Seo, B. R.; Vasilyev, N. V.; Vlassak, J. J.; Suo, Z.; Mooney, D. J.

2018-01-01

Adhesion to wet and dynamic surfaces, including biological tissues, is important in many fields, but has proven extremely challenging. Existing adhesives are either cytotoxic, adhere weakly to tissues, or cannot be utilized in wet environments. We report a bio-inspired design for adhesives consisting of two layers: an adhesive surface and a dissipative matrix. The former adheres to the substrate by electrostatic interactions, covalent bonds, and physical interpenetration. The latter amplifies energy dissipation through hysteresis. The two layers synergistically lead to higher adhesion energy on wet surfaces than existing adhesives. Adhesion occurs within minutes, independent of blood exposure, and compatible with in vivo dynamic movements. This family of adhesives may be useful in many areas of application, including tissue adhesives, wound dressings and tissue repair. PMID:28751604

Supercooling of Hydrogen on Template Materials to Deterministically Seed Ignition-Quality Solid Fuel Layers

DOE PAGES

Shin, S. J.; Zepeda-Ruiz, L. A.; Lee, J. R. I.; ...

2016-09-01

In this study, we explored templating effects of various materials for hydrogen (H 2 and D 2) solidification by measuring the degree of supercooling required for liquid hydrogen to solidify below each triple point. The results show high supercooling (>100 mK) for most metallic, covalent, and ionic solids, and low supercooling (<100 mK) for van der Waals (vdW) solids. We attribute the low supercooling of vdW solids to the weak interaction of the substrate and hydrogen. Highly ordered pyrolytic graphite showed the lowest supercooling among materials that are solid at room temperature, but did not exhibit a templating effect withinmore » a fill-tube and capsule assembly.« less

Spectroscopic study of proflavine adsorption on the carbon nanotube surface.

PubMed

Buchelnikov, Anatoly S; Dovbeshko, Galina I; Voronin, Dmitry P; Trachevsky, Vladimir V; Kostjukov, Viktor V; Evstigneev, Maxim P

2014-01-01

Despite the fact that non-covalent interactions between various aromatic compounds and carbon nanotubes are being extensively investigated now, there is still a lack of understanding about the nature of such interactions. The present paper sheds light on one of the possible mechanisms of interaction between the typical aromatic dye proflavine and the carbon nanotube surface, namely, π-stacking between aromatic rings of these compounds. To investigate such a complexation, a qualitative analysis was performed by means of ultraviolet visible, infrared, and nuclear magnetic resonance spectroscopy. The data obtained suggest that π-stacking brings the major contribution to the stabilization of the complex between proflavine and the carbon nanotube.

Protein-Protein Interaction Site Predictions with Three-Dimensional Probability Distributions of Interacting Atoms on Protein Surfaces

PubMed Central

Chen, Ching-Tai; Peng, Hung-Pin; Jian, Jhih-Wei; Tsai, Keng-Chang; Chang, Jeng-Yih; Yang, Ei-Wen; Chen, Jun-Bo; Ho, Shinn-Ying; Hsu, Wen-Lian; Yang, An-Suei

2012-01-01

Protein-protein interactions are key to many biological processes. Computational methodologies devised to predict protein-protein interaction (PPI) sites on protein surfaces are important tools in providing insights into the biological functions of proteins and in developing therapeutics targeting the protein-protein interaction sites. One of the general features of PPI sites is that the core regions from the two interacting protein surfaces are complementary to each other, similar to the interior of proteins in packing density and in the physicochemical nature of the amino acid composition. In this work, we simulated the physicochemical complementarities by constructing three-dimensional probability density maps of non-covalent interacting atoms on the protein surfaces. The interacting probabilities were derived from the interior of known structures. Machine learning algorithms were applied to learn the characteristic patterns of the probability density maps specific to the PPI sites. The trained predictors for PPI sites were cross-validated with the training cases (consisting of 432 proteins) and were tested on an independent dataset (consisting of 142 proteins). The residue-based Matthews correlation coefficient for the independent test set was 0.423; the accuracy, precision, sensitivity, specificity were 0.753, 0.519, 0.677, and 0.779 respectively. The benchmark results indicate that the optimized machine learning models are among the best predictors in identifying PPI sites on protein surfaces. In particular, the PPI site prediction accuracy increases with increasing size of the PPI site and with increasing hydrophobicity in amino acid composition of the PPI interface; the core interface regions are more likely to be recognized with high prediction confidence. The results indicate that the physicochemical complementarity patterns on protein surfaces are important determinants in PPIs, and a substantial portion of the PPI sites can be predicted correctly with the physicochemical complementarity features based on the non-covalent interaction data derived from protein interiors. PMID:22701576

New coordination features; a bridging pyridine and the forced shortest non-covalent distance between two CO3 2– species† †Electronic supplementary information (ESI) available: Mass Spectrometry and BVS analysis CCDC 996546–996548. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4sc02491e Click here for additional data file. Click here for additional data file.

PubMed Central

Velasco, V.; Aguilà, D.; Barrios, L. A.; Borilovic, I.; Roubeau, O.; Ribas-Ariño, J.; Fumanal, M.; Teat, S. J.

2015-01-01

The aerobic reaction of the multidentate ligand 2,6-bis-(3-oxo-3-(2-hydroxyphenyl)-propionyl)-pyridine, H4L, with Co(ii) salts in strong basic conditions produces the clusters [Co4(L)2(OH)(py)7]NO3 (1) and [Co8Na4(L)4(OH)2(CO3)2(py)10](BF4)2 (2). Analysis of their structure unveils unusual coordination features including a very rare bridging pyridine ligand or two trapped carbonate anions within one coordination cage, forced to stay at an extremely close distance (d O···O = 1.946 Å). This unprecedented non-bonding proximity represents a meeting point between long covalent interactions and “intermolecular” contacts. These original motifs have been analysed here through DFT calculations, which have yielded interaction energies and the reduced repulsion energy experimented by both CO3 2– anions when located in close proximity inside the coordination cage. PMID:28616127

Non-covalently anchored multi-walled carbon nanotubes with hexa-decafluorinated zinc phthalocyanine as ppb level chemiresistive chlorine sensor

NASA Astrophysics Data System (ADS)

Sharma, Anshul Kumar; Mahajan, Aman; Bedi, R. K.; Kumar, Subodh; Debnath, A. K.; Aswal, D. K.

2018-01-01

A cost effective solution assembly method has been explored for preparing zinc(II)1,2,3,4,8,9,10,11,15,16,17,18,22,23,24,25-hexa-decafluoro-29H,31H-phthalocyanine/multi-walled carbon nanotubes (F16ZnPc/MWCNTs-COOH) hybrid. Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, transmission electron microscopy (TEM) and field emission scanning electron microscopy (FE-SEM) investigations confirm the non-covalent anchoring of F16ZnPc onto MWCNTs-COOH through п-п stacking interactions. Further, a highly sensitive and selective chemiresistive Cl2 sensor has been fabricated using F16ZnPc/MWCNTs-COOH hybrid. The response of sensor is found to be 21.28% for 2 ppm of Cl2 with a response time of 14 s and theoretical detection limit of the sensor is found down to 0.06 ppb. The improved Cl2 sensing characteristics of hybrid are found to be originated from the synergetic interaction between F16ZnPc and MWCNTs-COOH. The underlying mechanism for improved gas sensing performance of F16ZnPc/MWCNTs-COOH sensor towards Cl2 has been explained using Raman, X-ray photoelectron spectroscopy (XPS) and electrochemical impedance spectroscopy (EIS) studies.

Surface functionalization of liposomes with proteins and carbohydrates for use in anti-cancer applications

NASA Astrophysics Data System (ADS)

Platt, Virginia M.

Liposomes can be used to exploit the altered biology of cancer thereby increasing delivery of liposome-associated anti-cancer drugs. In this dissertation, I explore methods that utilize the unique cancer expression of the polymeric glycosaminoglycan hyaluronan (HA) and the HA receptor CD44 to target liposomes to tumors, using liposomes functionalized with proteins or oligosaccharides on their surface. To make it easier to prepare protein-functionalized liposomes, a non-covalent protein/liposome association method based upon metal chelation/his 6 interaction was devised and characterized. I evaluated non-covalent attachment of the prodrug converting enzyme yeast cytosine deaminase, the far-red fluorescent protein mKate, two antigens ovalbumin and the membrane proximal region of an HIV GAG and hyaluronidase, a HA-degrading enzyme. In Chapter 2, I describe the synthesis of hyaluronan-oligosaccharide (HA-O) lipid conjugates and their incorporation into liposomes to target CD44-overexpressing cancer cells. HA-O ligands of defined-length, up to 10 monosaccharides, were attached to lipids via various linkers by reductive amination. The HA-lipids were easily incorporated into liposomes but did not mediate binding of liposomes to CD44 overexpressing cells. In Chapter 3, I evaluate the capacity of tris-NTA-Ni-lipids incorporated within a liposome bilayer to associate with his6-tagged proteins. Tris-NTA-lipids of differing structures and avidities were used to associate yeast cytosine deaminase and mKate to the surface of liposomes. Two tris-NTA-lipids and a mono-NTA lipid associated his-tagged proteins to a 1:1 molar ratio in solution. The proteins remained active while associated with the liposome surface. When challenged in vitro with fetal calf serum, tris-NTA-containing liposomes retained his-tagged proteins longer than mono-NTA. However, the tris-NTA/his6 interaction was found to be in a dynamic state; free yeast cytosine deaminase rapidly competed with pre-bound mKate for NTA occupancy. In the circulation of mice, his-tagged proteins associated with NTA-liposomes were cleared as rapidly as free protein. In Chapter 4, I study the effect of NTA/his-tag avidity on immune response when NTA-containing liposomes are used as non-covalent, particulate adjuvants. Two his-tagged antigens, ovalbumin and the membrane proximal portion of HIV Gag, were associated with NTA-liposomes containing either mono-NTA or tris-NTA lipids. The immune response to each antigen was compared to control adjuvant formulations in which antigens were admixed with or covalently-conjugated to liposomes. The weaker antigen, the HIV Gag peptide, induced a stronger immune response when associated with NTA-containing liposomes than when admixed with liposomes. Ovalbumin preparations in which the protein was admixed with particles or non-covalently associated with NTA-liposomes elicited a higher immune response than free ovalbumin or ovalbumin admixed with the control adjuvant alum. For both antigens, NTA-liposome responses were less than the response to antigens covalently linked to the liposome. In Chapter 5, I evaluate the potential for hyaluronidase to target conjugated liposomes to tumors or improve liposome motility within hyaluronan-rich tumors. Ovine hyaluronidase was modified using iminothiolane to introduce sulfhydryl groups into the enzyme. The enzyme was attached to liposomes via maleimide lipids or to maleimidehis10 in order to engineer non-covalent NTA-liposome association. Enzyme activity was retained after sulfhydryl addition and after attachment to liposomes. Liposome-conjugated hyaluronidase degraded an HA-gel at the same rate as admixed liposomes. When hyaluronidase-liposomes were injected intravenously in mice, the hyaluronidase conjugated-liposomes experienced faster clearance than control liposomes but slower clearance than free hyaluronidase. As a whole, these studies may help develop universal methods for a range of protein therapeutics and anti-cancer targeting agents.

Electrostatic study of Alanine mutational effects on transcription: application to GATA-3:DNA interaction complex.

PubMed

El-Assaad, Atlal; Dawy, Zaher; Nemer, Georges

2015-01-01

Protein-DNA interaction is of fundamental importance in molecular biology, playing roles in functions as diverse as DNA transcription, DNA structure formation, and DNA repair. Protein-DNA association is also important in medicine; understanding Protein-DNA binding kinetics can assist in identifying disease root causes which can contribute to drug development. In this perspective, this work focuses on the transcription process by the GATA Transcription Factor (TF). GATA TF binds to DNA promoter region represented by `G,A,T,A' nucleotides sequence, and initiates transcription of target genes. When proper regulation fails due to some mutations on the GATA TF protein sequence or on the DNA promoter sequence (weak promoter), deregulation of the target genes might lead to various disorders. In this study, we aim to understand the electrostatic mechanism behind GATA TF and DNA promoter interactions, in order to predict Protein-DNA binding in the presence of mutations, while elaborating on non-covalent binding kinetics. To generate a family of mutants for the GATA:DNA complex, we replaced every charged amino acid, one at a time, with a neutral amino acid like Alanine (Ala). We then applied Poisson-Boltzmann electrostatic calculations feeding into free energy calculations, for each mutation. These calculations delineate the contribution to binding from each Ala-replaced amino acid in the GATA:DNA interaction. After analyzing the obtained data in view of a two-step model, we are able to identify potential key amino acids in binding. Finally, we applied the model to GATA-3:DNA (crystal structure with PDB-ID: 3DFV) binding complex and validated it against experimental results from the literature.

Λ N → NN EFT potentials and hypertriton non-mesonic weak decay

NASA Astrophysics Data System (ADS)

Pérez-Obiol, Axel; Entem, David R.; Nogga, Andreas

2018-05-01

The potential for the Λ N → NN weak transition, the main responsible for the non-mesonic weak decay of hypernuclei, has been developed within the framework of effective field theory (EFT) up to next-to-leading order (NLO). The leading order (LO) and NLO contributions have been calculated in both momentum and coordinate space, and have been organised into the different operators which mediate the N → NN transition. We compare the ranges of the one-meson and two-pion exchanges for each operator. The non-mesonic weak decay of the hypertriton has been computed within the plane-wave approximation using the LO weak potential and modern strong EFT NN potentials. Formally, two methods to calculate the final state interactions among the decay products are presented. We briefly comment on the calculation of the {}{{Λ }}{}3H{\\to }3 He+{π }- mesonic weak decay.

Covalent docking of selected boron-based serine beta-lactamase inhibitors

NASA Astrophysics Data System (ADS)

Sgrignani, Jacopo; Novati, Beatrice; Colombo, Giorgio; Grazioso, Giovanni

2015-05-01

AmpC β-lactamase is a hydrolytic enzyme conferring resistance to β-lactam antibiotics in multiple Gram-negative bacteria. Therefore, identification of non-β-lactam compounds able to inhibit the enzyme is crucial for the development of novel antibacterial therapies. In general, AmpC inhibitors have to engage the highly solvent-exposed catalytic site of the enzyme. Therefore, understanding the implications of ligand-protein induced-fit and water-mediated interactions behind the inhibitor-enzyme recognition process is fundamental for undertaking structure-based drug design process. Here, we focus on boronic acids, a promising class of beta-lactamase covalent inhibitors. First, we optimized a docking protocol able to reproduce the experimentally determined binding mode of AmpC inhibitors bearing a boronic group. This goal was pursued (1) performing rigid and flexible docking calculations aiming to establish the role of the side chain conformations; and (2) investigating the role of specific water molecules in shaping the enzyme active site and mediating ligand protein interactions. Our calculations showed that some water molecules, conserved in the majority of the considered X-ray structures, are needed to correctly predict the binding pose of known covalent AmpC inhibitors. On this basis, we formalized our findings in a docking and scoring protocol that could be useful for the structure-based design of new boronic acid AmpC inhibitors.

Characterization and kinetics of surface functionalization and binding of biologically and chemically significant molecules

NASA Astrophysics Data System (ADS)

Steiner, Rachel

The purpose of this project is to investigate intermolecular interactions of organic molecular assemblies. By understanding the structure and physical interactions in these assemblies, we gain insights into practical applications for nanoscale systems built upon these surface structures. It is possible for organic chemists to create many forms of modified organic molecules, functionalizing them with specific reactive end groups. Through surface functionalization, enabling covalent or highly associative binding, it is possible to create ordered molecular assemblies of these molecules. Scientists can study the nature of this structure and the intermolecular interactions through spectroscopic, optical, and scattering experiments. To understand the self-assembly process in molecular systems, we preliminarily created monolayer films on silica substrates with a variety of organic molecules. In particular, we functionalized silica substrates with hydroxyl groups and covalently bound acid chloride functionalized aromatic compounds, with and without an underlying adhesion layer of 3-aminopropyltriethoxysilane. We characterized the monolayer assemblies with ellipsometry, UV-vis absorption spectroscopy, FTIR spectroscopy, and fluorescence/photoemission spectroscopy, obtaining a quantitative measure of the molecular surface coverage. In order to understand the nature of these molecular assemblies, we also pursued an in-depth kinetic study to control and optimize the monolayer formation process. Through use of UV-vis spectroscopy, we determined that the monolayer formation can best be modeled with diffusion-limited Langmuir kinetics. Specifically, we concluded that for anthracene acid chloride in dichloromethane the average diffusion coefficient was 1.6x10-7 cm2/sec. Additionally, we find we are able to achieve surface coverages of approximately 2x1014 molecules/cm2. Having established the ability to create ordered molecular assemblies, through surface functionalization, enabling covalent or highly associative binding, we continued to explore the field of molecular assemblies by studying the binding and structure of molecules to carbon nanostructures. Previous studies have shown that alkyl side chains and aromatic compounds, such as pyrene, will bind non-covalently to the sidewalls of carbon nanotubes through pi-pi interactions. We explored functionalization of carbon nanotubes and graphene by using microscopy to examine the adsorption of biomolecules onto nanotube sidewalls and graphene.

The Role of Wheat and Egg Constituents in the Formation of a Covalent and Non-covalent Protein Network in Fresh and Cooked Egg Noodles.

PubMed

Lambrecht, Marlies A; Rombouts, Ine; Nivelle, Mieke A; Delcour, Jan A

2017-01-01

Noodles of constant protein content and flour-to-egg protein ratio were made with whole egg, egg white, or egg yolk. The optimal cooking time, water absorption, and cooking loss of salted whole egg noodles was respectively lower and higher than of egg white and egg yolk noodles. However, cooked whole egg noodles showed the best Kieffer-rig extensibility. Differences in noodle properties were linked to protein network formation. Disulfide bonds in whole egg noodles developed faster and to a larger extent during cooking than in egg yolk noodles but slower and to a lower extent than in egg white noodles. The balance between the rate of protein cross-linking and starch swelling determines cooked noodle properties. Ionic and hydrophobic protein interactions increase the optimum cooking time and total work in Kieffer-rig extensibility testing of fresh noodles. Hydrogen bonds and covalent cross-links are probably the main determinants of the extensibility of cooked noodles. © 2016 Institute of Food Technologists®.

Drug allergy

PubMed Central

Warrington, Richard

2012-01-01

Allergic drug reactions occur when a drug, usually a low molecular weight molecule, has the ability to stimulate an immune response. This can be done in one of two ways. The first is by binding covalently to a self-protein, to produce a haptenated molecule that can be processed and presented to the adaptive immune system to induce an immune response. Sometimes the drug itself cannot do this but a reactive breakdown product of the drug is able to bind covalently to the requisite self-protein or peptide. The second way in which drugs can stimulate an immune response is by binding non-covalently to antigen presenting or antigen recognition molecules such as the major histocompatibility complex (MHC) or the T cell receptor. This is known as the p-I or pharmacological interaction hypothesis. The drug binding in this situation is reversible and stimulation of the response may occur on first exposure, not requiring previous sensitization. There is probably a dependence on the presence of certain MHC alleles and T cell receptor structures for this type of reaction to occur. PMID:22922763

Air and moisture stable covalently-bonded tin(ii) coordination polymers.

PubMed

de Lima, G M; Walton, R I; Clarkson, G J; Bitzer, R S; Ardisson, J D

2018-06-05

Four covalently-bonded tin(ii) coordination polymers, (1)-(4), were hydrothermally prepared in aqueous alkaline media by the reactions of SnSO4 with 1,2,4,5-benzenetetracarboxylic acid (1), 1,3,5-benzenetricarboxylic acid (2), 4-hydroxypyridine-2,6-dicarboxylic acid (3), and 1,3,5-cyclohexanetricarboxylic acid (4). All products were structurally authenticated by single-crystal X-ray diffraction, and the number of different tin centres and their oxidation states were confirmed by 119Sn Mössbauer spectroscopy. In addition, the comparison between experimental and simulated X-ray powder diffraction patterns confirmed the authenticity of the samples. Our crystallographic results for (1)-(4) show that the Sn(ii) centres are tetracoordinated and exhibit distorted disphenoidal geometries, corroborating the presence of one stereochemically active lone electron pair at each metal site. Products (1) and (2) display bi-dimensional polymeric structures, (3) exhibits a one-dimensional architecture, whereas (4) shows a remarkable three-dimensional coordination network. Hirshfeld surface and supramolecular analyses for the repeating units of (1)-(4) were also performed in order to identify structurally important non-covalent interactions.

NMR insight into myosin-binding subunit coiled-coil structure reveals binding interface with protein kinase G-Iα leucine zipper in vascular function.

PubMed

Sharma, Alok K; Birrane, Gabriel; Anklin, Clemens; Rigby, Alan C; Alper, Seth L

2017-04-28

Nitrovasodilators relax vascular smooth-muscle cells in part by modulating the interaction of the C-terminal coiled-coil domain (CC) and/or the leucine zipper (LZ) domain of the myosin light-chain phosphatase component, myosin-binding subunit (MBS), with the N-terminal LZ domain of protein kinase G (PKG)-Iα. Despite the importance of vasodilation in cardiovascular homeostasis and therapy, our structural understanding of the MBS CC interaction with LZ PKG-1α has remained limited. Here, we report the 3D NMR solution structure of homodimeric CC MBS in which amino acids 932-967 form a coiled-coil of two monomeric α-helices in parallel orientation. We found that the structure is stabilized by non-covalent interactions, with dominant contributions from hydrophobic residues at a and d heptad positions. Using NMR chemical-shift perturbation (CSP) analysis, we identified a subset of hydrophobic and charged residues of CC MBS (localized within and adjacent to the C-terminal region) contributing to the dimer-dimer interaction interface between homodimeric CC MBS and homodimeric LZ PKG-Iα. 15 N backbone relaxation NMR revealed the dynamic features of the CC MBS interface residues identified by NMR CSP. Paramagnetic relaxation enhancement- and CSP-NMR-guided HADDOCK modeling of the dimer-dimer interface of the heterotetrameric complex exhibits the involvement of non-covalent intermolecular interactions that are localized within and adjacent to the C-terminal regions of each homodimer. These results deepen our understanding of the binding restraints of this CC MBS·LZ PKG-Iα low-affinity heterotetrameric complex and allow reevaluation of the role(s) of myosin light-chain phosphatase partner polypeptides in regulation of vascular smooth-muscle cell contractility. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Variation of the chemical reactivity of Thermus thermophilus HB8 ribosomal proteins as a function of pH.

PubMed

Running, William E; Reilly, James P

2010-10-01

Ribosomes occupy a central position in cellular metabolism, converting stored genetic information into active cellular machinery. Ribosomal proteins modulate both the intrinsic function of the ribosome and its interaction with other cellular complexes, such as chaperonins or the signal recognition particle. Chemical modification of proteins combined with mass spectrometric detection of the extent and position of covalent modifications is a rapid, sensitive method for the study of protein structure and flexibility. By altering the pH of the solution, we have induced non-denaturing changes in the structure of bacterial ribosomal proteins and detected these conformational changes by covalent labeling. Changes in ribosomal protein modification across a pH range from 6.6 to 8.3 are unique to each protein, and correlate with their structural environment in the ribosome. Lysine residues whose extent of modification increases as a function of increasing pH are on the surface of proteins, but in close proximity either to glutamate and aspartate residues, or to rRNA backbone phosphates. Increasing pH disrupts tertiary and quaternary interactions mediated by hydrogen bonding or ionic interactions, and regions of protein structure whose conformations are sensitive to these changes are of potential importance in modulating the flexibility of the ribosome or its interaction with other cellular complexes.

A novel model of interaction between high frequency electromagnetic non-ionizing fields and microtubules viewed as coupled two-degrees of freedom harmonic oscillators.

PubMed

Caligiuri, Luigi Maxmilian

2015-01-01

The question regarding the potential biological and adverse health effects of non-ionizing electromagnetic fields on living organisms is of primary importance in biophysics and medicine. Despite the several experimental evidences showing such occurrence in a wide frequency range from extremely low frequency to microwaves, a definitive theoretical model able to explain a possible mechanism of interaction between electromagnetic fields and living matter, especially in the case of weak and very weak intensities, is still missing. In this paper it has been suggested a possible mechanism of interaction involving the resonant absorption of electromagnetic radiation by microtubules. To this aim these have been modeled as non-dissipative forced harmonic oscillators characterized by two coupled "macroscopic" degrees of freedom, respectively describing longitudinal and transversal vibrations induced by the electromagnetic field. We have shown that the proposed model, although at a preliminary stage, is able to explain the ability of even weak electromagnetic radiating electromagnetic fields to transfer high quantities of energy to living systems by means of a resonant mechanism, so capable to easily damage microtubules structure.

Quantifying covalent interactions with resonant inelastic soft X-ray scattering: Case study of Ni 2+ aqua complex

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

Kunnus, K.; Josefsson, I.; Schreck, S.

We analyze the effects of covalent interactions in Ni 2p3d resonant inelastic X-ray scattering (RIXS) spectra from aqueous Ni 2+ ions and find that the relative RIXS intensities of ligand-to-metal charge-transfer final states with respect to the ligand-field final states reflect the covalent mixing between Ni 3d and water orbitals. Specifically, the experimental intensity ratio at the Ni L 3-edge allows to determine that the Ni 3d orbitals have on average 5.5% of water character. Here, we propose that 2p3d RIXS at the Ni L 3-edge can be utilized to quantify covalency in Ni complexes without the use of externalmore » references or simulations.« less

Quantifying covalent interactions with resonant inelastic soft X-ray scattering: Case study of Ni 2+ aqua complex

DOE PAGES

Kunnus, K.; Josefsson, I.; Schreck, S.; ...

2016-12-23

We analyze the effects of covalent interactions in Ni 2p3d resonant inelastic X-ray scattering (RIXS) spectra from aqueous Ni 2+ ions and find that the relative RIXS intensities of ligand-to-metal charge-transfer final states with respect to the ligand-field final states reflect the covalent mixing between Ni 3d and water orbitals. Specifically, the experimental intensity ratio at the Ni L 3-edge allows to determine that the Ni 3d orbitals have on average 5.5% of water character. Here, we propose that 2p3d RIXS at the Ni L 3-edge can be utilized to quantify covalency in Ni complexes without the use of externalmore » references or simulations.« less

Ensemble-based ADME-Tox profiling and virtual screening for the discovery of new inhibitors of the Leishmania mexicana cysteine protease CPB2.8ΔCTE.

PubMed

Scala, Angela; Rescifina, Antonio; Micale, Nicola; Piperno, Anna; Schirmeister, Tanja; Maes, Louis; Grassi, Giovanni

2018-02-01

In an effort to identify novel molecular warheads able to inhibit Leishmania mexicana cysteine protease CPB2.8ΔCTE, fused benzo[b]thiophenes and β,β'-triketones emerged as covalent inhibitors binding the active site cysteine residue. Enzymatic screening showed a moderate-to-excellent activity (12%-90% inhibition of the target enzyme at 20 μm). The most promising compounds were selected for further profiling including in vitro cell-based assays and docking studies. Computational data suggest that benzo[b]thiophenes act immediately as non-covalent inhibitors and then as irreversible covalent inhibitors, whereas a reversible covalent mechanism emerged for the 1,3,3'-triketones with a Y-topology. Based on the predicted physicochemical and ADME-Tox properties, compound 2b has been identified as a new drug-like, non-mutagen, non-carcinogen, and non-neurotoxic lead candidate. © 2017 John Wiley & Sons A/S.

Supramolecular features of 2-(chlorophenyl)-3-[(chlorobenzylidene)-amino]-2,3-dihydroquinazolin-4(1H)-ones: A combined experimental and computational study

NASA Astrophysics Data System (ADS)

Mandal, Arkalekha; Patel, Bhisma K.

2018-03-01

The molecular structures of two isomeric 2-(chlorophenyl)-3-[(chlorobenzylidene)-amino] substituted 2,3-dihydroquinazolin-4(1H)-ones have been determined via single crystal XRD. Both isomers contain chloro substitutions on each of the phenyl rings and as a result a broad spectrum of halogen mediated weak interactions are viable in their crystal structures. The crystal packing of these compounds is stabilized by strong N-H⋯O hydrogen bond and various weak, non-classical hydrogen bonds acting synergistically. Both the molecules contain a chiral center and the weak interactions observed in them are either chiral self-discriminatory or chiral self-recognizing in nature. The weak interactions and spectral features of the compounds have been studied through experimental as well as computational methods including DFT, MEP, NBO and Hiresfeld surface analyses. In addition, the effect of different weak interactions to dictate either chiral self-recognition or self-discrimination in crystal packing has been elucidated.

Application of the Covalent Bond Classification Method for the Teaching of Inorganic Chemistry

ERIC Educational Resources Information Center

Green, Malcolm L. H.; Parkin, Gerard

2014-01-01

The Covalent Bond Classification (CBC) method provides a means to classify covalent molecules according to the number and types of bonds that surround an atom of interest. This approach is based on an elementary molecular orbital analysis of the bonding involving the central atom (M), with the various interactions being classified according to the…

Theoretical Insights into Monometallofullerene Th@C76: Strong Covalent Interaction between Thorium and the Carbon Cage.

PubMed

Zhao, Pei; Zhao, Xiang; Ehara, Masahiro

2018-03-19

Th@C 76 has been studied by density functional theory combined with statistical mechanics calculations. The results reveal that Th@ T d (19151)-C 76 satisfying the isolated pentagon rule possesses the lowest energy. Nevertheless, considering the enthalpy-entropy interplay, Th@ C 1 (17418)-C 76 with one pair of adjacent pentagons is thermodynamically favorable at elevated temperatures, which is reported for the first time. The bonding critical points in both isomers were analyzed to disclose covalent interactions between the inner Th and cages. In addition, the Wiberg bond orders of M-C bonding in different endohedral metallofullerenes (EMFs) were investigated to prove stronger covalent interactions of Th-C in Th-based EMFs.

Photoactivatable protein labeling by singlet oxygen mediated reactions.

PubMed

To, Tsz-Leung; Medzihradszky, Katalin F; Burlingame, Alma L; DeGrado, William F; Jo, Hyunil; Shu, Xiaokun

2016-07-15

Protein-protein interactions regulate many biological processes. Identification of interacting proteins is thus an important step toward molecular understanding of cell signaling. The aim of this study was to investigate the use of photo-generated singlet oxygen and a small molecule for proximity labeling of interacting proteins in cellular environment. The protein of interest (POI) was fused with a small singlet oxygen photosensitizer (miniSOG), which generates singlet oxygen ((1)O2) upon irradiation. The locally generated singlet oxygen then activated a biotin-conjugated thiol molecule to form a covalent bond with the proteins nearby. The labeled proteins can then be separated and subsequently identified by mass spectrometry. To demonstrate the applicability of this labeling technology, we fused the miniSOG to Skp2, an F-box protein of the SCF ubiquitin ligase, and expressed the fusion protein in mammalian cells and identified that the surface cysteine of its interacting partner Skp1 was labeled by the biotin-thiol molecule. This photoactivatable protein labeling method may find important applications including identification of weak and transient protein-protein interactions in the native cellular context, as well as spatial and temporal control of protein labeling. Copyright © 2016 Elsevier Ltd. All rights reserved.

Improving monoclonal antibody selection and engineering using measurements of colloidal protein interactions

PubMed Central

Geng, Steven B.; Cheung, Jason K.; Narasimhan, Chakravarthy; Shameem, Mohammed; Tessier, Peter M.

2014-01-01

A limitation of using monoclonal antibodies as therapeutic molecules is their propensity to associate with themselves and/or with other molecules via non-affinity (colloidal) interactions. This can lead to a variety of problems ranging from low solubility and high viscosity to off-target binding and fast antibody clearance. Measuring such colloidal interactions is challenging given that they are weak and potentially involve diverse target molecules. Nevertheless, assessing these weak interactions – especially during early antibody discovery and lead candidate optimization – is critical to preventing problems that can arise later in the development process. Here we review advances in developing and implementing sensitive methods for measuring antibody colloidal interactions as well as using these measurements for guiding antibody selection and engineering. These systematic efforts to minimize non-affinity interactions are expected to yield more effective and stable monoclonal antibodies for diverse therapeutic applications. PMID:25209466

Probing Protein Structure by Amino Acid-Specific Covalent Labeling and Mass Spectrometry

PubMed Central

Mendoza, Vanessa Leah; Vachet, Richard W.

2009-01-01

For many years, amino acid-specific covalent labeling has been a valuable tool to study protein structure and protein interactions, especially for systems that are difficult to study by other means. These covalent labeling methods typically map protein structure and interactions by measuring the differential reactivity of amino acid side chains. The reactivity of amino acids in proteins generally depends on the accessibility of the side chain to the reagent, the inherent reactivity of the label and the reactivity of the amino acid side chain. Peptide mass mapping with ESI- or MALDI-MS and peptide sequencing with tandem MS are typically employed to identify modification sites to provide site-specific structural information. In this review, we describe the reagents that are most commonly used in these residue-specific modification reactions, details about the proper use of these covalent labeling reagents, and information about the specific biochemical problems that have been addressed with covalent labeling strategies. PMID:19016300

Covalent inhibitors: an opportunity for rational target selectivity.

PubMed

Lagoutte, Roman; Patouret, Remi; Winssinger, Nicolas

2017-08-01

There is a resurging interest in compounds that engage their target through covalent interactions. Cysteine's thiol is endowed with enhanced reactivity, making it the nucleophile of choice for covalent engagement with a ligand aligning an electrophilic trap with a cysteine residue in a target of interest. The paucity of cysteine in the proteome coupled to the fact that closely related proteins do not necessarily share a given cysteine residue enable a level of unprecedented rational target selectivity. The recent demonstration that a lysine's amine can also be engaged covalently with a mild electrophile extends the potential of covalent inhibitors. The growing database of protein structures facilitates the discovery of covalent inhibitors while the advent of proteomic technologies enables a finer resolution in the selectivity of covalently engaged proteins. Here, we discuss recent examples of discovery and design of covalent inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Crystal structure of the dithiol oxidase DsbA enzyme from proteus mirabilis bound non-covalently to an active site peptide ligand.

PubMed

Kurth, Fabian; Duprez, Wilko; Premkumar, Lakshmanane; Schembri, Mark A; Fairlie, David P; Martin, Jennifer L

2014-07-11

The disulfide bond forming DsbA enzymes and their DsbB interaction partners are attractive targets for development of antivirulence drugs because both are essential for virulence factor assembly in Gram-negative pathogens. Here we characterize PmDsbA from Proteus mirabilis, a bacterial pathogen increasingly associated with multidrug resistance. PmDsbA exhibits the characteristic properties of a DsbA, including an oxidizing potential, destabilizing disulfide, acidic active site cysteine, and dithiol oxidase catalytic activity. We evaluated a peptide, PWATCDS, derived from the partner protein DsbB and showed by thermal shift and isothermal titration calorimetry that it binds to PmDsbA. The crystal structures of PmDsbA, and the active site variant PmDsbAC30S were determined to high resolution. Analysis of these structures allows categorization of PmDsbA into the DsbA class exemplified by the archetypal Escherichia coli DsbA enzyme. We also present a crystal structure of PmDsbAC30S in complex with the peptide PWATCDS. The structure shows that the peptide binds non-covalently to the active site CXXC motif, the cis-Pro loop, and the hydrophobic groove adjacent to the active site of the enzyme. This high-resolution structural data provides a critical advance for future structure-based design of non-covalent peptidomimetic inhibitors. Such inhibitors would represent an entirely new antibacterial class that work by switching off the DSB virulence assembly machinery. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

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

System in biology leading to cell pathology: stable protein-protein interactions after covalent modifications by small molecules or in transgenic cells.

PubMed

Malina, Halina Z

2011-01-19

The physiological processes in the cell are regulated by reversible, electrostatic protein-protein interactions. Apoptosis is such a regulated process, which is critically important in tissue homeostasis and development and leads to complete disintegration of the cell. Pathological apoptosis, a process similar to apoptosis, is associated with aging and infection. The current study shows that pathological apoptosis is a process caused by the covalent interactions between the signaling proteins, and a characteristic of this pathological network is the covalent binding of calmodulin to regulatory sequences. Small molecules able to bind covalently to the amino group of lysine, histidine, arginine, or glutamine modify the regulatory sequences of the proteins. The present study analyzed the interaction of calmodulin with the BH3 sequence of Bax, and the calmodulin-binding sequence of myristoylated alanine-rich C-kinase substrate in the presence of xanthurenic acid in primary retinal epithelium cell cultures and murine epithelial fibroblast cell lines transformed with SV40 (wild type [WT], Bid knockout [Bid-/-], and Bax-/-/Bak-/- double knockout [DKO]). Cell death was observed to be associated with the covalent binding of calmodulin, in parallel, to the regulatory sequences of proteins. Xanthurenic acid is known to activate caspase-3 in primary cell cultures, and the results showed that this activation is also observed in WT and Bid-/- cells, but not in DKO cells. However, DKO cells were not protected against death, but high rates of cell death occurred by detachment. The results showed that small molecules modify the basic amino acids in the regulatory sequences of proteins leading to covalent interactions between the modified sequences (e.g., calmodulin to calmodulin-binding sites). The formation of these polymers (aggregates) leads to an unregulated and, consequently, pathological protein network. The results suggest a mechanism for the involvement of small molecules in disease development. In the knockout cells, incorrect interactions between proteins were observed without the protein modification by small molecules, indicating the abnormality of the protein network in the transgenic system. The irreversible protein-protein interactions lead to protein aggregation and cell degeneration, which are observed in all aging-associated diseases.

System in biology leading to cell pathology: stable protein-protein interactions after covalent modifications by small molecules or in transgenic cells

PubMed Central

2011-01-01

Background The physiological processes in the cell are regulated by reversible, electrostatic protein-protein interactions. Apoptosis is such a regulated process, which is critically important in tissue homeostasis and development and leads to complete disintegration of the cell. Pathological apoptosis, a process similar to apoptosis, is associated with aging and infection. The current study shows that pathological apoptosis is a process caused by the covalent interactions between the signaling proteins, and a characteristic of this pathological network is the covalent binding of calmodulin to regulatory sequences. Results Small molecules able to bind covalently to the amino group of lysine, histidine, arginine, or glutamine modify the regulatory sequences of the proteins. The present study analyzed the interaction of calmodulin with the BH3 sequence of Bax, and the calmodulin-binding sequence of myristoylated alanine-rich C-kinase substrate in the presence of xanthurenic acid in primary retinal epithelium cell cultures and murine epithelial fibroblast cell lines transformed with SV40 (wild type [WT], Bid knockout [Bid-/-], and Bax-/-/Bak-/- double knockout [DKO]). Cell death was observed to be associated with the covalent binding of calmodulin, in parallel, to the regulatory sequences of proteins. Xanthurenic acid is known to activate caspase-3 in primary cell cultures, and the results showed that this activation is also observed in WT and Bid-/- cells, but not in DKO cells. However, DKO cells were not protected against death, but high rates of cell death occurred by detachment. Conclusions The results showed that small molecules modify the basic amino acids in the regulatory sequences of proteins leading to covalent interactions between the modified sequences (e.g., calmodulin to calmodulin-binding sites). The formation of these polymers (aggregates) leads to an unregulated and, consequently, pathological protein network. The results suggest a mechanism for the involvement of small molecules in disease development. In the knockout cells, incorrect interactions between proteins were observed without the protein modification by small molecules, indicating the abnormality of the protein network in the transgenic system. The irreversible protein-protein interactions lead to protein aggregation and cell degeneration, which are observed in all aging-associated diseases. PMID:21247434

Theoretical study of X⁻ · 1 · YF (1 = triazine, X = Cl, Br and I, Y = H, Cl, Br, I, PH₂ and AsH₂): noncovalently electron-withdrawing effects on anion-arene interactions.

PubMed

Chen, Yishan; Yao, Lifeng

2014-01-01

The ternary complexes X(-) · 1 · YF (1 = triazine, X = Cl, Br and I, Y = H, Cl, Br, I, PH2 and AsH2) have been investigated by MP2 calculations to understand the noncovalently electron-withdrawing effects on anion-arene interactions. The results indicate that in binary complexes (1 · X(-)), both weak σ-type and anion-π complexes can be formed for Cl(-) and Br(-), but only anion-π complex can be formed for I(-). Moreover, the hydrogen-bonding complex is the global minimum for all three halides in binary complexes. However, in ternary complexes, anion-π complex become unstable and only σ complex can retain in many cases for Cl(-) and Br(-). Anion-π complex keeps stable only when YF = HF. In contrast with binary complexes, σ complex become the global minimum for Cl(-) and Br(-) in ternary complexes. These changes in binding mode and strength are consistent with the results of covalently electron-withdrawing effects. However, in contrast with the covalently electron-withdrawing substituents, Cl(-) and Br(-) can attack the aromatic carbon atom to form a strong σ complex when the noncovalently electron-withdrawing effect is induced by halogen bonding. The binding behavior for I(-) is different from that for Cl(-) and Br(-) in two aspects. First, the anion-π complex for I(-) can also keep stable when the noncovalent interaction is halogen bonding. Second, the anion-π complex for I(-) is the global minimum when it can retain as a stable structure.

Effect of HPV16 L1 virus-like particles on the aggregation of non-functionalized gold nanoparticles.

PubMed

Palomino-Vizcaino, Giovanni; Valencia Reséndiz, Diana Gabriela; Benítez-Hess, María Luisa; Martínez-Acuña, Natalia; Tapia-Vieyra, Juana Virginia; Bahena, Daniel; Díaz-Sánchez, Mauricio; García-González, Octavio Patricio; Alvarez-Sandoval, Brenda Arizaí; Alvarez-Salas, Luis Marat

2018-02-15

Colorimetric assays based on gold nanoparticles (GNPs) are of considerable interest for diagnostics because of their simplicity and low-cost. Nevertheless, a deep understanding of the interaction between the GNPs and the intended molecular target is critical for the development of reliable detection technologies. The present report describes the spontaneous interaction between HPV16 L1 virus-like particles (VLPs) and non-functionalized GNPs (nfGNPs) resulting in the inhibition of nfGNPs salt-induced aggregation and the stabilization of purified VLPs. Ionic-competition experiments suggested that the nature of nfGNPs-VLPs interaction is non-covalent. Adsorption of an RNA aptamer on nfGNPs surface showed an additive aggregation-inhibitory effect. The use of mutant VLPs confirmed that the interaction nfGNPs-VLPs is not mediated by the opposing superficial electrostatic charges, suggesting that non-electrostatic forces participate in the arrangement of nfGNPs on the VLPs surface. Competition experiments using increasing ethanol concentrations on nfGNPs-VLPs complexes suggested hydrophobic interactions as the main stabilizing force. Therefore, the nfGNPs-VLPs interaction described here should facilitate the development of adsorption assays based on nfGNPs for HPV detection and cervical cancer prevention. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemical Functionalization of Graphene Family Members

NASA Astrophysics Data System (ADS)

Vacchi, Isabella Anna; Ménard-Moyon, Cécilia; Bianco, Alberto

2017-01-01

Thanks to their outstanding physicochemical properties, graphene and its derivatives are interesting nanomaterials with a high potential in several fields. Graphene, graphene oxide, and reduced graphene oxide, however, differ partially in their characteristics due to their diverse surface composition. Those differences influence the chemical reactivity of these materials. In the following chapter the reactivity and main functionalization reactions performed on graphene, graphene oxide, and reduced graphene oxide are discussed. A part is also dedicated to the main analytical techniques used for characterization of these materials. Functionalization of graphene and its derivatives is highly important to modulate their characteristics and design graphene-based conjugates with novel properties. Functionalization can be covalent by forming strong and stable bonds with the graphene surface, or non-covalent via π-π, electrostatic, hydrophobic, and/or van der Waals interactions. Both types of functionalization are currently exploited.

