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Sample records for cleaves strong c-h

  1. Spectroscopic Evidence for the Two C-H-Cleaving Intermediates of Aspergillus nidulans Isopenicillin N Synthase.

    PubMed

    Tamanaha, Esta; Zhang, Bo; Guo, Yisong; Chang, Wei-Chen; Barr, Eric W; Xing, Gang; St Clair, Jennifer; Ye, Shengfa; Neese, Frank; Bollinger, J Martin; Krebs, Carsten

    2016-07-20

    The enzyme isopenicillin N synthase (IPNS) installs the β-lactam and thiazolidine rings of the penicillin core into the linear tripeptide l-δ-aminoadipoyl-l-Cys-d-Val (ACV) on the pathways to a number of important antibacterial drugs. A classic set of enzymological and crystallographic studies by Baldwin and co-workers established that this overall four-electron oxidation occurs by a sequence of two oxidative cyclizations, with the β-lactam ring being installed first and the thiazolidine ring second. Each phase requires cleavage of an aliphatic C-H bond of the substrate: the pro-S-CCys,β-H bond for closure of the β-lactam ring, and the CVal,β-H bond for installation of the thiazolidine ring. IPNS uses a mononuclear non-heme-iron(II) cofactor and dioxygen as cosubstrate to cleave these C-H bonds and direct the ring closures. Despite the intense scrutiny to which the enzyme has been subjected, the identities of the oxidized iron intermediates that cleave the C-H bonds have been addressed only computationally; no experimental insight into their geometric or electronic structures has been reported. In this work, we have employed a combination of transient-state-kinetic and spectroscopic methods, together with the specifically deuterium-labeled substrates, A[d2-C]V and AC[d8-V], to identify both C-H-cleaving intermediates. The results show that they are high-spin Fe(III)-superoxo and high-spin Fe(IV)-oxo complexes, respectively, in agreement with published mechanistic proposals derived computationally from Baldwin's founding work. PMID:27193226

  2. Formation and High Reactivity of the anti-Dioxo Form of High-Spin μ-Oxodioxodiiron(IV) as the Active Species That Cleaves Strong C-H Bonds.

    PubMed

    Kodera, Masahito; Ishiga, Shin; Tsuji, Tomokazu; Sakurai, Katsutoshi; Hitomi, Yutaka; Shiota, Yoshihito; Sajith, P K; Yoshizawa, Kazunari; Mieda, Kaoru; Ogura, Takashi

    2016-04-18

    Recently, it was shown that μ-oxo-μ-peroxodiiron(III) is converted to high-spin μ-oxodioxodiiron(IV) through O-O bond scission. Herein, the formation and high reactivity of the anti-dioxo form of high-spin μ-oxodioxodiiron(IV) as the active oxidant are demonstrated on the basis of resonance Raman and electronic-absorption spectral changes, detailed kinetic studies, DFT calculations, activation parameters, kinetic isotope effects (KIE), and catalytic oxidation of alkanes. Decay of μ-oxodioxodiiron(IV) was greatly accelerated on addition of substrate. The reactivity order of substrates is tolueneC-H bond cleavage of ethylbenzene than the most reactive diiron system reported so far. The KIE for the reaction with toluene/[D8 ]toluene is 95 at -30 °C, which the largest in diiron systems reported so far. The present diiron complex efficiently catalyzes the oxidation of various alkanes with H2 O2 . PMID:26970337

  3. Substrate-Triggered Formation and Remarkable Stability of the C-H-Cleaving Chloroferryl Intermediate in the Aliphatic Halogenase, SyrB2†

    PubMed Central

    Matthews, Megan L.; Krest, Courtney M.; Barr, Eric W.; Vaillancourt, Frédéric H.; Walsh, Christopher T.; Green, Michael T.; Krebs, Carsten; Bollinger, J. Martin