Anomalous Quasiparticle Symmetries and Non-Abelian Defects on Symmetrically Gapped Surfaces of Weak Topological Insulators.

PubMed

Mross, David F; Essin, Andrew; Alicea, Jason; Stern, Ady

2016-01-22

We show that boundaries of 3D weak topological insulators can become gapped by strong interactions while preserving all symmetries, leading to Abelian surface topological order. The anomalous nature of weak topological insulator surfaces manifests itself in a nontrivial action of symmetries on the quasiparticles; most strikingly, translations change the anyon types in a manner impossible in strictly 2D systems with the same symmetry. As a further consequence, screw dislocations form non-Abelian defects that trap Z_{4} parafermion zero modes.

Molecular Motions in Functional Self-Assembled Nanostructures

PubMed Central

Dhotel, Alexandre; Chen, Ziguang; Delbreilh, Laurent; Youssef, Boulos; Saiter, Jean-Marc; Tan, Li

2013-01-01

The construction of “smart” materials able to perform specific functions at the molecular scale through the application of various stimuli is highly attractive but still challenging. The most recent applications indicate that the outstanding flexibility of self-assembled architectures can be employed as a powerful tool for the development of innovative molecular devices, functional surfaces and smart nanomaterials. Structural flexibility of these materials is known to be conferred by weak intermolecular forces involved in self-assembly strategies. However, some fundamental mechanisms responsible for conformational lability remain unexplored. Furthermore, the role played by stronger bonds, such as coordination, ionic and covalent bonding, is sometimes neglected while they can be employed readily to produce mechanically robust but also chemically reversible structures. In this review, recent applications of structural flexibility and molecular motions in self-assembled nanostructures are discussed. Special focus is given to advanced materials exhibiting significant performance changes after an external stimulus is applied, such as light exposure, pH variation, heat treatment or electromagnetic field. The crucial role played by strong intra- and weak intermolecular interactions on structural lability and responsiveness is highlighted. PMID:23348927

Ubiquitous long-range antiferromagnetic coupling across the interface between superconducting and ferromagnetic oxides

DOE PAGES

De Luca, G. M.; Ghiringhelli, G.; Perroni, C. A.; ...

2014-11-24

The so-called proximity effect is the manifestation, across an interface, of the systematic competition between magnetic order and superconductivity. This phenomenon has been well documented and understood for conventional superconductors coupled with metallic ferromagnets; however it is still less known for oxide materials, where much higher critical temperatures are offered by copper oxide-based superconductors. In this paper, we show that, even in the absence of direct Cu–O–Mn covalent bonding, the interfacial CuO 2 planes of superconducting La 1.85Sr 0.15CuO 4 thin films develop weak ferromagnetism associated to the charge transfer of spin-polarised electrons from the La 0.66Sr 0.33MnO 3 ferromagnet.more » Theoretical modelling confirms that this effect is general to all cuprate/manganite heterostructures and the presence of direct bonding only affects the strength of the coupling. Finally, the Dzyaloshinskii–Moriya interaction, also at the origin of the weak ferromagnetism of bulk cuprates, propagates the magnetisation from the interface CuO 2 planes into the superconductor, eventually depressing its critical temperature.« less

NMR characterization of weak interactions between RhoGDI2 and fragment screening hits.

PubMed

Liu, Jiuyang; Gao, Jia; Li, Fudong; Ma, Rongsheng; Wei, Qingtao; Wang, Aidong; Wu, Jihui; Ruan, Ke

2017-01-01

The delineation of intrinsically weak interactions between novel targets and fragment screening hits has long limited the pace of hit-to-lead evolution. Rho guanine-nucleotide dissociation inhibitor 2 (RhoGDI2) is a novel target that lacks any chemical probes for the treatment of tumor metastasis. Protein-observed and ligand-observed NMR spectroscopy was used to characterize the weak interactions between RhoGDI2 and fragment screening hits. We identified three hits of RhoGDI2 using streamlined NMR fragment-based screening. The binding site residues were assigned using non-uniformly sampled C α - and H α -based three dimensional NMR spectra. The molecular docking to the proposed geranylgeranyl binding pocket of RhoGDI2 was guided by NMR restraints of chemical shift perturbations and ligand-observed transferred paramagnetic relaxation enhancement. We further validated the weak RhoGDI2-hit interactions using mutagenesis and structure-affinity analysis. Weak interactions between RhoGDI2 and fragment screening hits were delineated using an integrated NMR approach. Binders to RhoGDI2 as a potential anti-cancer target have been first reported, and their weak interactions were depicted using NMR spectroscopy. Our work highlights the powerfulness and the versatility of the integrative NMR techniques to provide valuable structural insight into the intrinsically weak interactions between RhoGDI2 and the fragment screening hits, which could hardly be conceived using other biochemical techniques. Copyright © 2016 Elsevier B.V. All rights reserved.

Covalent bond force profile and cleavage in a single polymer chain

NASA Astrophysics Data System (ADS)

Garnier, Lionel; Gauthier-Manuel, Bernard; van der Vegte, Eric W.; Snijders, Jaap; Hadziioannou, Georges

2000-08-01

We present here the measurement of the single-polymer entropic elasticity and the single covalent bond force profile, probed with two types of atomic force microscopes (AFM) on a synthetic polymer molecule: polymethacrylic acid in water. The conventional AFM allowed us to distinguish two types of interactions present in this system when doing force spectroscopic measurements: the first interaction is associated with adsorption sites of the polymer chains onto a bare gold surface, the second interaction is directly correlated to the rupture process of a single covalent bond. All these bridging interactions allowed us to stretch the single polymer chain and to determine the various factors playing a role in the elasticity of these molecules. To obtain a closer insight into the bond rupture process, we moved to a force sensor stable in position when measuring attractive forces. By optimizing the polymer length so as to fulfill the elastic stability conditions, we were able for the first time to map out the entire force profile associated with the cleavage of a single covalent bond. Experimental data coupled with molecular quantum mechanical calculations strongly suggest that the breaking bond is located at one end of the polymer chain.

Beyond cysteine: recent developments in the area of targeted covalent inhibition.

PubMed

Mukherjee, Herschel; Grimster, Neil P

2018-05-29

Over the past decade targeted covalent inhibitors have undergone a renaissance due to the clinical validation and regulatory approval of several small molecule therapeutics that are designed to irreversibly modify their target protein. Invariably, these compounds rely on the serendipitous placement of a cysteine residue proximal to the small molecule binding site; while this strategy has afforded numerous successes, it necessarily limits the number of proteins that can be targeted by this approach. This drawback has led several research groups to develop novel methodologies that target non-cysteine residues for covalent modification. Herein, we survey the current literature of warheads that covalently modify non-cysteine amino acids in proteins. Copyright © 2018 Elsevier Ltd. All rights reserved.

Asymmetric Cooperative Catalysis of Strong Brønsted Acid-Promoted Reactions Using Chiral Ureas

PubMed Central

Xu, Hao; Zuend, Stephan J.; Woll, Matthew G.; Tao, Ye; Jacobsen, Eric N.

2010-01-01

Cationic organic intermediates participate in a wide variety of useful synthetic transformations, but their high reactivity can render selectivity in competing pathways difficult to control. We describe a strategy for inducing enantioselectivity in reactions of protio-iminium ions, wherein a chiral catalyst interacts with the highly reactive intermediate through a network of non-covalent interactions. This leads to an attenuation of the reactivity of the iminium ion, and allows high enantioselectivity in cycloadditions with electron-rich alkenes (the Povarov reaction). A detailed experimental and computational analysis of this catalyst system has revealed the precise nature of the catalyst-substrate interactions and the likely basis for enantioinduction. PMID:20167783

Genome-wide Mapping of Cellular Protein–RNA Interactions Enabled by Chemical Crosslinking

PubMed Central

Li, Xiaoyu; Song, Jinghui; Yi, Chengqi

2014-01-01

RNA–protein interactions influence many biological processes. Identifying the binding sites of RNA-binding proteins (RBPs) remains one of the most fundamental and important challenges to the studies of such interactions. Capturing RNA and RBPs via chemical crosslinking allows stringent purification procedures that significantly remove the non-specific RNA and protein interactions. Two major types of chemical crosslinking strategies have been developed to date, i.e., UV-enabled crosslinking and enzymatic mechanism-based covalent capture. In this review, we compare such strategies and their current applications, with an emphasis on the technologies themselves rather than the biology that has been revealed. We hope such methods could benefit broader audience and also urge for the development of new methods to study RNA−RBP interactions. PMID:24747191

Highly biocompatible collagen-Delonix regia seed polysaccharide hybrid scaffolds for antimicrobial wound dressing.

PubMed

Cheirmadurai, Kalirajan; Thanikaivelan, Palanisamy; Murali, Ragothaman

2016-02-10

Biomaterials based entirely on biological resources are ideal for tissue engineering applications. Here we report the preparation of hybrid collagen scaffolds comprising gulmohar seed polysaccharide (GSP) and cinnamon bark extract as cross-linking agent. (1)H NMR spectrum of GSP confirms the presence of galactose and mannose in the ratio of 1:1.54, which was further corroborated using FT-IR. The hybrid scaffolds show better enzyme and thermal stability in contrast to pure collagen scaffold probably due to weak interactions from GSP and covalent interaction through cinnamaldehyde. Gas permeability and scanning electron microscopic analysis show that the porosity of the hybrid scaffolds is slightly reduced with the increase in the concentration of GSP. The infrared and circular dichroic spectral studies show that the secondary structure of the collagen did not change after the interaction with GSP and cinnamaldehyde. The hybrid scaffolds stabilized with cinnamaldehyde show good antimicrobial activity against the common multi-drug resistant wound pathogens. These results suggest that the prepared hybrid scaffolds have great potential for antimicrobial wound dressing applications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Thermostability promotes the cooperative function of split adenylate kinases.

PubMed

Nguyen, Peter Q; Liu, Shirley; Thompson, Jeremy C; Silberg, Jonathan J

2008-05-01

Proteins can often be cleaved to create inactive polypeptides that associate into functional complexes through non-covalent interactions, but little is known about what influences the cooperative function of the ensuing protein fragments. Here, we examine whether protein thermostability affects protein fragment complementation by characterizing the function of split adenylate kinases from the mesophile Bacillus subtilis (AKBs) and the hyperthermophile Thermotoga neapolitana (AKTn). Complementation studies revealed that the split AKTn supported the growth of Escherichia coli with a temperature-sensitive AK, but not the fragmented AKBs. However, weak complementation occurred when the AKBs fragments were fused to polypeptides that strongly associate, and this was enhanced by a Q16L mutation that thermostabilizes the full-length protein. To examine how the split AK homologs differ in structure and function, their catalytic activity, zinc content, and circular dichroism spectra were characterized. The reconstituted AKTn had higher levels of zinc, greater secondary structure, and >10(3)-fold more activity than the AKBs pair, albeit 17-fold less active than full-length AKTn. These findings provide evidence that the design of protein fragments that cooperatively function can be improved by choosing proteins with the greatest thermostability for bisection, and they suggest that this arises because hyperthermophilic protein fragments exhibit greater residual structure compared to their mesophilic counterparts.

Conjugated block copolymers as model materials to examine charge transfer in donor-acceptor systems

NASA Astrophysics Data System (ADS)

Gomez, Enrique; Aplan, Melissa; Lee, Youngmin

Weak intermolecular interactions and disorder at junctions of different organic materials limit the performance and stability of organic interfaces and hence the applicability of organic semiconductors to electronic devices. The lack of control of interfacial structure has also prevented studies of how driving forces promote charge photogeneration, leading to conflicting hypotheses in the organic photovoltaic literature. Our approach has focused on utilizing block copolymer architectures -where critical interfaces are controlled and stabilized by covalent bonds- to provide the hierarchical structure needed for high-performance organic electronics from self-assembled soft materials. For example, we have demonstrated control of donor-acceptor heterojunctions through microphase-separated conjugated block copolymers to achieve 3% power conversion efficiencies in non-fullerene photovoltaics. Furthermore, incorporating the donor-acceptor interface within the molecular structure facilitates studies of charge transfer processes. Conjugated block copolymers enable studies of the driving force needed for exciton dissociation to charge transfer states, which must be large to maximize charge photogeneration but must be minimized to prevent losses in photovoltage in solar cell devices. Our work has systematically varied the chemical structure, energetics, and dielectric constant to perturb charge transfer. As a consequence, we predict a minimum dielectric constant needed to minimize the driving force and therefore simultaneously maximize photocurrent and photovoltage in organic photovoltaic devices.

Non-covalent binding of nucleic acids with gold nanoparticles provides their stability and effective desorption in environment mimicking biological media.

PubMed

Epanchintseva, Anna; Dolodoev, Anton; Grigor'eva, Alina; Chelobanov, Boris; Pyshnyi, Dmitrii; Ryabchikova, Elena; Pyshnaya, Inna

2018-08-31

The ability of gold nanoparticles to bind different substances has resulted in the high interest of researchers determining their usage as a promising carrier of various biological substances including nucleic acids (NAs) for therapeutic applications. Most publications report covalent binding (conjugation) of an NA to spherical AuNPs via the Au-S bond. In this work, we obtained non-covalent associates of different ssDNA, ssRNA and siRNAs with spherical gold nanoparticles (AuNPs) and examined their physico-chemical properties and stability in media mimicking intracellular space (bacterial 'cytosol') and cell culture media (10% FBS in DMEM). The 'cytosol' was obtained from E. coli and possessed nuclease activity. For the first time, we used the phosphoryl guanidine (dimethylimidazolidin-2-imine, Dmi) group for modification of 3'-ends to enhance the stability of ssRNAs and siRNAs against nuclease destruction. Trying to evaluate the material balance, we analyzed the whole nucleotide species obtained after incubation of NA-AuNPs associates in 'cytosol' and FBS and evaluated the degree of NAs destruction, a share of full-size NAs remained on the surface of the AuNPs and in the solution. Native ss- and siRNAs, both free and in composition of non-covalent associates with AuNPs, were less resistant to degrading factors than ssDNA. The introduction of two Dmi-groups into the ssDNA increased its stability in 'cytosol' three times within 2.5 h. Dmi-modified siRNAs in non-covalent associates with AuNPs were two times more stable than unmodified siRNA within 4 h. We showed that non-covalent siRNA-AuNPs associates serve as a kind of storage for full-size NAs and thereby prolong their presence in nuclease-active media. Our study showed that non-covalent binding of siRNAs with a surface of AuNPs provides desorption of both strands, which is necessary for siRNA functioning in living cells, and could be considered as an important way to construct siRNA and ssDNA delivery systems based on AuNPs.

Host-Guest Complexes of Cyclodextrins and Nanodiamonds as a Strong Non-Covalent Binding Motif for Self-Assembled Nanomaterials

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

Schibilla, Frauke; Voskuhl, Jens; Fokina, Natalie A.

We report the inclusion of carboxy- and amine-substituted molecular nanodiamonds (NDs) adamantane, diamantane, and triamantane by β-cyclodextrin and γ-cyclodextrin (β-CD and γ-CD), which have particularly well-suited hydrophobicity and symmetry for an optimal fit of the host and guest molecules. We studied the host–guest interactions in detail and generally observed 1:1 association of the NDs with the larger γ-CD cavity, but observed 1:2 association for the largest ND in the series (triamantane) with β-CD. Here, we found higher binding affinities for carboxy-substituted NDs than for amine-substituted NDs. Additionally, cyclodextrin vesicles (CDVs) were decorated with d-mannose by using adamantane, diamantane, and triamantanemore » as non-covalent anchors, and the resulting vesicles were compared with the lectin concanavalin A in agglutination experiments. Agglutination was directly correlated to the host–guest association: adamantane showed lower agglutination than di- or triamantane with β-CDV and almost no agglutination with γ-CDV, whereas high agglutination was observed for di- and triamantane with γ-CDV.« less

Host-Guest Complexes of Cyclodextrins and Nanodiamonds as a Strong Non-Covalent Binding Motif for Self-Assembled Nanomaterials

DOE PAGES

Schibilla, Frauke; Voskuhl, Jens; Fokina, Natalie A.; ...

2017-11-06

We report the inclusion of carboxy- and amine-substituted molecular nanodiamonds (NDs) adamantane, diamantane, and triamantane by β-cyclodextrin and γ-cyclodextrin (β-CD and γ-CD), which have particularly well-suited hydrophobicity and symmetry for an optimal fit of the host and guest molecules. We studied the host–guest interactions in detail and generally observed 1:1 association of the NDs with the larger γ-CD cavity, but observed 1:2 association for the largest ND in the series (triamantane) with β-CD. Here, we found higher binding affinities for carboxy-substituted NDs than for amine-substituted NDs. Additionally, cyclodextrin vesicles (CDVs) were decorated with d-mannose by using adamantane, diamantane, and triamantanemore » as non-covalent anchors, and the resulting vesicles were compared with the lectin concanavalin A in agglutination experiments. Agglutination was directly correlated to the host–guest association: adamantane showed lower agglutination than di- or triamantane with β-CDV and almost no agglutination with γ-CDV, whereas high agglutination was observed for di- and triamantane with γ-CDV.« less

Anion-π interaction in metal-organic networks formed by metal halides and tetracyanopyrazine

NASA Astrophysics Data System (ADS)

Rosokha, Sergiy V.; Kumar, Amar

2017-06-01

Co-crystallization of tetracyanopyrazine, TCP, with the tetraalkylammonium salts of linear [CuBr2]-, planar [PtCl4]2- or [Pt2Br6]2-, or octahedral [PtBr6]2- complexes resulted in formation of the alternating [MlXn]m-/TCP stacks separated by the Alk4N+ cations. These hybrid stacks showed multiple short contacts between halide ligands of the [MlXn]m- complexes and carbon atoms of the TCP acceptor indicating strong anion-π bonding between these species. It confirmed that the anion-π interaction is sufficiently strong to bring together such disparate components as ionic metal complexes and neutral aromatic molecules regardless of the geometry of the coordination compound. Structural features of the solid-state stacks and [MlXn]m-·TCP dyads resulted from the quantum-mechanical computations suggests that the molecular-orbital (weakly-covalent) component play an important role in association of the [MlXn]m- complexes with the TCP acceptor.

Main-chain metallopolymers at the static-dynamic boundary based on nickelocene

NASA Astrophysics Data System (ADS)

Musgrave, Rebecca A.; Russell, Andrew D.; Hayward, Dominic W.; Whittell, George R.; Lawrence, Paul G.; Gates, Paul J.; Green, Jennifer C.; Manners, Ian

2017-08-01

Interactions between metal ions and ligands in metal-containing polymers involve two bonding extremes: persistent covalent bonding, in which the polymers are essentially static in nature, or labile coordination bonding, which leads to dynamic supramolecular materials. Main-chain polymetallocenes based on ferrocene and cobaltocene fall into the former category because of the presence of strong metal-cyclopentadienyl bonds. Herein, we describe a main-chain polynickelocene—formed by ring-opening polymerization of a moderately strained [3]nickelocenophane monomer—that can be switched between static and dynamic states because of the relatively weak nickel-cyclopentadienyl ligand interactions. This is illustrated by the observation that, at a low concentration or at an elevated temperature in a coordinating or polar solvent, depolymerization of the polynickelocene occurs. A study of this dynamic polymer-monomer equilibrium by 1H NMR spectroscopy allowed the determination of the associated thermodynamic parameters. Microrheology data, however, indicated that under similar conditions the polynickelocene is considered to be static on the shorter rheological timescale.

High strength films from oriented, hydrogen-bonded "graphamid" 2D polymer molecular ensembles.

PubMed

Sandoz-Rosado, Emil; Beaudet, Todd D; Andzelm, Jan W; Wetzel, Eric D

2018-02-27

The linear polymer poly(p-phenylene terephthalamide), better known by its tradename Kevlar, is an icon of modern materials science due to its remarkable strength, stiffness, and environmental resistance. Here, we propose a new two-dimensional (2D) polymer, "graphamid", that closely resembles Kevlar in chemical structure, but is mechanically advantaged by virtue of its 2D structure. Using atomistic calculations, we show that graphamid comprises covalently-bonded sheets bridged by a high population of strong intermolecular hydrogen bonds. Molecular and micromechanical calculations predict that these strong intermolecular interactions allow stiff, high strength (6-8 GPa), and tough films from ensembles of finite graphamid molecules. In contrast, traditional 2D materials like graphene have weak intermolecular interactions, leading to ensembles of low strength (0.1-0.5 GPa) and brittle fracture behavior. These results suggest that hydrogen-bonded 2D polymers like graphamid would be transformative in enabling scalable, lightweight, high performance polymer films of unprecedented mechanical performance.

Synthesis of 1D-glyconanomaterials by a hybrid noncovalent-covalent functionalization of single wall carbon nanotubes: a study of their selective interactions with lectins and with live cells.

PubMed

Pernía Leal, M; Assali, M; Cid, J J; Valdivia, V; Franco, J M; Fernández, I; Pozo, D; Khiar, N

2015-12-07

To take full advantage of the remarkable applications of carbon nanotubes in different fields, there is a need to develop effective methods to improve their water dispersion and biocompatibility while maintaining their physical properties. In this sense, current approaches suffer from serious drawbacks such as loss of electronic structure together with low surface coverage in the case of covalent functionalizations, or instability of the dynamic hybrids obtained by non-covalent functionalizations. In the present work, we examined the molecular basis of an original strategy that combines the advantages of both functionalizations without their main drawbacks. The hierarchical self-assembly of diacetylenic-based neoglycolipids into highly organized and compacted rings around the nanotubes, followed by photopolymerization leads to the formation of nanotubes covered with glyconanorings with a shish kebab-type topology exposing the carbohydrate ligands to the water phase in a multivalent fashion. The glyconanotubes obtained are fully functional, and able to establish specific interactions with their cognate receptors. In fact, by taking advantage of this selective binding, an easy method to sense lectins as a working model of toxin detection was developed based on a simple analysis of TEM images. Remarkably, different experimental settings to assess cell membrane integrity, cell growth kinetics and cell cycle demonstrated the cellular biocompatibility of the sugar-coated carbon nanotubes compared to pristine single-walled carbon nanotubes.

Carbon nanotube/biocompatible bola-amphiphile supramolecular biohybrid materials: preparation and their application in bacterial cell agglutination.

PubMed

Yu, Guocan; Li, Jinying; Yu, Wei; Han, Chengyou; Mao, Zhengwei; Gao, Changyou; Huang, Feihe

2013-11-26

Supramolecular biohybrid materials were successfully constructed driven by non-covalent interactions between three biocompatible bolaform amphiphiles and single walled carbon nanotubes (SWNTs). The existence of galactoses in these supramolecular systems endowed the hybrid materials with interesting bio-function. By introducing the SWNTs as semi-flexible platforms, these supramolecular biohybrid materials display excellent agglutination ability for E. coli. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nano/biosensors based on large-area graphene

NASA Astrophysics Data System (ADS)

Ducos, Pedro Jose

Two dimensional materials have properties that make them ideal for applications in chemical and biomolecular sensing. Their high surface/volume ratio implies that all atoms are exposed to the environment, in contrast to three dimensional materials with most atoms shielded from interactions inside the bulk. Graphene additionally has an extremely high carrier mobility, even at ambient temperature and pressure, which makes it ideal as a transduction device. The work presented in this thesis describes large-scale fabrication of Graphene Field Effect Transistors (GFETs), their physical and chemical characterization, and their application as biomolecular sensors. Initially, work was focused on developing an easily scalable fabrication process. A large-area graphene growth, transfer and photolithography process was developed that allowed the scaling of production of devices from a few devices per single transfer in a chip, to over a thousand devices per transfer in a full wafer of fabrication. Two approaches to biomolecules sensing were then investigated, through nanoparticles and through chemical linkers. Gold and platinum Nanoparticles were used as intermediary agents to immobilize a biomolecule. First, gold nanoparticles were monodispersed and functionalized with thiolated probe DNA to yield DNA biosensors with a detection limit of 1 nM and high specificity against noncomplementary DNA. Second, devices are modified with platinum nanoparticles and functionalized with thiolated genetically engineered scFv HER3 antibodies to realize a HER3 biosensor. Sensors retain the high affinity from the scFv fragment and show a detection limit of 300 pM. We then show covalent and non-covalent chemical linkers between graphene and antibodies. The chemical linker 1-pyrenebutanoic acid succinimidyl ester (pyrene) stacks to the graphene by Van der Waals interaction, being a completely non-covalent interaction. The linker 4-Azide-2,3,5,6-tetrafluorobenzoic acid, succinimidyl ester (azide) is a photoactivated perfluorophenyl azide that covalently binds to graphene. A comparison is shown for genetically engineered scFv HER3 antibodies and show a low detection limit of 10 nM and 100 pM for the pyrene and azide, respectively. Finally, we use the azide linker to demonstrate a large-scale fabrication of a multiplexed array for Lyme disease. Simultaneous detection of a mixture of two target proteins of the Lyme disease bacterium (Borrelia burgdorferi), this is done by separating the antibodies corresponding to each target in the mixture to different regions of the chip. We show we can differentiate concentrations of the two targets.

Protein–Hydrogel Interactions in Tissue Engineering: Mechanisms and Applications

PubMed Central

Zustiak, Silviya P.; Wei, Yunqian

2013-01-01

Recent advances in our understanding of the sophistication of the cellular microenvironment and the dynamics of tissue remodeling during development, disease, and regeneration have increased our appreciation of the current challenges facing tissue engineering. As this appreciation advances, we are better equipped to approach problems in the biology and therapeutics of even more complex fields, such as stem cells and cancer. To aid in these studies, as well as the established areas of tissue engineering, including cardiovascular, musculoskeletal, and neural applications, biomaterials scientists have developed an extensive array of materials with specifically designed chemical, mechanical, and biological properties. Herein, we highlight an important topic within this area of biomaterials research, protein–hydrogel interactions. Due to inherent advantages of hydrated scaffolds for soft tissue engineering as well as specialized bioactivity of proteins and peptides, this field is well-posed to tackle major needs within emerging areas of tissue engineering. We provide an overview of the major modes of interactions between hydrogels and proteins (e.g., weak forces, covalent binding, affinity binding), examples of applications within growth factor delivery and three-dimensional scaffolds, and finally future directions within the area of hydrogel–protein interactions that will advance our ability to control the cell–biomaterial interface. PMID:23150926

The Importance of Water for High Fidelity Information Processing and for Life

NASA Technical Reports Server (NTRS)

Hoehler, Tori M.; Pohorille, Andrew

2011-01-01

Is water an absolute prerequisite for life? Life depends on a variety of non-covalent interactions among molecules, the nature of which is determined as much by the solvent in which they occur as by the molecules themselves. Catalysis and information processing, two essential functions of life, require non-covalent molecular recognition with very high specificity. For example, to correctly reproduce a string consisting of 600,000 units of information (e.g ., 600 kilobases, equivalent to the genome of the smallest free living terrestrial organisms) with a 90% success rate requires specificity > 107 : 1 for the target molecule vs. incorrect alternatives. Such specificity requires (i) that the correct molecular association is energetically stabilized by at least 40 kJ/mol relative to alternatives, and (ii) that the system is able to sample among possible states (alternative molecular associations) rapidly enough to allow the system to fall under thermodynamic control and express the energetic stabilization. We argue that electrostatic interactions are required to confer the necessary energetic stabilization vs. a large library of molecular alternatives, and that a solvent with polarity and dielectric properties comparable to water is required for the system to sample among possible states and express thermodynamic control. Electrostatic associations can be made in non-polar solvents, but the resulting complexes are too stable to be "unmade" with sufficient frequency to confer thermodynamic control on the system. An electrostatic molecular complex representing 3 units of information (e.g., 3 base pairs) with specificity > 107 per unit has a stability in non-polar solvent comparable to that of a carbon-carbon bond at room temperature. These considerations suggest that water, or a solvent with properties very like water, is necessary to support high-fidelity information processing, and can therefore be considered a critical prerequisite for life.

Spectroscopic, single crystal X-ray, Hirshfeld, in vitro and in silico biological evaluation of a new series of potent thiazole nucleus integrated with pyrazoline scaffolds

NASA Astrophysics Data System (ADS)

Salian, Vinutha V.; Narayana, Badiadka; Sarojini, Balladka K.; Kumar, Madan S.; Nagananda, Govinahalli S.; Byrappa, Kullaiah; Kudva, Avinash K.

2017-03-01

In the present study, the spectroscopic characterization of a new series of substituted thiazole linked pyrazoline scaffolds 4a-l was performed. The formation of 4a-l from the intermediate 3-(4-chlorophenyl)-5-[4-(propan-2-yl)phenyl]-4,5-dihydro-1H-pyrazole-1-carbothioamide 2 and substituted 2-bromo-1-phenylethanone 3a-l was evidenced through the changes in FTIR, 1H NMR, 13C NMR, LCMS data. The X-ray diffraction studies revealed that compound 2 and 4g crystallized in monoclinic crystal system with P21/n space group. Compound 4j crystallized in triclinic system, P1¯ space group with Z = 4. The percentage of intermolecular contacts and distribution of electrostatic potential of molecular crystal structures was resolved by Hirshfeld surface analysis with 2D finger plots and electrostatic potential map. The newly synthesized derivatives were screened for their in vitro antioxidant and antimicrobial activity. The single crystal studies revealed that, for compounds 2, 4g and 4j the isopropyl phenyl ring is positioned at near right angle with the other rings. Due to the lack of planarity of bulkier group substituted to phenyl ring (ring B), all the synthesized molecules showed weak to moderate radical scavenging capacity owing to the destabilization of the radical formed during oxidation. Also, on performing molecular docking studies to explore the interactions of ligand with the target pyrimidine nucleoside hydrolase YbeK with bound ribose complex (PNH, PDB ID-3GHW), disclosed that active compounds emerged for in vitro studies also bound to PNH more efficiently. The compounds with polar group substitution interacted through hydrogen bonding while other molecules with non-covalent interactions.

Covalent bonding in heavy metal oxides

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

Bagus, Paul S.; Nelin, Connie J.; Hrovat, Dave A.

Novel theoretical methods were used to quantify the magnitude and the energetic contributions of 4f/5f-O2p and 5d/6d-O2p interactions to covalent bonding in lanthanide and actinide oxides. Although many analyses have neglected the involvement of the frontier d orbitals, the present study shows that f and d covalency are of comparable importance. Two trends are identified. As is expected, the covalent mixing is larger when the nominal oxidation state is higher. More subtly, the importance of the nf covalent mixing decreases sharply relative to (n+1)d as the nf occupation increases. Atomic properties of the metal cations that drive these trends aremore » identified.« less

Decoherence suppression of tripartite entanglement in non-Markovian environments by using weak measurements

NASA Astrophysics Data System (ADS)

Ding, Zhi-yong; He, Juan; Ye, Liu

2017-02-01

A feasible scheme for protecting the Greenberger-Horne-Zeilinger (GHZ) entanglement state in non-Markovian environments is proposed. It consists of prior weak measurement on each qubit before the interaction with decoherence environments followed by post quantum measurement reversals. It is shown that both the fidelity and concurrence of the GHZ state can be effectively improved. Meanwhile, we also verified that our scenario can enhance tripartite nonlocality remarkably. In addition, the result indicates that the larger the weak measurement strength, the better the effectiveness of the scheme with the lower success probability.

Pili and flagella biology, structure, and biotechnological applications.

PubMed

Van Gerven, Nani; Waksman, Gabriel; Remaut, Han

2011-01-01

Bacteria and Archaea expose on their outer surfaces a variety of thread-like proteinaceous organelles with which they interact with their environments. These structures are repetitive assemblies of covalently or non-covalently linked protein subunits, organized into filamentous polymers known as pili ("hair"), flagella ("whips") or injectisomes ("needles"). They serve different roles in cell motility, adhesion and host invasion, protein and DNA secretion and uptake, conductance, or cellular encapsulation. Here we describe the functional, morphological and genetic diversity of these bacterial filamentous protein structures. The organized, multi-copy build-up and/or the natural function of pili and flagella have lead to their biotechnological application as display and secretion tools, as therapeutic targets or as molecular motors. We review the documented and potential technological exploitation of bacterial surface filaments in light of their structural and functional traits. Copyright © 2011 Elsevier Inc. All rights reserved.

Efficient photosensitized splitting of the thymine dimer/oxetane unit on its modifying beta-cyclodextrin by a binding electron donor.

PubMed

Tang, Wen-Jian; Song, Qin-Hua; Wang, Hong-Bo; Yu, Jing-Yu; Guo, Qing-Xiang

2006-07-07

Two modified beta-cyclodextrins (beta-CDs) with a thymine dimer and a thymine oxetane adduct respectively, TD-CD and Ox-CD, have been prepared, and utilized to bind an electron-rich chromophore, indole or N,N-dimethylaniline (DMA), to form a supramolecular complex. We have examined the photosensitized splitting of the dimer/oxetane unit in TD-CD/Ox-CD by indole or DMA via an electron-transfer pathway, and observed high splitting efficiencies of the dimer/oxetane unit. On the basis of measurements of fluorescence spectra and splitting quantum yields, it is suggested that the splitting reaction occurs in a supramolecular complex by an inclusion interaction between the modified beta-CDs and DMA or indole. The back electron transfer, which leads low splitting efficiencies for the covalently-linked chromophore-dimer/oxetane compounds, is suppressed in the non-covalently-bound complex, and the mechanism has been discussed.

Intracellular and transdermal protein delivery mediated by non-covalent interactions with a synthetic guanidine-rich molecular carrier.

PubMed

Im, Jungkyun; Das, Sanket; Jeong, Dongjun; Kim, Chang-Jin; Lim, Hyun-Suk; Kim, Ki Hean; Chung, Sung-Kee

2017-08-07

The impermeability of the cell plasma membrane is one of the major barriers for protein transduction into mammalian cells, and it also limits the use of proteins as therapeutic agents. Protein transduction has usually been achieved based on certain invasive processes or cell penetrating peptides (CPP). Herein we report our study in which a synthetic guanidine-rich molecular carrier is used as a delivery vector for intracellular and transdermal delivery of proteins. First a sorbitol-based molecular carrier having 8 guanidine units (Sor-G8) was synthesized, and then was simply mixed with a cargo protein of varying sizes to form the non-covalent complex of carrier-cargo proteins. These ionic complexes were shown to have efficient cellular uptake properties. The optimum conditions including the molar ratio between cargo protein and carrier, and the treatment time have been defined. Several protein cargoes were successfully examined with differing sizes and molecular weights: green fluorescent protein (MW 27kDa), albumin (66kDa), concanavalin A (102kDa), and immunoglobulin G (150kDa). These non-covalent complexes were also found to have excellent transdermal penetration ability into the mouse skin. The skin penetration depth was studied histologically by light microscopy as well as two-photon microscopy thus generating a depth profile. These complexes were largely found in the epidermis and dermis layers, i.e. down to ca. 100μm depth of the mouse skin. Our synthetic Sor-G8 carrier was found to be substantially more efficient that Arg8 in both the intracellular transduction and the transdermal delivery of proteins. The mechanism of the cellular uptake of the complex was briefly studied, and the results suggested macropinocytosis. Copyright © 2017 Elsevier B.V. All rights reserved.

Crystal structures of Mycobacterium tuberculosis GlgE and complexes with non-covalent inhibitors

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

Lindenberger, Jared J.; Kumar Veleti, Sri; Wilson, Brittney N.

GlgE is a bacterial maltosyltransferase that catalyzes the elongation of a cytosolic, branched α-glucan. In Mycobacterium tuberculosis (M. tb), inactivation of GlgE (Mtb GlgE) results in the rapid death of the organism due to a toxic accumulation of the maltosyl donor, maltose-1-phosphate (M1P), suggesting that GlgE is an intriguing target for inhibitor design. In this study, the crystal structures of the Mtb GlgE in a binary complex with maltose and a ternary complex with maltose and a maltosyl-acceptor molecule, maltohexaose, were solved to 3.3 Å and 4.0 Å, respectively. The maltohexaose structure reveals a dominant site for α-glucan binding. Tomore » obtain more detailed interactions between first generation, non-covalent inhibitors and GlgE, a variant Streptomyces coelicolor GlgEI (Sco GlgEI-V279S) was made to better emulate the Mtb GlgE M1P binding site. The structure of Sco GlgEI-V279S complexed with α-maltose-C-phosphonate (MCP), a non-hydrolyzable substrate analogue, was solved to 1.9 Å resolution, and the structure of Sco GlgEI-V279S complexed with 2,5-dideoxy-3-O-α-D-glucopyranosyl-2,5-imino-D-mannitol (DDGIM), an oxocarbenium mimic, was solved to 2.5 Å resolution. These structures detail important interactions that contribute to the inhibitory activity of these compounds, and provide information on future designs that may be exploited to improve upon these first generation GlgE inhibitors.« less

How the cation-cation π-π stacking occurs: A theoretical investigation into ionic clusters of imidazolium.

PubMed

Gao, Wei; Tian, Yong; Xuan, Xiaopeng

2015-07-01

The cation-cation π-π stacking is uncommon but it is essential for the understanding of some supramolecular structures. We explore theoretically the nature of non-covalent interaction occurring in the stacked structure within modeled clusters of 1,3-dimethylimidazolium and halide. The evidences of the energy decomposition analysis (EDA) and reduced density gradient (RDG) approach are different from those of common π-π interaction. Isosurfaces with RDG also illustrate the strength of the titled π-π interaction and their region. Additionally, we find that the occurrence of this interaction is attributed to a few C-H···X interactions, as depicted using atom in molecule (AIM) method. This work presents a clear picture of the typical cation-cation π-π interaction and can serve to advance the understanding of this uncommon interaction. Copyright © 2015 Elsevier Inc. All rights reserved.

Protein adsorption on dopamine-melanin films: role of electrostatic interactions inferred from zeta-potential measurements versus chemisorption.

PubMed

Bernsmann, Falk; Frisch, Benoît; Ringwald, Christian; Ball, Vincent

2010-04-01

We recently showed the possibility to build dopamine-melanin films of controlled thickness by successive immersions of a substrate in alkaline solutions of dopamine [F. Bernsmann, A. Ponche, C. Ringwald, J. Hemmerlé, J. Raya, B. Bechinger, J.-C. Voegel, P. Schaaf, V. Ball, J. Phys. Chem. C 113 (2009) 8234-8242]. In this work the structure and properties of such films are further explored. The zeta-potential of dopamine-melanin films is measured as a function of the total immersion time to build the film. It appears that the film bears a constant zeta-potential of (-39+/-3) mV after 12 immersion steps. These data are used to calculate the surface density of charged groups of the dopamine-melanin films at pH 8.5 that are mostly catechol or quinone imine chemical groups. Furthermore the zeta-potential is used to explain the adsorption of three model proteins (lysozyme, myoglobin, alpha-lactalbumin), which is monitored by quartz crystal microbalance. We come to the conclusion that protein adsorption on dopamine-melanin is not only determined by possible covalent binding between amino groups of the proteins and catechol groups of dopamine-melanin but that electrostatic interactions contribute to protein binding. Part of the adsorbed proteins can be desorbed by sodium dodecylsulfate solutions at the critical micellar concentration. The fraction of weakly bound proteins decreases with their isoelectric point. Additionally the number of available sites for covalent binding of amino groups on melanin grains is quantified. Copyright 2009 Elsevier Inc. All rights reserved.

Nanoparticle mediated non-covalent drug delivery☆

PubMed Central

Doane, Tennyson; Burda, Clemens

2013-01-01

The use of nanoparticles (NPs) for enhanced drug delivery has been heavily explored during the last decade. Within the field, it is has become increasingly apparent that the physical properties of the particles themselves dictate their efficacy, and the relevant non-covalent chemistry at the NP interface also influences how drugs are immobilized and delivered. In this review, we reflect on the physical chemistry of NP mediated drug delivery (and more specifically, non-covalent drug delivery) at the three main experimental stages of drug loading, NP–drug conjugate transport, and the resulting cellular drug delivery. Through a critical evaluation of advances in drug delivery within the last decade, an outlook for biomedical applications of nanoscale transport vectors will be presented. PMID:22664231

Surface plasmon resonance label-free monitoring of antibody antigen interactions in real time

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

Kausaite, A.; van Dijk, M.; Castrop, J.

2007-01-01

Detection of biologically active compounds is one of the most important topics in molecular biology and biochemistry. One of the most promising detection methods is based on the application of surface plasmon resonance for label-free detection of biologically active compounds. This method allows one to monitor binding events in real time without labeling. The system can therefore be used to determine both affinity and rate constants for interactions between various types of molecules. Here, we describe the application of a surface plasmon resonance biosensor for label-free investigation of the interaction between an immobilized antigen bovine serum albumin (BSA) and antibodymore » rabbit anti-cow albumin IgG1 (anti-BSA). The formation of a self-assembled monolayer (SAM) over a gold surface is introduced into this laboratory training protocol as an effective immobilization method, which is very promising in biosensing systems based on detection of affinity interactions. In the next step, covalent attachment via artificially formed amide bonds is applied for the immobilization of proteins on the formed SAM surface. These experiments provide suitable experience for postgraduate students to help them understand immobilization of biologically active materials via SAMs, fundamentals of surface plasmon resonance biosensor applications, and determination of non-covalent biomolecular interactions. The experiment is designed for master and/or Ph.D. students. In some particular cases, this protocol might be adoptable for bachelor students that already have completed an extended biochemistry program that included a background in immunology.« less

Inhibition of HIV Virus by Neutralizing Vhh Attached to Dual Functional Liposomes Encapsulating Dapivirine.

PubMed

Wang, Scarlet Xiaoyan; Michiels, Johan; Ariën, Kevin K; New, Roger; Vanham, Guido; Roitt, Ivan

2016-12-01

Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high efficacy in reducing viral replication in vitro. Thus, dual function liposomes may lead to a novel strategy for the prophylaxis of HIV/AIDS by combining the neutralizing activity of Vhh with antiviral effects of high drug concentrations.

Inhibition of HIV Virus by Neutralizing Vhh Attached to Dual Functional Liposomes Encapsulating Dapivirine

NASA Astrophysics Data System (ADS)

Wang, Scarlet Xiaoyan; Michiels, Johan; Ariën, Kevin K.; New, Roger; Vanham, Guido; Roitt, Ivan

2016-07-01

Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high efficacy in reducing viral replication in vitro. Thus, dual function liposomes may lead to a novel strategy for the prophylaxis of HIV/AIDS by combining the neutralizing activity of Vhh with antiviral effects of high drug concentrations.

DFT and TD-DFT study of the adsorption and detection of sulfur mustard chemical warfare agent by the C24, C12Si12, Al12N12, Al12P12, Be12O12, B12N12 and Mg12O12 nanocages

NASA Astrophysics Data System (ADS)

Jouypazadeh, Hamidreza; Farrokhpour, Hossein

2018-07-01

In the present research, the interaction of sulfur mustard, a chemical warfare agent, with the surface of C24, C12Si12, Al12N12, Al12P12, Be12O12, B12N12 and Mg12O12 nanocages was studied using the dispersion corrected density function theory (DFT-D3) method. The calculated adsorption energies of sulfur mustard on the surface of the nanocages showed that the Al12N12, C12Si12 and Mg12O12 are useful for the adsorption of the sulfur mustard. The quantum theory atom in molecule (QTAIM) analysis was used to study the nature of interactions of sulfur mustard with the surface of the selected nanocages. Based on QTAIM analysis, the majority of interactions of sulfur and chlorine atoms of sulfur mustard with the surface of the considered nanocages are covalent and quasi covalent whereas the interactions of hydrogen atoms of sulfur mustard with the surface of the nanocages are generally non-covalent. The charge transfer between sulfur mustard and the nanocages as well as chemical quantum descriptors of complexes were calculated using natural bond orbital (NBO) method. The most electron charge transfers from the sulfur mustard to B12N12 nanocage where the S atom of sulfur mustard donor a chemical bond to B atom of the nanocage. The ability of the considered nanocages for detecting sulfur mustard was studied using time-dependent density function theory (TD-DFT) and density of state (DOS) diagram. It is found that the C24, Al12P12, Be12O12 and B12N12 nanocages are useful sensors for this chemical agent.

Novel Materials Containing Single-Wall Carbon Nanotubes Wrapped in Polymer Molecules

NASA Technical Reports Server (NTRS)

Smalley, Richard E.; O'Connell, Michael J.; Smith, Kenneth; Colbert, Daniel T.

2009-01-01

In this design, single-wall carbon nanotubes (SWNTs) have been coated in polymer molecules to create a new type of material that has low electrical conductivity, but still contains individual nanotubes, and small ropes of individual nanotubes, which are themselves good electrical conductors and serve as small conducting rods immersed in an electrically insulating matrix. The polymer is attached through weak chemical forces that are primarily non-covalent in nature, caused primarily through polarization rather than the sharing of valence electrons. Therefore, the electronic structure of the SWNT involved is substantially the same as that of free, individual (and small ropes of) SWNT. Their high conductivity makes the individual nanotubes extremely electrically polarizable, and materials containing these individual, highly polarizable molecules exhibit novel electrical properties including a high dielectric constant.

A novel covalent approach to bio-conjugate silver coated single walled carbon nanotubes with antimicrobial peptide.

PubMed

Chaudhari, Atul A; Ashmore, D'andrea; Nath, Subrata Deb; Kate, Kunal; Dennis, Vida; Singh, Shree R; Owen, Don R; Palazzo, Chris; Arnold, Robert D; Miller, Michael E; Pillai, Shreekumar R

2016-07-13

Due to increasing antibiotic resistance, the use of silver coated single walled carbon nanotubes (SWCNTs-Ag) and antimicrobial peptides (APs) is becoming popular due to their antimicrobial properties against a wide range of pathogens. However, stability against various conditions and toxicity in human cells are some of the major drawbacks of APs and SWCNTs-Ag, respectively. Therefore, we hypothesized that APs-functionalized SWCNTs-Ag could act synergistically. Various covalent functionalization protocols described previously involve harsh treatment of carbon nanotubes for carboxylation (first step in covalent functionalization) and the non-covalently functionalized SWCNTs are not satisfactory. The present study is the first report wherein SWCNTs-Ag were first carboxylated using Tri sodium citrate (TSC) at 37 °C and then subsequently functionalized covalently with an effective antimicrobial peptide from Therapeutic Inc., TP359 (FSWCNTs-Ag). SWCNTs-Ag were also non covalently functionalized with TP359 by simple mixing (SWCNTs-Ag-M) and both, the FSWCNTs-Ag (covalent) and SWCNTs-Ag-M (non-covalent), were characterized by Fourier transform infrared spectroscopy (FT-IR), Ultraviolet visualization (UV-VIS) and transmission electron microscopy (TEM). Further the antibacterial activity of both and TP359 were investigated against two gram positive (Staphylococcus aureus and Streptococcus pyogenes) and two gram negative (Salmonella enterica serovar Typhimurium and Escherichia coli) pathogens and the cellular toxicity of TP359 and FSWCNTs-Ag was compared with plain SWCNTs-Ag using murine macrophages and lung carcinoma cells. FT-IR analysis revealed that treatment with TSC successfully resulted in carboxylation of SWCNTs-Ag and the peptide was indeed attached to the SWCNTs-Ag evidenced by TEM images. More importantly, the present study results further showed that the minimum inhibitory concentration (MIC) of FSWCNTs-Ag were much lower (~7.8-3.9 µg/ml with IC50: ~4-5 µg/ml) compared to SWCNTs-Ag-M and plain SWCNTs-Ag (both 62.6 µg/ml, IC50: ~31-35 µg/ml), suggesting that the covalent conjugation of TP359 with SWCNTs-Ag was very effective on their counterparts. Additionally, FSWCNTs-Ag are non-toxic to the eukaryotic cells at their MIC concentrations (5-2.5 µg/ml) compared to SWCNTs-Ag (62.5 µg/ml). In conclusion, we demonstrated that covalent functionalization of SWCNTs-Ag and TP359 exhibited an additive antibacterial activity. This study described a novel approach to prepare SWCNT-Ag bio-conjugates without loss of antimicrobial activity and reduced toxicity, and this strategy will aid in the development of novel and biologically important nanomaterials.

Ab initio calculations, structure, NBO and NCI analyses of Xsbnd H⋯π interactions

NASA Astrophysics Data System (ADS)

Wu, Qiyang; Su, He; Wang, Hongyan; Wang, Hui

2018-02-01

The performance of ab initio methods (MP2, DFT/B3LYP, random-phase approximation (RPA), CCSD(T) and QCISD(T)) in predicting interaction energy of Xsbnd H⋯π (Xsbnd H = HCCH, HCl, HF; π = C2H2, C2H4, C6H6) hydrogen complexes are assessed systematically. The CCSD(T)/CBS benchmarks of interaction energy are reported. It is found that RPA agrees well with CCSD(T)/CBS benchmarks and experimental results. CCSD(T) and QCISD(T) perform the best only when compared with CCSD(T)/CBS benchmarks, MP2 performs well only for experimental data. B3LYP provides the worst accuracy. Additionally, the equilibrium structure, interaction type of Xsbnd H⋯π hydrogen complexes are investigated by the natural bond orbital (NBO) and the non-covalent interaction index (NCI).

Ionic and Covalent Stabilization of Intermediates and Transition States in Catalysis by Solid Acids

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

Deshlahra, Prashant; Carr, Robert T.; Iglesia, Enrique

Reactivity descriptors describe catalyst properties that determine the stability of kinetically relevant transition states and adsorbed intermediates. Theoretical descriptors, such as deprotonation energies (DPE), rigorously account for Brønsted acid strength for catalytic solids with known structure. Here, mechanistic interpretations of methanol dehydration turnover rates are used to assess how charge reorganization (covalency) and electrostatic interactions determine DPE and how such interactions are recovered when intermediates and transition states interact with the conjugate anion in W and Mo polyoxometalate (POM) clusters and gaseous mineral acids. Turnover rates are lower and kinetically relevant species are less stable on Mo than W POMmore » clusters with similar acid strength, and such species are more stable on mineral acids than that predicted from W-POM DPE–reactivity trends, indicating that DPE and acid strength are essential but incomplete reactivity descriptors. Born–Haber thermochemical cycles indicate that these differences reflect more effective charge reorganization upon deprotonation of Mo than W POM clusters and the much weaker reorganization in mineral acids. Such covalency is disrupted upon deprotonation but cannot be recovered fully upon formation of ion pairs at transition states. Predictive descriptors of reactivity for general classes of acids thus require separate assessments of the covalent and ionic DPE components. Here, we describe methods to estimate electrostatic interactions, which, taken together with energies derived from density functional theory, give the covalent and ionic energy components of protons, intermediates, and transition states. In doing so, we provide a framework to predict the reactive properties of protons for chemical reactions mediated by ion-pair transition states.« less

Preparation and properties of electro-conductive fabrics based on polypyrrole: covalent vs. non-covalent attachment

NASA Astrophysics Data System (ADS)

David, N. C.; Anavi, D.; Milanovich, M.; Popowski, Y.; Frid, L.; Amir, E.

2017-10-01

Electro-conductive fabrics were prepared via in situ oxidative polymerization of pyrrole (Py) in the presence of unmodified and chemically modified cotton fabrics. Chemical modification of cotton fabric was achieved by covalent attachment of a bifunctional linker molecule to the surface of the fabric, followed by incorporation of a monomer unit onto the linker. The fabrics were characterized using Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, scanning electron spectroscopy, and thermal analysis. Furthermore, the effect of Py concentration on the degree of polypyrrole (PPy) grafting, surface morphology, electrical resistivity, and laundering durability were studied for both types of cotton fabrics. Reductions of several orders of magnitude in surface and volume electrical resistivities were observed for both non-covalently and covalently linked cotton-PPy systems, whereas the effect of covalent pre-treatment of the fabric was stronger at low Py concentration. On the other hand, at higher monomer concentration, the electrical properties and laundering durability of the fabrics we comparable for both unmodified and chemically pre-treated cotton fabrics, indicating that only a small fraction of PPy chains were chemically grafted onto the fabric surface with the majority of the polymer being connected to the fabric through hydrogen bonds.

Crystal Structures of Covalent Complexes of [beta]-Lactam Antibiotics with Escherichia coli Penicillin-Binding Protein 5: Toward an Understanding of Antibiotic Specificity

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

Nicola, George; Tomberg, Joshua; Pratt, R.F.

Penicillin-binding proteins (PBPs) are the molecular targets for the widely used {beta}-lactam class of antibiotics, but how these compounds act at the molecular level is not fully understood. We have determined crystal structures of Escherichia coli PBP 5 as covalent complexes with imipenem, cloxacillin, and cefoxitin. These antibiotics exhibit very different second-order rates of acylation for the enzyme. In all three structures, there is excellent electron density for the central portion of the {beta}-lactam, but weak or absent density for the R1 or R2 side chains. Areas of contact between the antibiotics and PBP 5 do not correlate with themore » rates of acylation. The same is true for conformational changes, because although a shift of a loop leading to an electrostatic interaction between Arg248 and the {beta}-lactam carboxylate, which occurs completely with cefoxitin and partially with imipenem and is absent with cloxacillin, is consistent with the different rates of acylation, mutagenesis of Arg248 decreased the level of cefoxitin acylation only 2-fold. Together, these data suggest that structures of postcovalent complexes of PBP 5 are unlikely to be useful vehicles for the design of new covalent inhibitors of PBPs. Finally, superimposition of the imipenem-acylated complex with PBP 5 in complex with a boronic acid peptidomimetic shows that the position corresponding to the hydrolytic water molecule is occluded by the ring nitrogen of the {beta}-lactam. Because the ring nitrogen occupies a similar position in all three complexes, this supports the hypothesis that deacylation is blocked by the continued presence of the leaving group after opening of the {beta}-lactam ring.« less

Protein-protein interactions during high-moisture extrusion for fibrous meat analogues and comparison of protein solubility methods using different solvent systems.

PubMed

Liu, KeShun; Hsieh, Fu-Hung

2008-04-23

Soy protein, mixed with gluten and starch, was extruded into fibrous meat analogues under high-moisture and high-temperature conditions. The protein solubility of samples collected at different extruder zones and extrudates made with different moistures was determined by 11 extraction solutions consisting of 6 selective reagents and their combinations: phosphate salts, urea, DTT, thiourea, Triton X-100, and CHAPS. Protein solubility by most extractants showed decreasing patterns as the material passed through the extruder, but the solution containing all 6 reagents, known as isoelectric focus (IEF) buffer, solubilized the highest levels and equal amounts of proteins in all samples, indicating that there are no other covalent bonds involved besides disulfide bonds. With regard to relative importance between disulfide bonds and non-covalent interactions, different conclusions could be made from protein solubility patterns, depending on the type of extracting systems and a baseline used for comparison. The observation points out pitfalls and limitation of current protein solubility methodology and explains why controversy exists in the literature. Using the IEF buffer system with omission of one or more selective reagents is considered to be the right methodology to conduct protein solubility study and thus recommended. Results obtained with this system indicate that disulfide bonding plays a more important role than non-covalent bonds in not only holding the rigid structure of extrudates but also forming fibrous texture. The sharpest decrease in protein solubility occurred when the mix passed through the intermediate section of the extruder barrel, indicating formation of new disulfide bonds during the stage of dramatic increase in both temperature and moisture. After this stage, although the physical form of the product might undergo change and fiber formation might occur as it passed through the cooling die, the chemical nature of the product did not change significantly.

Solid State Chemistry of Clathrate Phases: Crystal Structure, Chemical Bonding and Preparation Routes

NASA Astrophysics Data System (ADS)

Baitinger, Michael; Böhme, Bodo; Ormeci, Alim; Grin, Yuri

Clathrates represent a family of inorganic materials called cage compounds. The key feature of their crystal structures is a three-dimensional (host) framework bearing large cavities (cages) with 20-28 vertices. These polyhedral cages bear—as a rule—guest species. Depending on the formal charge of the framework, clathrates are grouped in anionic, cationic and neutral. While the bonding in the framework is of (polar) covalent nature, the guest-host interaction can be ionic, covalent or even van-der Waals, depending on the chemical composition of the clathrates. The chemical composition and structural features of the cationic clathrates can be described by the enhanced Zintl concept, whereas the composition of the anionic clathrates deviates often from the Zintl counts, indicating additional atomic interactions in comparison with the ionic-covalent Zintl model. These interactions can be visualized and studied by applying modern quantum chemical approaches such as electron localizability.

A high throughput mutagenic analysis of yeast sumo structure and function

PubMed Central

Newman, Heather A.; Lu, Jian; Carson, Caryn; Boeke, Jef D.

2017-01-01

Sumoylation regulates a wide range of essential cellular functions through diverse mechanisms that remain to be fully understood. Using S. cerevisiae, a model organism with a single essential SUMO gene (SMT3), we developed a library of >250 mutant strains with single or multiple amino acid substitutions of surface or core residues in the Smt3 protein. By screening this library using plate-based assays, we have generated a comprehensive structure-function based map of Smt3, revealing essential amino acid residues and residues critical for function under a variety of genotoxic and proteotoxic stress conditions. Functionally important residues mapped to surfaces affecting Smt3 precursor processing and deconjugation from protein substrates, covalent conjugation to protein substrates, and non-covalent interactions with E3 ligases and downstream effector proteins containing SUMO-interacting motifs. Lysine residues potentially involved in formation of polymeric chains were also investigated, revealing critical roles for polymeric chains, but redundancy in specific chain linkages. Collectively, our findings provide important insights into the molecular basis of signaling through sumoylation. Moreover, the library of Smt3 mutants represents a valuable resource for further exploring the functions of sumoylation in cellular stress response and other SUMO-dependent pathways. PMID:28166236

Weak Interactions

DOE R&D Accomplishments Database

Lee, T. D.

1957-06-01

Experimental results on the non-conservation of parity and charge conservation in weak interactions are reviewed. The two-component theory of the neutrino is discussed. Lepton reactions are examined under the assumption of the law of conservation of leptons and that the neutrino is described by a two- component theory. From the results of this examination, the universal Fermi interactions are analyzed. Although reactions involving the neutrino can be described, the same is not true of reactions which do not involve the lepton, as the discussion of the decay of K mesons and hyperons shows. The question of the invariance of time reversal is next examined. (J.S.R.)

Effects of multiple enzyme-substrate interactions in basic units of cellular signal processing

NASA Astrophysics Data System (ADS)

Seaton, D. D.; Krishnan, J.

2012-08-01

Covalent modification cycles are a ubiquitous feature of cellular signalling networks. In these systems, the interaction of an active enzyme with the unmodified form of its substrate is essential for signalling to occur. However, this interaction is not necessarily the only enzyme-substrate interaction possible. In this paper, we analyse the behaviour of a basic model of signalling in which additional, non-essential enzyme-substrate interactions are possible. These interactions include those between the inactive form of an enzyme and its substrate, and between the active form of an enzyme and its product. We find that these additional interactions can result in increased sensitivity and biphasic responses, respectively. The dynamics of the responses are also significantly altered by the presence of additional interactions. Finally, we evaluate the consequences of these interactions in two variations of our basic model, involving double modification of substrate and scaffold-mediated signalling, respectively. We conclude that the molecular details of protein-protein interactions are important in determining the signalling properties of enzymatic signalling pathways.

Interactions of NO and CO with Pd and Pt atoms

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

Smith, G.W.; Carter, E.A.

1991-03-21

The authors report ab initio generalized valence bond and correlation-consistent configuration interaction studies of CO and NO interacting with Pd and Pt atoms. They find dramatically different bonding mechanisms for the two ligands, which are easily understood in terms of changes in the electronic structure of the metal and the ligand. CO bonds to both Pd and pt by a {sigma} donor/{pi} back-bonding mechanism, yielding linear geometries. Their calculations predict that the ground ({sup 1}{Sigma}{sup +}) state of PdCO is bound by 27 kcal/mol, while the ground ({sup 1}{Sigma}{sup +}) state of PtCO is bound by only 18.5 kcal/mol. Bymore » contrast, PdNO and PtNO are both bent, with the dominant bonding involving a covalent {sigma} bond between a singly occupied metal d{sigma} orbital and the singly occupied NO 2{pi}* orbital. While the ground ({sup 2}A{prime}) state of PtNO is strongly bound (D{sub e}(Pt-NO) {approximately} 20 kcal/mol), NO binds very weakly to Pd (D{sub e}(Pd-NO) {le} 4 kcal/mol). Linear excited states ({sup 2}{Sigma} and {sup 2}{Pi}) of PtNO and PdNO are predicted to be only weakly bound or unbound. However, corresponding linear cationic states ({sup 1}{Sigma}{sup +} and {sup 3}{Pi}) are strongly bound, but the cationic bent ({sup 1}A{prime}) states are still the ground states of PtNO{sup +} and PdNO{sup +}. These stark contrasts, in which NO binds strongly to Pt but weakly to Pd while CO binds much more strongly to Pd, are due to the preference for closed-shell species to bind strongly to other closed-shell species (e.g., CO to Pd) and for radicals to bind strongly to other radicals (e.g., NO to Pt).« less

Fibrinogen, Riboflavin, and UVA to Immobilize a Corneal Flap – Molecular Mechanisms

PubMed Central

Littlechild, Stacy L.; Zhang, Yuntao; Tomich, John M.; Conrad, Gary W.

2012-01-01

Purpose. Tissue glue containing fibrinogen (FIB) and riboflavin (RF), upon exposure to long wavelength ultraviolet light (UVA, 365 nM) has been proposed potentially to solve long-standing problems presented by corneal wound and epithelial ingrowth side-effects from laser-assisted in situ keratomileuis (LASIK). Data presented in a previous study demonstrated an ability of FIB + RF + UVA to adhere two stromal surfaces; however, to our knowledge no molecular mechanisms have been proposed to account for interactions occurring between corneal extracellular matrix (ECM) and tissue glue molecules. Here, we document several covalent and noncovalent interactions between these classes of macromolecules. Methods. SDS-PAGE and Western blot techniques were used to identify covalent interactions between tissue glue molecules and corneal ECM molecules in either the presence or absence of RF and UVA, in vitro and ex vivo. Surface plasmon resonance (SPR) was used to characterize noncovalent interactions, and obtain ka, kd, and KD binding affinity values. Results. SDS-PAGE and Western blot analyses indicated that covalent interactions occurred between neighboring FIB molecules, as well as between FIB and collagen type I (Coll-I) proteins (in vitro and ex vivo). These interactions occurred only in the presence of RF and UVA. SPR data demonstrated the ability of FIB to bind noncovalently to corneal stroma molecules, Coll-I, decorin, dermatan sulfate, and corneal basement membrane molecules, laminin and heparan sulfate – only in the presence of Zn2+. Conclusions. Covalent and (zinc-mediated) noncovalent mechanisms involving FIB and stromal ECM molecules contribute to the adhesion created by FIB + RF + UVA. PMID:22879413

Nanoparticle decoration with surfactants: Molecular interactions, assembly, and applications

NASA Astrophysics Data System (ADS)

Heinz, Hendrik; Pramanik, Chandrani; Heinz, Ozge; Ding, Yifu; Mishra, Ratan K.; Marchon, Delphine; Flatt, Robert J.; Estrela-Lopis, Irina; Llop, Jordi; Moya, Sergio; Ziolo, Ronald F.

2017-02-01

Nanostructures of diverse chemical nature are used as biomarkers, therapeutics, catalysts, and structural reinforcements. The decoration with surfactants has a long history and is essential to introduce specific functions. The definition of surfactants in this review is very broad, following its lexical meaning ;surface active agents;, and therefore includes traditional alkyl modifiers, biological ligands, polymers, and other surface active molecules. The review systematically covers covalent and non-covalent interactions of such surfactants with various types of nanomaterials, including metals, oxides, layered materials, and polymers as well as their applications. The major themes are (i) molecular recognition and noncovalent assembly mechanisms of surfactants on the nanoparticle and nanocrystal surfaces, (ii) covalent grafting techniques and multi-step surface modification, (iii) dispersion properties and surface reactions, (iv) the use of surfactants to influence crystal growth, as well as (v) the incorporation of biorecognition and other material-targeting functionality. For the diverse materials classes, similarities and differences in surfactant assembly, function, as well as materials performance in specific applications are described in a comparative way. Major factors that lead to differentiation are the surface energy, surface chemistry and pH sensitivity, as well as the degree of surface regularity and defects in the nanoparticle cores and in the surfactant shell. The review covers a broad range of surface modifications and applications in biological recognition and therapeutics, sensors, nanomaterials for catalysis, energy conversion and storage, the dispersion properties of nanoparticles in structural composites and cement, as well as purification systems and classical detergents. Design principles for surfactants to optimize the performance of specific nanostructures are discussed. The review concludes with challenges and opportunities.

Double layer effects in electrocatalysis: The oxygen reduction reaction and ethanol oxidation reaction on Au(111), Pt(111) and Ir(111) in alkaline media containing Na and Li cations

DOE PAGES

Lopes, Pietro P.; Strmcnik, Dusan; Jirkovsky, Jakub S.; ...

2015-09-28

Oxygen reduction and ethanol oxidation reactions were studied on Au(111), Pt(111) and Ir(111) in alkaline solutions containing sodium and/or lithium cations. By keeping the same (111) surface orientation and exploring oxophilicity trends and non-covalent interactions between OH ad and alkali metal cations (AMC n+), we were able to gain deep insights into the multiple roles that OH ad plays in these important electrocatalytic reactions. Cyclic voltammetry experiments revealed that OH ad formation initiates at distinct electrode potentials, governed by the oxophilicity of the specific metal surface, with further OH ad adlayer stabilization by non-covalent alkali-cation interactions and affecting the formationmore » of a “true oxide” layer at higher electrode potentials. Although OH ad is a simple spectator for the ORR, it promotes the ethanol oxidation reaction (EOR) at lower potentials and act as spectator at high OHad coverages. By changing the alkali metal cation at the interface (Li +) on more oxophilic surfaces, it was possible to promote the EOR even more, relative to Na +, without changing the product distribution for the reaction. This cation effect suggests that OH ad—Li +(H 2O) x clusters can stabilize the ethoxide adlayer, thus improving the EOR activity. Finally, our results indicate the importance of the entire electrochemical interface in determining the electrocatalytic activity during reaction.« less

Applications of nuclear magnetic resonance spectroscopy for the understanding of enantiomer separation mechanisms in capillary electrophoresis.

PubMed

Salgado, Antonio; Chankvetadze, Bezhan

2016-10-07

This review deals with the applications of nuclear magnetic resonance (NMR) spectroscopy to understand the mechanisms of chiral separation in capillary electrophoresis (CE). It is accepted that changes observed in the separation process, including the reversal of enantiomer migration order (EMO), can be caused by subtle modifications in the molecular recognition mechanisms between enantiomer and chiral selector. These modifications may imply minor structural differences in those selector-selectand complexes that arise from the above mentioned interactions. Therefore, it is mandatory to understand the fine intermolecular interactions between analytes and chiral selectors. In other words, it is necessary to know in detail the structures of the complexes formed by the enantiomer (selectand) and the selector. Any differences in the structures of these complexes arising from either enantiomer should be detected, so that enantiomeric bias in the separation process could be explained. As to the nature of these interactions, those have been extensively reviewed, and it is not intended to be discussed here. These interactions contemplate ionic, ion-dipole and dipole-dipole interactions, hydrogen bonding, van der Waals forces, π-π stacking, steric and hydrophobic interactions. The main subject of this review is to describe how NMR spectroscopy helps to gain insight into the non-covalent intermolecular interactions between selector and selectand that lead to enantiomer separation by CE. Examples in which diastereomeric species are created by covalent (irreversible) derivatization will not be considered here. This review is structured upon the different structural classes of chiral selectors employed in CE, in which NMR spectroscopy has made substantial contributions to rationalize the observed enantioseparations. Cases in which other techniques complement NMR spectroscopic data are also mentioned. Copyright © 2016 Elsevier B.V. All rights reserved.

Mechanism of amido-thiourea catalyzed enantioselective imine hydrocyanation: transition state stabilization via multiple non-covalent interactions.

PubMed

Zuend, Stephan J; Jacobsen, Eric N

2009-10-28

An experimental and computational investigation of amido-thiourea promoted imine hydrocyanation has revealed a new and unexpected mechanism of catalysis. Rather than direct activation of the imine by the thiourea, as had been proposed previously in related systems, the data are consistent with a mechanism involving catalyst-promoted proton transfer from hydrogen isocyanide to imine to generate diastereomeric iminium/cyanide ion pairs that are bound to catalyst through multiple noncovalent interactions; these ion pairs collapse to form the enantiomeric alpha-aminonitrile products. This mechanistic proposal is supported by the observation of a statistically significant correlation between experimental and calculated enantioselectivities induced by eight different catalysts (P < 0.01). The computed models reveal a basis for enantioselectivity that involves multiple stabilizing and destabilizing interactions between substrate and catalyst, including thiourea-cyanide and amide-iminium interactions.

Halogen-bonding-triggered supramolecular gel formation

NASA Astrophysics Data System (ADS)

Meazza, Lorenzo; Foster, Jonathan A.; Fucke, Katharina; Metrangolo, Pierangelo; Resnati, Giuseppe; Steed, Jonathan W.

2013-01-01

Supramolecular gels are topical soft materials involving the reversible formation of fibrous aggregates using non-covalent interactions. There is significant interest in controlling the properties of such materials by the formation of multicomponent systems, which exhibit non-additive properties emerging from interaction of the components. The use of hydrogen bonding to assemble supramolecular gels in organic solvents is well established. In contrast, the use of halogen bonding to trigger supramolecular gel formation in a two-component gel (‘co-gel’) is essentially unexplored, and forms the basis for this study. Here, we show that halogen bonding between a pyridyl substituent in a bis(pyridyl urea) and 1,4-diiodotetrafluorobenzene brings about gelation, even in polar media such as aqueous methanol and aqueous dimethylsulfoxide. This demonstrates that halogen bonding is sufficiently strong to interfere with competing gel-inhibitory interactions and create a ‘tipping point’ in gel assembly. Using this concept, we have prepared a halogen bond donor bis(urea) gelator that forms co-gels with halogen bond acceptors.

Similarity-transformed perturbation theory on top of truncated local coupled cluster solutions: Theory and applications to intermolecular interactions

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

Azar, Richard Julian, E-mail: julianazar2323@berkeley.edu; Head-Gordon, Martin, E-mail: mhg@cchem.berkeley.edu

2015-05-28

Your correspondents develop and apply fully nonorthogonal, local-reference perturbation theories describing non-covalent interactions. Our formulations are based on a Löwdin partitioning of the similarity-transformed Hamiltonian into a zeroth-order intramonomer piece (taking local CCSD solutions as its zeroth-order eigenfunction) plus a first-order piece coupling the fragments. If considerations are limited to a single molecule, the proposed intermolecular similarity-transformed perturbation theory represents a frozen-orbital variant of the “(2)”-type theories shown to be competitive with CCSD(T) and of similar cost if all terms are retained. Different restrictions on the zeroth- and first-order amplitudes are explored in the context of large-computation tractability and elucidationmore » of non-local effects in the space of singles and doubles. To accurately approximate CCSD intermolecular interaction energies, a quadratically growing number of variables must be included at zeroth-order.« less

Non-Covalent Functionalisation of C30 Fullerene by Pyrrole-n-Carboxylic Acid (n=2, 3): Density Functional Theory Studies

NASA Astrophysics Data System (ADS)

Harismah, Kun; Mirzaei, Mahmoud; Ghasemi, Nahid; Nejati, Mohammad

2017-12-01

For functionalisation of a representative C30 fullerene nanostructure by pyrrole-n-carboxylic acid (PnCA; n=2, 3) their stabilities and properties were investigated based on density functional theory calculations. Parallel calculations were also done for C60 fullerene as evidence for comparing the results. Non-covalent interactions are considered to make the functionalised structures. In contrast with the spherical shape of C60, the shape of C30 fullerene is elliptical; therefore, the functionalisation processes were done for both axial and equatorial elliptical positions (AC30 and EC30). The results indicated that both the positions of C30 have almost equivalent chances to be functionalised by PnCA; but functionalisation by P2CA is slightly more favourable than P3CA, either for C60. The illustrated molecular orbitals' distributions indicated that the direction of charge transfer could be considered from PnCA counterparts to fullerene counterparts. The molecular properties indicated more reactivity for C30 than for C60 fullerene. Finally, the atomic scale quadrupole coupling constants indicated different roles for N and O atoms of PnCA in the functionalised models.

Optical fingerprint of non-covalently functionalized transition metal dichalcogenides

NASA Astrophysics Data System (ADS)

Feierabend, Maja; Malic, Ermin; Knorr, Andreas; Berghäuser, Gunnar

2017-09-01

Atomically thin transition metal dichalcogenides (TMDs) hold promising potential for applications in optoelectronics. Due to their direct band gap and the extraordinarily strong Coulomb interaction, TMDs exhibit efficient light-matter coupling and tightly bound excitons. Moreover, large spin orbit coupling in combination with circular dichroism allows for spin and valley selective optical excitation. As atomically thin materials, they are very sensitive to changes in the surrounding environment. This motivates a functionalization approach, where external molecules are adsorbed to the materials surface to tailor its optical properties. Here, we apply the density matrix theory to investigate the potential of non-covalently functionalized monolayer TMDs. Considering exemplary molecules with a strong dipole moment, we predict spectral redshifts and the appearance of an additional side peak in the absorption spectrum of functionalized TMDs. We show that the molecular characteristics, e.g. coverage, orientation and dipole moment, crucially influence the optical properties of TMDs, leaving a unique optical fingerprint in the absorption spectrum. Furthermore, we find that the molecular dipole moments open a channel for coherent intervalley coupling between the high-symmetry K and K\\prime points which may create new possibilities for spin-valleytronics application.

Catalyst recycling via specific non-covalent adsorption on modified silicas.

PubMed

Kluwer, Alexander M; Simons, Chretien; Knijnenburg, Quinten; van der Vlugt, Jarl Ivar; de Bruin, Bas; Reek, Joost N H

2013-03-14

This article describes a new strategy for the recycling of a homogeneous hydroformylation catalyst, by selective adsorption of the catalyst to tailor-made supports after a batchwise reaction. The separation of the catalyst from the product mixture is based on selective non-covalent supramolecular interactions between a ligand and the support. Changing the solvent releases the active catalyst back into the reactor and allows a subsequent batch reaction with the recycled active catalyst. For this purpose, the bidentate NixantPhos ligand has been equipped with a pyridine group. The corresponding rhodium pre-catalyst [Rh(Nix-py)(acac)] (acac = acetylacetonate) forms a very selective, active and highly stable catalyst, and able to reach a turnover number (TON) of 170 000 in a single run (reaction performed in nearly neat 1-octene, S/C ratio of 200 000, at 140 °C, 20 bars syngas pressure). Various commercially available supports have been explored in binding studies and recycling experiments. The end-capped silica-alumina performs the best so far with respect to ligand-adsorbing properties for the current purpose. Although this system has not been fully optimized, four recycling runs could be performed successfully.

Copper(II) complexes with uridine, uridine 5'-monophosphate, spermidine, or spermine in aqueous solution.

PubMed

Lomozik, Lechoslaw; Jastrzab, Renata

2003-01-15

Molecular complexes of the types (Urd)H(x)(PA) and (UMP)H(x)(PA) are formed in the uridine (Urd) or uridine 5'-monophosphate (UMP) plus spermidine or spermine systems, as shown by the results of equilibrium and spectral studies. Overall stability constants of the adducts and equilibrium constants of their formation have been determined. An increase in the efficiency of the reaction between the bioligands is observed with increasing length of the polyamine. The pH range of adduct formation is found to coincide with that in which the polyamine is protonated while uridine or its monophosphate is deprotonated. The -NH(x)(+) groups from PA and the N(3) atom of the purine base as well as phosphate groups from the nucleotides have been identified as the significant centres of non-covalent interactions. Compared to cytidine, the pH range of Urd adduct formation is shifted significantly higher due to differences in the protonation constants of the endocyclic N(3) donor atoms of particular nucleosides. Overall stability constants of the Cu(II) complexes with uridine and uridine 5'-monophosphate in ternary systems with spermidine or spermine have been determined. It has been found from spectral data that in the Cu(II) ternary complexes with nucleosides and polyamines the reaction of metallation involves mainly N(3) atoms from the pyrimidine bases, as well as the amine groups of PA. This unexpected type of interaction has been evidenced in the coordination mode of the complexes forming in the Cu-UMP systems including spermidine or spermine. Results of spectral and equilibrium studies indicate that the phosphate groups taking part in metallation are at the same time involved in non-covalent interaction with the protonated polyamine.

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

Zhang, Jiang; Malmirchegini, G. Reza; Clubb, Robert T.

Native mass spectrometry (MS) has become an invaluable tool for the characterization of proteins and non-covalent protein complexes under near physiological solution conditions. Here we report the structural characterization of human hemoglobin (Hb), a 64 kDa oxygen-transporting protein complex, by high resolution native top-down mass spectrometry using electrospray ionization (ESI) and a 15-Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Native MS preserves the non-covalent interactions between the globin subunits, and electron capture dissociation (ECD) produces fragments directly from the intact Hb complex without dissociating the subunits. Using activated ion ECD, we observe the gradual unfolding process of themore » Hb complex in the gas phase. Without protein ion activation, the native Hb shows very limited ECD fragmentation from the N-termini, suggesting a tightly packed structure of the native complex and therefore low fragmentation efficiency. Precursor ion activation allows steady increase of N-terminal fragment ions, while the C-terminal fragments remain limited (38 c ions and 4 z ions on the α chain; 36 c ions and 2 z ions on the β chain). This ECD fragmentation pattern suggests that upon activation, the Hb complex starts to unfold from the N-termini of both subunits, whereas the C-terminal regions and therefore the potential regions involved in the subunit binding interactions remain intact. ECD-MS of the Hb dimer show similar fragmentation patterns as the Hb tetramer, providing further evidence for the hypothesized unfolding process of the Hb complex in the gas phase. Native top-down ECD-MS allows efficient probing of the Hb complex structure and the subunit binding interactions in the gas phase. Finally, it may provide a fast and effective means to probe the structure of novel protein complexes that are intractable to traditional structural characterization tools.« less

Tailor Made Synthesis of T-Shaped and π-STACKED Dimers in the Gas Phase: Concept for Efficient Drug Design and Material Synthesis

NASA Astrophysics Data System (ADS)

Kumar, Sumit; Das, Aloke

2013-06-01

Non-covalent interactions play a key role in governing the specific functional structures of biomolecules as well as materials. Thus molecular level understanding of these intermolecular interactions can help in efficient drug design and material synthesis. It has been found from X-ray crystallography that pure hydrocarbon solids (i.e. benzene, hexaflurobenzene) have mostly slanted T-shaped (herringbone) packing arrangement whereas mixed solid hydrocarbon crystals (i.e. solid formed from mixtures of benzene and hexafluorobenzene) exhibit preferentially parallel displaced (PD) π-stacked arrangement. Gas phase spectroscopy of the dimeric complexes of the building blocks of solid pure benzene and mixed benzene-hexafluorobenzene adducts exhibit similar structural motifs observed in the corresponding crystal strcutures. In this talk, I will discuss about the jet-cooled dimeric complexes of indole with hexafluorobenzene and p-xylene in the gas phase using Resonant two photon ionzation and IR-UV double resonance spectroscopy combined with quantum chemistry calculations. In stead of studying benzene...p-xylene and benzene...hexafluorobenzene dimers, we have studied corresponding indole complexes because N-H group is much more sensitive IR probe compared to C-H group. We have observed that indole...hexafluorobenzene dimer has parallel displaced (PD) π-stacked structure whereas indole...p-xylene has slanted T-shaped structure. We have shown here selective switching of dimeric structure from T-shaped to π-stacked by changing the substituent from electron donating (-CH3) to electron withdrawing group (fluorine) in one of the complexing partners. Thus, our results demonstrate that efficient engineering of the non-covalent interactions can lead to efficient drug design and material synthesis.

Nucleophilicities of Lewis Bases B and Electrophilicities of Lewis Acids A Determined from the Dissociation Energies of Complexes B⋯A Involving Hydrogen Bonds, Tetrel Bonds, Pnictogen Bonds, Chalcogen Bonds and Halogen Bonds.

PubMed

Alkorta, Ibon; Legon, Anthony C

2017-10-23

It is shown that the dissociation energy D e for the process B⋯A = B + A for 250 complexes B⋯A composed of 11 Lewis bases B (N₂, CO, HC≡CH, CH₂=CH₂, C₃H₆, PH₃, H₂S, HCN, H₂O, H₂CO and NH₃) and 23 Lewis acids (HF, HCl, HBr, HC≡CH, HCN, H₂O, F₂, Cl₂, Br₂, ClF, BrCl, H₃SiF, H₃GeF, F₂CO, CO₂, N₂O, NO₂F, PH₂F, AsH₂F, SO₂, SeO₂, SF₂, and SeF₂) can be represented to good approximation by means of the equation D e = c ' N B E A , in which N B is a numerical nucleophilicity assigned to B, E A is a numerical electrophilicity assigned to A, and c ' is a constant, conveniently chosen to have the value 1.00 kJ mol -1 here. The 250 complexes were chosen to cover a wide range of non-covalent interaction types, namely: (1) the hydrogen bond; (2) the halogen bond; (3) the tetrel bond; (4) the pnictogen bond; and (5) the chalcogen bond. Since there is no evidence that one group of non-covalent interaction was fitted any better than the others, it appears the equation is equally valid for all the interactions considered and that the values of N B and E A so determined define properties of the individual molecules. The values of N B and E A can be used to predict the dissociation energies of a wide range of binary complexes B⋯A with reasonable accuracy.

Real-Space Bonding Indicator Analysis of the Donor-Acceptor Complexes X3BNY3, X3AlNY3, X3BPY3, and X3AlPY3 (X, Y = H, Me, Cl).

PubMed

Mebs, Stefan; Beckmann, Jens

2017-10-12

Calculations of real-space bonding indicators (RSBI) derived from Atoms-In-Molecules (AIM), Electron Localizability Indicator (ELI-D), Non-Covalent Interactions index (NCI), and Density Overlap Regions Indicator (DORI) toolkits for a set of 36 donor-acceptor complexes X 3 BNY 3 (1, 1a-1h), X 3 AlNY 3 (2, 2a-2h), X 3 BPY 3 (3, 3a-3h), and X 3 AlPY 3 (4, 4a-4h) reveal that the donor-acceptor bonds comprise covalent and ionic interactions in varying extents (X = Y = H for 1-4; X = H, Y = Me for 1a-4a; X = H, Y = Cl for 1b-4b; X = Me, Y = H for 1c-4c; X, Y = Me for 1d-4d; X = Me, Y = Cl for 1e-4e; X = Cl, Y = H for 1f-4f; X = Cl, Y = Me for 1g-4g; X, Y = Cl for 1h-4h). The phosphinoboranes X 3 BPY 3 (3, 3a-3h) in general and Cl 3 BPMe 3 (3f) in particular show the largest covalent contributions and the least ionic contributions. The aminoalanes X 3 AlNY 3 (2, 2a-2h) in general and Me 3 AlNCl 3 (2e) in particular show the least covalent contributions and the largest ionic contributions. The aminoboranes X 3 BNY 3 (1, 1a-1h) and the phosphinoalanes X 3 AlPY 3 (4, 4a-4h) are midway between phosphinoboranes and aminoalanes. The degree of covalency and ionicity correlates with the electronegativity difference BP (ΔEN = 0.15) < AlP (ΔEN = 0.58) < BN (ΔEN = 1.00) < AlN (ΔEN = 1.43) and a previously published energy decomposition analysis (EDA). To illustrate the importance of both contributions in Lewis formula representations, two resonance formulas should be given for all compounds, namely, the canonical form with formal charges denoting covalency and the arrow notation pointing from the donor to the acceptor atom to emphasis ionicity. If the Lewis formula mainly serves to show the atomic connectivity, the most significant should be shown. Thus, it is legitimate to present aminoalanes using arrows; however, for phosphinoboranes the canonical form with formal charges is more appropriate.

Defining the Human Deubiquitinating Enzyme Interaction Landscape

PubMed Central

Sowa, Mathew E.; Bennett, Eric J.; Gygi, Steven P.; Harper, J. Wade

2009-01-01

Summary Deubiquitinating enzymes (Dubs) function to remove covalently attached ubiquitin from proteins, thereby controlling substrate activity and/or abundance. For most Dubs, their functions, targets, and regulation are poorly understood. To systematically investigate Dub function, we initiated a global proteomic analysis of Dubs and their associated protein complexes. This was accomplished through the development of a software platform, called CompPASS, which uses unbiased metrics to assign confidence measurements to interactions from parallel non-reciprocal proteomic datasets. We identified 774 candidate interacting proteins associated with 75 Dubs. Using Gene Ontology, interactome topology classification, sub-cellular localization and functional studies, we link Dubs to diverse processes, including protein turnover, transcription, RNA processing, DNA damage, and endoplasmic reticulum-associated degradation. This work provides the first glimpse into the Dub interaction landscape, places previously unstudied Dubs within putative biological pathways, and identifies previously unknown interactions and protein complexes involved in this increasingly important arm of the ubiquitin-proteasome pathway. PMID:19615732

Inhibition of interaction between epigallocatechin-3-gallate and myofibrillar protein by cyclodextrin derivatives improves gel quality under oxidative stress.