    2009-01-01

    Aliphatic halogenases activate O2, cleave α-ketoglutarate (αKG) to CO2 and succinate, and form haloferryl [X-Fe(IV)=O; X = Cl, Br] complexes that cleave aliphatic C-H bonds to install halogens during the biosynthesis of natural products by non-ribosomal peptide synthetases (NRPSs). For the related αKG-dependent dioxygenases, it has been shown that reaction of the Fe(II) cofactor with O2 to form the C-H-cleaving ferryl complex is “triggered” by binding of the target substrate. In this study, we have tested for and defined structural determinants of substrate triggering (ST) in the halogenase, SyrB2, from the syringomycin E biosynthetic NRPS of Pseudomonas syringae B301D. As for other halogen ases, the substrate of SyrB2 is complex, consisting of l-Thr tethered via thioester linkage to a covalently bound phosphopantetheine (PPant) cofactor of a carrier protein, SyrB1. Without an appended amino acid, SyrB1 does not trigger formation of the chloroferryl intermediate state in SyrB2, even in the presence of free l-Thr or its analogues, but SyrB1 charged either by l-Thr or by any of several non-native amino acids does trigger the reaction by as much as 8,000-fold (for l-Thr-S-SyrB1). Triggering efficacy is sensitive to the structures of both the amino acid and the carrier protein, being diminished by 5–20-fold when the native l-Thr is replaced by another amino acid and by ∼ 40-fold when SyrB1 is replaced by a heterologous carrier protein, CytC2. The directing effect of the carrier protein and consequent tolerance for profound modifications to the target amino acid allow the chloroferryl state to be formed in the presence of substrates that perturb the ratio of its two putative coordination isomers, lack the target C-H bond (l-Ala-S-SyrB1), or contain a C-H bond of enhanced strength (l-cyclopropylglycyl-S-SyrB1). For the latter two cases, the SyrB2 chloroferryl state so formed exhibits unprecedented stability (t1/2 = 30 – 110 min at 0 °C), can be trapped in

  4. Trapping a Highly Reactive Nonheme Iron Intermediate That Oxygenates Strong C-H Bonds with Stereoretention.

    PubMed

    Serrano-Plana, Joan; Oloo, Williamson N; Acosta-Rueda, Laura; Meier, Katlyn K; Verdejo, Begoña; García-España, Enrique; Basallote, Manuel G; Münck, Eckard; Que, Lawrence; Company, Anna; Costas, Miquel

    2015-12-23

    An unprecedentedly reactive iron species (2) has been generated by reaction of excess peracetic acid with a mononuclear iron complex [Fe(II)(CF3SO3)2(PyNMe3)] (1) at cryogenic temperatures, and characterized spectroscopically. Compound 2 is kinetically competent for breaking strong C-H bonds of alkanes (BDE ≈ 100 kcal·mol(-1)) through a hydrogen-atom transfer mechanism, and the transformations proceed with stereoretention and regioselectively, responding to bond strength, as well as to steric and polar effects. Bimolecular reaction rates are at least an order of magnitude faster than those of the most reactive synthetic high-valent nonheme oxoiron species described to date. EPR studies in tandem with kinetic analysis show that the 490 nm chromophore of 2 is associated with two S = 1/2 species in rapid equilibrium. The minor component 2a (∼5% iron) has g-values at 2.20, 2.19, and 1.99 characteristic of a low-spin iron(III) center, and it is assigned as [Fe(III)(OOAc)(PyNMe3)](2+), also by comparison with the EPR parameters of the structurally characterized hydroxamate analogue [Fe(III)(tBuCON(H)O)(PyNMe3)](2+) (4). The major component 2b (∼40% iron, g-values = 2.07, 2.01, 1.95) has unusual EPR parameters, and it is proposed to be [Fe(V)(O)(OAc)(PyNMe3)](2+), where the O-O bond in 2a has been broken. Consistent with this assignment, 2b undergoes exchange of its acetate ligand with CD3CO2D and very rapidly reacts with olefins to produce the corresponding cis-1,2-hydroxoacetate product. Therefore, this work constitutes the first example where a synthetic nonheme iron species responsible for stereospecific and site selective C-H hydroxylation is spectroscopically trapped, and its catalytic reactivity against C-H bonds can be directly interrogated by kinetic methods. The accumulated evidence indicates that 2 consists mainly of an extraordinarily reactive [Fe(V)(O)(OAc)(PyNMe3)](2+) (2b) species capable of hydroxylating unactivated alkyl C-H bonds with

  5. Weak O-Assistance Outcompeting Strong N,N-Bidentate Directing Groups in Copper-Catalyzed C-H Chalcogenation.

    PubMed

    Cera, Gianpiero; Ackermann, Lutz

    2016-06-13

    A copper-mediated C-H chalcogenation of triazoles has been achieved by weak coordination. The user-friendly protocol showed high functional-group tolerance and ample substrate scope, yielding fully substituted 1,2,3-triazoles with complete positional site-selectivity. The C-H selenylation could likewise be achieved by means of copper catalysis. Our findings highlight for the first time that weak O-coordination can outcompete the strong N,N-bidentate coordination mode in C-H functionalization technology. PMID:27124082