PubMed

Zhang, Yumeng; Chen, Lin; Lv, Yuanqi; Wang, Shuangxi; Suo, Zhiyao; Cheng, Xingguang; Xu, Xinglian; Zhou, Guanghong; Li, Zhixi; Feng, Xianchao

2018-06-01

High levels of polyphenols can interact with myofibrillar proteins (MPs), causing damage to a MP emulsion gel. In this study, β-cyclodextrins were used to reduce covalent and non-covalent interaction between epigallocatechin-3-gallate (EGCG) and MPs under oxidative stress. The loss of both thiol and free amine groups and the unfolding of MPs caused by EGCG (80 μM/g protein) were significantly prevented by β-cyclodextrins, and the structural stability and solubility were improved. MP emulsion gel treated with EGCG (80 μM/g protein) had the highest cooking loss (68.64%) and gel strength (0.51 N). Addition of β-cyclodextrins significantly reduced cooking loss (26.24-58.20%) and improved gel strength (0.31-0.41 N) of MP emulsion gel jeopardized by EGCG under oxidative stress. Damage to the emulsifying properties of MPs caused by EGCG was significantly prevented by addition of β-cyclodextrins. β-cyclodextrins reduced interaction between EGCG and MPs in the order Methyl-β-cyclodextrin > (2-Hydroxypropyl)-β-cyclodextrin > β-cyclodextrin. In absence of EGCG, addition of β-cyclodextrins partly protected MPs from oxidative attack and improved its solubility. It is concluded that β-cyclodextrins does not markedly reduce the antioxidant ability of EGCG according to carbonyl analysis, and can effectively increase EGCG loading to potentially provide more durable antioxidant effect for meat products during processing, transportation and storage. Copyright © 2018 Elsevier Ltd. All rights reserved.

The interplay of covalency, hydrogen bonding, and dispersion leads to a long range chiral network: The example of 2-butanol

NASA Astrophysics Data System (ADS)

Liriano, Melissa L.; Carrasco, Javier; Lewis, Emily A.; Murphy, Colin J.; Lawton, Timothy J.; Marcinkowski, Matthew D.; Therrien, Andrew J.; Michaelides, Angelos; Sykes, E. Charles H.

2016-03-01

The assembly of complex structures in nature is driven by an interplay between several intermolecular interactions, from strong covalent bonds to weaker dispersion forces. Understanding and ultimately controlling the self-assembly of materials requires extensive study of how these forces drive local nanoscale interactions and how larger structures evolve. Surface-based self-assembly is particularly amenable to modeling and measuring these interactions in well-defined systems. This study focuses on 2-butanol, the simplest aliphatic chiral alcohol. 2-butanol has recently been shown to have interesting properties as a chiral modifier of surface chemistry; however, its mode of action is not fully understood and a microscopic understanding of the role non-covalent interactions play in its adsorption and assembly on surfaces is lacking. In order to probe its surface properties, we employed high-resolution scanning tunneling microscopy and density functional theory (DFT) simulations. We found a surprisingly rich degree of enantiospecific adsorption, association, chiral cluster growth and ultimately long range, highly ordered chiral templating. Firstly, the chiral molecules acquire a second chiral center when adsorbed to the surface via dative bonding of one of the oxygen atom lone pairs. This interaction is controlled via the molecule's intrinsic chiral center leading to monomers of like chirality, at both chiral centers, adsorbed on the surface. The monomers then associate into tetramers via a cyclical network of hydrogen bonds with an opposite chirality at the oxygen atom. The evolution of these square units is surprising given that the underlying surface has a hexagonal symmetry. Our DFT calculations, however, reveal that the tetramers are stable entities that are able to associate with each other by weaker van der Waals interactions and tessellate in an extended square network. This network of homochiral square pores grows to cover the whole Au(111) surface. Our data reveal that the chirality of a simple alcohol can be transferred to its surface binding geometry, drive the directionality of hydrogen-bonded networks and ultimately extended structure. Furthermore, this study provides the first microscopic insight into the surface properties of this important chiral modifier and provides a well-defined system for studying the network's enantioselective interaction with other molecules.

The interplay of covalency, hydrogen bonding, and dispersion leads to a long range chiral network: The example of 2-butanol

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

Liriano, Melissa L.; Lewis, Emily A.; Murphy, Colin J.

The assembly of complex structures in nature is driven by an interplay between several intermolecular interactions, from strong covalent bonds to weaker dispersion forces. Understanding and ultimately controlling the self-assembly of materials requires extensive study of how these forces drive local nanoscale interactions and how larger structures evolve. Surface-based self-assembly is particularly amenable to modeling and measuring these interactions in well-defined systems. This study focuses on 2-butanol, the simplest aliphatic chiral alcohol. 2-butanol has recently been shown to have interesting properties as a chiral modifier of surface chemistry; however, its mode of action is not fully understood and a microscopicmore » understanding of the role non-covalent interactions play in its adsorption and assembly on surfaces is lacking. In order to probe its surface properties, we employed high-resolution scanning tunneling microscopy and density functional theory (DFT) simulations. We found a surprisingly rich degree of enantiospecific adsorption, association, chiral cluster growth and ultimately long range, highly ordered chiral templating. Firstly, the chiral molecules acquire a second chiral center when adsorbed to the surface via dative bonding of one of the oxygen atom lone pairs. This interaction is controlled via the molecule’s intrinsic chiral center leading to monomers of like chirality, at both chiral centers, adsorbed on the surface. The monomers then associate into tetramers via a cyclical network of hydrogen bonds with an opposite chirality at the oxygen atom. The evolution of these square units is surprising given that the underlying surface has a hexagonal symmetry. Our DFT calculations, however, reveal that the tetramers are stable entities that are able to associate with each other by weaker van der Waals interactions and tessellate in an extended square network. This network of homochiral square pores grows to cover the whole Au(111) surface. Our data reveal that the chirality of a simple alcohol can be transferred to its surface binding geometry, drive the directionality of hydrogen-bonded networks and ultimately extended structure. Furthermore, this study provides the first microscopic insight into the surface properties of this important chiral modifier and provides a well-defined system for studying the network’s enantioselective interaction with other molecules.« less

Electron tunneling through covalent and noncovalent pathways in proteins

NASA Technical Reports Server (NTRS)

Beratan, David N.; Onuchic, Jose Nelson; Hopfield, J. J.

1987-01-01

A model is presented for electron tunneling in proteins which allows the donor-acceptor interaction to be mediated by the covalent bonds between amino acids and noncovalent contacts between amino acid chains. The important tunneling pathways are predicted to include mostly bonded groups with less favorable nonbonded interactions being important when the through bond pathway is prohibitively long. In some cases, vibrational motion of nonbonded groups along the tunneling pathway strongly influences the temperature dependence of the rate. Quantitative estimates for the sizes of these noncovalent interactions are made and their role in protein mediated electron transport is discussed.

Design and Mechanism of Tetrahydrothiophene-based GABA Aminotransferase Inactivators

PubMed Central

Le, Hoang V.; Hawker, Dustin D.; Wu, Rui; Doud, Emma; Widom, Julia; Sanishvili, Ruslan; Liu, Dali; Kelleher, Neil L.; Silverman, Richard B.

2015-01-01

Low levels of γ-aminobutyric acid (GABA), one of two major neurotransmitters that regulate brain neuronal activity, are associated with many neurological disorders, such as epilepsy, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, and cocaine addiction. One of the main methods to raise the GABA level in human brain is to use small molecules that cross the blood-brain barrier and inhibit the activity of γ-aminobutyric acid aminotransferase (GABA-AT), the enzyme that degrades GABA. We have designed a series of conformationally-restricted, tetrahydrothiophene-based GABA analogs with a properly-positioned leaving group that could facilitate a ring-opening mechanism, leading to inactivation of GABA-AT. One compound in the series is eight times more efficient an inactivator of GABA-AT than vigabatrin, the only FDA-approved inactivator of GABA-AT. Our mechanistic studies show that the compound inactivates GABA-AT by a new mechanism. The metabolite resulting from inactivation does not covalently bind to amino acid residues of GABA-AT but stays in the active site via H-bond interactions with Arg-192, a π-π interaction with Phe-189, and a weak nonbonded S···O=C interaction with Glu-270, thereby inactivating the enzyme. PMID:25781189

Design and Mechanism of Tetrahydrothiophene-Based γ-Aminobutyric Acid Aminotransferase Inactivators

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

Le, Hoang V.; Hawker, Dustin D.; Wu, Rui

Low levels of gamma-aminobutyric acid (GABA), one of two major neurotransmitters that regulate brain neuronal activity, are associated with many neurological disorders, such as epilepsy, Parkinsons disease, Alzheimers disease, Huntingtons disease, and cocaine addiction. One of the main methods to raise the GABA level in human brain is to use small molecules that cross the bloodbrain barrier and inhibit the activity of gamma-aminobutyric acid aminotransferase (GABA-AT), the enzyme that degrades GABA. We have designed a series of conformationally restricted tetrahydrothiophene-based GABA analogues with a properly positioned leaving group that could facilitate a ring-opening mechanism, leading to inactivation of GABA-AT. Onemore » compound in the series is 8 times more efficient an inactivator of GABA-AT than vigabatrin, the only FDA-approved inactivator of GABA-AT. Our mechanistic studies show that the compound inactivates GABA-AT by a new mechanism. The metabolite resulting from inactivation does not covalently bind to amino acid residues of GABA-AT but stays in the active site via H-bonding interactions with Arg-192, a pi-pi interaction with Phe-189, and a weak nonbonded (SO)-O-...=C interaction with Glu-270, thereby inactivating the enzyme.« less

Design and mechanism of tetrahydrothiophene-based γ-aminobutyric acid aminotransferase inactivators.

PubMed

Le, Hoang V; Hawker, Dustin D; Wu, Rui; Doud, Emma; Widom, Julia; Sanishvili, Ruslan; Liu, Dali; Kelleher, Neil L; Silverman, Richard B

2015-04-08

Low levels of γ-aminobutyric acid (GABA), one of two major neurotransmitters that regulate brain neuronal activity, are associated with many neurological disorders, such as epilepsy, Parkinson's disease, Alzheimer's disease, Huntington's disease, and cocaine addiction. One of the main methods to raise the GABA level in human brain is to use small molecules that cross the blood-brain barrier and inhibit the activity of γ-aminobutyric acid aminotransferase (GABA-AT), the enzyme that degrades GABA. We have designed a series of conformationally restricted tetrahydrothiophene-based GABA analogues with a properly positioned leaving group that could facilitate a ring-opening mechanism, leading to inactivation of GABA-AT. One compound in the series is 8 times more efficient an inactivator of GABA-AT than vigabatrin, the only FDA-approved inactivator of GABA-AT. Our mechanistic studies show that the compound inactivates GABA-AT by a new mechanism. The metabolite resulting from inactivation does not covalently bind to amino acid residues of GABA-AT but stays in the active site via H-bonding interactions with Arg-192, a π-π interaction with Phe-189, and a weak nonbonded S···O═C interaction with Glu-270, thereby inactivating the enzyme.

Measurement of monomolecular binding constants of neutral phenols into the beta-cyclodextrin by continuous frontal analysis in capillary and microchip electrophoresis via a competitive assay.

PubMed

Le Saux, Thomas; Hisamoto, Hideaki; Terabe, Shigeru

2006-02-03

Measurement of binding constant by chip electrophoresis is a very promising technique for the high throughput screening of non-covalent interactions. Among the different electrophoretic methods available that yield the binding parameters, continuous frontal analysis is the most appropriate for a transposition from capillary electrophoresis (CE) to microchip electrophoresis. Implementation of this methodology in microchip was exemplified by the measurement of inclusion constants of 2-naphtalenesulfonate and neutral phenols (phenol, 4-chlorophenol and 4-nitrophenol) into beta-cyclodextrin by competitive assays. The issue of competitor choice is discussed in relation to its appropriateness for proper monitoring of the interaction.

Photodissociation of Non-Covalent Peptide-Crown Ether Complexes

PubMed Central

Wilson, Jeffrey J.; Kirkovits, Gregory J.; Sessler, Jonathan L.; Brodbelt, Jennifer S.

2008-01-01

Highly chromogenic 18-crown-6-dipyrrolylquinoxaline coordinates primary amines of peptides, forming non-covalent complexes that can be transferred to the gas phase by electrospray ionization. The appended chromogenic crown ether facilitates efficient energy transfer to the peptide upon ultraviolet irradiation in the gas phase, resulting in diagnostic peptide fragmentation. Collisional activated dissociation (CAD) and infrared multiphoton dissociation (IRMPD) of these non-covalent complexes results only in their disassembly with the charge retained on either the peptide or crown ether, yielding no sequence ions. Upon UV photon absorption the intermolecular energy transfer is facilitated by the fast activation time scale of UVPD (< 10 ns) and by the collectively strong hydrogen bonding between the crown ether and peptide, thus allowing effective transfer of energy to the peptide moiety prior to disruption of the intermolecular hydrogen bonds. PMID:18077179

ATP and Mg2+ Promote the Reversible Oligomerization and Aggregation of Chloroplast 2-Cys Peroxiredoxin*

PubMed Central

Aran, Martín; Ferrero, Diego; Wolosiuk, Alejandro; Mora-García, Santiago; Wolosiuk, Ricardo A.

2011-01-01

2-Cys peroxiredoxins (2-Cys Prxs) are ubiquitous peroxidases with important roles in cellular antioxidant defense and hydrogen peroxide-mediated signaling. Post-translational modifications of conserved cysteines cause the transition from low to high molecular weight oligomers, triggering the functional change from peroxidase to molecular chaperone. However, it remains unclear how non-covalent interactions of 2-Cys Prx with metabolites modulate the quaternary structure. Here, we disclose that ATP and Mg2+ (ATP/Mg) promote the self-polymerization of chloroplast 2-Cys Prx (polypeptide 23.5 kDa) into soluble higher order assemblies (>2 MDa) that proceed to insoluble aggregates beyond 5 mm ATP. Remarkably, the withdrawal of ATP or Mg2+ brings soluble oligomers and insoluble aggregates back to the native conformation without compromising the associated functions. As confirmed by transmission electron microscopy, ATP/Mg drive the toroid-like decamers (diameter 13 nm) to the formation of large sphere-like particles (diameter ∼30 nm). Circular dichroism studies on ATP-labeled 2-Cys Prx reveal that ATP/Mg enhance the proportion of β-sheets with the concurrent decrease in the content of α-helices. In line with this observation, the formation of insoluble aggregates is strongly prevented by 2,2,2-trifluoroethanol, a cosolvent employed to induce α-helical conformations. We further find that the response of self-polymerization to ATP/Mg departs abruptly from that of the associated peroxidase and chaperone activities when two highly conserved residues, Arg129 and Arg152, are mutated. Collectively, our data uncover that non-covalent interactions of ATP/Mg with 2-Cys Prx modulate dynamically the quaternary structure, thereby coupling the non-redox chemistry of cell energy with redox transformations at cysteine residues. PMID:21525006

Heath Sector Network Governance and State-building in South Kivu, Democratic Republic of Congo.

PubMed

Bwimana, Aembe

2017-12-01

Longstanding patterns of interaction exist between state and non-state actors seeking to improve public health in Democratic Republic of Congo (DRC). DRC is a weak state, and, in many cases, private actors have stepped in to fill the void created by the lack of state health care provision. However, the role of these interactions in creating a governance network in the health sector has been underexplored. Using data from 18 months of qualitative field research, this study aimed to explore governance networks in DRC's health sector, examining how multiple stakeholders work to manage the health system and how the resulting governance network has been relevant for the state-building process. The findings demonstrate that the health sector in South Kivu is emerging as an arena of networked governance based on active partnerships between state institutions and non-state actors. Interactions between state and non-state actors account for the persistence of the health sector in a setting characterized by state weakness. However, networked governance does not function optimally, because, although non-state interventions fill the void where the state falls short, the DRC state has faced the challenge of interacting with partners with fragmented and horizontally competing agendas. Although weak, the shadow of state authority is present in the arena of stakeholders' interactions, as the state plays a determining role by providing a regulatory framework. Overall, the findings show that the interactive engagement of non-state actors contributes to improving institutional capacity through these actors' engagement with state institutions for health system management and institutional development. However, although networked health sector governance does contribute to state capacity, it is difficult to assess the real influence of these interactions on the state-building process in a context of critical fragility, where coordination and alignment have been problematic. © The Author 2017. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Polyethyleneglycol/silver functionalized reduced graphene oxide aerogel for environmental application

NASA Astrophysics Data System (ADS)

Kumari, G. Vanitha; Asha, S.; Ananth, A. Nimrodh; Rajan, M. A. Jothi; Mathavan, T.

2018-04-01

Polyethylene glycol (PEG)/Silver (Ag) functionalized reduced graphene oxide aerogel (RGOA) was synthesized. PEG/Ag decorated reduced graphene oxide aerogel was characterized using XRD, Raman spectroscopy, Fourier transform infrared spectroscopy (FT-IR). The surface morphology of PEG/Ag/RGOA was analyzed using scanning electron microscope. The non-covalent interaction between reduced graphene oxide layers and the interaction between PEG and Ag on RGOA were studied by FT-IR spectra. It was observed that the interaction between Ag and PEG could enhance the properties of RGOA. Methyl Orange (MO) dye degradation was observed from UV-Vis Spectra. The process was studied by monitoring the simultaneous decrease in the height of UV-Vis absorption peak of dye solution. The results show that PEG/RGOA and PEG/Ag/RGOA are an efficient catalyst for dye degradation.

Long-range Coulomb forces and localized bonds.

PubMed

Preiser; Lösel; Brown; Kunz; Skowron

1999-10-01

The ionic model is shown to be applicable to all compounds in which the atoms carry a net charge and their electron density is spherically symmetric regardless of the covalent character of the bonding. By examining the electric field generated by an array of point charges placed at the positions of the ions in over 40 inorganic compounds, we show that the Coulomb field naturally partitions itself into localized regions (bonds) which are characterized by the electric flux that links neighbouring ions of opposite charge. This flux is identified with the bond valence, and Gauss' law with the valence-sum rule, providing a secure theoretical foundation for the bond-valence model. The localization of the Coulomb field provides an unambiguous definition of coordination number and our calculations show that, in addition to the expected primary coordination sphere, there are a number of weak bonds between cations and the anions in the second coordination sphere. Long-range Coulomb interactions are transmitted through the crystal by the application of Gauss' law at each of the intermediate atoms. Bond fluxes have also been calculated for compounds containing ions with non-spherical electron densities (e.g. cations with stereoactive lone electron pairs). In these cases the point-charge model continues to describe the distant field, but multipoles must be added to the point charges to give the correct local field.

Development of molecularly imprinted polymer in porous film format for binding of phenol and alkylphenols from water.

PubMed

Gryshchenko, Andriy O; Bottaro, Christina S

2014-01-20

Molecularly imprinted polymers (MIPs) were fabricated on glass slides with a "sandwich" technique giving ~20 µm thick films. Methanol/water as a solvent, and polyethyleneglycol and polyvinylacetate as solvent modifiers, were used to give a porous morphology, which was studied with scanning electron microscopy and gravimetric analysis. Various MIPs were synthesized through non-covalent imprinting with phenol as the template; itaconic acid, 4-vinylpyridine, and styrene as monomers; ethylene glycol dimethacrylate, triethylene glycol dimethacrylate, and pentaerythritol triacrylate (PETA) as cross-linkers. Binding and imprinting properties of the MIPs were evaluated based on phenol adsorption isotherms. Since phenol has only one weakly acidic hydroxyl group and lacks unique structural characteristics necessary for binding specificity, the preparation of selective MIPs was challenging. The recognition of phenol via hydrogen bonding is suppressed in water, while hydrophobic interactions, though promoted, are not specific enough for highly-selective phenol recognition. Nevertheless, the styrene-PETA MIP gave modest imprinting effects, which were higher at lower concentrations (Imprinting Factor (IF) = 1.16 at 0.5 mg·L(-1)). The isotherm was of a Freundlich type over 0.1-40 mg·L(-1) and there was broad cross-reactivity towards other structurally similar phenols. This shows that phenol MIPs or simple adsorbents can be developed based on styrene for hydrophobic binding, and PETA to form a tighter, hydrophilic network.

Attractive noncovalent interactions in asymmetric catalysis: Links between enzymes and small molecule catalysts

PubMed Central

Knowles, Robert R.; Jacobsen, Eric N.

2010-01-01

Catalysis by neutral, organic, small molecules capable of binding and activating substrates solely via noncovalent interactions—particularly H-bonding—has emerged as an important approach in organocatalysis. The mechanisms by which such small molecule catalysts induce high enantioselectivity may be quite different from those used by catalysts that rely on covalent interactions with substrates. Attractive noncovalent interactions are weaker, less distance dependent, less directional, and more affected by entropy than covalent interactions. However, the conformational constraint required for high stereoinduction may be achieved, in principle, if multiple noncovalent attractive interactions are operating in concert. This perspective will outline some recent efforts to elucidate the cooperative mechanisms responsible for stereoinduction in highly enantioselective reactions promoted by noncovalent catalysts. PMID:20956302

On Interactions of Oscillation Modes for a Weakly Non-Linear Undamped Elastic Beam with AN External Force

NASA Astrophysics Data System (ADS)

BOERTJENS, G. J.; VAN HORSSEN, W. T.

2000-08-01

In this paper an initial-boundary value problem for the vertical displacement of a weakly non-linear elastic beam with an harmonic excitation in the horizontal direction at the ends of the beam is studied. The initial-boundary value problem can be regarded as a simple model describing oscillations of flexible structures like suspension bridges or iced overhead transmission lines. Using a two-time-scales perturbation method an approximation of the solution of the initial-boundary value problem is constructed. Interactions between different oscillation modes of the beam are studied. It is shown that for certain external excitations, depending on the phase of an oscillation mode, the amplitude of specific oscillation modes changes.

Photoreactive Stapled BH3 Peptides to Dissect the BCL-2 Family Interactome

PubMed Central

Braun, Craig R.; Mintseris, Julian; Gavathiotis, Evripidis; Bird, Gregory H.; Gygi, Steven P.; Walensky, Loren D.

2010-01-01

SUMMARY Defining protein interactions forms the basis for discovery of biological pathways, disease mechanisms, and opportunities for therapeutic intervention. To harness the robust binding affinity and selectivity of structured peptides for interactome discovery, we engineered photoreactive stapled BH3 peptide helices that covalently capture their physiologic BCL-2 family targets. The crosslinking α-helices covalently trap both static and dynamic protein interactors, and enable rapid identification of interaction sites, providing a critical link between interactome discovery and targeted drug design. PMID:21168768

Synthesis of 1D-glyconanomaterials by a hybrid noncovalent-covalent functionalization of single wall carbon nanotubes: a study of their selective interactions with lectins and with live cells

NASA Astrophysics Data System (ADS)

Pernía Leal, M.; Assali, M.; Cid, J. J.; Valdivia, V.; Franco, J. M.; Fernández, I.; Pozo, D.; Khiar, N.

2015-11-01

To take full advantage of the remarkable applications of carbon nanotubes in different fields, there is a need to develop effective methods to improve their water dispersion and biocompatibility while maintaining their physical properties. In this sense, current approaches suffer from serious drawbacks such as loss of electronic structure together with low surface coverage in the case of covalent functionalizations, or instability of the dynamic hybrids obtained by non-covalent functionalizations. In the present work, we examined the molecular basis of an original strategy that combines the advantages of both functionalizations without their main drawbacks. The hierarchical self-assembly of diacetylenic-based neoglycolipids into highly organized and compacted rings around the nanotubes, followed by photopolymerization leads to the formation of nanotubes covered with glyconanorings with a shish kebab-type topology exposing the carbohydrate ligands to the water phase in a multivalent fashion. The glyconanotubes obtained are fully functional, and able to establish specific interactions with their cognate receptors. In fact, by taking advantage of this selective binding, an easy method to sense lectins as a working model of toxin detection was developed based on a simple analysis of TEM images. Remarkably, different experimental settings to assess cell membrane integrity, cell growth kinetics and cell cycle demonstrated the cellular biocompatibility of the sugar-coated carbon nanotubes compared to pristine single-walled carbon nanotubes.To take full advantage of the remarkable applications of carbon nanotubes in different fields, there is a need to develop effective methods to improve their water dispersion and biocompatibility while maintaining their physical properties. In this sense, current approaches suffer from serious drawbacks such as loss of electronic structure together with low surface coverage in the case of covalent functionalizations, or instability of the dynamic hybrids obtained by non-covalent functionalizations. In the present work, we examined the molecular basis of an original strategy that combines the advantages of both functionalizations without their main drawbacks. The hierarchical self-assembly of diacetylenic-based neoglycolipids into highly organized and compacted rings around the nanotubes, followed by photopolymerization leads to the formation of nanotubes covered with glyconanorings with a shish kebab-type topology exposing the carbohydrate ligands to the water phase in a multivalent fashion. The glyconanotubes obtained are fully functional, and able to establish specific interactions with their cognate receptors. In fact, by taking advantage of this selective binding, an easy method to sense lectins as a working model of toxin detection was developed based on a simple analysis of TEM images. Remarkably, different experimental settings to assess cell membrane integrity, cell growth kinetics and cell cycle demonstrated the cellular biocompatibility of the sugar-coated carbon nanotubes compared to pristine single-walled carbon nanotubes. Electronic supplementary information (ESI) available: Experimental procedures for the synthesis of compounds 12-10, 12-15, 17-20, 22-25, 27-30, NMR spectra, and additional TEM images. See DOI: 10.1039/c5nr05956a

Explaining reaction mechanisms using the dual descriptor: a complementary tool to the molecular electrostatic potential.

PubMed

Martínez-Araya, Jorge Ignacio

2013-07-01

The intrinsic reactivity of cyanide when interacting with a silver cation was rationalized using the dual descriptor (DD) as a complement to the molecular electrostatic potential (MEP) in order to predict interactions at the local level. It was found that DD accurately explains covalent interactions that cannot be explained by MEP, which focuses on essentially ionic interactions. This allowed the rationalization of the reaction mechanism that yields silver cyanide in the gas phase. Other similar reaction mechanisms involving a silver cation interacting with water, ammonia, and thiosulfate were also explained by the combination of MEP and DD. This analysis provides another example of the usefulness of DD as a tool for gaining a deeper understanding of any reaction mechanism that is mainly governed by covalent interactions.

Tissue Plasminogen Activator Binding to Superparamagnetic Iron Oxide Nanoparticle—Covalent Versus Adsorptive Approach

NASA Astrophysics Data System (ADS)

Friedrich, Ralf P.; Zaloga, Jan; Schreiber, Eveline; Tóth, Ildikó Y.; Tombácz, Etelka; Lyer, Stefan; Alexiou, Christoph

2016-06-01

Functionalized superparamagnetic iron oxide nanoparticles are frequently used to develop vehicles for drug delivery, hyperthermia, and photodynamic therapy and as tools used for magnetic separation and purification of proteins or for biomolecular imaging. Depending on the application, there are various possible covalent and non-covalent approaches for the functionalization of particles, each of them shows different advantages and disadvantages for drug release and activity at the desired location.

Conformational behavior of phenylglycines and hydroxyphenylglycines and non-planarity of phenyl rings.

PubMed

Nandel, Fateh S; Shafique, Mohd

2014-10-01

The non-proteinogenic amino acids--phenylglycine (PG) and hydroxyphenylglycine (HPG) are crucial components of certain peptidic natural products and are important for the preparation of various medicines. In this, study, the conformation of model dipeptides Ac-X-NHMe of PG, p-HPG and 3, 5-di-hydroxyphenylglycine (3, 5-DHPG) was studied both in R and S form by quantum mechanical (QM) and molecular dynamics approaches. On the energy scale, the conformational states of these molecules in both the R and S were found to be degenerate by QM studies, stabilized by non-covalent interactions like carbonyl--carbonyl interactions, carbonyl-lp .. π (aromatic ring) interactions etc. These interactions disappeared/weakened due to interaction of water molecules with carbonyl groups of backbone in simulation and water was found to interact with the aromatic ring through O(w)-H .. π or O(w)lp .. π interactions. The degeneracy of conformational states was lifted in favor of R-form of PG and DHPG and water molecules interactions with aromatic ring led to non-planarity of the aromatic ring. In simulation studies, irrespective of the starting geometry, the Φ, ψ values for the R form correspond to inverse β/inverse collagen region and for the S-form, the Φ, ψ values correspond to β/collagen region i.e., adopt single conformation. The obtained results were in conformity with the CD spectroscopic data on D-PG and D-p-HPG. The conformational behavior of the unusual amino acids might be of great help in designing of bioactive peptides/peptide based drugs to be realized in single conformation--an essential requirement.

Synthesis, structures and fluorescent properties of two novel lanthanide [Ln = Ce(III), Pr(III)] coordination polymers based on 1,3-benzenedicarboxylate and 2-(4-methoxyphenyl)-1H-imidazo[4,5-f][1,10]phenanthroline ligands

NASA Astrophysics Data System (ADS)

Wang, Lei; Ni, Liang; yao, Jia

2012-09-01

Two structurally diverse coordination polymers [Ce2(m-BDC)2(m-HBDC)2(MOPIP)2·3/2H2O]n (1) and [Pr2(m-BDC)3(MOPIP)2·H2O]n(2) have been synthesized by hydrothermal reaction of lanthanide chloride with mixed ligands benzene-1,3-dicarboxylic acid and 2-(4-methoxyphenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (MOPIP). The crystal structures of the complexes are zipper-like chains of octacoordinate Ln3+ ions, in which Ln3+ ions are bridged in different coordination modes by m-BDC2+ and decorated by MOPIP ligands. These chains are further assembled into three-dimensional supramolecular framework by π⋯π stacking and hydrogen bonding interactions. The fluorescent property and thermal stability were also investigated. Additionally, Natural bond orbital (NBO) analysis of complex 2 shows a weak covalent interaction between the coordinated atoms and Pr3+ ions.

Advances in wave turbulence: rapidly rotating flows

NASA Astrophysics Data System (ADS)

Cambon, C.; Rubinstein, R.; Godeferd, F. S.

2004-07-01

At asymptotically high rotation rates, rotating turbulence can be described as a field of interacting dispersive waves by the general theory of weak wave turbulence. However, rotating turbulence has some complicating features, including the anisotropy of the wave dispersion relation and the vanishing of the wave frequency on a non-vanishing set of 'slow' modes. These features prevent straightforward application of existing theories and lead to some interesting properties, including the transfer of energy towards the slow modes. This transfer competes with, and might even replace, the transfer to small scales envisioned in standard turbulence theories. In this paper, anisotropic spectra for rotating turbulence are proposed based on weak turbulence theory; some evidence for their existence is given based on numerical calculations of the wave turbulence equations. Previous arguments based on the properties of resonant wave interactions suggest that the slow modes decouple from the others. Here, an extended wave turbulence theory with non-resonant interactions is proposed in which all modes are coupled; these interactions are possible only because of the anisotropy of the dispersion relation. Finally, the vanishing of the wave frequency on the slow modes implies that these modes cannot be described by weak turbulence theory. A more comprehensive approach to rotating turbulence is proposed to overcome this limitation.

Comparison of analytical protein separation characteristics for three amine-based capillary-channeled polymer (C-CP) stationary phases.

PubMed

Jiang, Liuwei; Marcus, R Kenneth

2016-02-01

Capillary-channeled polymer (C-CP) fiber stationary phases are finding utility in the realms of protein analytics as well as downstream processing. We have recently described the modification of poly(ethylene terephthalate) (PET) C-CP fibers to affect amine-rich phases for the weak anion-exchange (WAX) separation of proteins. Polyethylenimine (PEI) is covalently coupled to the PET surface, with subsequent cross-linking imparted by treatment with 1,4-butanediol diglycidyl ether (BUDGE). These modifications yield vastly improved dynamic binding capacities over the unmodified fibers. We have also previously employed native (unmodified) nylon 6 C-CP fibers as weak anion/cation-exchange (mixed-mode) and hydrophobic interaction chromatography (HIC) phases for protein separations. Polyamide, nylon 6, consists of amide groups along the polymer backbone, with primary amines and carboxylic acid end groups. The analytical separation characteristics of these three amine-based C-CP fiber phases are compared here. Each of the C-CP fiber columns in this study was shown to be able to separate a bovine serum albumin/hemoglobin/lysozyme mixture at high mobile phase linear velocity (∼70 mm s(-1)) but with different elution characteristics. These differences reflect the types of protein-surface interactions that are occurring, based on the active group composition of the fiber surfaces. This study provides important fundamental understanding for the development of surface-modified C-CP fiber columns for protein separation.

A periodic energy decomposition analysis method for the investigation of chemical bonding in extended systems

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

Raupach, Marc; Tonner, Ralf, E-mail: tonner@chemie.uni-marburg.de

The development and first applications of a new periodic energy decomposition analysis (pEDA) scheme for extended systems based on the Kohn-Sham approach to density functional theory are described. The pEDA decomposes the bonding energy between two fragments (e.g., the adsorption energy of a molecule on a surface) into several well-defined terms: preparation, electrostatic, Pauli repulsion, and orbital relaxation energies. This is complemented by consideration of dispersion interactions via a pairwise scheme. One major extension toward a previous implementation [Philipsen and Baerends, J. Phys. Chem. B 110, 12470 (2006)] lies in the separate discussion of electrostatic and Pauli and the additionmore » of a dispersion term. The pEDA presented here for an implementation based on atomic orbitals can handle restricted and unrestricted fragments for 0D to 3D systems considering periodic boundary conditions with and without the determination of fragment occupations. For the latter case, reciprocal space sampling is enabled. The new method gives comparable results to established schemes for molecular systems and shows good convergence with respect to the basis set (TZ2P), the integration accuracy, and k-space sampling. Four typical bonding scenarios for surface-adsorbate complexes were chosen to highlight the performance of the method representing insulating (CO on MgO(001)), metallic (H{sub 2} on M(001), M = Pd, Cu), and semiconducting (CO and C{sub 2}H{sub 2} on Si(001)) substrates. These examples cover diverse substrates as well as bonding scenarios ranging from weakly interacting to covalent (shared electron and donor acceptor) bonding. The results presented lend confidence that the pEDA will be a powerful tool for the analysis of surface-adsorbate bonding in the future, enabling the transfer of concepts like ionic and covalent bonding, donor-acceptor interaction, steric repulsion, and others to extended systems.« less

Calixarenes and Their Biomimetic Applications

PubMed Central

Agrawal, Y. K.; Bhatt, Harshit

2004-01-01

The synthetic models for the structures, spectroscopic properties and catalytic activities of metalloprotein active sites have been reviewed. Calixarenes were used as new biomimetic catalysts because of their advantage of providing preorganiiation of the catalytic group, which can bind the substrate dynamically that results in fast turnover and fast release of the products. Functional and structural models based on calixarenes are presented and in addition importance of molecular recognition and non-covalent interactions e.g. hydrogen bonding and their role in biological systems are discussed with the help of synthetic systems. PMID:18365079

Rheological Properties of Gels from Pyrene Based Low Molecular Weight Gelators

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

Leivo, Kimmo T.; Hahma, Arno P.

2008-07-07

Gels of pyrene derived low molecular weight organogelators (LMOGs) in primary alcohols have been characterized by rheometry and scanning electron microscopy. Total gelator concentration was 1-2.7 % w/w depending on the solvent and the gelator, including equimolar amounts of the gelator and 2,4,7-trinitrofluorenone (TNF), which is necessary for gelation. Thermoreversible and strongly shear thinning gels were achieved as the two components interact non-covalently to form a gel network. A qualitative correlation between the rheological properties and the nanoscale gel structure were found.

Rheological Properties of Gels from Pyrene Based Low Molecular Weight Gelators

NASA Astrophysics Data System (ADS)

Leivo, Kimmo T.; Hahma, Arno P.

2008-07-01

Gels of pyrene derived low molecular weight organogelators (LMOGs) in primary alcohols have been characterized by rheometry and scanning electron microscopy. Total gelator concentration was 1-2.7 % w/w depending on the solvent and the gelator, including equimolar amounts of the gelator and 2,4,7-trinitrofluorenone (TNF), which is necessary for gelation. Thermoreversible and strongly shear thinning gels were achieved as the two components interact non-covalently to form a gel network. A qualitative correlation between the rheological properties and the nanoscale gel structure were found.

Covalent layer-by-layer films: chemistry, design, and multidisciplinary applications.

PubMed

An, Qi; Huang, Tao; Shi, Feng

2018-05-16

Covalent layer-by-layer (LbL) assembly is a powerful method used to construct functional ultrathin films that enables nanoscopic structural precision, componential diversity, and flexible design. Compared with conventional LbL films built using multiple noncovalent interactions, LbL films prepared using covalent crosslinking offer the following distinctive characteristics: (i) enhanced film endurance or rigidity; (ii) improved componential diversity when uncharged species or small molecules are stably built into the films by forming covalent bonds; and (iii) increased structural diversity when covalent crosslinking is employed in componential, spacial, or temporal (labile bonds) selective manners. In this review, we document the chemical methods used to build covalent LbL films as well as the film properties and applications achievable using various film design strategies. We expect to translate the achievement in the discipline of chemistry (film-building methods) into readily available techniques for materials engineers and thus provide diverse functional material design protocols to address the energy, biomedical, and environmental challenges faced by the entire scientific community.

The shape-memory effect in ionic elastomers: fixation through ionic interactions.

PubMed

González-Jiménez, Antonio; Malmierca, Marta A; Bernal-Ortega, Pilar; Posadas, Pilar; Pérez-Aparicio, Roberto; Marcos-Fernández, Ángel; Mather, Patrick T; Valentín, Juan L

2017-04-19

Shape-memory elastomers based on a commercial rubber cross-linked by both ionic and covalent bonds have been developed. The elastomeric matrix was a carboxylated nitrile rubber (XNBR) vulcanized with magnesium oxide (MgO) providing ionic interactions that form hierarchical structures. The so-named ionic transition is used as the unique thermal transition responsible for the shape-memory effect (SME) in these elastomers. These ionic interactions fix the temporary shape due to their behavior as dynamic cross-links with temperature changes. Covalent cross-links were incorporated with the addition of different proportions of dicumyl peroxide (DCP) to the ionic elastomer to establish and recover the permanent shape. In this article, the SME was modulated by modifying the degree of covalent cross-linking, while keeping the ionic contribution constant. In addition, different programming parameters, such as deformation temperature, heating/cooling rate, loading/unloading rate and percentage of tensile strain, were evaluated for their effects on shape-memory behavior.

Single functional group interactions with individual carbon nanotubes

NASA Astrophysics Data System (ADS)

Friddle, Raymond W.; Lemieux, Melburne C.; Cicero, Giancarlo; Artyukhin, Alexander B.; Tsukruk, Vladimir V.; Grossman, Jeffrey C.; Galli, Giulia; Noy, Aleksandr

2007-11-01

Carbon nanotubes display a consummate blend of materials properties that affect applications ranging from nanoelectronic circuits and biosensors to field emitters and membranes. These applications use the non-covalent interactions between the nanotubes and chemical functionalities, often involving a few molecules at a time. Despite their wide use, we still lack a fundamental understanding and molecular-level control of these interactions. We have used chemical force microscopy to measure the strength of the interactions of single chemical functional groups with the sidewalls of vapour-grown individual single-walled carbon nanotubes. Surprisingly, the interaction strength does not follow conventional trends of increasing polarity or hydrophobicity, and instead reflects the complex electronic interactions between the nanotube and the functional group. Ab initio calculations confirm the observed trends and predict binding force distributions for a single molecular contact that match the experimental results. Our analysis also reveals the important role of molecular linkage dynamics in determining interaction strength at the single functional group level.

Controlling quantum memory-assisted entropic uncertainty in non-Markovian environments

NASA Astrophysics Data System (ADS)

Zhang, Yanliang; Fang, Maofa; Kang, Guodong; Zhou, Qingping

2018-03-01

Quantum memory-assisted entropic uncertainty relation (QMA EUR) addresses that the lower bound of Maassen and Uffink's entropic uncertainty relation (without quantum memory) can be broken. In this paper, we investigated the dynamical features of QMA EUR in the Markovian and non-Markovian dissipative environments. It is found that dynamical process of QMA EUR is oscillation in non-Markovian environment, and the strong interaction is favorable for suppressing the amount of entropic uncertainty. Furthermore, we presented two schemes by means of prior weak measurement and posterior weak measurement reversal to control the amount of entropic uncertainty of Pauli observables in dissipative environments. The numerical results show that the prior weak measurement can effectively reduce the wave peak values of the QMA-EUA dynamic process in non-Markovian environment for long periods of time, but it is ineffectual on the wave minima of dynamic process. However, the posterior weak measurement reversal has an opposite effects on the dynamic process. Moreover, the success probability entirely depends on the quantum measurement strength. We hope that our proposal could be verified experimentally and might possibly have future applications in quantum information processing.

Synthesis and Catalytic Applications of Multi-Walled Carbon Nanotube-Polyamidoamine Dendrimer Hybrids.

PubMed

Desmecht, Antonin; Steenhaut, Timothy; Pennetreau, Florence; Hermans, Sophie; Riant, Olivier

2018-06-20

Polyamidoamine (PAMAM) dendrimers were covalently immobilized on multi-walled carbon nanotubes (MWNT) via two 'grafting to' strategies. We demonstrate the existence of non-covalent interactions between the two components but outline the superiority of our two grafting approaches, namely xanthate and click chemistry. MWNT surfaces were functionalized with activated ester and propargylic moieties prior to their reaction with PAMAM or azido-PAMAM dendrimers, respectively. The grafting of PAMAM generations 0 to 3 was evaluated with X-ray photoelectron spectroscopy (XPS), thermogravimetric analysis (TGA) and transmission electron microscopy (TEM). The versatility of our hybrids was demonstrated by post-functionalization sequences involving copper alkyne-azide cycloaddition (CuAAC). We synthesized homogeneous supported iridium complexes at the extremities of the dendrimers. In addition, our materials were used as template for the encapsulation of Pd nanoparticles (NP), validating our nanocomposites for catalytic applications. The palladium-based catalyst was active for carbonylative coupling during 5 consecutive runs without loss of activity. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Photocurrent in Multilayered Assemblies of Porphyrin-Fullerene Covalent Dyads: Evidence for Channels for Charge Transport.

PubMed

Konev, Alexander S; Khlebnikov, Alexander F; Levin, Oleg V; Lukyanov, Daniil A; Zorin, Ivan M

2016-04-07

Specially designed porphyrin-fullerene dyads have been synthesized to verify literature predictions based on quantum chemistry calculations that certain porphyrin-fullerene dyads are able to self-arrange into specific structures providing channels for charge transport in a bulk mass of organic compound. According to AFM and SEM data, the newly synthesized compounds were indeed prone to some kind of self-arrangement, although to a lesser degree than was expected. A dispersion corrected DFT study of the molecular non-covalent interactions performed at the DFT-D3 (B3LYP, 6-31G*) level of theory showed that the least energy corresponded to head-to-head dimers, with close contacts of porphyrin-porphyrin and fullerene-fullerene fragments, thus providing a unit building block of the channel for charge transport. Experimental proof for the existence of channels for charge transport was obtained by observing a photocurrent in a simple photovoltaic cell. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dendrimers for Drug Delivery.

PubMed

Chauhan, Abhay Singh

2018-04-18

Dendrimers have come a long way in the last 25 years since their inception. Originally created as a wonder molecule of chemistry, dendrimer is now in the fourth class of polymers. Dr. Donald Tomalia first published his seminal work on Poly(amidoamine) (PAMAM) dendrimers in 1985. Application of dendrimers as a drug delivery system started in late 1990s. Dendrimers for drug delivery are employed using two approaches: (i) formulation and (ii) nanoconstruct. In the formulation approach, drugs are physically entrapped in a dendrimer using non-covalent interactions, whereas drugs are covalently coupled on dendrimers in the nanoconstruct approach. We have demonstrated the utility of PAMAM dendrimers for enhancing solubility, stability and oral bioavailability of various drugs. Drug entrapment and drug release from dendrimers can be controlled by modifying dendrimer surfaces and generations. PAMAM dendrimers are also shown to increase transdermal permeation and specific drug targeting. Dendrimer platforms can be engineered to attach targeting ligands and imaging molecules to create a nanodevice. Dendrimer nanotechnology, due to its multifunctional ability, has the potential to create next generation nanodevices.

Crystal Structure of the ERp44-Peroxiredoxin 4 Complex Reveals the Molecular Mechanisms of Thiol-Mediated Protein Retention.

PubMed

Yang, Kai; Li, De-Feng; Wang, Xi'e; Liang, Jinzhao; Sitia, Roberto; Wang, Chih-Chen; Wang, Xi

2016-10-04

ERp44 controls the localization and transport of diverse proteins in the early secretory pathway. The mechanisms that allow client recognition and the source of the oxidative power for forming intermolecular disulfides are as yet unknown. Here we present the structure of ERp44 bound to a client, peroxiredoxin 4. Our data reveal that ERp44 binds the oxidized form of peroxiredoxin 4 via thiol-disulfide interchange reactions. The structure explains the redox-dependent recognition and characterizes the essential non-covalent interactions at the interface. The ERp44-Prx4 covalent complexes can be reduced by glutathione and protein disulfide isomerase family members in the ER, allowing the two components to recycle. This work provides insights into the mechanisms of thiol-mediated protein retention and indicates the key roles of ERp44 in this biochemical cycle to optimize oxidative folding and redox homeostasis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Changes in type I collagen following laser welding.

PubMed

Bass, L S; Moazami, N; Pocsidio, J; Oz, M C; LoGerfo, P; Treat, M R

1992-01-01

Selection of ideal laser parameters for tissue welding is inhibited by poor understanding of the mechanism. We investigated structural changes in collagen molecules extracted from rat tail tendon (> 90% type I collagen) after tissue welding using an 808 nm diode laser and indocyanine green dye applied to the weld site. Mobility patterns on SDS-PAGE were identical in the lasered and untreated tendon extracts with urea or acetic acid. Pepsin incubation after acetic acid extraction revealed a reduction of collagen alpha and beta bands in lasered compared with untreated specimens. Circular dichroism studies of rat tail tendon showed absence of helical structure in collagen from lasered tendon. No evidence for covalent bonding was present in laser-treated tissues. Collagen molecules are denatured by the laser wavelength and parameters used in this study. No significant amount of helical structure is regenerated on cooling. We conclude that non-covalent interactions between denatured collagen molecules may be responsible for the creation of tissue welding.

A computational search for lipases that can preferentially hydrolyze long-chain omega-3 fatty acids from fish oil triacylglycerols.

PubMed

Kamal, Md Zahid; Barrow, Colin J; Rao, Nalam Madhusudhana

2015-04-15

Consumption of long-chain omega-3 fatty acids is known to decrease the risk of major cardiovascular events. Lipases, a class of triacylglycerol hydrolases, have been extensively tested to concentrate omega-3 fatty acids from fish oils, under mild enzymatic conditions. However, no lipases with preference for omega-3 fatty acids selectivity have yet been discovered or developed. In this study we performed an exhaustive computational study of substrate-lipase interactions by docking, both covalent and non-covalent, for 38 lipases with a large number of structured triacylglycerols containing omega-3 fatty acids. We identified some lipases that have potential to preferentially hydrolyze omega-3 fatty acids from structured triacylglycerols. However omega-3 fatty acid preferences were found to be modest. Our study provides an explanation for absence of reports of lipases with omega-3 fatty acid hydrolyzing ability and suggests methods for developing these selective lipases. Copyright © 2014 Elsevier Ltd. All rights reserved.

The single NqrB and NqrC subunits in the Na(+)-translocating NADH: quinone oxidoreductase (Na(+)-NQR) from Vibrio cholerae each carry one covalently attached FMN.

PubMed

Casutt, Marco S; Schlosser, Andreas; Buckel, Wolfgang; Steuber, Julia

2012-10-01

The Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR) is the prototype of a novel class of flavoproteins carrying a riboflavin phosphate bound to serine or threonine by a phosphodiester bond to the ribityl side chain. This membrane-bound, respiratory complex also contains one non-covalently bound FAD, one non-covalently bound riboflavin, ubiquinone-8 and a [2Fe-2S] cluster. Here, we report the quantitative analysis of the full set of flavin cofactors in the Na(+)-NQR and characterize the mode of linkage of the riboflavin phosphate to the membrane-bound NqrB and NqrC subunits. Release of the flavin by β-elimination and analysis of the cofactor demonstrates that the phosphate group is attached at the 5'-position of the ribityl as in authentic FMN and that the Na(+)-NQR contains approximately 1.7mol covalently bound FMN per mol non-covalently bound FAD. Therefore, each of the single NqrB and NqrC subunits in the Na(+)-NQR carries a single FMN. Elimination of the phosphodiester bond yields a dehydro-2-aminobutyrate residue, which is modified with β-mercaptoethanol by Michael addition. Proteolytic digestion followed by mass determination of peptide fragments reveals exclusive modification of threonine residues, which carry FMN in the native enzyme. The described reactions allow quantification and localization of the covalently attached FMNs in the Na(+)-NQR and in related proteins belonging to the Rhodobacter nitrogen fixation (RNF) family of enzymes. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012). Copyright © 2012 Elsevier B.V. All rights reserved.

Selective Attachment of Nucleic Acid Molecules to Patterned Self-Assembled Surfaces.

DTIC Science & Technology

1994-12-01

of different sequence is accomplished by placement of 8 liquid portions of nucleic acids at the desired position on the 9 filter. This method is...acids are selectively 24 bound from regions to which nucleic acids are excluded, other than 25 by placement of liquid aliquots (generally >1 Al) of...is typically non-covalent (i.e., ionic 16 bonding, or, less often, hydrogen bonding). Advantageously, non- 17 covalent bonding of nucleic acid

Second-Generation Non-Covalent NAAA Inhibitors are Protective in a Model of Multiple Sclerosis.

PubMed

Migliore, Marco; Pontis, Silvia; Fuentes de Arriba, Angel Luis; Realini, Natalia; Torrente, Esther; Armirotti, Andrea; Romeo, Elisa; Di Martino, Simona; Russo, Debora; Pizzirani, Daniela; Summa, Maria; Lanfranco, Massimiliano; Ottonello, Giuliana; Busquet, Perrine; Jung, Kwang-Mook; Garcia-Guzman, Miguel; Heim, Roger; Scarpelli, Rita; Piomelli, Daniele

2016-09-05

Palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are endogenous lipid mediators that suppress inflammation. Their actions are terminated by the intracellular cysteine amidase, N-acylethanolamine acid amidase (NAAA). Even though NAAA may offer a new target for anti-inflammatory therapy, the lipid-like structures and reactive warheads of current NAAA inhibitors limit the use of these agents as oral drugs. A series of novel benzothiazole-piperazine derivatives that inhibit NAAA in a potent and selective manner by a non-covalent mechanism are described. A prototype member of this class (8) displays high oral bioavailability, access to the central nervous system (CNS), and strong activity in a mouse model of multiple sclerosis (MS). This compound exemplifies a second generation of non-covalent NAAA inhibitors that may be useful in the treatment of MS and other chronic CNS disorders. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mixed non-covalent assemblies of ethynyl nile red and ethynyl pyrene along oligonucleotide templates.

PubMed

Ensslen, Philipp; Fritz, Yannic; Wagenknecht, Hans-Achim

2015-01-14

Ethynyl pyrene and ethynyl nile red as modifications at the 5-position of 2'-deoxyuridines self-assemble non-covalently and specifically along oligo-2'-deoxyadenosines as templates. Oligo-2'-deoxyadenosines of the lengths (dA)10-(dA)20 are able to retain nearly exactly as many ethynyl nile red units in solution as binding sites are available on these templates. In contrast, in the presence of oligo-2'-thymidines the ethynyl nile red moieties are similarly insoluble to those in the absence of any oligonucleotide and yield an aggregate. The mixed assemblies of both chromophores are highly ordered, show left-handed chirality and yield dual fluorescence. The strong excitonic coupling indicates assemblies with a high degree of order. These results show that DNA represents an important supramolecular scaffold for the templated, helical and non-covalent arrangement not only for one type of chromophore but also for mixtures of two different chromophores.

Structural study of Ni- or Mg-based complexes incorporated within UiO-66-NH{sub 2} framework and their impact on hydrogen sorption properties

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

Žunkovič, E.; Mazaj, M.; Mali, G.

2015-05-15

Nickel and magnesium acetylacetonate molecular complexes were post-synthetically incorporated into microporous zirconium-based MOF (UiO-66-NH{sub 2}) in order to introduce active open-metal sites for hydrogen sorption. Elemental analysis, nitrogen physisorption and DFT calculations revealed that 5 molecules of Ni(acac){sub 2} or 2 molecules of Mg(acac){sub 2} were incorporated into one unit cell of UiO-66-NH{sub 2}. {sup 1}H–{sup 13}C CPMAS and {sup 1}H MAS NMR spectroscopy showed that, although embedded within the pores, both Ni- and Mg-complexes interacted with the UiO-66-NH{sub 2} framework only through weak van der Waals bonds. Inclusion of metal complexes led to the decrease of hydrogen sorption capacitiesmore » in Ni-modified as well as in Mg-modified samples in comparison with the parent UiO-66-NH{sub 2}. The isosteric hydrogen adsorption enthalpy slightly increased in the case of Ni-modified material, but not in the case of Mg-modified analogue. - Graphical abstract: A post-synthesis impregnation of Mg- and Ni-acetylacetonate complexes performed on zirconium-based MOF UiO-66-NH{sub 2} does influence the hydrogen sorption performance with respect to the parent matrix. The structural study revealed that Mg- and Ni-acetylacetonate molecules interact with zirconium-terephthalate framework only by weak interactions and they are not covalently bonded to aminoterephthalate ligand. Still, they remain confined into the pores even after hydrogen sorption experiments. - Highlights: • Mg- and Ni-acetylacetonate molecules embedded in the pores of UiO-66-NH{sub 2} by PSM. • Molecules of complexes interact with framework only by van der Waals interactions. • Type/structure of deposited metal-complex impact hydrogen enthalpy of adsorption.« less

Fluctuation, dissipation, and a non-equilibrium ``equation of state'' via nonlinear microrheology of hydrodynamically interacting colloids

NASA Astrophysics Data System (ADS)

Chu, Henry; Zia, Roseanna

2014-11-01

In our recently developed non-equilibrium Stokes-Einstein relation for microrheology, we showed that, in the absence of hydrodynamic interactions, the stress in a suspension is given by a balance between fluctuation and dissipation. Here we generalize our theory to develop a simple analytical relation connecting diffusive fluctuation, viscous dissipation and suspension stress in systems of hydrodynamically interacting colloids. In active microrheology, a Brownian probe is driven through a complex medium. The strength of probe forcing compared to the entropic restoring force defines a Peclet number, Pe. In the absence of hydrodynamics, normal stress differences scale as Pe4 and Pe for weak and strong probe forcing, respectively. But as hydrodynamics become important, interparticle forces give way to lubrication interactions and the normal stresses scale as Pe2 and Peδln(Pe), where 0.773 <= δ <= 1 as hydrodynamics vary from strong to weak. The new phenomenological theory is shown to agree with standard micromechanical definitions of the stress. A connection is made between the stress and an effective temperature of the medium, prompting the interpretation of the particle stress as the energy density, and the expression for osmotic pressure as a ``non-equilibrium equation of state.''

Artificial photosynthetic systems: assemblies of slipped cofacial porphyrins and phthalocyanines showing strong electronic coupling.

PubMed

Satake, Akiharu; Kobuke, Yoshiaki

2007-06-07

This paper reviews selected types of structurally well defined assemblies of porphyrins and phthalocyanines with strong electronic coupling. Face-to-face, head-to-tail, slipped cofacial, and non-parallel dimeric motifs constructed by covalent and non-covalent bonds are compared in the earlier sections. Their molecular orientation, electronic overlap, and absorption and fluorescence properties are discussed with a view towards the development of artificial photosynthetic systems and molecular electronics. Complementary coordination dimers are fully satisfactory in terms of structural stability, orientation factor, pi-electronic overlap, and zero fluorescence quenching. In later sections, several polymeric and macrocyclic porphyrin assemblies constructed by a combination of covalent bonds and complementary coordination bonds are discussed from the viewpoint of light-harvesting antenna functions.

Sky-blue emitting bridged diiridium complexes: beneficial effects of intramolecular π-π stacking.

PubMed

Congrave, Daniel G; Hsu, Yu-Ting; Batsanov, Andrei S; Beeby, Andrew; Bryce, Martin R

2018-02-06

The potential of intramolecular π-π interactions to influence the photophysical properties of diiridium complexes is an unexplored topic, and provides the motivation for the present study. A series of diarylhydrazide-bridged diiridium complexes functionalised with phenylpyridine (ppy)-based cyclometalating ligands is reported. It is shown by NMR studies in solution and single crystal X-ray analysis that intramolecular π-π interactions between the bridging and cyclometalating ligands rigidify the complexes leading to high luminescence quantum efficiencies in solution and in doped films. Fluorine substituents on the phenyl rings of the bridge promote the intramolecular π-π interactions. Notably, these non-covalent interactions are harnessed in the rational design and synthesis of the first examples of highly emissive sky-blue diiridium complexes featuring conjugated bridging ligands, for which they play a vital role in the structural and photophysical properties. Experimental results are supported by computational studies.

Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds

NASA Astrophysics Data System (ADS)

Harada, Shusaku; Hiromori, Youhei; Nakamura, Shota; Kawahara, Kazuki; Fukakusa, Shunsuke; Maruno, Takahiro; Noda, Masanori; Uchiyama, Susumu; Fukui, Kiichi; Nishikawa, Jun-Ichi; Nagase, Hisamitsu; Kobayashi, Yuji; Yoshida, Takuya; Ohkubo, Tadayasu; Nakanishi, Tsuyoshi

2015-02-01

Organotin compounds such as triphenyltin (TPT) and tributyltin (TBT) act as endocrine disruptors through the peroxisome proliferator-activated receptor γ (PPARγ) signaling pathway. We recently found that TPT is a particularly strong agonist of PPARγ. To elucidate the mechanism underlying organotin-dependent PPARγ activation, we here analyzed the interactions of PPARγ ligand-binding domain (LBD) with TPT and TBT by using X-ray crystallography and mass spectroscopy in conjunction with cell-based activity assays. Crystal structures of PPARγ-LBD/TBT and PPARγ-LBD/TPT complexes were determined at 1.95 Å and 1.89 Å, respectively. Specific binding of organotins is achieved through non-covalent ionic interactions between the sulfur atom of Cys285 and the tin atom. Comparisons of the determined structures suggest that the strong activity of TPT arises through interactions with helix 12 of LBD primarily via π-π interactions. Our findings elucidate the structural basis of PPARγ activation by TPT.

Structural basis for PPARγ transactivation by endocrine-disrupting organotin compounds

PubMed Central

Harada, Shusaku; Hiromori, Youhei; Nakamura, Shota; Kawahara, Kazuki; Fukakusa, Shunsuke; Maruno, Takahiro; Noda, Masanori; Uchiyama, Susumu; Fukui, Kiichi; Nishikawa, Jun-ichi; Nagase, Hisamitsu; Kobayashi, Yuji; Yoshida, Takuya; Ohkubo, Tadayasu; Nakanishi, Tsuyoshi

2015-01-01

Organotin compounds such as triphenyltin (TPT) and tributyltin (TBT) act as endocrine disruptors through the peroxisome proliferator–activated receptor γ (PPARγ) signaling pathway. We recently found that TPT is a particularly strong agonist of PPARγ. To elucidate the mechanism underlying organotin-dependent PPARγ activation, we here analyzed the interactions of PPARγ ligand-binding domain (LBD) with TPT and TBT by using X-ray crystallography and mass spectroscopy in conjunction with cell-based activity assays. Crystal structures of PPARγ-LBD/TBT and PPARγ-LBD/TPT complexes were determined at 1.95 Å and 1.89 Å, respectively. Specific binding of organotins is achieved through non-covalent ionic interactions between the sulfur atom of Cys285 and the tin atom. Comparisons of the determined structures suggest that the strong activity of TPT arises through interactions with helix 12 of LBD primarily via π-π interactions. Our findings elucidate the structural basis of PPARγ activation by TPT. PMID:25687586

Compounds from Sichuan and Melegueta peppers activate, covalently and non-covalently, TRPA1 and TRPV1 channels

PubMed Central

Riera, CE; Menozzi-Smarrito, C; Affolter, M; Michlig, S; Munari, C; Robert, F; Vogel, H; Simon, SA; le Coutre, J

2009-01-01

Background and purpose: Oily extracts of Sichuan and Melegueta peppers evoke pungent sensations mediated by different alkylamides [mainly hydroxy-α-sanshool (α-SOH)] and hydroxyarylalkanones (6-shogaol and 6-paradol). We assessed how transient receptor potential ankyrin 1 (TRPA1) and TRP vanilloid 1 (TRPV1), two chemosensory ion channels, participate in these pungent sensations. Experimental approach: The structure–activity relationships of these molecules on TRPA1 and TRPV1 was measured by testing natural and synthetic analogues using calcium and voltage imaging on dissociated dorsal root ganglia neurons and human embryonic kidney 293 cells expressing the wild-type channels or specific cysteine mutants using glutathione trapping as a model to probe TRPA1 activation. In addition, using Trpv1 knockout mice, the compounds' aversive responses were measured in a taste brief-access test. Key results: For TRPA1 activation, the cis C6 double bond in the polyenic chain of α-SOH was critical, whereas no structural specificity was required for activation of TRPV1. Both 6-shogaol and 6-paradol were found to activate TRPV1 and TRPA1 channels, whereas linalool, an abundant terpene in Sichuan pepper, activated TRPA1 but not TRPV1 channels. Alkylamides and 6-shogaol act on TRPA1 by covalent bonding whereas none of these compounds activated TRPV1 through such interactions. Finally, TRPV1 mutant mice retained sensitivity to 6-shogaol but were not responsive to α-SOH. Conclusions and implications: The pungent nature of components of Sichuan and Melegueta peppers was mediated via interactions with TRPA1 and TRPV1 channels and may explain the aversive properties of these compounds. PMID:19594761

Covalency in Americium(III) Hexachloride

DOE PAGES

Cross, Justin Neil; Su, Jing; Batista, Enrigue R.; ...

2017-06-14

Developing a better understanding of covalency (or orbital mixing) is of fundamental importance. Covalency occupies a central role in directing chemical and physical properties for almost any given compound or material. Hence, the concept of covalency has potential to generate broad and substantial scientific advances, ranging from biological applications to condensed matter physics. Given the importance orbital mixing combined with the difficultly in measuring covalency, estimating or inferring covalency often leads to fiery debate. Consider the 60-year controversy sparked by SEABORG and COWORKERS (1954) when it was proposed that covalency from 5f-orbitals contributed to the unique behavior of americium inmore » chloride matrixes. Herein, we describe the use of ligand K-edge X-ray absorption spectroscopy (XAS) and electronic structure calculations to quantify the extent of covalent bonding in – arguably – one of the most difficult systems to study, the Am–Cl interaction within AmCl 6 3-. We observed both 5fand 6d-orbital mixing with the Cl-3p orbitals; however, contributions from the 6d-orbitals were more substantial. Comparisons with the isoelectronic EuCl 6 3- indicated similar bonding for the Am III 6d- and Eu III 5d-orbitals. Meanwhile, the results confirmed SEABORG’S 1954 hypothesis that Am III 5f-orbital covalency was more substantial than 4forbital mixing for Eu III.« less

The versatility of boron in biological target engagement

NASA Astrophysics Data System (ADS)

Diaz, Diego B.; Yudin, Andrei K.

2017-08-01

Boron-containing molecules have been extensively used for the purposes of chemical sensing, biological probe development and drug discovery. Due to boron's empty p orbital, it can coordinate to heteroatoms such as oxygen and nitrogen. This reversible covalent mode of interaction has led to the use of boron as bait for nucleophilic residues in disease-associated proteins, culminating in the approval of new therapeutics that work by covalent mechanisms. Our analysis of a wide range of covalent inhibitors with electrophilic groups suggests that boron is a unique electrophile in its chameleonic ability to engage protein targets. Here we review boron's interactions with a range of protein side-chain residues and reveal that boron's properties are nuanced and arise from its uncommon coordination preferences. These mechanistic and structural insights should serve as a guide for the development of selective boron-based bioactive molecules.

Preparation of thick silica coatings on carbon fibers with fine-structured silica nanotubes induced by a self-assembly process

PubMed Central

Baumgärtner, Benjamin; Möller, Hendrik; Neumann, Thomas

2017-01-01

A facile method to coat carbon fibers with a silica shell is presented in this work. By immobilizing linear polyamines on the carbon fiber surface, the high catalytic activity of polyamines in the sol–gel-processing of silica precursors is used to deposit a silica coating directly on the fiber’s surface. The surface localization of the catalyst is achieved either by attaching short-chain polyamines (e.g., tetraethylenepentamine) via covalent bonds to the carbon fiber surface or by depositing long-chain polyamines (e.g., linear poly(ethylenimine)) on the carbon fiber by weak non-covalent bonding. The long-chain polyamine self-assembles onto the carbon fiber substrate in the form of nanoscopic crystallites, which serve as a template for the subsequent silica deposition. The silicification at close to neutral pH is spatially restricted to the localized polyamine and consequently to the fiber surface. In case of the linear poly(ethylenimine), silica shells of several micrometers in thickness can be obtained and their morphology is easily controlled by a considerable number of synthesis parameters. A unique feature is the hierarchical biomimetic structure of the silica coating which surrounds the embedded carbon fiber by fibrillar and interconnected silica fine-structures. The high surface area of the nanostructured composite fiber may be exploited for catalytic applications and adsorption purposes. PMID:28685115

Preparation of thick silica coatings on carbon fibers with fine-structured silica nanotubes induced by a self-assembly process.

PubMed

Baumgärtner, Benjamin; Möller, Hendrik; Neumann, Thomas; Volkmer, Dirk

2017-01-01

A facile method to coat carbon fibers with a silica shell is presented in this work. By immobilizing linear polyamines on the carbon fiber surface, the high catalytic activity of polyamines in the sol-gel-processing of silica precursors is used to deposit a silica coating directly on the fiber's surface. The surface localization of the catalyst is achieved either by attaching short-chain polyamines (e.g., tetraethylenepentamine) via covalent bonds to the carbon fiber surface or by depositing long-chain polyamines (e.g., linear poly(ethylenimine)) on the carbon fiber by weak non-covalent bonding. The long-chain polyamine self-assembles onto the carbon fiber substrate in the form of nanoscopic crystallites, which serve as a template for the subsequent silica deposition. The silicification at close to neutral pH is spatially restricted to the localized polyamine and consequently to the fiber surface. In case of the linear poly(ethylenimine), silica shells of several micrometers in thickness can be obtained and their morphology is easily controlled by a considerable number of synthesis parameters. A unique feature is the hierarchical biomimetic structure of the silica coating which surrounds the embedded carbon fiber by fibrillar and interconnected silica fine-structures. The high surface area of the nanostructured composite fiber may be exploited for catalytic applications and adsorption purposes.

The third-order optical nonlinearities of Ge-Ga-Sb(In)-S chalcogenide glasses

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

Guo, Haitao, E-mail: guoht_001@opt.ac.cn; Chen, Hongyan; Hou, Chaoqi

2011-05-15

Research highlights: {yields} It is firstly demonstrated that the nonlinear refractive index n{sub 2} is dependent on the covalency of bonds in chalcogenide glass. {yields} Homopolar metallic bonds in chalcogenide glass have positive contribution to large nonlinear refractive index n{sub 2} also. {yields} The 80GeS{sub 2}.20Sb{sub 2}S{sub 3} glass would be expected to be used in the all-optical switches working at 1330 nm and 1550 nm telecommunication wavelengths. -- Abstract: The third-order optical nonlinearities of 80GeS{sub 2}.(20 - x)Ga{sub 2}S{sub 3}.xY{sub 2}S{sub 3} (x = 0, 5, 10, 15, 20 and Y = Sb or In) chalcogenide glasses were investigatedmore » utilizing the Z-scan method at the wavelength of 800 nm and their linear optical properties and structure were also studied. By analyzing the compositional dependences and possible influencing factors including the linear refractive index, the concentration of lone electron pairs, the optical bandgap and the amount of weak covalent/homopolar bonds, it indicates that the electronic contribution in weak heteropolar covalent and homopolar metallic bonds is responsible for large nonlinear refractive index n{sub 2} in the chalcogenide glasses. These chalcogenide glasses have characteristics of environmentally friendship, wide transparency in the visible region, high nonlinear refractive index n{sub 2} and low nonlinear absorption coefficient {beta}, and would be expected to be used in the all-optical switches working at 1330 nm and 1550 nm telecommunication wavelengths.« less

Metallic-covalent bonding conversion and thermoelectric properties of Al-based icosahedral quasicrystals and approximants.

PubMed

Takagiwa, Yoshiki; Kimura, Kaoru

2014-08-01

In this article, we review the characteristic features of icosahedral cluster solids, metallic-covalent bonding conversion (MCBC), and the thermoelectric properties of Al-based icosahedral quasicrystals and approximants. MCBC is clearly distinguishable from and closely related to the well-known metal-insulator transition. This unique bonding conversion has been experimentally verified in 1/1-AlReSi and 1/0-Al 12 Re approximants by the maximum entropy method and Rietveld refinement for powder x-ray diffraction data, and is caused by a central atom inside the icosahedral clusters. This helps to understand pseudogap formation in the vicinity of the Fermi energy and establish a guiding principle for tuning the thermoelectric properties. From the electron density distribution analysis, rigid heavy clusters weakly bonded with glue atoms are observed in the 1/1-AlReSi approximant crystal, whose physical properties are close to icosahedral Al-Pd-TM (TM: Re, Mn) quasicrystals. They are considered to be an intermediate state among the three typical solids: metals, covalently bonded networks (semiconductor), and molecular solids. Using the above picture and detailed effective mass analysis, we propose a guiding principle of weakly bonded rigid heavy clusters to increase the thermoelectric figure of merit ( ZT ) by optimizing the bond strengths of intra- and inter-icosahedral clusters. Through element substitutions that mainly weaken the inter-cluster bonds, a dramatic increase of ZT from less than 0.01 to 0.26 was achieved. To further increase ZT , materials should form a real gap to obtain a higher Seebeck coefficient.

Bose-Einstein condensation on a manifold with non-negative Ricci curvature

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

Akant, Levent, E-mail: levent.akant@boun.edu.tr; Ertuğrul, Emine, E-mail: emine.ertugrul@boun.edu.tr; Tapramaz, Ferzan, E-mail: waskhez@gmail.com

The Bose-Einstein condensation for an ideal Bose gas and for a dilute weakly interacting Bose gas in a manifold with non-negative Ricci curvature is investigated using the heat kernel and eigenvalue estimates of the Laplace operator. The main focus is on the nonrelativistic gas. However, special relativistic ideal gas is also discussed. The thermodynamic limit of the heat kernel and eigenvalue estimates is taken and the results are used to derive bounds for the depletion coefficient. In the case of a weakly interacting gas, Bogoliubov approximation is employed. The ground state is analyzed using heat kernel methods and finite sizemore » effects on the ground state energy are proposed. The justification of the c-number substitution on a manifold is given.« less

The Use of Gel Electrophoresis to Study the Reactions of Activated Amino Acids with Oligonucleotides

NASA Technical Reports Server (NTRS)

Zieboll, Gerhard; Orgel, Leslie E.

1994-01-01

We have used gel electrophoresis to study the primary covalent addition of amino acids to oligonu-cleotides or their analogs and the subsequent addition of further molecules of the amino acids to generate peptides covalently linked to the oligonucleotides. We have surveyed the reactions of a variety of amino acids with the phosphoramidates derived from oligonucleotide 5 inches phosphates and ethylenediamine. We find that arginine and amino acids can interact with oligonucleotidesl through stacking interactions react most efficiently. D- and L-amino acids give indistinguishable families of products.

Extreme Activity of Drug Nanocrystals Coated with A Layer of Non-Covalent Polymers from Self-Assembled Boric Acid

NASA Astrophysics Data System (ADS)

Zhan, Honglei; Liang, Jun F.

2016-12-01

Non-covalent polymers have remarkable advantages over synthetic polymers for wide biomedical applications. In this study, non-covalent polymers from self-assembled boric acid were used as the capping reagent to replace synthetic polymers in drug crystallization. Under acidic pH, boric acid self-assembled on the surface of drug nanocrystals to form polymers with network-like structures held together by hydrogen bonds. Coating driven by boric acid self-assembly had negligible effects on drug crystallinity and structure but resulted in drug nanocrystals with excellent dispersion properties that aided in the formation of a more stable suspension. Boric acid coating improved drug stability dramatically by preventing drug molecules from undergoing water hydrolysis in a neutral environment. More importantly, the specific reactivity of orthoboric groups to diols in cell glycocalyx facilitated a rapid cross-membrane translocation of drug nanocrystals, leading to efficient intracellular drug delivery, especially on cancer cells with highly expressed sialic acids. Boric acid coated nanocrystals of camptothecin, an anticancer drug with poor aqueous solubility and stability, demonstrated extreme cytotoxic activity (IC50 < 5.0 μg/mL) to cancer cells compared to synthetic polymer coated CPT nanocrystals and free CPT. Surface coating using non-covalent polymers from self-assembled boric acid will have wide biomedical applications especially in biomaterials and drug delivery field.

Extreme Activity of Drug Nanocrystals Coated with A Layer of Non-Covalent Polymers from Self-Assembled Boric Acid.

PubMed

Zhan, Honglei; Liang, Jun F

2016-12-09

Non-covalent polymers have remarkable advantages over synthetic polymers for wide biomedical applications. In this study, non-covalent polymers from self-assembled boric acid were used as the capping reagent to replace synthetic polymers in drug crystallization. Under acidic pH, boric acid self-assembled on the surface of drug nanocrystals to form polymers with network-like structures held together by hydrogen bonds. Coating driven by boric acid self-assembly had negligible effects on drug crystallinity and structure but resulted in drug nanocrystals with excellent dispersion properties that aided in the formation of a more stable suspension. Boric acid coating improved drug stability dramatically by preventing drug molecules from undergoing water hydrolysis in a neutral environment. More importantly, the specific reactivity of orthoboric groups to diols in cell glycocalyx facilitated a rapid cross-membrane translocation of drug nanocrystals, leading to efficient intracellular drug delivery, especially on cancer cells with highly expressed sialic acids. Boric acid coated nanocrystals of camptothecin, an anticancer drug with poor aqueous solubility and stability, demonstrated extreme cytotoxic activity (IC 50  < 5.0 μg/mL) to cancer cells compared to synthetic polymer coated CPT nanocrystals and free CPT. Surface coating using non-covalent polymers from self-assembled boric acid will have wide biomedical applications especially in biomaterials and drug delivery field.

Extreme Activity of Drug Nanocrystals Coated with A Layer of Non-Covalent Polymers from Self-Assembled Boric Acid

PubMed Central

Zhan, Honglei; Liang, Jun F.

2016-01-01

Non-covalent polymers have remarkable advantages over synthetic polymers for wide biomedical applications. In this study, non-covalent polymers from self-assembled boric acid were used as the capping reagent to replace synthetic polymers in drug crystallization. Under acidic pH, boric acid self-assembled on the surface of drug nanocrystals to form polymers with network-like structures held together by hydrogen bonds. Coating driven by boric acid self-assembly had negligible effects on drug crystallinity and structure but resulted in drug nanocrystals with excellent dispersion properties that aided in the formation of a more stable suspension. Boric acid coating improved drug stability dramatically by preventing drug molecules from undergoing water hydrolysis in a neutral environment. More importantly, the specific reactivity of orthoboric groups to diols in cell glycocalyx facilitated a rapid cross-membrane translocation of drug nanocrystals, leading to efficient intracellular drug delivery, especially on cancer cells with highly expressed sialic acids. Boric acid coated nanocrystals of camptothecin, an anticancer drug with poor aqueous solubility and stability, demonstrated extreme cytotoxic activity (IC50 < 5.0 μg/mL) to cancer cells compared to synthetic polymer coated CPT nanocrystals and free CPT. Surface coating using non-covalent polymers from self-assembled boric acid will have wide biomedical applications especially in biomaterials and drug delivery field. PMID:27934922

Mucoadhesion mechanism of chitosan and thiolated chitosan-poly(isobutyl cyanoacrylate) core-shell nanoparticles.

PubMed

Bravo-Osuna, Irene; Vauthier, Christine; Farabollini, Alessandra; Palmieri, Giovanni Filippo; Ponchel, Gilles

2007-04-01

The study is focused on the evaluation of the potential bioadhesive behaviour of chitosan and thiolated chitosan (chitosan-TBA)-coated poly(isobutyl cyanoacrylates) (PIBCA) nanoparticles. Nanoparticles were obtained by radical emulsion polymerisation with chitosan of different molecular weight and with different proportions of chitosan/chitosan-TBA. Mucoadhesion was ex vivo evaluated under static conditions by applying nanoparticle suspensions on rat intestinal mucosal surfaces and evaluating the amount of nanoparticles remaining attached to the mucosa after incubation. The analysis of the results obtained demonstrated that the presence of either chitosan or thiolated chitosan on the PIBCA nanoparticle surface clearly enhanced the mucoadhesion behaviour thanks to non-covalent interactions (ionic interaction and hydrogen bonds) with mucus chains. Both, the molecular weight of chitosan and the proportion of chitosan-TBA in the formulation influenced the nanoparticle hydrodynamic diameter and hence their transport through the mucus layer. Improved interpenetration ability with the mucus chain during the attachment process was suggested for the chitosan of high molecular weight, enhancing the bioadhesiveness of the system. The presence of thiol groups on the nanoparticle surface at high concentration (200 x 10(-6) micromol SH/cm2) increased the mucoadhesion capacity of nanoparticles by forming covalent bonds with the cysteine residues of the mucus glycoproteins.

Mechanical Failure in Colloidal Gels

NASA Astrophysics Data System (ADS)

Kodger, Thomas Edward

When colloidal particles in a dispersion are made attractive, they aggregate into fractal clusters which grow to form a space-spanning network, or gel, even at low volume fractions. These gels are crucial to the rheological behavior of many personal care, food products and dispersion-based paints. The mechanical stability of these products relies on the stability of the colloidal gel network which acts as a scaffold to provide these products with desired mechanical properties and to prevent gravitational sedimentation of the dispersed components. Understanding the mechanical stability of such colloidal gels is thus of crucial importance to predict and control the properties of many soft solids. Once a colloidal gel forms, the heterogeneous structure bonded through weak physical interactions, is immediately subject to body forces, such as gravity, surface forces, such as adhesion to a container walls and shear forces; the interplay of these forces acting on the gel determines its stability. Even in the absence of external stresses, colloidal gels undergo internal rearrangements within the network that may cause the network structure to evolve gradually, in processes known as aging or coarsening or fail catastrophically, in a mechanical instability known as syneresis. Studying gel stability in the laboratory requires model colloidal system which may be tuned to eliminate these body or endogenous forces systematically. Using existing chemistry, I developed several systems to study delayed yielding by eliminating gravitational stresses through density matching and cyclic heating to induce attraction; and to study syneresis by eliminating adhesion to the container walls, altering the contact forces between colloids, and again, inducing gelation through heating. These results elucidate the varied yet concomitant mechanisms by which colloidal gels may locally or globally yield, but then reform due to the nature of the physical, or non-covalent, interactions which form them.

Phase Diagram of the Bose Hubbard Model with Weak Links

NASA Astrophysics Data System (ADS)

Hettiarachchilage, Kalani; Rousseau, Valy; Tam, Ka-Ming; Moreno, Juana; Jarrell, Mark; Sheehy, Daniel

2012-02-01

We study the ground state phase diagram of strongly interacting ultracold Bose gas in a one-dimensional optical lattice with a tunable weak link, by means of Quantum Monte Carlo simulation. This model contains an on-site repulsive interaction (U) and two different near-neighbor hopping terms, J and t, for the weak link and the remainder of the chain, respectively. We show that by reducing the strength of J, a novel intermediate phase develops which is compressible and non-superfluid. This novel phase is identified as a Normal Bose Liquid (NBL) which does not appear in the phase diagram of the homogeneous bosonic Hubbard model. Further, we find a linear variation of the phase boundary of Normal Bose Liquid (NBL) to SuperFluid (SF) as a function of the strength of the weak link. These results may provide a new path to design advanced atomtronic devices in the future.

Non-covalent interactions across organic and biological subsets of chemical space: Physics-based potentials parametrized from machine learning

NASA Astrophysics Data System (ADS)

Bereau, Tristan; DiStasio, Robert A.; Tkatchenko, Alexandre; von Lilienfeld, O. Anatole

2018-06-01

Classical intermolecular potentials typically require an extensive parametrization procedure for any new compound considered. To do away with prior parametrization, we propose a combination of physics-based potentials with machine learning (ML), coined IPML, which is transferable across small neutral organic and biologically relevant molecules. ML models provide on-the-fly predictions for environment-dependent local atomic properties: electrostatic multipole coefficients (significant error reduction compared to previously reported), the population and decay rate of valence atomic densities, and polarizabilities across conformations and chemical compositions of H, C, N, and O atoms. These parameters enable accurate calculations of intermolecular contributions—electrostatics, charge penetration, repulsion, induction/polarization, and many-body dispersion. Unlike other potentials, this model is transferable in its ability to handle new molecules and conformations without explicit prior parametrization: All local atomic properties are predicted from ML, leaving only eight global parameters—optimized once and for all across compounds. We validate IPML on various gas-phase dimers at and away from equilibrium separation, where we obtain mean absolute errors between 0.4 and 0.7 kcal/mol for several chemically and conformationally diverse datasets representative of non-covalent interactions in biologically relevant molecules. We further focus on hydrogen-bonded complexes—essential but challenging due to their directional nature—where datasets of DNA base pairs and amino acids yield an extremely encouraging 1.4 kcal/mol error. Finally, and as a first look, we consider IPML for denser systems: water clusters, supramolecular host-guest complexes, and the benzene crystal.

The S-layer Associated Serine Protease Homolog PrtX Impacts Cell Surface-Mediated Microbe-Host Interactions of Lactobacillus acidophilus NCFM

PubMed Central

Johnson, Brant R.; O’Flaherty, Sarah; Goh, Yong Jun; Carroll, Ian; Barrangou, Rodolphe; Klaenhammer, Todd R.

2017-01-01

Health-promoting aspects attributed to probiotic microorganisms, including adhesion to intestinal epithelia and modulation of the host mucosal immune system, are mediated by proteins found on the bacterial cell surface. Notably, certain probiotic and commensal bacteria contain a surface (S-) layer as the outermost stratum of the cell wall. S-layers are non-covalently bound semi-porous, crystalline arrays of self-assembling, proteinaceous subunits called S-layer proteins (SLPs). Recent evidence has shown that multiple proteins are non-covalently co-localized within the S-layer, designated S-layer associated proteins (SLAPs). In Lactobacillus acidophilus NCFM, SLP and SLAPs have been implicated in both mucosal immunomodulation and adhesion to the host intestinal epithelium. In this study, a S-layer associated serine protease homolog, PrtX (prtX, lba1578), was deleted from the chromosome of L. acidophilus NCFM. Compared to the parent strain, the PrtX-deficient strain (ΔprtX) demonstrated increased autoaggregation, an altered cellular morphology, and pleiotropic increases in adhesion to mucin and fibronectin, in vitro. Furthermore, ΔprtX demonstrated increased in vitro immune stimulation of IL-6, IL-12, and IL-10 compared to wild-type, when exposed to mouse dendritic cells. Finally, in vivo colonization of germ-free mice with ΔprtX led to an increase in epithelial barrier integrity. The absence of PrtX within the exoproteome of a ΔprtX strain caused morphological changes, resulting in a pleiotropic increase of the organisms’ immunomodulatory properties and interactions with some intestinal epithelial cell components. PMID:28713337

Vibrational dynamics of glass forming: 2-phenylbutan-1-ol (BEP), 2-(trifluoromethyl)phenethyl alcohol (2TFMP) and 4-(trifluoromethyl)phenethyl alcohol (4TFMP) in their thermodynamic phases

NASA Astrophysics Data System (ADS)

Juszyńska-Gałązka, Ewa; Zając, Wojciech; Saito, Kazuya; Yamamura, Yasuhisa; Juruś, Natalia

2018-02-01

The complex polymorphism and vibrational dynamics of three glass-forming single-phenyl-ring alcohols (with and without fluorine atoms) have been studied by complementary methods. Glass of isotropic liquid phase and cold crystallization of metastable supercooled liquid state were detected. Temperature investigations of vibrational motions show important role of hydrogen bonds in interactions between molecules. Theoretical calculations for isolated molecule, as well as dimer- and tetramer-type aggregates of non-covalently bound molecules, allow for a good description of experimental spectra. Intermolecular interactions of molecules with ortho and para positions of CF3 group in phenyl ring have a similar influence on the spectra observed.

Drug/protein interactions studied by time-resolved fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Gustavsson, Thomas; Markovitsi, Dimitra; Vayá, Ignacio; Bonancía, Paula; Jiménez, M. C.; Miranda, Miguel A.

2014-09-01

We report here on a recent time-resolved fluorescence study [1] of the interaction between flurbiprofen (FBP), a chiral non-steroidal anti-inflammatory drug, and human serum albumin (HSA), the main transport protein in the human body. We compare the results obtained for the drug-protein complex with those of various covalently linked flurbiprofentryptophan dyads having well-defined geometries. In all cases stereoselective dynamic fluorescence quenching is observed, varying greatly from one system to another. In addition, the fluorescence anisotropy decays also display a clear stereoselectivity. For the drug-protein complexes, this can be interpreted in terms of the protein microenvironment playing a significant role in the conformational relaxation of FBP, which is more restricted in the case of the (R)- enantiomer.

Supramolecular biomaterials

NASA Astrophysics Data System (ADS)

Webber, Matthew J.; Appel, Eric A.; Meijer, E. W.; Langer, Robert

2016-01-01

Polymers, ceramics and metals have historically dominated the application of materials in medicine. Yet rationally designed materials that exploit specific, directional, tunable and reversible non-covalent interactions offer unprecedented advantages: they enable modular and generalizable platforms with tunable mechanical, chemical and biological properties. Indeed, the reversible nature of supramolecular interactions gives rise to biomaterials that can sense and respond to physiological cues, or that mimic the structural and functional aspects of biological signalling. In this Review, we discuss the properties of several supramolecular biomaterials, as well as their applications in drug delivery, tissue engineering, regenerative medicine and immunology. We envision that supramolecular biomaterials will contribute to the development of new therapies that combine highly functional materials with unmatched patient- and application-specific tailoring of both material and biological properties.

Dynamic nanoplatforms in biosensor and membrane constitutional systems.

PubMed

Mahon, Eugene; Aastrup, Teodor; Barboiu, Mihail

2012-01-01

Molecular recognition in biological systems occurs mainly at interfacial environments such as membrane surfaces, enzyme active sites, or the interior of the DNA double helix. At the cell membrane surface, carbohydrate-protein recognition principles apply to a range of specific non-covalent interactions including immune response, cell proliferation, adhesion and death, cell-cell interaction and communication. Protein-protein recognition meanwhile accounts for signalling processes and ion channel structure. In this chapter we aim to describe such constitutional dynamic interfaces for biosensing and membrane transport applications. Constitutionally adaptive interfaces may mimic the recognition capabilities intrinsic to natural recognition processes. We present some recent examples of 2D and 3D constructed sensors and membranes of this type and describe their sensing and transport capabilities.

Mechanochemistry of nucleosides, nucleotides and related materials

PubMed Central

Eguaogie, Olga; Conlon, Patrick F; Gîlea, Manuela A; Liang, Yipei

2018-01-01

The application of mechanical force to induce the formation and cleavage of covalent bonds is a rapidly developing field within organic chemistry which has particular value in reducing or eliminating solvent usage, enhancing reaction rates and also in enabling the preparation of products which are otherwise inaccessible under solution-phase conditions. Mechanochemistry has also found recent attention in materials chemistry and API formulation during which rearrangement of non-covalent interactions give rise to functional products. However, this has been known to nucleic acids science almost since its inception in the late nineteenth century when Miescher exploited grinding to facilitate disaggregation of DNA from tightly bound proteins through selective denaturation of the latter. Despite the wide application of ball milling to amino acid chemistry, there have been limited reports of mechanochemical transformations involving nucleoside or nucleotide substrates on preparative scales. A survey of these reactions is provided, the majority of which have used a mixer ball mill and display an almost universal requirement for liquid to be present within the grinding vessel. Mechanochemistry of charged nucleotide substrates, in particular, provides considerable benefits both in terms of efficiency (reducing total processing times from weeks to hours) and by minimising exposure to aqueous conditions, access to previously elusive materials. In the absence of large quantities of solvent and heating, side-reactions can be reduced or eliminated. The central contribution of mechanochemistry (and specifically, ball milling) to the isolation of biologically active materials derived from nuclei by grinding will also be outlined. Finally non-covalent associative processes involving nucleic acids and related materials using mechanochemistry will be described: specifically, solid solutions, cocrystals, polymorph transitions, carbon nanotube dissolution and inclusion complex formation. PMID:29765475

An ion mobility-mass spectrometry investigation of monocyte chemoattractant protein-1

NASA Astrophysics Data System (ADS)

Schenauer, Matthew R.; Leary, Julie A.

2009-10-01

In the present article we describe the gas-phase dissociation behavior of the dimeric form of monocyte chemoattractant protein-1 (MCP-1) using quadrupole-traveling wave ion mobility spectrometry-time of flight mass spectrometry (q-TWIMS-TOF MS) (Waters Synapt(TM)). Through investigation of the 9+ charge state of the dimer, we were able to monitor dissociation product ion (monomer) formation as a function of activation energy. Using ion mobility, we were able to observe precursor ion structural changes occurring throughout the activation process. Arrival time distributions (ATDs) for the 5+ monomeric MCP-1 product ions, derived from the gas-phase dissociation of the 9+ dimer, were then compared with ATDs obtained for the 5+ MCP-1 monomer isolated directly from solution. The results show that the dissociated monomer is as compact as the monomer arising from solution, regardless of the trap collision energy (CE) used in the dissociation. The solution-derived monomer, when collisionally activated, also resists significant unfolding within measure. Finally, we compared the collisional activation data for the MCP-1 dimer with an MCP-1 dimer non-covalently bound to a single molecule of the semi-synthetic glycosaminoglycan (GAG) analog Arixtra(TM); the latter a therapeutic anti-thrombin III-activating pentasaccharide. We observed that while dimeric MCP-1 dissociated at relatively low trap CEs, the Arixtra-bound dimer required much higher energies, which also induced covalent bond cleavage in the bound Arixtra molecule. Both the free and Arixtra-bound dimers became less compact and exhibited longer arrival times with increasing trap CEs, albeit the Arixtra-bound complex at slightly higher energies. That both dimers shifted to longer arrival times with increasing activation energy, while the dissociated MCP-1 monomers remained compact, suggests that the longer arrival times of the Arixtra-free and Arixtra-bound dimers may represent a partial breach of non-covalent interactions between the associated MCP-1 monomers, rather than extensive unfolding of individual subunits. The fact that Arixtra preferentially binds MCP-1 dimers and prevents dimer dissociation at comparable activation energies to the Arixtra-free dimer, may suggest that the drug interacts across the two monomers, thereby inhibiting their dissociation.

Detecting and distinguishing among covalent and non-covalent differences in proteins: Shiga toxins and prions

USDA-ARS?s Scientific Manuscript database

The structural variety of food associated contaminants is remarkable. This diversity spans compounds from small molecules to protein toxins to infectious proteins. The small molecules are stoichiometric toxins while the proteins are catalytic toxins. This means that the molar amount of a protein to...

Matrix-assisted laser desorption-ionization time-of-flight mass spectrometry in the subunit stoichiometry study of high-mass non-covalent complexes

NASA Astrophysics Data System (ADS)

Moniatte, M.; Lesieur, C.; Vecsey-Semjen, B.; Buckley, J. T.; Pattus, F.; van der Goot, F. G.; van Dorsselaer, A.

1997-12-01

This study explores the potential of MALDI-TOF MS for the mass measurement of large non-covalent protein complexes. The following non-covalent complexes have been investigated: aerolysin from Aeromonas hydrophila (335 kDa) and [alpha]-haemolysin from Staphylococcus aureus (233 kDa) which are both cytolytic toxins, three enzymes known to be homotetramers in solution: bovine liver catalase (235 kDa), rabbit muscle pyruvate kinase (232 kDa), yeast alcohol dehydrogenase (147 kDa) and finally a lectin, concanavalin A (102 kDa). Three different matrix preparations were systematically tested under various conditions: ferulic acid dissolved in THF, 2,6-dihydroxyacetophenone in 20 mM aqueous ammonium citrate and a two-step sample preparation with sinapinic acid. It was possible to find a suitable combination of matrix and preparation type which allowed the molecularity of all complexes tested to be deduced from the MALDI mass spectrum. Trimeric and tetrameric intermediates accumulating during the formation of the active heptameric aerolysin complex were also identified, this allowing a formation mechanism to be proposed. The observation of large specific non-covalent complexes has been found to be dependent on the choice of matrix, the type of sample preparation used, the solvent evaporation speed, the pH of the resulting matrix-sample mixture and the number of shots acquired on a given area. From this set of experiments, some useful guidelines for the observation of large complexes by MALDI could therefore be deduced. Fast evaporation of the solvent is particularly necessary in the case of pH sensitive complexes. An ESMS study on the same non-covalent complexes indicated that, rather surprisingly, reliable results could be obtained by MALDI-TOF MS on several very large complexes (above 200 kDa) for which ESMS yielded no clear spectra.

An alternate binding site for PPARγ ligands

PubMed Central

Hughes, Travis S.; Giri, Pankaj Kumar; de Vera, Ian Mitchelle S.; Marciano, David P.; Kuruvilla, Dana S.; Shin, Youseung; Blayo, Anne-Laure; Kamenecka, Theodore M.; Burris, Thomas P.; Griffin, Patrick R.; Kojetin, Douglas J.

2014-01-01

PPARγ is a target for insulin sensitizing drugs such as glitazones, which improve plasma glucose maintenance in patients with diabetes. Synthetic ligands have been designed to mimic endogenous ligand binding to a canonical ligand-binding pocket to hyperactivate PPARγ. Here we reveal that synthetic PPARγ ligands also bind to an alternate site, leading to unique receptor conformational changes that impact coregulator binding, transactivation and target gene expression. Using structure-function studies we show that alternate site binding occurs at pharmacologically relevant ligand concentrations, and is neither blocked by covalently bound synthetic antagonists nor by endogenous ligands indicating non-overlapping binding with the canonical pocket. Alternate site binding likely contributes to PPARγ hyperactivation in vivo, perhaps explaining why PPARγ full and partial or weak agonists display similar adverse effects. These findings expand our understanding of PPARγ activation by ligands and suggest that allosteric modulators could be designed to fine tune PPARγ activity without competing with endogenous ligands. PMID:24705063

Fluoride-Mediated Capture of a Noncovalent Bound State of a Reversible Covalent Enzyme Inhibitor: X-ray Crystallographic Analysis of an Exceptionally Potent [alpha]-Ketoheterocycle Inhibitor of Fatty Acid Amide Hydrolase

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

Mileni, Mauro; Garfunkle, Joie; Ezzili, Cyrine

2011-11-02

Two cocrystal X-ray structures of the exceptionally potent {alpha}-ketoheterocycle inhibitor 1 (K{sub i} = 290 pM) bound to a humanized variant of rat fatty acid amide hydrolase (FAAH) are disclosed, representing noncovalently and covalently bound states of the same inhibitor with the enzyme. Key to securing the structure of the noncovalently bound state of the inhibitor was the inclusion of fluoride ion in the crystallization conditions that is proposed to bind the oxyanion hole precluding inhibitor covalent adduct formation with stabilization of the tetrahedral hemiketal. This permitted the opportunity to detect important noncovalent interactions stabilizing the binding of the inhibitormore » within the FAAH active site independent of the covalent reaction. Remarkably, noncovalently bound 1 in the presence of fluoride appears to capture the active site in the same 'in action' state with the three catalytic residues Ser241-Ser217-Lys142 occupying essentially identical positions observed in the covalently bound structure of 1, suggesting that this technique of introducing fluoride may have important applications in structural studies beyond inhibiting substrate or inhibitor oxyanion hole binding. Key insights to emerge from the studies include the observations that noncovalently bound 1 binds in its ketone (not gem diol) form, that the terminal phenyl group in the acyl side chain of the inhibitor serves as the key anchoring interaction overriding the intricate polar interactions in the cytosolic port, and that the role of the central activating heterocycle is dominated by its intrinsic electron-withdrawing properties. These two structures are also briefly compared with five X-ray structures of {alpha}-ketoheterocycle-based inhibitors bound to FAAH recently disclosed.« less

Exploring hydride-π interactions and their tuning by σ-hole bonds: an ab initio study

NASA Astrophysics Data System (ADS)

Esrafili, Mehdi D.; Asadollahi, Soheila; Mousavian, Parisasadat

2018-01-01

In the present work, ab initio calculations are performed to investigate the geometry, interaction energy and bonding properties of binary complexes formed between metal-hydrides HMX (M = Be, Mg, Zn and X = H, F, CH3) and a series of π-acidic heteroaromatic rings. In all the resulting complexes, the heteroaromatic ring acts as a Lewis acid (electron acceptor), while the H atom of the HMX molecule acts as a Lewis base (electron donor). The nature of this interaction, called 'hydride-π' interaction, is explored in terms of molecular electrostatic potential, non-covalent interaction, quantum theory of atoms in molecules and natural bond orbital analyses. The results show that the interaction energies of these hydride-π interactions are between -1.24 and -2.72 kcal/mol. Furthermore, mutual influence between the hydride-π and halogen- or pnicogen-bonding interactions is studied in complexes in which these interactions coexist. For a given π-acidic ring, the formation of the pnicogen-bonding induces a larger enhancing effect on the strength of hydride-π bond than the halogen-bonding.

Labelling of histone H5 and its interaction with DNA. 1. Histone H5 labelling with fluorescein isothiocyanate.

PubMed

Favazza, M; Lerho, M; Houssier, C

1990-06-01

Histone H5 has been labelled with fluorescein isothiocyanate (FITC) with particular attention to the reaction conditions (pH, reaction time and input FITC/H5 molar ratio) and to the complete elimination of non-covalently bound dye. We preferred to use reaction conditions which yielded non-specific uniform labelling rather than specific alpha-NH2 terminal labelling, in order to obtain higher sensitivity in further studies dealing with the detection of perturbation at the binding sites of H5 on DNA. FITC-labelled H5 was further characterized by absorption and circular dichroism spectroscopy, and the fluorescein probe titrated in the 4-8 pH range. The structural integrity of H5 was found to be preserved after labelling. The positive electrostatic potential of the environment in which the FITC probe is embedded in the arginine/lysine-rich tails of H5 is believed to be responsible for the drop of pK of 1 unit found for H5-FITC as compared to free FITC. For the globular part of H5, the pK of covalently-bound FITC was only slightly lowered; this is a consequence of the much lower content in positively-charged amino-acid side chains in this region.

CN-GELFrEE - Clear Native Gel-eluted Liquid Fraction Entrapment Electrophoresis

PubMed Central

Skinner, Owen S.; Do Vale, Luis H. F.; Catherman, Adam D.; Havugimana, Pierre C.; Valle de Sousa, Marcelo; Domont, Gilberto B.; Kelleher, Neil L.; Compton, Philip D.

2016-01-01

Protein complexes perform an array of crucial cellular functions. Elucidating their non-covalent interactions and dynamics is paramount for understanding the role of complexes in biological systems. While the direct characterization of biomolecular assemblies has become increasingly important in recent years, native fractionation techniques that are compatible with downstream analysis techniques, including mass spectrometry, are necessary to further expand these studies. Nevertheless, the field lacks a high-throughput, wide-range, high-recovery separation method for native protein assemblies. Here, we present clear native gel-eluted liquid fraction entrapment electrophoresis (CN-GELFrEE), which is a novel separation modality for non-covalent protein assemblies. CN-GELFrEE separation performance was demonstrated by fractionating complexes extracted from mouse heart. Fractions were collected over 2 hr and displayed discrete bands ranging from ~30 to 500 kDa. A consistent pattern of increasing molecular weight bandwidths was observed, each ranging ~100 kDa. Further, subsequent reanalysis of native fractions via SDS-PAGE showed molecular-weight shifts consistent with the denaturation of protein complexes. Therefore, CN-GELFrEE was proved to offer the ability to perform high-resolution and high-recovery native separations on protein complexes from a large molecular weight range, providing fractions that are compatible with downstream protein analyses. PMID:26967310

Covalently Bound Nitroxyl Radicals in an Organic Framework

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

Hughes, Barbara K.; Braunecker, Wade A.; Bobela, David C.

2016-09-15

A series of covalent organic framework (COF) structures is synthesized that possesses a tunable density of covalently bound nitroxyl radicals within the COF pores. The highest density of organic radicals produces an electron paramagnetic resonance (EPR) signal that suggests the majority of radicals strongly interact with other radicals, whereas for smaller loadings the EPR signals indicate the radicals are primarily isolated but with restricted motion. The dielectric loss as determined from microwave absorption of the framework structures compared with an amorphous control suggests that free motion of the radicals is inhibited when more than 25% of available sites are occupied.more » The ability to tune the mode of radical interactions and the subsequent effect on redox, electrical, and optical characteristics in a porous framework may lead to a class of structures with properties ideal for photoelectrochemistry or energy storage.« less

Interactions of hemin with bovine serum albumin and human hemoglobin: A fluorescence quenching study

NASA Astrophysics Data System (ADS)

Makarska-Bialokoz, Magdalena

2018-03-01

The binding interactions between hemin (Hmi) and bovine serum albumin (BSA) or human hemoglobin (HHb), respectively, have been examined in aqueous solution at pH = 7.4, applying UV-vis absorption, as well as steady-state, synchronous and three-dimensional fluorescence spectra techniques. Representative results received for both BSA and HHb intrinsic fluorescence proceeding from the interactions with hemin suggest the formation of stacking non-covalent and non-fluorescent complexes in both the Hmi-BSA and Hmi-HHb systems, with highly possible concurrent formation of a coordinate bond between a group on the protein surface and the metal in Hmi molecule. All the values of calculated parameters, the binding, fluorescence quenching and bimolecular quenching rate constants point to the involvement of static quenching in both the systems studied. The blue shift in the synchronous fluorescence spectra imply the participation of both tryptophan and tyrosine residues in quenching of BSA and HHb intrinsic fluorescence. Depicted outcomes suggest that hemin is supposedly able to influence the physiological functions of BSA and HHb, the most important blood proteins, particularly in case of its overuse.

Improving mechanical properties of carbon nanotube fibers through simultaneous solid-state cycloaddition and crosslinking

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

Lu, Xinyi; Hiremath, Nitilaksha; Hong, Kunlun

Individual carbon nanotubes (CNTs) exhibit exceptional mechanical properties. However, difficulties remain in fully realizing these properties in CNT macro-assemblies, because the weak inter-tube forces result in the CNTs sliding past one another. Here in this study, a simple solid-state reaction is presented that enhances the mechanical properties of carbon nanotube fibers (CNTFs) through simultaneous covalent functionalization and crosslinking. This is the first chemical crosslinking proposed without the involvement of a catalyst or byproducts. The specific tensile strength of CNTFs obtained from the treatment employing a benzocyclobutene-based polymer is improved by 40%. Such improvement can be attributed to a reduced numbermore » of voids, impregnation of the polymer, and the formation of covalent crosslinks. This methodology is confirmed using both multiwalled nanotube (MWNT) powders and CNTFs. Thermogravimetric analysis, differential scanning calorimetry, x-ray photoelectron spectroscopy, and transmission electron microscopy of the treated MWNT powders confirm the covalent functionalization and formation of inter-tube crosslinks. This simple one-step reaction can be applied to industrial-scale production of high-strength CNTFs.« less

Improving mechanical properties of carbon nanotube fibers through simultaneous solid-state cycloaddition and crosslinking

DOE PAGES

Lu, Xinyi; Hiremath, Nitilaksha; Hong, Kunlun; ...

2017-03-13

Individual carbon nanotubes (CNTs) exhibit exceptional mechanical properties. However, difficulties remain in fully realizing these properties in CNT macro-assemblies, because the weak inter-tube forces result in the CNTs sliding past one another. Here in this study, a simple solid-state reaction is presented that enhances the mechanical properties of carbon nanotube fibers (CNTFs) through simultaneous covalent functionalization and crosslinking. This is the first chemical crosslinking proposed without the involvement of a catalyst or byproducts. The specific tensile strength of CNTFs obtained from the treatment employing a benzocyclobutene-based polymer is improved by 40%. Such improvement can be attributed to a reduced numbermore » of voids, impregnation of the polymer, and the formation of covalent crosslinks. This methodology is confirmed using both multiwalled nanotube (MWNT) powders and CNTFs. Thermogravimetric analysis, differential scanning calorimetry, x-ray photoelectron spectroscopy, and transmission electron microscopy of the treated MWNT powders confirm the covalent functionalization and formation of inter-tube crosslinks. This simple one-step reaction can be applied to industrial-scale production of high-strength CNTFs.« less

Non-thermal damage to lead tungstate induced by intense short-wavelength laser radiation (Conference Presentation)

NASA Astrophysics Data System (ADS)

Vozda, Vojtech; Boháček, Pavel; Burian, Tomáš; Chalupský, Jaromir; Hájková, Vera; Juha, Libor; Vyšín, Ludek; Gaudin, Jérôme; Heimann, Philip A.; Hau-Riege, Stefan P.; Jurek, Marek; Klinger, Dorota; Krzywinski, Jacek; Messerschmidt, Marc; Moeller, Stefan P.; Nagler, Robert; Pelka, Jerzy B.; Rowen, Michael; Schlotter, William F.; Swiggers, Michele L.; Sinn, Harald; Sobierajski, Ryszard; Tiedtke, Kai; Toleikis, Sven; Tschentscher, Thomas; Turner, Joshua J.; Wabnitz, Hubertus; Nelson, Art J.; Kozlova, Maria V.; Vinko, Sam M.; Whitcher, Thomas; Dzelzainis, Thomas; Renner, Oldrich; Saksl, Karel; Fäustlin, Roland R.; Khorsand, Ali R.; Fajardo, Marta; Iwan, Bianca S.; Andreasson, Jakob; Hajdu, Janos; Timneanu, Nicusor; Wark, Justin S.; Riley, David; Lee, Richard W.; Nagasono, Mitsuru; Yabashi, Makina

2017-05-01

Interaction of short-wavelength free-electron laser (FEL) beams with matter is undoubtedly a subject to extensive investigation in last decade. During the interaction various exotic states of matter, such as warm dense matter, may exist for a split second. Prior to irreversible damage or ablative removal of the target material, complicated electronic processes at the atomic level occur. As energetic photons impact the target, electrons from inner atomic shells are almost instantly photo-ionized, which may, in some special cases, cause bond weakening, even breaking of the covalent bonds, subsequently result to so-called non-thermal melting. The subject of our research is ablative damage to lead tungstate (PbWO4) induced by focused short-wavelength FEL pulses at different photon energies. Post-mortem analysis of complex damage patterns using the Raman spectroscopy, atomic-force (AFM) and Nomarski (DIC) microscopy confirms an existence of non-thermal melting induced by high-energy photons in the ionic monocrystalline target. Results obtained at Linac Coherent Light Source (LCLS), Free-electron in Hamburg (FLASH), and SPring-8 Compact SASE Source (SCSS) are presented in this Paper.

Coval: Improving Alignment Quality and Variant Calling Accuracy for Next-Generation Sequencing Data

PubMed Central

Kosugi, Shunichi; Natsume, Satoshi; Yoshida, Kentaro; MacLean, Daniel; Cano, Liliana; Kamoun, Sophien; Terauchi, Ryohei

2013-01-01

Accurate identification of DNA polymorphisms using next-generation sequencing technology is challenging because of a high rate of sequencing error and incorrect mapping of reads to reference genomes. Currently available short read aligners and DNA variant callers suffer from these problems. We developed the Coval software to improve the quality of short read alignments. Coval is designed to minimize the incidence of spurious alignment of short reads, by filtering mismatched reads that remained in alignments after local realignment and error correction of mismatched reads. The error correction is executed based on the base quality and allele frequency at the non-reference positions for an individual or pooled sample. We demonstrated the utility of Coval by applying it to simulated genomes and experimentally obtained short-read data of rice, nematode, and mouse. Moreover, we found an unexpectedly large number of incorrectly mapped reads in ‘targeted’ alignments, where the whole genome sequencing reads had been aligned to a local genomic segment, and showed that Coval effectively eliminated such spurious alignments. We conclude that Coval significantly improves the quality of short-read sequence alignments, thereby increasing the calling accuracy of currently available tools for SNP and indel identification. Coval is available at http://sourceforge.net/projects/coval105/. PMID:24116042

Molecular cloning and biochemical characterization of rabbit factor XI.

PubMed Central

Sinha, Dipali; Marcinkiewicz, Mariola; Gailani, David; Walsh, Peter N

2002-01-01

Human factor XI, a plasma glycoprotein required for normal haemostasis, is a homodimer (160 kDa) formed by a single interchain disulphide bond linking the Cys-321 of each Apple 4 domain. Bovine, porcine and murine factor XI are also disulphide-linked homodimers. Rabbit factor XI, however, is an 80 kDa polypeptide on non-reducing SDS/PAGE, suggesting that rabbit factor XI exists and functions physiologically either as a monomer, as does prekallikrein, a structural homologue to factor XI, or as a non-covalent homodimer. We have investigated the structure and function of rabbit factor XI to gain insight into the relation between homodimeric structure and factor XI function. Characterization of the cDNA sequence of rabbit factor XI and its amino acid translation revealed that in the rabbit protein a His residue replaces the Cys-321 that forms the interchain disulphide linkage in human factor XI, explaining why rabbit factor XI is a monomer in non-reducing SDS/PAGE. On size-exclusion chromatography, however, purified plasma rabbit factor XI, like the human protein and unlike prekallikrein, eluted as a dimer, demonstrating that rabbit factor XI circulates as a non-covalent dimer. In functional assays rabbit factor XI and human factor XI behaved similarly. Both monomeric and dimeric factor XI were detected in extracts of cells expressing rabbit factor XI. We conclude that the failure of rabbit factor XI to form a covalent homodimer due to the replacement of Cys-321 with His does not impair its functional activity because it exists in plasma as a non-covalent homodimer and homodimerization is an intracellular process. PMID:12084014

Holistic Approach to Partial Covalent Interactions in Protein Structure Prediction and Design with Rosetta.

PubMed

Combs, Steven A; Mueller, Benjamin K; Meiler, Jens

2018-05-29

Partial covalent interactions (PCIs) in proteins, which include hydrogen bonds, salt bridges, cation-π, and π-π interactions, contribute to thermodynamic stability and facilitate interactions with other biomolecules. Several score functions have been developed within the Rosetta protein modeling framework that identify and evaluate these PCIs through analyzing the geometry between participating atoms. However, we hypothesize that PCIs can be unified through a simplified electron orbital representation. To test this hypothesis, we have introduced orbital based chemical descriptors for PCIs into Rosetta, called the PCI score function. Optimal geometries for the PCIs are derived from a statistical analysis of high-quality protein structures obtained from the Protein Data Bank (PDB), and the relative orientation of electron deficient hydrogen atoms and electron-rich lone pair or π orbitals are evaluated. We demonstrate that nativelike geometries of hydrogen bonds, salt bridges, cation-π, and π-π interactions are recapitulated during minimization of protein conformation. The packing density of tested protein structures increased from the standard score function from 0.62 to 0.64, closer to the native value of 0.70. Overall, rotamer recovery improved when using the PCI score function (75%) as compared to the standard Rosetta score function (74%). The PCI score function represents an improvement over the standard Rosetta score function for protein model scoring; in addition, it provides a platform for future directions in the analysis of small molecule to protein interactions, which depend on partial covalent interactions.

The different effector function capabilities of the seven equine IgG subclasses have implications for vaccine strategies

PubMed Central

Lewis, Melanie J.; Wagner, Bettina; Woof, Jenny M.

2008-01-01

Recombinant versions of the seven equine IgG subclasses were expressed in CHO cells. All assembled into intact immunoglobulins stabilised by disulphide bridges, although, reminiscent of human IgG4, a small proportion of equine IgG4 and IgG7 were held together by non-covalent bonds alone. All seven IgGs were N-glycosylated. In addition IgG3 appeared to be O-glycosylated and could bind the lectin jacalin. Staphylococcal protein A displayed weak binding for the equine IgGs in the order: IgG1 > IgG3 > IgG4 > IgG7 > IgG2 = IgG5 > IgG6. Streptococcal protein G bound strongly to IgG1, IgG4 and IgG7, moderately to IgG3, weakly to IgG2 and IgG6, and not at all to IgG5. Analysis of antibody effector functions revealed that IgG1, IgG3, IgG4, IgG5 and IgG7, but not IgG2 and IgG6, were able to elicit a strong respiratory burst from equine peripheral blood leukocytes, predicting that the former five IgG subclasses are able to interact with Fc receptors on effector cells. IgG1, IgG3, IgG4 and IgG7, but not IgG2, IgG5 and IgG6, were able to bind complement C1q and activate complement via the classical pathway. The differential effector function capabilities of the subclasses suggest that, for maximum efficacy, equine vaccine strategies should seek to elicit antibody responses of the IgG1, IgG3, IgG4, and IgG7 subclasses. PMID:17669496

Supramolecular architectures constructed through self-assembly of a chalcone and substituted diazo-β-diketones

NASA Astrophysics Data System (ADS)

Prajapati, R.; Mishra, L.; Grabowski, S. J.; Govil, G.; Dubey, S. K.

2008-05-01

Organic compounds namely pyridyl chalcone viz. 3-[4-(3-oxo-3-pyridin-2-yl-propenyl)-phenyl]-1-pyridin-2-yl-propenone (L 1), p-cholorophenyldiazopentane-2,4-dione (L 2) and p-methyl phenyldiazopentane-2,4-dione (L 3) have been characterized by their single-crystal X-ray crystallographic studies. Several structural motifs resulting upon their self-association through probable non-covalent interactions have been discussed. The studies of related motifs found in Cambridge Structural Database are performed and the results are related to the structural data obtained for crystal structures reported here in.

Large Frequency Change with Thickness in Interlayer Breathing Mode—Significant Interlayer Interactions in Few Layer Black Phosphorus

NASA Astrophysics Data System (ADS)

Luo, Xin; Lu, Xin; Koon, Gavin Kok Wai; Castro Neto, Antonio H.; Özyilmaz, Barbaros; Xiong, Qihua; Quek, Su Ying

2015-06-01

Bulk black phosphorus (BP) consists of puckered layers of phosphorus atoms. Few-layer BP, obtained from bulk BP by exfoliation, is an emerging candidate as a channel material in post-silicon electronics. A deep understanding of its physical properties and its full range of applications are still being uncovered. In this paper, we present a theoretical and experimental investigation of phonon properties in few-layer BP, focusing on the low-frequency regime corresponding to interlayer vibrational modes. We show that the interlayer breathing mode A3g shows a large redshift with increasing thickness; the experimental and theoretical results agreeing well. This thickness dependence is two times larger than that in the chalcogenide materials such as few-layer MoS2 and WSe2, because of the significantly larger interlayer force constant and smaller atomic mass in BP. The derived interlayer out-of-plane force constant is about 50% larger than that in graphene and MoS2. We show that this large interlayer force constant arises from the sizable covalent interaction between phosphorus atoms in adjacent layers, and that interlayer interactions are not merely of the weak van der Waals type. These significant interlayer interactions are consistent with the known surface reactivity of BP, and have been shown to be important for electric-field induced formation of Dirac cones in thin film BP.

Large Frequency Change with Thickness in Interlayer Breathing Mode--Significant Interlayer Interactions in Few Layer Black Phosphorus.

PubMed

Luo, Xin; Lu, Xin; Koon, Gavin Kok Wai; Castro Neto, Antonio H; Özyilmaz, Barbaros; Xiong, Qihua; Quek, Su Ying

2015-06-10

Bulk black phosphorus (BP) consists of puckered layers of phosphorus atoms. Few-layer BP, obtained from bulk BP by exfoliation, is an emerging candidate as a channel material in post-silicon electronics. A deep understanding of its physical properties and its full range of applications are still being uncovered. In this paper, we present a theoretical and experimental investigation of phonon properties in few-layer BP, focusing on the low-frequency regime corresponding to interlayer vibrational modes. We show that the interlayer breathing mode A(3)g shows a large redshift with increasing thickness; the experimental and theoretical results agree well. This thickness dependence is two times larger than that in the chalcogenide materials, such as few-layer MoS2 and WSe2, because of the significantly larger interlayer force constant and smaller atomic mass in BP. The derived interlayer out-of-plane force constant is about 50% larger than that of graphene and MoS2. We show that this large interlayer force constant arises from the sizable covalent interaction between phosphorus atoms in adjacent layers and that interlayer interactions are not merely of the weak van der Waals type. These significant interlayer interactions are consistent with the known surface reactivity of BP and have been shown to be important for electric-field induced formation of Dirac cones in thin film BP.

Note: Nonpolar solute partial molar volume response to attractive interactions with water.

PubMed

Williams, Steven M; Ashbaugh, Henry S

2014-01-07

The impact of attractive interactions on the partial molar volumes of methane-like solutes in water is characterized using molecular simulations. Attractions account for a significant 20% volume drop between a repulsive Weeks-Chandler-Andersen and full Lennard-Jones description of methane interactions. The response of the volume to interaction perturbations is characterized by linear fits to our simulations and a rigorous statistical thermodynamic expression for the derivative of the volume to increasing attractions. While a weak non-linear response is observed, an average effective slope accurately captures the volume decrease. This response, however, is anticipated to become more non-linear with increasing solute size.

Note: Nonpolar solute partial molar volume response to attractive interactions with water

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

Williams, Steven M.; Ashbaugh, Henry S., E-mail: hanka@tulane.edu

2014-01-07

The impact of attractive interactions on the partial molar volumes of methane-like solutes in water is characterized using molecular simulations. Attractions account for a significant 20% volume drop between a repulsive Weeks-Chandler-Andersen and full Lennard-Jones description of methane interactions. The response of the volume to interaction perturbations is characterized by linear fits to our simulations and a rigorous statistical thermodynamic expression for the derivative of the volume to increasing attractions. While a weak non-linear response is observed, an average effective slope accurately captures the volume decrease. This response, however, is anticipated to become more non-linear with increasing solute size.

Global Well-posedness of the Spatially Homogeneous Kolmogorov-Vicsek Model as a Gradient Flow

NASA Astrophysics Data System (ADS)

Figalli, Alessio; Kang, Moon-Jin; Morales, Javier

2018-03-01

We consider the so-called spatially homogenous Kolmogorov-Vicsek model, a non-linear Fokker-Planck equation of self-driven stochastic particles with orientation interaction under the space-homogeneity. We prove the global existence and uniqueness of weak solutions to the equation. We also show that weak solutions exponentially converge to a steady state, which has the form of the Fisher-von Mises distribution.

Immunodetection of human topoisomerase I-DNA covalent complexes

PubMed Central

Patel, Anand G.; Flatten, Karen S.; Peterson, Kevin L.; Beito, Thomas G.; Schneider, Paula A.; Perkins, Angela L.; Harki, Daniel A.; Kaufmann, Scott H.

2016-01-01

A number of established and investigational anticancer drugs slow the religation step of DNA topoisomerase I (topo I). These agents induce cytotoxicity by stabilizing topo I-DNA covalent complexes, which in turn interact with advancing replication forks or transcription complexes to generate lethal lesions. Despite the importance of topo I-DNA covalent complexes, it has been difficult to detect these lesions within intact cells and tumors. Here, we report development of a monoclonal antibody that specifically recognizes covalent topo I-DNA complexes, but not free topo I or DNA, by immunoblotting, immunofluorescence or flow cytometry. Utilizing this antibody, we demonstrate readily detectable topo I-DNA covalent complexes after treatment with camptothecins, indenoisoquinolines and cisplatin but not nucleoside analogues. Topotecan-induced topo I-DNA complexes peak at 15–30 min after drug addition and then decrease, whereas indotecan-induced complexes persist for at least 4 h. Interestingly, simultaneous staining for covalent topo I-DNA complexes, phospho-H2AX and Rad51 suggests that topotecan-induced DNA double-strand breaks occur at sites distinct from stabilized topo I-DNA covalent complexes. These studies not only provide new insight into the action of topo I-directed agents, but also illustrate a strategy that can be applied to study additional topoisomerases and their inhibitors in vitro and in vivo. PMID:26917015

VEGF internalization is not required for VEGFR-2 phosphorylation in bioengineered surfaces with covalently linked VEGF

PubMed Central

Anderson, Sean M.; Shergill, Bhupinder; Barry, Zachary T.; Manousiouthakis, Eleana; Chen, Tom T.; Botvinick, Elliot; Platt, Manu O.; Iruela-Arispe, M. Luisa; Segura, Tatiana

2011-01-01

Vascular endothelial growth factor (VEGF) is known to activate proliferation, migration, and survival pathways in endothelial cells through phosphorylation of VEGF receptor-2 (VEGFR-2). VEGF has been incorporated into biomaterials through encapsulation, electrostatic sequestration, and covalent attachment, but the effect of these immobilization strategies on VEGF signaling has not been thoroughly investigated. Further, although growth factor internalization along with the receptor generally occurs in a physiological setting, whether this internalization is needed for receptor phosphorylation is not entirely clear. Here we show that VEGF covalently bound through a modified heparin molecule elicits an extended response of pVEGFR-2 in human umbilical vein endothelial cells (HUVECs) and that the covalent linkage reduces internalization of the growth factor during receptor endocytosis. Optical tweezer measurements show that the rupture force required to disrupt the heparin-VEGF-VEGFR-2 interaction increases from 3–8 pN to 6–12 pN when a covalent bond is introduced between VEGF and heparin. Importantly, by covalently binding VEGF to a heparin substrate, the stability (half-life) of VEGF is extended over three-fold. Here, mathematical models support the biological conclusions, further suggesting that VEGF internalization is significantly reduced when covalently bound, and indicating that VEGF is available for repeated phosphorylation events. PMID:21826315

Multifunctional polymer-capped mesoporous silica nanoparticles for pH-responsive targeted drug delivery.

PubMed

Niedermayer, Stefan; Weiss, Veronika; Herrmann, Annika; Schmidt, Alexandra; Datz, Stefan; Müller, Katharina; Wagner, Ernst; Bein, Thomas; Bräuchle, Christoph

2015-05-07

A highly stable modular platform, based on the sequential covalent attachment of different functionalities to the surface of core-shell mesoporous silica nanoparticles (MSNs) for targeted drug delivery is presented. A reversible pH-responsive cap system based on covalently attached poly(2-vinylpyridine) (PVP) was developed as drug release mechanism. Our platform offers (i) tuneable interactions and release kinetics with the cargo drug in the mesopores based on chemically orthogonal core-shell design, (ii) an extremely robust and reversible closure and release mechanism based on endosomal acidification of the covalently attached PVP polymer block, (iii) high colloidal stability due to a covalently coupled PEG shell, and (iv) the ability to covalently attach a wide variety of dyes, targeting ligands and other functionalities at the outer periphery of the PEG shell. The functionality of the system was demonstrated in several cell studies, showing pH-triggered release in the endosome, light-triggered endosomal escape with an on-board photosensitizer, and efficient folic acid-based cell targeting.

Novel Cholinesterase Inhibitors Based on O-Aromatic N,N-Disubstituted Carbamates and Thiocarbamates.

PubMed

Krátký, Martin; Štěpánková, Šárka; Vorčáková, Katarína; Švarcová, Markéta; Vinšová, Jarmila

2016-02-11

Based on the presence of carbamoyl moiety, twenty salicylanilide N,N-disubstituted (thio)carbamates were investigated using Ellman's method for their ability to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). O-Aromatic (thio)carbamates exhibited weak to moderate inhibition of both cholinesterases with IC50 values within the range of 1.60 to 311.0 µM. IC50 values for BChE were mostly lower than those obtained for AChE; four derivatives showed distinct selectivity for BChE. All of the (thio)carbamates produced a stronger inhibition of AChE than rivastigmine, and five of them inhibited BChE more effectively than both established drugs rivastigmine and galantamine. In general, 5-chloro-2-hydroxy-N-[4-(trifluoromethyl)-phenyl]benzamide, 2-hydroxy-N-phenylbenzamide as well as N-methyl-N-phenyl carbamate derivatives led to the more potent inhibition. O-{4-Chloro-2-[(4-chlorophenyl)carbamoyl]phenyl} dimethylcarbamothioate was identified as the most effective AChE inhibitor (IC50 = 38.98 µM), while 2-(phenylcarbamoyl)phenyl diphenylcarbamate produced the lowest IC50 value for BChE (1.60 µM). Results from molecular docking studies suggest that carbamate compounds, especially N,N-diphenyl substituted representatives with considerable portion of aromatic moieties may work as non-covalent inhibitors displaying many interactions at peripheral anionic sites of both enzymes. Mild cytotoxicity for HepG2 cells and consequent satisfactory calculated selectivity indexes qualify several derivatives for further optimization.

[Effects of glycerol on the spectral properties of sodium caseinate].

PubMed

Li, Yan; Chang, Fen-fen; Gao, Huan-yuan; Cao, Qing; Jin, Li-e

2015-01-01

Although the immigration of water molecule, and diffusion and traversing of oxygen can be prevented by the edible film prepared through sodium caseinate, which plays a good protection role for the food, the strong hydrophilicity makes its watertightness and mechanical properties become inferior. Because the toughness and water resistance of SC films can be enhanced by glycerol (G) as an additive, it is necessary to elucidate the interaction between G and SC through the spectral characteristics such as fluorescence spectra, infrared spectra and UV spectra. The results show that the fluorescence intensity of SC decreases due to the addition of G. The binding constant obtained by the double logarithmic regression curve analysis is 1. 127 x 10(3) L . mol-1 and the number of binding sites reaches 1. 161. It indicates that the weak chemical bond is primary between G and SC molecules; From IR the absorption peaks of SC are almost the same before and after adding G. However, there is a certain difference among their absorption intensities. It reveals that the secondary structure of SC is affected, β folding length decreases, α helix, random coil structure, β angle structure increases, and the intermolecular hydrogen bond is strengthened; From UV the peptide bond structure of SC is not changed after the addition of G, but the polymer with larger molecular weight, which is formed by non-covalent bond, makes the peak intensity decrease. The research gives the mode of G and SC from the molecular level.

Non-covalent S···O interactions control conformation in a scaffold that disrupts islet amyloid polypeptide fibrillation† †Electronic supplementary information (ESI) available: Experimental procedures; 1H, 13C and NOESY spectra; HRMS, and IR values. CCDC 1453550 (24), ThT assay data, computation, electron microscopy. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6sc00756b Click here for additional data file.

PubMed Central

Peacock, Hayden; Luo, Jinghui; Yamashita, Tohru; Luccarelli, James

2016-01-01

Conformationally-constrained molecules that selectively recognise the surfaces of proteins have the potential to direct the path of protein folding. Such molecules are of therapeutic interest because the misfolding of proteins, especially that which results in fibrillation and aggregation, is strongly correlated with numerous diseases. Here we report the novel use of S···O interactions as a conformational control element in a new class of non-peptidic scaffold that mimics key elements of protein surfaces. These molecules disrupt the fibrillation of islet amyloid polypeptide (IAPP), a process that is implicated in the pathology of type II diabetes. PMID:28451100

Cocrystals Strategy towards Materials for Near-Infrared Photothermal Conversion and Imaging.

PubMed

Wang, Yu; Zhu, Weigang; Du, Wenna; Liu, Xinfeng; Zhang, Xiaotao; Dong, Huanli; Hu, Wenping

2018-04-03

A cocrystal strategy with a simple preparation process is developed to prepare novel materials for near-infrared photothermal (PT) conversion and imaging. DBTTF and TCNB are selected as electron donor (D) and electron acceptor (A) to self-assemble into new cocrystals through non-covalent interactions. The strong D-A interaction leads to a narrow band gap with NIR absorption and that both the ground state and lowest-lying excited state are charge transfer states. Under the NIR laser illumination, the temperature of the cocrystal sharply increases in a short time with high PT conversion efficiency (η=18.8 %), which is due to the active non-radiative pathways and inhibition of radiative transition process, as revealed by femtosecond transient absorption spectroscopy. This is the first PT conversion cocrystal, which not only provides insights for the development of novel PT materials, but also paves the way of designing functional materials with appealing applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Gelation induced supramolecular chirality: chirality transfer, amplification and application.

PubMed

Duan, Pengfei; Cao, Hai; Zhang, Li; Liu, Minghua

2014-08-14

Supramolecular chirality defines chirality at the supramolecular level, and is generated from the spatial arrangement of component molecules assembling through non-covalent interactions such as hydrogen bonding, van der Waals interactions, π-π stacking, hydrophobic interactions and so on. During the formation of low molecular weight gels (LMWGs), one kind of fascinating soft material, one frequently encounters the phenomenon of chirality as well as chiral nanostructures, either from chiral gelators or even achiral gelators. A view of gelation-induced supramolecular chirality will be very helpful to understand the self-assembly process of the gelator molecules as well as the chiral structures, the regulation of the chirality in the gels and the development of the "smart" chiral materials such as chiroptical devices, catalysts and chiral sensors. It necessitates fundamental understanding of chirality transfer and amplification in these supramolecular systems. In this review, recent progress in gelation-induced supramolecular chirality is discussed.

Non-covalent interactions in 2-methylimidazolium copper(II) complex (MeImH)2[Cu(pfbz)4]: Synthesis, characterization, single crystal X-ray structure and packing analysis

NASA Astrophysics Data System (ADS)

Sharma, Raj Pal; Saini, Anju; Kumar, Santosh; Kumar, Jitendra; Sathishkumar, Ranganathan; Venugopalan, Paloth

2017-01-01

A new anionic copper(II) complex, (MeImH)2 [Cu(pfbz)4] (1) where, MeImH = 2-methylimidazolium and pfbz = pentafluorobenzoate has been isolated by reacting copper(II) sulfate pentahydrate, pentafluorobenzoic acid and 2-methylimidazole in ethanol: water mixture in 1:2:2 molar ratio. This complex 1 has been characterized by elemental analysis, thermogravimetric analysis, spectroscopic techniques (UV-Vis, FT-IR) and conductance measurements. The complex salt crystallizes in monoclinic crystal system with space group C2/c. Single crystal X-ray structure determination revealed the presence of discrete ions: [Cu(pfbz)4]2- anion and two 2-methylimidazolium cation (C4H7N2)+. The crystal lattice is stabilized by strong hydrogen bonding and F⋯F interactions between cationic-anionic and the anionic-anionic moieties respectively, besides π-π interactions.

Spin interactions in Graphene-Single Molecule Magnets Hybrids

NASA Astrophysics Data System (ADS)

Cervetti, Christian; Rettori, Angelo; Pini, Maria Gloria; Cornia, Andrea; Repollés, Aña; Luis, Fernando; Rauschenbach, Stephan; Dressel, Martin; Kern, Klaus; Burghard, Marko; Bogani, Lapo

2014-03-01

Graphene is a potential component of novel spintronics devices owing to its long spin diffusion length. Besides its use as spin-transport channel, graphene can be employed for the detection and manipulation of molecular spins. This requires an appropriate coupling between the sheets and the single molecular magnets (SMM). Here, we present a comprehensive characterization of graphene-Fe4 SMM hybrids. The Fe4 clusters are anchored non-covalently to the graphene following a diffusion-limited assembly and can reorganize into random networks when subjected to slightly elevated temperature. Molecules anchored on graphene sheets show unaltered static magnetic properties, whilst the quantum dynamics is profoundly modulated. Interaction with Dirac fermions becomes the dominant spin-relaxation channel, with observable effects produced by graphene phonons and reduced dipolar interactions. Coupling to graphene drives the spins over Villain's threshold, allowing the first observation of strongly-perturbative tunneling processes. Preliminary spin-transport experiments at low-temperature are further presented.

Effects of functionalization of carbon nanotubes on their dispersion in an ethylene glycol-water binary mixture--a molecular dynamics and ONIOM investigation.

PubMed

Balamurugan, Kanagasabai; Baskar, Prathab; Kumar, Ravva Mahesh; Das, Sumitesh; Subramanian, Venkatesan

2014-11-28

The present work utilizes classical molecular dynamics simulations to investigate the covalent functionalization of carbon nanotubes (CNTs) and their interaction with ethylene glycol (EG) and water molecules. The MD simulation reveals the dispersion of functionalized carbon nanotubes and the prevention of aggregation in aqueous medium. Further, residue-wise radial distribution function (RRDF) and atomic radial distribution function (ARDF) calculations illustrate the extent of interaction of -OH and -COOH functionalized CNTs with water molecules and the non-functionalized CNT surface with EG. As the presence of the number of functionalized nanotubes increases, enhancement in the propensity for the interaction with water molecules can be observed. However, the same trend decreases for the interaction of EG molecules. In addition, the ONIOM (M06-2X/6-31+G**:AM1) calculations have also been carried out on model systems to quantitatively determine the interaction energy (IE). It is found from these calculations that the relative enhancement in the interaction of water molecules with functionalized CNTs is highly favorable when compared to the interaction of EG.

Scrambling in the quantum Lifshitz model

NASA Astrophysics Data System (ADS)

Plamadeala, Eugeniu; Fradkin, Eduardo

2018-06-01

We study signatures of chaos in the quantum Lifshitz model through out-of-time ordered correlators (OTOC) of current operators. This model is a free scalar field theory with dynamical critical exponent z  =  2. It describes the quantum phase transition in 2D systems, such as quantum dimer models, between a phase with a uniform ground state to another one with spontaneously broken translation invariance. At the lowest temperatures the chaotic dynamics are dominated by a marginally irrelevant operator which induces a temperature dependent stiffness term. The numerical computations of OTOC exhibit a non-zero Lyapunov exponent (LE) in a wide range of temperatures and interaction strengths. The LE (in units of temperature) is a weakly temperature-dependent function; it vanishes at weak interaction and saturates for strong interaction. The Butterfly velocity increases monotonically with interaction strength in the studied region while remaining smaller than the interaction-induced velocity/stiffness.

From non-covalent binding to irreversible DNA lesions: nile blue and nile red as photosensitizing agents

PubMed Central

Gattuso, Hugo; Besancenot, Vanessa; Grandemange, Stéphanie; Marazzi, Marco; Monari, Antonio

2016-01-01

We report a molecular modeling study, coupled with spectroscopy experiments, on the behavior of two well known organic dyes, nile blue and nile red, when interacting with B-DNA. In particular, we evidence the presence of two competitive binding modes, for both drugs. However their subsequent photophysical behavior is different and only nile blue is able to induce DNA photosensitization via an electron transfer mechanism. Most notably, even in the case of nile blue, its sensitization capabilities strongly depend on the environment resulting in a single active binding mode: the minor groove. Fluorescence spectroscopy confirms the presence of competitive interaction modes for both sensitizers, while the sensitization via electron transfer, is possible only in the case of nile blue. PMID:27329409

Albumin-based drug delivery: harnessing nature to cure disease.

PubMed

Larsen, Maja Thim; Kuhlmann, Matthias; Hvam, Michael Lykke; Howard, Kenneth A

2016-01-01

The effectiveness of a drug is dependent on accumulation at the site of action at therapeutic levels, however, challenges such as rapid renal clearance, degradation or non-specific accumulation requires drug delivery enabling technologies. Albumin is a natural transport protein with multiple ligand binding sites, cellular receptor engagement, and a long circulatory half-life due to interaction with the recycling neonatal Fc receptor. Exploitation of these properties promotes albumin as an attractive candidate for half-life extension and targeted intracellular delivery of drugs attached by covalent conjugation, genetic fusions, association or ligand-mediated association. This review will give an overview of albumin-based products with focus on the natural biological properties and molecular interactions that can be harnessed for the design of a next-generation drug delivery platform.

25th anniversary article: supramolecular materials for regenerative medicine.

PubMed

Boekhoven, Job; Stupp, Samuel I

2014-03-19

In supramolecular materials, molecular building blocks are designed to interact with one another via non-covalent interactions in order to create function. This offers the opportunity to create structures similar to those found in living systems that combine order and dynamics through the reversibility of intermolecular bonds. For regenerative medicine there is a great need to develop materials that signal cells effectively, deliver or bind bioactive agents in vivo at controlled rates, have highly tunable mechanical properties, but at the same time, can biodegrade safely and rapidly after fulfilling their function. These requirements make supramolecular materials a great platform to develop regenerative therapies. This review illustrates the emerging science of these materials and their use in a number of applications for regenerative medicine. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Interpenetrating and non-interpenetrating 3-dimensional coordination polymer frameworks from multiple building blocks

NASA Astrophysics Data System (ADS)

Bradshaw, Darren; Rosseinsky, Matthew J.

2005-12-01

Reaction of Co(NO3)2ṡ6H2O with the multidentate ligands benzene-1,3,5-tricarboxylate (btc) and the flexible bipyridyl ligand 1,2-bis(4-pyridyl)ethane (bpe) affords the 3-dimensional coordination polymers [Co3(btc)2(bpe)3(eg)2]ṡ(guests) 1, where eg = ethylene glycol, and [Co2(Hbtc)2(bpe)2]ṡ(bpe) 2. Both phases are comprised of infinite metal-carboxylate dimer chains, linked into 2-dimensional sheets by the bpe ligands. These sheets are further linked to adjacent sheets through covalent interactions, 1, or through hydrogen-bonding interactions, 2, to yield the 3-dimensional structures. Phase 1 exhibits solvent filled 1-dimensional pores, whereas 2 is triply-interpenetrated to form a dense solid array.

Native top-down mass spectrometry for the structural characterization of human hemoglobin

DOE PAGES

Zhang, Jiang; Malmirchegini, G. Reza; Clubb, Robert T.; ...

2015-06-09

Native mass spectrometry (MS) has become an invaluable tool for the characterization of proteins and non-covalent protein complexes under near physiological solution conditions. Here we report the structural characterization of human hemoglobin (Hb), a 64 kDa oxygen-transporting protein complex, by high resolution native top-down mass spectrometry using electrospray ionization (ESI) and a 15-Tesla Fourier transform ion cyclotron resonance (FTICR) mass spectrometer. Native MS preserves the non-covalent interactions between the globin subunits, and electron capture dissociation (ECD) produces fragments directly from the intact Hb complex without dissociating the subunits. Using activated ion ECD, we observe the gradual unfolding process of themore » Hb complex in the gas phase. Without protein ion activation, the native Hb shows very limited ECD fragmentation from the N-termini, suggesting a tightly packed structure of the native complex and therefore low fragmentation efficiency. Precursor ion activation allows steady increase of N-terminal fragment ions, while the C-terminal fragments remain limited (38 c ions and 4 z ions on the α chain; 36 c ions and 2 z ions on the β chain). This ECD fragmentation pattern suggests that upon activation, the Hb complex starts to unfold from the N-termini of both subunits, whereas the C-terminal regions and therefore the potential regions involved in the subunit binding interactions remain intact. ECD-MS of the Hb dimer show similar fragmentation patterns as the Hb tetramer, providing further evidence for the hypothesized unfolding process of the Hb complex in the gas phase. Native top-down ECD-MS allows efficient probing of the Hb complex structure and the subunit binding interactions in the gas phase. Finally, it may provide a fast and effective means to probe the structure of novel protein complexes that are intractable to traditional structural characterization tools.« less

Supramolecular Assembly of Uridine Monophosphate (UMP) and Thymidine Monophosphate (TMP) with a Dinuclear Copper(II) Receptor.

PubMed

Rhaman, Md Mhahabubur; Powell, Douglas R; Hossain, Md Alamgir

2017-11-30

Understanding the intermolecular interactions between nucleotides and artificial receptors is crucial to understanding the role of nucleic acids in living systems. However, direct structural evidence showing precise interactions and bonding features of a nucleoside monophosphate (NMP) with a macrocycle-based synthetic molecule has not been provided so far. Herein, we present two novel crystal structures of uridine monophosphate (UMP) and thymidine monophosphate (TMP) complexes with a macrocycle-based dinuclear receptor. Structural characterization of these complexes reveals that the receptor recognizes UMP through coordinate-covalent interactions with phosphates and π-π stackings with nucleobases and TMP through coordinate-covalent interactions with phosphate groups. Furthermore, the receptor has been shown to effectively bind nucleoside monophosphates in the order of GMP > AMP > UMP > TMP > CMP in water at physiological pH, as investigated by an indicator displacement assay.

Design and synthesis of novel pyrimidine analogs as highly selective, non-covalent BTK inhibitors.

PubMed

Kawahata, Wataru; Asami, Tokiko; Irie, Takayuki; Sawa, Masaaki

2018-01-15

BTK is a promising target for the treatment of multiple diseases such as B cell malignances, asthma, and rheumatoid arthritis. Here, we report the discovery of a series of novel pyrimidine analogs as potent, highly selective, non-covalent inhibitors of BTK. Compound 25d demonstrated higher affinity to an unactivated conformation of BTK that resulted in an excellent kinase selectivity. Compound 25d showed a good oral bioavailability in mice, and significantly inhibits the PCA reaction in mice. Copyright © 2017 Elsevier Ltd. All rights reserved.

Purification and Crystallization of Murine Myostatin: A Negative Regulator of Muscle Mass

NASA Technical Reports Server (NTRS)

Hong, Young S.; Adamek, Daniel; Bridge, Kristi; Malone, Christine C.; Young, Ronald B.; Miller, Teresa; Karr, Laurel

2004-01-01

Myostatin (MSTN) has been crystallized and its preliminary X-ray diffraction data were collected. MSTN is a negative regulator of muscle growt/differentiation and suppressor of fat accumulation. It is a member of TGF-b family of proteins. Like other members of this family, the regulation of MSTN is critically tied to its process of maturation. This process involves the formation of a homodimer followed by two proteolytic steps. The first proteolytic cleavage produces a species where the n-terminal portion of the dimer is covalently separated from, but remains non-covalently bound to, the c-terminal, functional, portion of the protein. The protein is activated upon removal of the n-terminal "pro-segment" by a second n-terminal proteolytic cut by BMP-1 in vivo, or by acid treatment in vitro. Understanding the structural nature and physical interactions involved in these regulatory processes is the objective of our studies. Murine MSTN was purified from culture media of genetically engineered Chinese Hamster Ovary cells by multicolumn purification process and crystallized using the vapor diffusion method.

Physicochemical approach to freshwater microalgae harvesting with magnetic particles.

PubMed

Prochazkova, Gita; Podolova, Nikola; Safarik, Ivo; Zachleder, Vilem; Branyik, Tomas

2013-12-01

Magnetic harvesting of microalgal biomass provides an attractive alternative to conventional methods. The approach to this issue has so far been pragmatic, focused mainly on finding cheap magnetic agents in combination with harvestable microalgae species. The aim of this work was to study experimentally and theoretically the mechanisms leading to cell-magnetic agent attachment/detachment using real experiments and predictions made by colloidal adhesion (XDLVO) model. Two types of well defined magnetic beads (MBs) carrying ion exchange functional groups (DEAE - diethylaminoethyl and PEI - polyethylenimine) were studied in connection with microalgae (Chlorella vulgaris). Optimal harvesting efficiencies (>90%) were found for DEAE and PEI MBs, while efficient detachment was achieved only for DEAE MBs (>90%). These findings were in accordance with the predictions by XDLVO model. Simultaneously there was found a discrepancy between the XDLVO prediction and the poor detachment of PEI MBs from microalgal surface. This can be ascribed to an additional interaction (probably covalent bonds) between PEI and algal surface, which the XDLVO model is unable to capture given by its non-covalent nature. Copyright © 2013 Elsevier B.V. All rights reserved.

Evidence of covalent synergy in silicon–sulfur–graphene yielding highly efficient and long-life lithium-ion batteries

DOE PAGES

Hassan, Fathy M.; Batmaz, Rasim; Li, Jingde; ...

2015-10-26

Silicon has the potential to revolutionize the energy storage capacities of lithium-ion batteries to meet the ever increasing power demands of next generation technologies. To avoid the operational stability problems of silicon-based anodes, we propose synergistic physicochemical alteration of electrode structures during their design. This capitalizes on covalent interaction of Si nanoparticles with sulfur-doped graphene and with cyclized polyacrylonitrile to provide a robust nanoarchitecture. This hierarchical structure stabilized the solid electrolyte interphase leading to superior reversible capacity of over 1,000 mAh g -1 for 2,275 cycles at 2 A g -1. Furthermore, the nanoarchitectured design lowered the contact of themore » electrolyte to the electrode leading to not only high coulombic efficiency of 99.9% but also maintaining high stability even with high electrode loading associated with 3.4 mAh cm -2. As a result, the excellent performance combined with the simplistic, scalable and non-hazardous approach render the process as a very promising candidate for Li-ion battery technology.« less

Attomolar electrochemical detection of the BCR/ABL fusion gene based on an amplifying self-signal metal nanoparticle-conducting polymer hybrid composite.

PubMed

Avelino, Karen Y P S; Frias, Isaac A M; Lucena-Silva, Norma; Gomes, Renan G; de Melo, Celso P; Oliveira, Maria D L; Andrade, César A S

2016-12-01

In the last ten years, conjugated polymers started to be used in the immobilization of nucleic acids via non-covalent interactions. In the present study, we describe the construction and use of an electrochemical DNA biosensor based on a nanostructured polyaniline-gold composite, specifically developed for the detection of the BCR/ABL chimeric oncogene. This chromosome translocation is used as a biomarker to confirm the clinical diagnosis of both chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL). The working principle of the biosensor rests on measuring the conductivity resulting from the non-covalent interactions between the hybrid nanocomposite and the DNA probe. The nanostructured platform exhibits a large surface area that enhances the conductivity. Positive cases, which result from the hybridization between DNA probe and targeted gene, induce changes in the amperometric current and in the charge transfer resistance (R CT ) responses. Atomic force microscopy (AFM) images showed changes in the genosensor surface after exposure to cDNA sample of patient with leukemia, evidencing the hybridization process. This new hybrid sensing-platform displayed high specificity and selectivity, and its detection limit is estimated to be as low as 69.4 aM. The biosensor showed excellent analytical performance for the detection of the BCR/ABL oncogene in clinical samples of patients with leukemia. Hence, this electrochemical sensor appears as a simple and attractive tool for the molecular diagnosis of the BCR/ABL oncogene even in early-stage cases of leukemia and for the monitoring of minimum levels of residual disease. Copyright © 2016 Elsevier B.V. All rights reserved.

Development of hyperbranched polymers with non-covalent interactions for extraction and determination of aflatoxins in cereal samples.

PubMed

Liu, Xiaoyan; Li, Huihui; Xu, Zhigang; Peng, Jialin; Zhu, Shuqiang; Zhang, Haixia

2013-10-03

A novel approach for assembling homogeneous hyperbranched polymers based on non-covalent interactions with aflatoxins was developed; the polymers were used to evaluate the extraction of aflatoxins B1, B2, G1 and G2 (AFB1, AFB2, AFG1 and AFG2) in simulant solutions. The results showed that the extraction efficiencies of three kinds of synthesized polymers for the investigated analytes were not statistically different; as a consequence, one of the representative polymers (polymer I) was used as the solid-phase extraction (SPE) sorbent to evaluate the influences of various parameters, such as desorption conditions, pH, ionic strength, concentration of methanol in sample solutions, and the mass of the sorbent on the extraction efficiency. In addition, the extraction efficiencies for these aflatoxins were compared between the investigated polymer and the traditional sorbent C18. The results showed that the investigated polymer had superior extraction efficiencies. Subsequently, the proposed polymer for the SPE packing material was employed to enrich and analyze four aflatoxins in the cereal powder samples. The limits of detection (LODs) at a signal-to-noise (S/N) ratio of 3 were in the range of 0.012-0.120 ng g(-1) for four aflatoxins, and the limits of quantification (LOQs) calculated at S/N=10 were from 0.04 to 0.40 ng g(-1) for four aflatoxins. The recoveries of four aflatoxins from cereal powder samples were in the range of 82.7-103% with relative standard deviations (RSDs) lower than 10%. The results demonstrate the suitability of the SPE approach for the analysis of trace aflatoxins in cereal powder samples. Copyright © 2013 Elsevier B.V. All rights reserved.

Towards 4th generation biomaterials: a covalent hybrid polymer-ormoglass architecture

NASA Astrophysics Data System (ADS)

Sachot, N.; Mateos-Timoneda, M. A.; Planell, J. A.; Velders, A. H.; Lewandowska, M.; Engel, E.; Castaño, O.

2015-09-01

Hybrid materials are being extensively investigated with the aim of mimicking the ECM microenvironment to develop effective solutions for bone tissue engineering. However, the common drawbacks of a hybrid material are the lack of interactions between the scaffold's constituents and the masking of its bioactive phase. Conventional hybrids often degrade in a non-homogeneous manner and the biological response is far from optimal. We have developed a novel material with strong interactions between constituents. The bioactive phase is directly exposed on its surface mimicking the structure of the ECM of bone. Here, polylactic acid electrospun fibers have been successfully and reproducibly coated with a bioactive organically modified glass (ormoglass, Si-Ca-P2 system) covalently. In comparison with the pure polymeric mats, the fibers obtained showed improved hydrophilicity and mechanical properties, bioactive ion release, exhibited a nanoroughness and enabled good cell adhesion and spreading after just one day of culture (rMSCs and rEPCs). The fibers were coated with different ormoglass compositions to tailor their surface properties (roughness, stiffness, and morphology) by modifying the experimental parameters. Knowing that cells modulate their behavior according to the exposed physical and chemical signals, the development of this instructive material is a valuable advance in the design of functional regenerative biomaterials.Hybrid materials are being extensively investigated with the aim of mimicking the ECM microenvironment to develop effective solutions for bone tissue engineering. However, the common drawbacks of a hybrid material are the lack of interactions between the scaffold's constituents and the masking of its bioactive phase. Conventional hybrids often degrade in a non-homogeneous manner and the biological response is far from optimal. We have developed a novel material with strong interactions between constituents. The bioactive phase is directly exposed on its surface mimicking the structure of the ECM of bone. Here, polylactic acid electrospun fibers have been successfully and reproducibly coated with a bioactive organically modified glass (ormoglass, Si-Ca-P2 system) covalently. In comparison with the pure polymeric mats, the fibers obtained showed improved hydrophilicity and mechanical properties, bioactive ion release, exhibited a nanoroughness and enabled good cell adhesion and spreading after just one day of culture (rMSCs and rEPCs). The fibers were coated with different ormoglass compositions to tailor their surface properties (roughness, stiffness, and morphology) by modifying the experimental parameters. Knowing that cells modulate their behavior according to the exposed physical and chemical signals, the development of this instructive material is a valuable advance in the design of functional regenerative biomaterials. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr04275e

Critical exponents and universal magnetic behavior of noncentrosymmetric Fe0.6Co0.4Si

NASA Astrophysics Data System (ADS)

Shanmukharao Samatham, S.; Suresh, K. G.

2018-05-01

The critical magnetic properties of a non-centrosymmetric B20 cubic helimagnet Fe0.6Co0.4Si are investigated using magnetization isotherms. It belongs to the 3D-Heisenberg universality class with short range magnetic coupling as inferred from the self-consistent critical exponents , , and in combination with exchange interaction . Itinerant magnetic nature of the compound is realized by the Rhodes–Wholfarth analysis. Field-induced weak first (parahelical) to second (parafield-polarized) order transition is reported to occur at low critical field due to the weak spin–orbit coupling arising from the weak Dzyaloshinksii–Moriya interactions. Our study suggests the distinct phenomenological magnetic structures for Fe-based cubic magnets (Fe1‑x Co x Si and FeGe) and MnSi which cause contrasting physical properties.

Can biological homochirality result from a phase transition?

PubMed

Figureau, A; Duval, E; Boukenter, A

1995-06-01

The problem of chiral purity in living organisms is still one of the prominent difficulties in the study of the origins of life. In particular the parity non-conservation known to occur in weak interactions could not be related to this lack of symmetry: these physical forces, though universal, are very weak and up to now no amplification process had been proposed. In 1991, A. Salam remarked that, due to the attractive character of the parity violating force in electro-weak interactions, a phase transition at low temperature should exist, leading eventually to enantiomeric purity. We undertook then a series of experimental tests, looking for a sizeable change in the optical activity of cystine molecules. We found no evidence for the phase transition down to 0.01 K. The interpretation of these negative results will be discussed, and future experiments proposed.

Surface-induced dissociation: a unique tool for studying energetics and kinetics of the gas-phase fragmentation of large ions

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

Laskin, Julia

2015-01-01

Surface-induced dissociation (SID) is valuable tool for investigating activation and dissociation of large ions in tandem mass spectrometry. This account summarizes key findings from studies of the energetics and mechanisms of complex ion dissociation, in which SID experiments were combined with Rice-Ramsperger-Kassel-Marcus (RRKM) modeling of the experimental data. These studies used time- and collision-energy-resolved SID experiments and SID combined with resonant ejection of selected fragment ions on a specially designed Fourier transform ion cyclotron resonance mass spectrometer (FT-ICR MS). Fast ion activation by collision with a surface combined with the long and variable timescale of a FT-ICR MS is perfectlymore » suited for studying the energetics and dynamics of complex ion dissociation in the gas phase. Modeling of time- and collision-energy-resolved SID enables accurate determination of energy and entropy effects in the dissociation process. It has been demonstrated that entropy effects play an important role in determining the dissociation rates of both covalent and non-covalent bonds in large gaseous ions. SID studies have provided important insights on the competition between charge-directed and charge-remote fragmentation in even-electron peptide ions and the role of charge and radical site on the energetics of the dissociation of odd-electron peptide ions. Furthermore, this work examined factors that affect the strength of non-covalent binding, as well as the competition between covalent and non-covalent bond cleavages and between proton and electron transfer in model systems. Finally, SID studies have been used to understand the factors affecting nucleation and growth of clusters in solution and the gas phase.« less

Adapting photosynthesis to the near-infrared: non-covalent binding of phycocyanobilin provides an extreme spectral red-shift to phycobilisome core-membrane linker from Synechococcus sp. PCC7335.

PubMed

Miao, Dan; Ding, Wen-Long; Zhao, Bao-Qing; Lu, Lu; Xu, Qian-Zhao; Scheer, Hugo; Zhao, Kai-Hong

2016-06-01

Phycobiliproteins that bind bilins are organized as light-harvesting complexes, phycobilisomes, in cyanobacteria and red algae. The harvested light energy is funneled to reaction centers via two energy traps, allophycocyanin B and the core-membrane linker, ApcE1 (conventional ApcE). The covalently bound phycocyanobilin (PCB) of ApcE1 absorbs near 660 nm and fluoresces near 675 nm. In cyanobacteria capable of near infrared photoacclimation, such as Synechococcus sp. PCC7335, there exist even further spectrally red shifted components absorbing >700 nm and fluorescing >710 nm. We expressed the chromophore domain of the extra core-membrane linker from Synechococcus sp. PCC7335, ApcE2, in E. coli together with enzymes generating the chromophore, PCB. The resulting chromoproteins, PCB-ApcE2(1-273) and the more truncated PCB-ApcE2(24-245), absorb at 700 nm and fluoresce at 714 nm. The red shift of ~40 nm compared with canonical ApcE1 results from non-covalent binding of the chromophore by which its full conjugation length including the Δ3,3(1) double bond is preserved. The extreme spectral red-shift could not be ascribed to exciton coupling: dimeric PCB-ApcE2(1-273) and monomeric-ApcE2(24-245) absorbed and fluoresced similarly. Chromophorylation of ApcE2 with phycoerythrobilin- or phytochromobilin resulted in similar red shifts (absorption at 615 and 711 nm, fluorescence at 628 or 726 nm, respectively), compared to the covalently bound chromophores. The self-assembled non-covalent chromophorylation demonstrates a novel access to red and near-infrared emitting fluorophores. Brightly fluorescent biomarking was exemplified in E. coli by single-plasmid transformation. Copyright © 2016 Elsevier B.V. All rights reserved.

Multifunctional clickable and protein-repellent magnetic silica nanoparticles

NASA Astrophysics Data System (ADS)

Estupiñán, Diego; Bannwarth, Markus B.; Mylon, Steven E.; Landfester, Katharina; Muñoz-Espí, Rafael; Crespy, Daniel

2016-01-01

Silica nanoparticles are versatile materials whose physicochemical surface properties can be precisely adjusted. Because it is possible to combine several functionalities in a single carrier, silica-based materials are excellent candidates for biomedical applications. However, the functionality of the nanoparticles can get lost upon exposure to biological media due to uncontrolled biomolecule adsorption. Therefore, it is important to develop strategies that reduce non-specific protein-particle interactions without losing the introduced surface functionality. Herein, organosilane chemistry is employed to produce magnetic silica nanoparticles bearing differing amounts of amino and alkene functional groups on their surface as orthogonally addressable chemical functionalities. Simultaneously, a short-chain zwitterion is added to decrease the non-specific adsorption of biomolecules on the nanoparticles surface. The multifunctional particles display reduced protein adsorption after incubation in undiluted fetal bovine serum as well as in single protein solutions (serum albumin and lysozyme). Besides, the particles retain their capacity to selectively react with biomolecules. Thus, they can be covalently bio-functionalized with an antibody by means of orthogonal click reactions. These features make the described multifunctional silica nanoparticles a promising system for the study of surface interactions with biomolecules, targeting, and bio-sensing.Silica nanoparticles are versatile materials whose physicochemical surface properties can be precisely adjusted. Because it is possible to combine several functionalities in a single carrier, silica-based materials are excellent candidates for biomedical applications. However, the functionality of the nanoparticles can get lost upon exposure to biological media due to uncontrolled biomolecule adsorption. Therefore, it is important to develop strategies that reduce non-specific protein-particle interactions without losing the introduced surface functionality. Herein, organosilane chemistry is employed to produce magnetic silica nanoparticles bearing differing amounts of amino and alkene functional groups on their surface as orthogonally addressable chemical functionalities. Simultaneously, a short-chain zwitterion is added to decrease the non-specific adsorption of biomolecules on the nanoparticles surface. The multifunctional particles display reduced protein adsorption after incubation in undiluted fetal bovine serum as well as in single protein solutions (serum albumin and lysozyme). Besides, the particles retain their capacity to selectively react with biomolecules. Thus, they can be covalently bio-functionalized with an antibody by means of orthogonal click reactions. These features make the described multifunctional silica nanoparticles a promising system for the study of surface interactions with biomolecules, targeting, and bio-sensing. Electronic supplementary information (ESI) available: Detailed synthetic procedures and additional experimental light scattering and zeta-potential data. See DOI: 10.1039/c5nr08258g

Natural product-based amyloid inhibitors.

PubMed

Velander, Paul; Wu, Ling; Henderson, Frances; Zhang, Shijun; Bevan, David R; Xu, Bin

2017-09-01

Many chronic human diseases, including multiple neurodegenerative diseases, are associated with deleterious protein aggregates, also called protein amyloids. One common therapeutic strategy is to develop protein aggregation inhibitors that can slow down, prevent, or remodel toxic amyloids. Natural products are a major class of amyloid inhibitors, and several dozens of natural product-based amyloid inhibitors have been identified and characterized in recent years. These plant- or microorganism-extracted compounds have shown significant therapeutic potential from in vitro studies as well as in vivo animal tests. Despite the technical challenges of intrinsic disordered or partially unfolded amyloid proteins that are less amenable to characterizations by structural biology, a significant amount of research has been performed, yielding biochemical and pharmacological insights into how inhibitors function. This review aims to summarize recent progress in natural product-based amyloid inhibitors and to analyze their mechanisms of inhibition in vitro. Major classes of natural product inhibitors and how they were identified are described. Our analyses comprehensively address the molecular interactions between the inhibitors and relevant amyloidogenic proteins. These interactions are delineated at molecular and atomic levels, which include covalent, non-covalent, and metal-mediated mechanisms. In vivo animal studies and clinical trials have been summarized as an extension. To enhance natural product bioavailability in vivo, emerging work using nanocarriers for delivery has also been described. Finally, issues and challenges as well as future development of such inhibitors are envisioned. Copyright © 2017 Elsevier Inc. All rights reserved.

Natural product-based amyloid inhibitors

PubMed Central

Velander, Paul; Wu, Ling; Henderson, Frances; Zhang, Shijun; Bevan, David R.; Xu, Bin

2018-01-01

Many chronic human diseases, including multiple neurodegenerative diseases, are associated with deleterious protein aggregates, also called protein amyloids. One common therapeutic strategy is to develop protein aggregation inhibitors that can slow down, prevent, or remodel toxic amyloids. Natural products are a major class of amyloid inhibitors, and several dozens of natural product-based amyloid inhibitors have been identified and characterized in recent years. These plant- or microorganism-extracted compounds have shown significant therapeutic potential from in vitro studies as well as in vivo animal tests. Despite the technical challenges of intrinsic disordered or partially unfolded amyloid proteins that are less amenable to characterizations by structural biology, a significant amount of research has been performed, yielding biochemical and pharmacological insights into how inhibitors function. This review aims to summarize recent progress in natural product-based amyloid inhibitors and to analyze their mechanisms of inhibition in vitro. Major classes of natural product inhibitors and how they were identified are described. Our analyses comprehensively address the molecular interactions between the inhibitors and relevant amyloidogenic proteins. These interactions are delineated at molecular and atomic levels, which include covalent, non-covalent, and metal-mediated mechanisms. In vivo animal studies and clinical trials have been summarized as an extension. To enhance natural product bioavailability in vivo, emerging work using nanocarriers for delivery has also been described. Finally, issues and challenges as well as future development of such inhibitors are envisioned. PMID:28390938

Performance of local correlation methods for halogen bonding: The case of Br{sub 2}–(H{sub 2}O){sub n},n = 4,5 clusters and Br{sub 2}@5{sup 12}6{sup 2} clathrate cage

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

Batista-Romero, Fidel A.; Bernal-Uruchurtu, Margarita I.; Hernández-Lamoneda, Ramón, E-mail: ramon@uaem.mx

The performance of local correlation methods is examined for the interactions present in clusters of bromine with water where the combined effect of hydrogen bonding (HB), halogen bonding (XB), and hydrogen-halogen (HX) interactions lead to many interesting properties. Local methods reproduce all the subtleties involved such as many-body effects and dispersion contributions provided that specific methodological steps are followed. Additionally, they predict optimized geometries that are nearly free of basis set superposition error that lead to improved estimates of spectroscopic properties. Taking advantage of the local correlation energy partitioning scheme, we compare the different interaction environments present in small clustersmore » and those inside the 5{sup 12}6{sup 2} clathrate cage. This analysis allows a clear identification of the reasons supporting the use of local methods for large systems where non-covalent interactions play a key role.« less

Enzyme catalysis: a new definition accounting for noncovalent substrate- and product-like states.

PubMed

Purich, D L

2001-07-01

Biological catalysis frequently causes changes in noncovalent bonding. By building on Pauling's assertion that any long-lived, chemically distinct interaction is a chemical bond, this article redefines enzyme catalysis as the facilitated making and/or breaking of chemical bonds, not just of covalent bonds. It is also argued that nearly every ATPase or GTPase is misnamed as a hydrolase and actually belongs to a distinct class of enzymes, termed here 'energases'. By transducing covalent bond energy into mechanical work, energases mediate such fundamental processes as protein folding, self-assembly, G-protein interactions, DNA replication, chromatin remodeling and even active transport.

Formation of contact active antimicrobial surfaces by covalent grafting of quaternary ammonium compounds.

PubMed

Elena, Poverenov; Miri, Klein

2018-05-16

Different synthetic strategies for the formation of contact active antimicrobial materials utilizing covalent linkage of quaternary ammonium compounds (QACs) were reviewed. There is a demand to find methods that will prevent bacterial fouling without the release of antimicrobial agents, because biocides cause environment pollution and promote the development of bacteria resistance mechanisms. The contact active antimicrobial surfaces may provide a useful tool for this purpose. The covalent surface grafting of QACs seems to be a feasible and promising approach for the formation of safe and effective antimicrobial materials that could be utilized for medical devices, food industry, water treatment systems and other applications. This manuscript reviews covalent attachment of QACs to form contact active antimicrobial materials based on glass, metals, synthetic and natural polymers. The review emphasizes the description of different synthetic methods that are used for the covalent linkage. Direct covalent linkage of QACs to the material surfaces, a linkage via auxiliary nanoparticles (NPs), or spacers, controlled radical polymerization techniques and a linkage to pre-activated surfaces are discussed. The physico-chemical properties and biological activity of the modified surfaces are also described. This review does not cover non-covalent grafting of QACs and incorporation of QACs into a bulk material. Copyright © 2018 Elsevier B.V. All rights reserved.

Experimental realization of two-dimensional boron sheets

NASA Astrophysics Data System (ADS)

Feng, Baojie; Zhang, Jin; Zhong, Qing; Li, Wenbin; Li, Shuai; Li, Hui; Cheng, Peng; Meng, Sheng; Chen, Lan; Wu, Kehui

2016-06-01

A variety of two-dimensional materials have been reported in recent years, yet single-element systems such as graphene and black phosphorus have remained rare. Boron analogues have been predicted, as boron atoms possess a short covalent radius and the flexibility to adopt sp2 hybridization, features that favour the formation of two-dimensional allotropes, and one example of such a borophene material has been reported recently. Here, we present a parallel experimental work showing that two-dimensional boron sheets can be grown epitaxially on a Ag(111) substrate. Two types of boron sheet, a β12 sheet and a χ3 sheet, both exhibiting a triangular lattice but with different arrangements of periodic holes, are observed by scanning tunnelling microscopy. Density functional theory simulations agree well with experiments, and indicate that both sheets are planar without obvious vertical undulations. The boron sheets are quite inert to oxidization and interact only weakly with their substrate. We envisage that such boron sheets may find applications in electronic devices in the future.

Gel characteristics and microstructure of fish myofibrillar protein/cassava starch composites.

PubMed

Fan, Mingcong; Hu, Ting; Zhao, Siming; Xiong, Shanbai; Xie, Jing; Huang, Qilin

2017-03-01

The changes in fish myofibrillar protein/cassava starch composites in the starch fraction range from 0 to 1, with their total content maintained at 60mg/mL, were investigated in terms of textural properties, rheological behaviours, morphology, spatial distribution and protein molecular structure. The results revealed that the starch fraction of 0.5 was a critical point for the conversion of the protein matrix to starch matrix and conversion of the gel from elastic to weak. Moreover, the protein-starch synergistic effect on the storage modulus was strongest at fractions of 0.5 and 0.6, due to the formation of a semi-interpenetrating network, with more amylose from the melted starch granules interpenetrated with the protein molecules, and the absorption of water by the starch granules to concentrate the protein matrix. Additionally, no covalent interaction between the protein and starch occurred with increasing starch fraction, thus having no significant influence on the protein secondary structure. Copyright © 2016 Elsevier Ltd. All rights reserved.

Host and adsorbate dynamics in silicates with flexible frameworks: Empirical force field simulation of water in silicalite

NASA Astrophysics Data System (ADS)

Bordat, Patrice; Cazade, Pierre-André; Baraille, Isabelle; Brown, Ross

2010-03-01

Molecular dynamics simulations are performed on the pure silica zeolite silicalite (MFI framework code), maintaining via a new force field both framework flexibility and realistic account of electrostatic interactions with adsorbed water. The force field is similar to the well-known "BKS" model [B. W. H. van Beest et al., Phys. Rev. Lett. 64, 1955 (1990)], but with reduced partial atomic charges and reoptimized covalent bond potential wells. The present force field reproduces the monoclinic to orthorhombic transition of silicalite. The force field correctly represents the hydrophobicity of pure silica silicalite, both the adsorption energy, and the molecular diffusion constants of water. Two types of adsorption, specific and weak unspecific, are predicted on the channel walls and at the channel intersection. We discuss molecular diffusion of water in silicalite, deducing a barrier to crossing between the straight and the zigzag channels. Analysis of the thermal motion shows that at room temperature, framework oxygen atoms incurring into the zeolite channels significantly influence the dynamics of adsorbed water.

Carbon dioxide capture using covalent organic frameworks (COFs) type material-a theoretical investigation.

PubMed

Dash, Bibek

2018-04-26

The present work deals with a density functional theory (DFT) study of porous organic framework materials containing - groups for CO 2 capture. In this study, first principle calculations were performed for CO 2 adsorption using N-containing covalent organic framework (COFs) models. Ab initio and DFT-based methods were used to characterize the N-containing porous model system based on their interaction energies upon complexing with CO 2 and nitrogen gas. Binding energies (BEs) of CO 2 and N 2 molecules with the polymer framework were calculated with DFT methods. Hybrid B3LYP and second order MP2 methods combined with of Pople 6-31G(d,p) and correlation consistent basis sets cc-pVDZ, cc-pVTZ and aug-ccVDZ were used to calculate BEs. The effect of linker groups in the designed covalent organic framework model system on the CO 2 and N 2 interactions was studied using quantum calculations.

New insights into organic-inorganic hybrid perovskite CH₃NH₃PbI₃ nanoparticles. An experimental and theoretical study of doping in Pb²⁺ sites with Sn²⁺, Sr²⁺, Cd²⁺ and Ca²⁺.

PubMed

Navas, Javier; Sánchez-Coronilla, Antonio; Gallardo, Juan Jesús; Hernández, Norge Cruz; Piñero, Jose Carlos; Alcántara, Rodrigo; Fernández-Lorenzo, Concha; De los Santos, Desireé M; Aguilar, Teresa; Martín-Calleja, Joaquín

2015-04-14

This paper presents the synthesis of the organic-inorganic hybrid perovskite, CH3NH3PbI3, doped in the Pb(2+) position with Sn(2+), Sr(2+), Cd(2+) and Ca(2+). The incorporation of the dopants into the crystalline structure was analysed, observing how the characteristics of the dopant affected properties such as the crystalline phase, emission and optical properties. XRD showed how doping with Sn(2+), Sr(2+) and Cd(2+) did not modify the normal tetragonal phase. When doping with Ca(2+), the cubic phase was obtained. Moreover, DR-UV-Vis spectroscopy showed how the band gap decreased with the dopants, the values following the trend Sr(2+) < Cd(2+) < Ca(2+) < CH3NH3PbI3 ≈ Sn(2+). The biggest decrease was generated by Sr(2+), which reduced the CH3NH3PbI3 value by 4.5%. In turn, cathodoluminescence (CL) measurements confirmed the band gap obtained. Periodic-DFT calculations were performed to understand the experimental structures. The DOS analysis confirmed the experimental results obtained using UV-Vis spectroscopy, with the values calculated following the trend Sn(2+) ≈ Pb(2+) > Cd(2+) > Sr(2+) for the tetragonal structure and Pb(2+) > Ca(2+) for the cubic phase. The electron localization function (ELF) analysis showed similar electron localizations for undoped and Sn(2+)-doped tetragonal structures, which were different from those doped with Sr(2+) and Cd(2+). Furthermore, when Cd(2+) was incorporated, the Cd-I interaction was strengthened. For Ca(2+) doping, the Ca-I interaction had a greater ionic nature than Cd-I. Finally, an analysis based on the non-covalent interaction (NCI) index is presented to determine the weak-type interactions of the CH3NH3 groups with the dopant and I atoms. To our knowledge, this kind of analysis with these hybrid systems has not been performed previously.

The Volume Field Model about Strong Interaction and Weak Interaction

NASA Astrophysics Data System (ADS)

Liu, Rongwu

2016-03-01

For a long time researchers have believed that strong interaction and weak interaction are realized by exchanging intermediate particles. This article proposes a new mechanism as follows: Volume field is a form of material existence in plane space, it takes volume-changing motion in the form of non-continuous motion, volume fields have strong interaction or weak interaction between them by overlapping their volume fields. Based on these concepts, this article further proposes a ``bag model'' of volume field for atomic nucleus, which includes three sub-models of the complex structure of fundamental body (such as quark), the atom-like structure of hadron, and the molecule-like structure of atomic nucleus. This article also proposes a plane space model and formulates a physics model of volume field in the plane space, as well as a model of space-time conversion. The model of space-time conversion suggests that: Point space-time and plane space-time convert each other by means of merging and rupture respectively, the essence of space-time conversion is the mutual transformations of matter and energy respectively; the process of collision of high energy hadrons, the formation of black hole, and the Big Bang of universe are three kinds of space-time conversions.

The role of CH/π interactions in the high affinity binding of streptavidin and biotin.

PubMed

Ozawa, Motoyasu; Ozawa, Tomonaga; Nishio, Motohiro; Ueda, Kazuyoshi

2017-08-01

The streptavidin-biotin complex has an extraordinarily high affinity (Ka: 10 15 mol -1 ) and contains one of the strongest non-covalent interactions known. This strong interaction is widely used in biological tools, including for affinity tags, detection, and immobilization of proteins. Although hydrogen bond networks and hydrophobic interactions have been proposed to explain this high affinity, the reasons for it remain poorly understood. Inspired by the deceased affinity of biotin observed for point mutations of streptavidin at tryptophan residues, we hypothesized that a CH/π interaction may also contribute to the strong interaction between streptavidin and biotin. CH/π interactions were explored and analyzed at the biotin-binding site and at the interface of the subunits by the fragment molecular orbital method (FMO) and extended applications: PIEDA and FMO4. The results show that CH/π interactions are involved in the high affinity for biotin at the binding site of streptavidin. We further suggest that the involvement of CH/π interactions at the subunit interfaces and an extended CH/π network play more critical roles in determining the high affinity, rather than involvement at the binding site. Copyright © 2017 Elsevier Inc. All rights reserved.

Cyclic peptides and their interaction with peptide coated surfaces

NASA Astrophysics Data System (ADS)

Palmer, F.; Tünnemann, R.; Leipert, D.; Stingel, C.; Jung, G.; Hoffmann, V.

2001-05-01

Focusing on biochemical and pharmaceutical inhibitor systems the interaction of cyclic peptides with model peptides have been investigated by ATR-FTIR-spectroscopy. Information about the participation of special functional groups e.g. COOH, COO -, NH 3+ or peptide backbone was gathered by observing cyclohexapeptides (c(X 1LX 2LX 3)) which are interacting with covalently coated Si-ATR-crystals ( L-arginine, tripeptide I (aNS), tripeptide II (SNa)). To determine the interaction, further studies about the band sequence (1800-1500 cm -1) for non-adsorbed cyclohexapeptides and for the interaction with the silicon surface (SiOH) were necessary. The spectra of the interacting cyclohexapeptides with the SiOH-groups were treated like reference spectra for the evaluation of the peptide-peptide interaction. Based on these spectra, we can conclude that there is peptide-peptide interaction with the coating and not with the residual OH-groups. Determination of interaction mechanisms was done by spectra which represent adsorbed molecules only. The amount of adsorbed molecules was considerably less than a monolayer. Therefore the intensities of the spectra are about 10 -4 absorbance units. The spectra contain information about both changes of the coating and of the cyclohexapeptide.

Facile synthesis of covalent probes to capture enzymatic intermediates during E1 enzyme catalysis.

PubMed

An, Heeseon; Statsyuk, Alexander V

2016-02-11

We report a facile synthetic strategy to prepare UBL-AMP electrophilic probes that form a covalent bond with the catalytic cysteine of cognate E1s, mimicking the tetrahedral intermediate of the E1-UBL-AMP complex. These probes enable the structural and biochemical study of both canonical- and non-canonical E1s.

Synthetic heparin-binding growth factor analogs

DOEpatents

Pena, Louis A.; Zamora, Paul; Lin, Xinhua; Glass, John D.

2007-01-23

The invention provides synthetic heparin-binding growth factor analogs having at least one peptide chain that binds a heparin-binding growth factor receptor, covalently bound to a hydrophobic linker, which is in turn covalently bound to a non-signaling peptide that includes a heparin-binding domain. The synthetic heparin-binding growth factor analogs are useful as soluble biologics or as surface coatings for medical devices.

Ionic complexation as a non-covalent approach for the design of folate anchored rifampicin Gantrez nanoparticles.

PubMed

Date, Praveen V; Patel, Mitesh D; Majee, Sharmila B; Samad, Abdul; Devarajan, Padma V

2013-05-01

The present study discloses the design of folate anchored Rifampicin-Poly methylvinylether maleic anhydride copolymer (Gantrez AN-119, Gantrez) nanoparticles (RFMGzFa) by ionic complexation. Folic acid was anchored to the preformed drug loaded nanoparticles. Folic acid was anchored in different concentration by simply varying the amount of folic acid added during preparation. RFMGzFa nanoparticles were prepared by emulsion solvent diffusion method. Gantrez AN-119 rapidly hydrolyzes in aqueous medium releasing carboxylic acid groups, to create an acidic environment. This facilitates protonation and subsequent ionic complexation of folic acid with the carboxylic groups, to enable anchoring. FTIR spectra confirmed this interaction. Infrared imaging revealed distribution of folic acid across the nanoparticle surface. Nanoparticles were obtained in the size range 350-450 nm with RFM loading of 12-14% w/w. Zeta potential confirmed colloidal stability. TEM/SEM revealed spherical morphology. RFMGzFa nanoparticles exhibited sustained release of RFM and folic acid. Folic acid showed sustained release upto 12 h, which was ion exchange mediated. A 480% enhancement in RFM uptake with RFMGzFa nanoparticles compared to 300% with RFMGz nanoparticles in-vitro, in human macrophage cell line U-937, suggested the role of folic acid in folate receptor mediated uptake. Ionic complexation represents a simple non-covalent approach for anchoring folic acid on polymeric nanoparticles of Gantrez.

Understanding the Effect of Preparative Approaches in the Formation of “Flower-like” Li 4Ti 5O 12 —Multiwalled Carbon Nanotube Composite Motifs with Performance as High-Rate Anode Materials for Li-Ion Battery Applications

DOE PAGES

Wang, Lei; Zhang, Yiman; McBean, Coray L.; ...

2017-01-18

Herein we highlight the significance of nanoscale attachment modality as an important determinant of observed electrochemical performance. Specifically, controlled loading ratios of multi-walled carbon nanotubes (MWNTs) have been successfully anchored onto the surfaces of a unique “flower-like” Li 4Ti 5O 12 (LTO) micro-scale sphere motif, for the first time, using a number of different and distinctive preparative approaches, including (i) a sonication method, (ii) an in situ direct-deposition approach, (iii) a covalent attachment protocol, as well as (iv) a π-π interaction strategy. In terms of structural characterization, the composites generated by physical sonication as well as non-covalent π-π interactions retainedmore » the intrinsic hierarchical “flower-like” morphology and exhibited a similar crystallinity profile as compared with that of pure LTO. By comparison, the composite prepared by an in situ direct deposition approach yielded not only a fragmented LTO structure, likely due to the possible interfering presence of the MWNTs themselves during the relevant hydrothermal reaction, but also a larger crystallite size, owing to the higher annealing temperature associated with its preparation. Finally, the composite created via covalent attachment was covered with an amorphous insulating linker, which probably led to a decreased contact area between the LTO and the MWNTs and hence, a lower crystallinity in the resulting composite. In addition electrode tests suggested that the composite generated by π-π interactions out-performed the other three analogous heterostructures, due to a smaller charge transfer resistance as well as a faster Li-ion diffusion. In particular, the LTO-MWNT composite, produced by π-π interactions, exhibited a reproducibly high rate capability as well as a reliably solid cycling stability, delivering 132 mA h g -1 at 50 C, after 100 discharge/charge cycles, including 40 cycles at a high (>20 C) rate. To conclude, such data denote the highest electrochemical performance measured to date as compared with any LTO-carbon nanotube-based composite materials previously reported, under high discharge rate conditions, and tangibly underscore the correlation between preparative methodology and the resulting performance metrics.« less

Understanding the Effect of Preparative Approaches in the Formation of “Flower-like” Li 4Ti 5O 12 —Multiwalled Carbon Nanotube Composite Motifs with Performance as High-Rate Anode Materials for Li-Ion Battery Applications

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

Wang, Lei; Zhang, Yiman; McBean, Coray L.

Herein we highlight the significance of nanoscale attachment modality as an important determinant of observed electrochemical performance. Specifically, controlled loading ratios of multi-walled carbon nanotubes (MWNTs) have been successfully anchored onto the surfaces of a unique “flower-like” Li 4Ti 5O 12 (LTO) micro-scale sphere motif, for the first time, using a number of different and distinctive preparative approaches, including (i) a sonication method, (ii) an in situ direct-deposition approach, (iii) a covalent attachment protocol, as well as (iv) a π-π interaction strategy. In terms of structural characterization, the composites generated by physical sonication as well as non-covalent π-π interactions retainedmore » the intrinsic hierarchical “flower-like” morphology and exhibited a similar crystallinity profile as compared with that of pure LTO. By comparison, the composite prepared by an in situ direct deposition approach yielded not only a fragmented LTO structure, likely due to the possible interfering presence of the MWNTs themselves during the relevant hydrothermal reaction, but also a larger crystallite size, owing to the higher annealing temperature associated with its preparation. Finally, the composite created via covalent attachment was covered with an amorphous insulating linker, which probably led to a decreased contact area between the LTO and the MWNTs and hence, a lower crystallinity in the resulting composite. In addition electrode tests suggested that the composite generated by π-π interactions out-performed the other three analogous heterostructures, due to a smaller charge transfer resistance as well as a faster Li-ion diffusion. In particular, the LTO-MWNT composite, produced by π-π interactions, exhibited a reproducibly high rate capability as well as a reliably solid cycling stability, delivering 132 mA h g -1 at 50 C, after 100 discharge/charge cycles, including 40 cycles at a high (>20 C) rate. To conclude, such data denote the highest electrochemical performance measured to date as compared with any LTO-carbon nanotube-based composite materials previously reported, under high discharge rate conditions, and tangibly underscore the correlation between preparative methodology and the resulting performance metrics.« less

Determination of the order of substrate addition to MspI DNA methyltransferase using a novel mechanism-based inhibitor.

PubMed Central

Taylor, C; Ford, K; Connolly, B A; Hornby, D P

1993-01-01

The cloning and overexpression of the MspI DNA methyltransferase as a functional fusion with glutathione S-transferase is described. The fusion enzyme retains full biological activity and has been used to investigate the interaction of substrates and inhibitors with MspI DNA methyltransferase. The fusion enzyme has been purified to homogeneity in a single step on GSH-agarose and is free from contaminating exonuclease activity. The enzyme can be photolabelled with S-adenosyl-L-methionine and the level of incorporation of label is enhanced by the presence of a nonspecific DNA duplex. In the presence of a cognate oligodeoxynucleotide, no photolabelling was observed since methyl transfer occurs instead. The inclusion of a mechanism-based inhibitor of C-5 deoxycytidine DNA methylation (an oligodeoxynucleotide containing the base 2-pyrimidinone-1-beta-D-2'-deoxyribofuranoside in the position of the deoxycytidine to which methyl addition occurs), which is thought to form a covalent interaction with the reactive cysteine of such enzymes, led to an enhancement of S-adenosyl-L-methionine photolabelling which suggests that, in contrast with results obtained with EcoRII DNA methyltransferase [Som and Friedman (1991) J. Biol. Chem. 266, 2937-2945], methylcysteine is not the photolabelled product. The implications of the results obtained with this mechanism-based inhibitor are discussed with respect to other C-5-specific DNA methyltransferases. Gel-retardation assays in the presence of cognate oligodeoxynucleotides that contain the reactive pyrimidinone base in place of the deoxycytidine target base are described. These demonstrate that most probably a stable covalent bond is formed between the methyltransferase and this oligodeoxynucleotide. However, the alternative of extremely tight non-covalent binding cannot be rigorously excluded. Furthermore, the results from these experiments indicate that the reaction mechanism proceeds in a manner similar to that of HhaI DNA methyltransferase with sequence-specific DNA binding being followed by addition of S-adenosyl-L-methionine and concomitant isomerization of the ternary complex leading to methyl transfer. S-Adenosyl-L-homocysteine appears to inhibit the reaction pathway as a result of either competition with the methyl donor and potentiation of a high-affinity interaction between the enzyme and DNA in an abortive ternary complex or through an allosteric interaction. Images Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 PMID:8484730

An accurate and linear-scaling method for calculating charge-transfer excitation energies and diabatic couplings

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

Pavanello, Michele; Van Voorhis, Troy; Visscher, Lucas

2013-02-07

Quantum-mechanical methods that are both computationally fast and accurate are not yet available for electronic excitations having charge transfer character. In this work, we present a significant step forward towards this goal for those charge transfer excitations that take place between non-covalently bound molecules. In particular, we present a method that scales linearly with the number of non-covalently bound molecules in the system and is based on a two-pronged approach: The molecular electronic structure of broken-symmetry charge-localized states is obtained with the frozen density embedding formulation of subsystem density-functional theory; subsequently, in a post-SCF calculation, the full-electron Hamiltonian and overlapmore » matrix elements among the charge-localized states are evaluated with an algorithm which takes full advantage of the subsystem DFT density partitioning technique. The method is benchmarked against coupled-cluster calculations and achieves chemical accuracy for the systems considered for intermolecular separations ranging from hydrogen-bond distances to tens of Angstroms. Numerical examples are provided for molecular clusters comprised of up to 56 non-covalently bound molecules.« less

An accurate and linear-scaling method for calculating charge-transfer excitation energies and diabatic couplings.

PubMed

Pavanello, Michele; Van Voorhis, Troy; Visscher, Lucas; Neugebauer, Johannes

2013-02-07

Quantum-mechanical methods that are both computationally fast and accurate are not yet available for electronic excitations having charge transfer character. In this work, we present a significant step forward towards this goal for those charge transfer excitations that take place between non-covalently bound molecules. In particular, we present a method that scales linearly with the number of non-covalently bound molecules in the system and is based on a two-pronged approach: The molecular electronic structure of broken-symmetry charge-localized states is obtained with the frozen density embedding formulation of subsystem density-functional theory; subsequently, in a post-SCF calculation, the full-electron Hamiltonian and overlap matrix elements among the charge-localized states are evaluated with an algorithm which takes full advantage of the subsystem DFT density partitioning technique. The method is benchmarked against coupled-cluster calculations and achieves chemical accuracy for the systems considered for intermolecular separations ranging from hydrogen-bond distances to tens of Ångstroms. Numerical examples are provided for molecular clusters comprised of up to 56 non-covalently bound molecules.

Oxadiazole-isopropylamides as Potent and Non-covalent Proteasome Inhibitors

PubMed Central

Ozcan, Sevil; Kazi, Aslamuzzaman; Marsilio, Frank; Fang, Bin; Guida, Wayne C.; Koomen, John; Lawrence, Harshani R.; Sebti, Saïd M.

2013-01-01

Screening of the 50,000 ChemBridge compound library led to the identification of the oxadiazole-isopropylamide 1 (PI-1833) which inhibited CT-L activity (IC50 0.60 μM) with little effects on the other 2 major proteasome proteolytic activities, T-L and PGPH-L. LC/MS-MS and dialysis show that 1 is a non-covalent and rapidly reversible CT-L inhibitor. Focused library synthesis provided 11ad (PI-1840) with CT-L activity (IC50 27 nM). Detailed SAR studies indicate that the amide moiety and the 2 phenyl rings are sensitive toward modifications. Hydrophobic residues, such as propyl or butyl, in the para-position (not ortho or meta) of the A-ring and a meta-pyridyl group as B-ring significantly improve activity. Compound 11ad (IC50 0.37 μM) is more potent than 1 (IC50 3.5 μM) at inhibiting CT-L activity in intact MDA-MB-468 human breast cancer cells and inhibiting their survival. The activity of 11ad warrants further pre-clinical investigation of this class as non-covalent proteasome inhibitors. PMID:23547706

The Top Quark, Its Discovery, and Subsequent Research

Science.gov Websites

theories of the strong, weak, and electromagnetic interactions and a wealth of experimental information had Subgroup, July 2006 The Collider Detector at Fermilab (CDF) Top Some links on this page may take you to non

Structural and biochemical analyses reveal insights into covalent flavinylation of the Escherichia coli Complex II homolog quinol:fumarate reductase

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

Starbird, C. A.; Maklashina, Elena; Sharma, Pankaj

The Escherichia coli Complex II homolog quinol:fumarate reductase (QFR, FrdABCD) catalyzes the interconversion of fumarate and succinate at a covalently attached FAD within the FrdA subunit. The SdhE assembly factor enhances covalent flavinylation of Complex II homologs, but the mechanisms underlying the covalent attachment of FAD remain to be fully elucidated. Here, we explored the mechanisms of covalent flavinylation of the E. coli QFR FrdA subunit. Using a ΔsdhE E. coli strain, we show that the requirement for the assembly factor depends on the cellular redox environment. We next identified residues important for the covalent attachment and selected the FrdAE245more » residue, which contributes to proton shuttling during fumarate reduction, for detailed biophysical and structural characterization. We found that QFR complexes containing FrdAE245Q have a structure similar to that of the WT flavoprotein, but lack detectable substrate binding and turnover. In the context of the isolated FrdA subunit, the anticipated assembly intermediate during covalent flavinylation, FrdAE245 variants had stability similar to that of WT FrdA, contained noncovalent FAD, and displayed a reduced capacity to interact with SdhE. However, small-angle X-ray scattering (SAXS) analysis of WT FrdA cross-linked to SdhE suggested that the FrdAE245 residue is unlikely to contribute directly to the FrdA-SdhE protein-protein interface. We also found that no auxiliary factor is absolutely required for flavinylation, indicating that the covalent flavinylation is autocatalytic. We propose that multiple factors, including the SdhE assembly factor and bound dicarboxylates, stimulate covalent flavinylation by preorganizing the active site to stabilize the quinone-methide intermediate.« less

Characterization of covalent binding of N'-nitrosonornicotine in rat liver microsomes

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

Hughes, M.F.; Brock, W.J.; Marion, L.J.

1986-01-01

The metabolism of the carcinogenic nitrosamine, N'-nitrosonornicotine (NNN), to reactive intermediates which bind covalently was assessed using male Sprague-Dawley rat liver microsomes. The NADPH-dependent covalent binding of (/sup 14/C)NNN was linear with time up to 90 min and protein concentration up to 3.0 mg/ml. The apparent Km and Vmax of the binding were determined from the initial velocities and found to be 0.91 mM and 4.7 pmol/min/mg protein, respectively. Although NNN is not a hepatocarcinogen, this amount of NADPH-dependent covalent binding is 7-fold greater than that reported for dimethylnitrosamine, a potent hepatocarcinogen. Extensive covalent binding of (/sup 14/C)NNN to livermore » and muscle microsomal protein was also present in the absence of an NADPH-generating system and in the presence of 50% methanol, indicating a non-enzymatically mediated reaction. Addition of the nucleophiles glutathione, cysteine and N-acetylcysteine significantly decreased (p less than 0.01) the non-NADPH-dependent binding, but did not affect NADPH-dependent binding. In vitro addition of the cytochrome P-450 inhibitors metyrapone, piperonyl butoxide and SKF-525A significantly decreased (p less than 0.05) NADPH-dependent binding of (14C)NNN by 27-40%. NADH did not replace NADPH in supporting covalent binding. Replacement of an air atmosphere with nitrogen or CO:O2 (8:2) significantly decreased (p less than 0.05) NADPH-dependent binding of (/sup 14/C)NNN by 40 and 27%, respectively. Aroclor 1254 pre-treatment of the rats did not enhance the NADPH-dependent binding of (/sup 14/C)NNN. These data indicate that cytochrome P-450 is at least in part responsible for the metabolic activation of the carcinogen NNN but also suggest additional mechanisms of activation.« less

Supramolecular Assembly of Uridine Monophosphate (UMP) and Thymidine Monophosphate (TMP) with a Dinuclear Copper(II) Receptor

PubMed Central

2017-01-01

Understanding the intermolecular interactions between nucleotides and artificial receptors is crucial to understanding the role of nucleic acids in living systems. However, direct structural evidence showing precise interactions and bonding features of a nucleoside monophosphate (NMP) with a macrocycle-based synthetic molecule has not been provided so far. Herein, we present two novel crystal structures of uridine monophosphate (UMP) and thymidine monophosphate (TMP) complexes with a macrocycle-based dinuclear receptor. Structural characterization of these complexes reveals that the receptor recognizes UMP through coordinate–covalent interactions with phosphates and π–π stackings with nucleobases and TMP through coordinate–covalent interactions with phosphate groups. Furthermore, the receptor has been shown to effectively bind nucleoside monophosphates in the order of GMP > AMP > UMP > TMP > CMP in water at physiological pH, as investigated by an indicator displacement assay. PMID:29214233

Photochemically enhanced binding of small molecules to the tumor necrosis factor receptor-1 inhibits the binding of TNF-[alpha

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

Carter, Percy H.; Scherle, Peggy A.; Muckelbauer, Jodi K.

2010-03-05

The binding of tumor necrosis factor alpha (TNF-{alpha}) to the type-1 TNF receptor (TNFRc1) plays an important role in inflammation. Despite the clinical success of biologics (antibodies, soluble receptors) for treating TNF-based autoimmune conditions, no potent small molecule antagonists have been developed. Our screening of chemical libraries revealed that N-alkyl 5-arylidene-2-thioxo-1,3-thiazolidin-4-ones were antagonists of this protein-protein interaction. After chemical optimization, we discovered IW927, which potently disrupted the binding of TNF-{alpha} to TNFRc1 (IC{sub 50} = 50 nM) and also blocked TNF-stimulated phosphorylation of I{kappa}-B in Ramos cells (IC{sub 50} = 600 nM). This compound did not bind detectably to themore » related cytokine receptors TNFRc2 or CD40, and did not display any cytotoxicity at concentrations as high as 100 {micro}M. Detailed evaluation of this and related molecules revealed that compounds in this class are 'photochemically enhanced' inhibitors, in that they bind reversibly to the TNFRc1 with weak affinity (ca. 40-100 mM) and then covalently modify the receptor via a photochemical reaction. We obtained a crystal structure of IV703 (a close analog of IW927) bound to the TNFRc1. This structure clearly revealed that one of the aromatic rings of the inhibitor was covalently linked to the receptor through the main-chain nitrogen of Ala-62, a residue that has already been implicated in the binding of TNF-{alpha} to the TNFRc1. When combined with the fact that our inhibitors are reversible binders in light-excluded conditions, the results of the crystallography provide the basis for the rational design of nonphotoreactive inhibitors of the TNF-{alpha}-TNFRc1 interaction.« less

Freestanding and Reactive Thin Films Fabricated by Covalent Layer-by-Layer Assembly and Subsequent Lift-Off of Azlactone-Containing Polymer Multilayers

PubMed Central

Buck, Maren E.

2010-01-01

We report an approach to the fabrication of freestanding and amine-reactive thin films that is based on the reactive layer-by-layer assembly and subsequent lift-off of azlactone-containing polymer multilayers. We demonstrate that covalently crosslinked multilayers fabricated using the azlactone-functionalized polymer poly(2-vinyl-4,4-dimethylazlactone) (PVDMA) and a primary amine-containing polymer [poly(ethyleneimine) (PEI)] can be delaminated from planar glass and silicon surfaces by immersion in mildly acidic aqueous environments to yield flexible freestanding membranes. These freestanding membranes are robust and can withstand exposure to strong acid, strong base, or incubation in high ionic strength solutions that typically lead to the disruption and erosion of polymer multilayers assembled by reversible weak interactions (e.g., ‘polyelectrolyte multilayers’ assembled by electrostatic interactions or hydrogen bonding). We demonstrate further that these PEI/PVDMA assemblies contain residual reactive azlactone functionality that can be exploited to chemically modify the films (either directly after fabrication or after they have been lifted off of the substrates on which they were fabricated) using a variety of amine-functionalized small molecules. These freestanding membranes can also be transferred readily onto other objects (for example, onto the surfaces of planar substrates containing holes or pores) to fabricate suspended polymer membranes and other film-functionalized interfaces. In addition to planar, two-dimensional freestanding films, this approach can be used to fabricate and isolate three-dimensional freestanding membranes (e.g., curved films or tubes) by layer-by-layer assembly on, and subsequent lift-off from, the surfaces of topologically complex substrates (e.g., the curved ends of glass tubing, etc.). The results of this investigation, when combined, suggest the basis of methods for the fabrication of stable, chemically-reactive, and flexible polymer thin films and membranes of potential utility in a variety of fundamental and applied contexts. PMID:20857952

Effects of deuteration of the methyl and phenyl hydrogens on the rotational spectrum of anisole-water

NASA Astrophysics Data System (ADS)

Giuliano, Barbara M.; Melandri, Sonia; Caminati, Walther

2017-07-01

The role of non-covalent interactions in determining the structure of the 1:1 anisole-water molecular complex has been investigated by the analysis of the rotational spectra of the complex formed by the C6H5OCD3 and C6D5OCH3 deuterated species of anisole recorded with pulsed jet Fourier transform microwave spectroscopy. The deuteration of the methyl and phenyl hydrogens does not affect the structure and the internal dynamics of the complex, differently from the deuteration of the water moiety, which leads to large isotopic effects (Giuliano et al., 2005).

Soliton interactions, Bäcklund transformations, Lax pair for a variable-coefficient generalized dispersive water-wave system

NASA Astrophysics Data System (ADS)

Liu, Lei; Tian, Bo; Zhen, Hui-Ling; Liu, De-Yin; Xie, Xi-Yang

2018-04-01

Under investigation in this paper is a variable-coefficient generalized dispersive water-wave system, which can simulate the propagation of the long weakly non-linear and weakly dispersive surface waves of variable depth in the shallow water. Under certain variable-coefficient constraints, by virtue of the Bell polynomials, Hirota method and symbolic computation, the bilinear forms, one- and two-soliton solutions are obtained. Bäcklund transformations and new Lax pair are also obtained. Our Lax pair is different from that previously reported. Based on the asymptotic and graphic analysis, with different forms of the variable coefficients, we find that there exist the elastic interactions for u, while either the elastic or inelastic interactions for v, with u and v as the horizontal velocity field and deviation height from the equilibrium position of the water, respectively. When the interactions are inelastic, we see the fission and fusion phenomena.

Non-equilibrium Stokes-Einstein relation via active microrheology of hydrodynamically interacting suspensions

NASA Astrophysics Data System (ADS)

Chu, Henry; Zia, Roseanna

In our recently developed non-equilibrium Stokes-Einstein relation, we showed that, in the absence of hydrodynamic interactions, the stress in a suspension is given by a balance between fluctuation and dissipation. Here, we generalize our theory for systems of hydrodynamically interacting colloids, via active microrheology, where motion of a Brownian probe through the medium reveals rheological properties. The strength of probe forcing compared to the entropic restoring force defines a Peclet number, Pe. In the absence of hydrodynamics, the first normal stress difference and the osmotic pressure scale as Pe4 and Pe2 respectively when probe forcing is weak, and uniformly as Pe for strong probe forcing. As hydrodynamics become important, interparticle forces give way to lubrication interactions. Hydrodynamic coupling leads to a new low-Pe scaling of the first normal stress difference and the osmotic pressure as Pe2, and high-Pe scaling as Peδ, where 0.799 <= δ <= 1 as hydrodynamics vary from strong to weak. For the entire range of the strength of hydrodynamic interactions and probe forcing, the new phenomenological theory is shown to agree with standard micromechanical definitions of the stress. We further draw a connection between the stress and the energy storage in a suspension, and the entropic nature of such storage is identified.

Tough bonding of hydrogels to diverse non-porous surfaces

NASA Astrophysics Data System (ADS)

Yuk, Hyunwoo; Zhang, Teng; Lin, Shaoting; Parada, German Alberto; Zhao, Xuanhe

2016-02-01

In many animals, the bonding of tendon and cartilage to bone is extremely tough (for example, interfacial toughness ~800 J m-2 refs ,), yet such tough interfaces have not been achieved between synthetic hydrogels and non-porous surfaces of engineered solids. Here, we report a strategy to design tough transparent and conductive bonding of synthetic hydrogels containing 90% water to non-porous surfaces of diverse solids, including glass, silicon, ceramics, titanium and aluminium. The design strategy is to anchor the long-chain polymer networks of tough hydrogels covalently to non-porous solid surfaces, which can be achieved by the silanation of such surfaces. Compared with physical interactions, the chemical anchorage results in a higher intrinsic work of adhesion and in significant energy dissipation of bulk hydrogel during detachment, which lead to interfacial toughness values over 1,000 J m-2. We also demonstrate applications of robust hydrogel-solid hybrids, including hydrogel superglues, mechanically protective hydrogel coatings, hydrogel joints for robotic structures and robust hydrogel-metal conductors.

Pentavalent neptunyl ([OΞNpΞO] +) cation–cation interactions in aqueous/polar organic mixed-solvent media

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

Burn, Adam G.; Martin, Leigh R.; Nash, Kenneth L.

Bonding interactions between polyvalent cations and oxo-anions are well known and characterized by predictably favorable Gibbs energies in solution-phase coordination chemistry. In contrast, interactions between ions of like charge are generally expected to be repulsive and strongly influenced by cation solvation. An exception to this instinctive rule is found in the existence of complexes resulting from interactions of pentavalent actinyl cations ([O≡An≡O] +) with selected polyvalent cations. Such cation–cation complexes have been known to exist since the 1960s, when they were first reported by Sullivan and co-workers. The weak actinyl cation–cation complex, resulting from a bonding interaction between a pentavalentmore » linear dioxo actinyl cation donor and hexavalent actinyl or trivalent/tetravalent metal cation acceptor, has been most commonly seen in media in which water activities are reduced, principally highly-salted aqueous media. Such interactions of pentavalent actinides are of relevance in ongoing research that focuses on advanced nuclear fuel processing systems based on the upper oxidation states of americium. This investigation focuses on exploring the thermodynamic stability of complexes between selected highly-charged metal cations (Al 3+, Sc 3+, Cr 3+, Fe 3+, In 3+ and UO 2+ 2) and the pentavalent neptunyl cation (NpO + 2, whose coordination chemistry is similar to that of AmO + 2 while exhibiting significantly greater oxidation state stability) in aqueous–polar organic mixed-solvents. As a result, the Gibbs energies for the cation–cation complexation reactions are correlated with general features of electrostatic bonding models; the NpO + 2 • Cr 3+ complex exhibits unexpectedly strong interactions that may indicate significant covalency in the cation–cation bonding interaction.« less

Pentavalent neptunyl ([OΞNpΞO] +) cation–cation interactions in aqueous/polar organic mixed-solvent media

DOE PAGES

Burn, Adam G.; Martin, Leigh R.; Nash, Kenneth L.

2017-06-17

Bonding interactions between polyvalent cations and oxo-anions are well known and characterized by predictably favorable Gibbs energies in solution-phase coordination chemistry. In contrast, interactions between ions of like charge are generally expected to be repulsive and strongly influenced by cation solvation. An exception to this instinctive rule is found in the existence of complexes resulting from interactions of pentavalent actinyl cations ([O≡An≡O] +) with selected polyvalent cations. Such cation–cation complexes have been known to exist since the 1960s, when they were first reported by Sullivan and co-workers. The weak actinyl cation–cation complex, resulting from a bonding interaction between a pentavalentmore » linear dioxo actinyl cation donor and hexavalent actinyl or trivalent/tetravalent metal cation acceptor, has been most commonly seen in media in which water activities are reduced, principally highly-salted aqueous media. Such interactions of pentavalent actinides are of relevance in ongoing research that focuses on advanced nuclear fuel processing systems based on the upper oxidation states of americium. This investigation focuses on exploring the thermodynamic stability of complexes between selected highly-charged metal cations (Al 3+, Sc 3+, Cr 3+, Fe 3+, In 3+ and UO 2+ 2) and the pentavalent neptunyl cation (NpO + 2, whose coordination chemistry is similar to that of AmO + 2 while exhibiting significantly greater oxidation state stability) in aqueous–polar organic mixed-solvents. As a result, the Gibbs energies for the cation–cation complexation reactions are correlated with general features of electrostatic bonding models; the NpO + 2 • Cr 3+ complex exhibits unexpectedly strong interactions that may indicate significant covalency in the cation–cation bonding interaction.« less

Interactions of hemin with bovine serum albumin and human hemoglobin: A fluorescence quenching study.

PubMed

Makarska-Bialokoz, Magdalena

2018-03-15

The binding interactions between hemin (Hmi) and bovine serum albumin (BSA) or human hemoglobin (HHb), respectively, have been examined in aqueous solution at pH=7.4, applying UV-vis absorption, as well as steady-state, synchronous and three-dimensional fluorescence spectra techniques. Representative results received for both BSA and HHb intrinsic fluorescence proceeding from the interactions with hemin suggest the formation of stacking non-covalent and non-fluorescent complexes in both the Hmi-BSA and Hmi-HHb systems, with highly possible concurrent formation of a coordinate bond between a group on the protein surface and the metal in Hmi molecule. All the values of calculated parameters, the binding, fluorescence quenching and bimolecular quenching rate constants point to the involvement of static quenching in both the systems studied. The blue shift in the synchronous fluorescence spectra imply the participation of both tryptophan and tyrosine residues in quenching of BSA and HHb intrinsic fluorescence. Depicted outcomes suggest that hemin is supposedly able to influence the physiological functions of BSA and HHb, the most important blood proteins, particularly in case of its overuse. Copyright © 2017 Elsevier B.V. All rights reserved.

Synthesis, characterisation and optical studies of new tetraethyl- rubyrin-graphene oxide covalent adducts

NASA Astrophysics Data System (ADS)

Garg, Kavita; Shanmugam, Ramakrishanan; Ramamurthy, Praveen C.

2018-02-01

Tetrathia-rubyrin and graphene oxide (GO) covalent adduct was synthesized, characterised and optical properties were studied. GO-Rubyrin adducts showed fluorescence quenching of rubyrin due to electron or energy transfer from rubyrin to graphene oxide, which also reflected in UV-vis absorbance spectroscopy. The non-linear optical responses were measured through Z scan technique in nano-second regime. The enhanced optical non-linearity was observed after attachment of GO with rubyrin, can be ascribed to the photo-induced electron or energy transfer from the electron rich rubyrin moiety to the electron deficient GO.

Biomimetic graphene sensors: functionalizing graphene with peptides

NASA Astrophysics Data System (ADS)

Ishigami, Masa; Nyon Kim, Sang; Naik, Rajesh; Tatulian, Suren A.; Katoch, Jyoti

2012-02-01

Non-covalent biomimetic functionalization of graphene using peptides is one of more promising methods for producing novel sensors with high sensitivity and selectivity. Here we combine atomic force microscopy, Raman spectroscopy, and attenuated total reflection Fourier transform infrared spectroscopy to investigate peptide binding to graphene and graphite. We choose to study a dodecamer peptide identified with phage display to possess affinities for graphite and we find that the peptide forms a complex mesh-like structure upon adsorption on graphene. Moreover, optical spectroscopy reveals that the peptide binds non-covalently to graphene and possesses an optical signature of an ?-helical conformation on graphene.

Curvaton scenario within the minimal supersymmetric standard model and predictions for non-Gaussianity.

PubMed

Mazumdar, Anupam; Nadathur, Seshadri

2012-03-16

We provide a model in which both the inflaton and the curvaton are obtained from within the minimal supersymmetric standard model, with known gauge and Yukawa interactions. Since now both the inflaton and curvaton fields are successfully embedded within the same sector, their decay products thermalize very quickly before the electroweak scale. This results in two important features of the model: first, there will be no residual isocurvature perturbations, and second, observable non-Gaussianities can be generated with the non-Gaussianity parameter f(NL)~O(5-1000) being determined solely by the combination of weak-scale physics and the standard model Yukawa interactions.

Critical exponents and universal magnetic behavior of noncentrosymmetric Fe0.6Co0.4Si.

PubMed

Samatham, S Shanmukharao; Suresh, K G

2018-05-31

The critical magnetic properties of a non-centrosymmetric B20 cubic helimagnet Fe 0.6 Co 0.4 Si are investigated using magnetization isotherms. It belongs to the 3D-Heisenberg universality class with short range magnetic coupling as inferred from the self-consistent critical exponents [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text] in combination with exchange interaction [Formula: see text]. Itinerant magnetic nature of the compound is realized by the Rhodes-Wholfarth analysis. Field-induced weak first (para[Formula: see text]helical) to second (para[Formula: see text]field-polarized) order transition is reported to occur at low critical field due to the weak spin-orbit coupling arising from the weak Dzyaloshinksii-Moriya interactions. Our study suggests the distinct phenomenological magnetic structures for Fe-based cubic magnets (Fe 1-x Co x Si and FeGe) and MnSi which cause contrasting physical properties.

Comparison of the fibrin-binding activities in the N- and C-termini of fibronectin.

PubMed

Rostagno, A A; Schwarzbauer, J E; Gold, L I

1999-03-01

Fibronectin (Fn) binds to fibrin in clots by covalent and non-covalent interactions. The N- and C-termini of Fn each contain one non-covalent fibrin-binding site, which are composed of type 1 (F1) structural repeats. We have previously localized the N-terminal site to the fourth and fifth F1 repeats (4F1.5F1). In the current studies, using proteolytic and recombinant proteins representing both the N- and C-terminal fibrin-binding regions, we localized and characterized the C-terminal fibrin-binding site, compared the relative fibrin-binding activities of both sites and determined the contribution of each site to the fibrin-binding activity of intact Fn. By fibrin-affinity chromatography, a protein composed of the 10F1 repeat through to the C-terminus of Fn (10F1-COOH), expressed in COS-1 cells, and 10F1-12F1, produced in Saccharomyces cerevisiae, displayed fibrin-binding activity. However, since 10F1 and 10F1.11F1 were not active, the presence of 12F1 is required for fibrin binding. A proteolytic fragment of 14.4 kDa, beginning 14 residues N-terminal to 10F1, was isolated from the fibrin-affinity matrix. Radio-iodinated 14.4 kDa fibrin-binding peptide/protein (FBP) demonstrated a dose-dependent and saturable binding to fibrin-coated wells that was both competitively inhibited and reversed by unlabelled 14.4 kDa FBP. Comparison of the fibrin-binding affinities of proteolytic FBPs from the N-terminus (25.9 kDa FBP), the C-terminus (14.4 kDa) and intact Fn by ELISA yielded estimated Kd values of 216, 18 and 2.1 nM, respectively. The higher fibrin-binding affinity of the N-terminus was substantiated by the ability of both a recombinant 4F1.5F1 and a monoclonal antibody (mAb) to this site to maximally inhibit biotinylated Fn binding to fibrin by 80%, and by blocking the 90% inhibitory activity of a polyclonal anti-Fn, by absorption with the 25.9 kDa FBP. We propose that whereas the N-terminal site appears to contribute to most of the binding activity of native Fn to fibrin, the specific binding of the C-terminal site may strengthen this interaction.

Comparison of the fibrin-binding activities in the N- and C-termini of fibronectin.

PubMed Central

Rostagno, A A; Schwarzbauer, J E; Gold, L I

1999-01-01

Fibronectin (Fn) binds to fibrin in clots by covalent and non-covalent interactions. The N- and C-termini of Fn each contain one non-covalent fibrin-binding site, which are composed of type 1 (F1) structural repeats. We have previously localized the N-terminal site to the fourth and fifth F1 repeats (4F1.5F1). In the current studies, using proteolytic and recombinant proteins representing both the N- and C-terminal fibrin-binding regions, we localized and characterized the C-terminal fibrin-binding site, compared the relative fibrin-binding activities of both sites and determined the contribution of each site to the fibrin-binding activity of intact Fn. By fibrin-affinity chromatography, a protein composed of the 10F1 repeat through to the C-terminus of Fn (10F1-COOH), expressed in COS-1 cells, and 10F1-12F1, produced in Saccharomyces cerevisiae, displayed fibrin-binding activity. However, since 10F1 and 10F1.11F1 were not active, the presence of 12F1 is required for fibrin binding. A proteolytic fragment of 14.4 kDa, beginning 14 residues N-terminal to 10F1, was isolated from the fibrin-affinity matrix. Radio-iodinated 14.4 kDa fibrin-binding peptide/protein (FBP) demonstrated a dose-dependent and saturable binding to fibrin-coated wells that was both competitively inhibited and reversed by unlabelled 14.4 kDa FBP. Comparison of the fibrin-binding affinities of proteolytic FBPs from the N-terminus (25.9 kDa FBP), the C-terminus (14.4 kDa) and intact Fn by ELISA yielded estimated Kd values of 216, 18 and 2.1 nM, respectively. The higher fibrin-binding affinity of the N-terminus was substantiated by the ability of both a recombinant 4F1.5F1 and a monoclonal antibody (mAb) to this site to maximally inhibit biotinylated Fn binding to fibrin by 80%, and by blocking the 90% inhibitory activity of a polyclonal anti-Fn, by absorption with the 25.9 kDa FBP. We propose that whereas the N-terminal site appears to contribute to most of the binding activity of native Fn to fibrin, the specific binding of the C-terminal site may strengthen this interaction. PMID:10024513

Structural and Functional Modifications of Corneal Crystallin ALDH3A1 by UVB Light

PubMed Central

Estey, Tia; Chen, Ying; Carpenter, John F.; Vasiliou, Vasilis

2010-01-01

As one of the most abundantly expressed proteins in the mammalian corneal epithelium, aldehyde dehydrogenase 3A1 (ALDH3A1) plays critical and multifaceted roles in protecting the cornea from oxidative stress. Recent studies have demonstrated that one protective mechanism of ALDH3A1 is the direct absorption of UV-energy, which reduces damage to other corneal proteins such as glucose-6-phosphate dehydrogenase through a competition mechanism. UV-exposure, however, leads to the inactivation of ALDH3A1 in such cases. In the current study, we demonstrate that UV-light caused soluble, non-native aggregation of ALDH3A1 due to both covalent and non-covalent interactions, and that the formation of the aggregates was responsible for the loss of ALDH3A1 enzymatic activity. Spectroscopic studies revealed that as a result of aggregation, the secondary and tertiary structure of ALDH3A1 were perturbed. LysC peptide mapping using MALDI-TOF mass spectrometry shows that UV-induced damage to ALDH3A1 also includes chemical modifications to Trp, Met, and Cys residues. Surprisingly, the conserved active site Cys of ALDH3A1 does not appear to be affected by UV-exposure; this residue remained intact after exposure to UV-light that rendered the enzyme completely inactive. Collectively, our data suggest that the UV-induced inactivation of ALDH3A1 is a result of non-native aggregation and associated structural changes rather than specific damage to the active site Cys. PMID:21203538

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.