  6. A Highly Reactive Mononuclear Non-Heme Manganese(IV)-Oxo Complex That Can Activate the Strong C-H Bonds of Alkanes

    SciTech Connect

    Wu, Xiujuan; Seo, Mi Sook; Davis, Katherine M; Lee, Yong-Min; Chen, Junying; Cho, Kyung-Bin; Pushkar, Yulia N; Nam, Wonwoo

    2012-03-15

    A mononuclear non-heme manganese(IV)-oxo complex has been synthesized and characterized using various spectroscopic methods. The Mn(IV)-oxo complex shows high reactivity in oxidation reactions, such as C-H bond activation, oxidations of olefins, alcohols, sulfides, and aromatic compounds, and N-dealkylation. In C-H bond activation, the Mn(IV)-oxo complex can activate C-H bonds as strong as those in cyclohexane. It is proposed that C-H bond activation by the non-heme Mn(IV)-oxo complex does not occur via an oxygen-rebound mechanism. The electrophilic character of the non-heme Mn(IV)-oxo complex is demonstrated by a large negative ρ value of ~4.4 in the oxidation of para-substituted thioanisoles.

  7. Cleaving DNA with DNA

    NASA Astrophysics Data System (ADS)

    Carmi, Nir; Balkhi, Shameelah R.; Breaker, Ronald R.

    1998-03-01

    A DNA structure is described that can cleave single-stranded DNA oligonucleotides in the presence of ionic copper. This ``deoxyribozyme'' can self-cleave or can operate as a bimolecular complex that simultaneously makes use of duplex and triplex interactions to bind and cleave separate DNA substrates. Bimolecular deoxyribozyme-mediated strand scission proceeds with a kobs of 0.2 min-1, whereas the corresponding uncatalyzed reaction could not be detected. The duplex and triplex recognition domains can be altered, making possible the targeted cleavage of single-stranded DNAs with different nucleotide sequences. Several small synthetic DNAs were made to function as simple ``restriction enzymes'' for the site-specific cleavage of single-stranded DNA.

  8. Nucleotide cleaving agents and method

    DOEpatents

    Que, Jr., Lawrence; Hanson, Richard S.; Schnaith, Leah M. T.

    2000-01-01

    The present invention provides a unique series of nucleotide cleaving agents and a method for cleaving a nucleotide sequence, whether single-stranded or double-stranded DNA or RNA, using and a cationic metal complex having at least one polydentate ligand to cleave the nucleotide sequence phosphate backbone to yield a hydroxyl end and a phosphate end.

  9. Adaptive and Unstructured Mesh Cleaving

    PubMed Central

    Bronson, Jonathan R.; Sastry, Shankar P.; Levine, Joshua A.; Whitaker, Ross T.

    2015-01-01

    We propose a new strategy for boundary conforming meshing that decouples the problem of building tetrahedra of proper size and shape from the problem of conforming to complex, non-manifold boundaries. This approach is motivated by the observation that while several methods exist for adaptive tetrahedral meshing, they typically have difficulty at geometric boundaries. The proposed strategy avoids this conflict by extracting the boundary conforming constraint into a secondary step. We first build a background mesh having a desired set of tetrahedral properties, and then use a generalized stenciling method to divide, or “cleave”, these elements to get a set of conforming tetrahedra, while limiting the impacts cleaving has on element quality. In developing this new framework, we make several technical contributions including a new method for building graded tetrahedral meshes as well as a generalization of the isosurface stuffing and lattice cleaving algorithms to unstructured background meshes. PMID:26137171

  10. Borylation and silylation of C-H bonds: a platform for diverse C-H bond functionalizations.

    PubMed

    Hartwig, John F

    2012-06-19

    -selectivity for C-H bond cleavage that depends on the steric accessibility of the C-H bonds. These complexes also catalyze the borylation of heteroarenes, and the selectivity for these substrates is more dependent on electronic effects than the borylation of arenes. The products from the borylation of arenes and heteroarenes are suitable for a wide range of subsequent conversions to phenols, arylamines, aryl ethers, aryl nitriles, aryl halides, arylboronic acids, and aryl trifluoroborates. Studies of the electronic properties of the ancillary ligand on the rate of the reaction show that the flat structure and the strong electron-donating property of the bipyridine ligands, along with the strong electron-donating property of the boryl group and the presence of a p-orbital on the metal-bound atom, lead to the increased reactivity of the iridium catalysts. Based on this hypothesis, we studied catalysts containing substituted phenanthroline ligands for a series of additional transformations, including the silylation of C-H bonds. A sequence involving the silylation of benzylic alcohols, followed by the dehydrogenative silylation of aromatic C-H bonds, leads to an overall directed silylation of the C-H bond ortho to hydroxyl functionality. PMID:22075137

  11. Synthetic Transformations through Alkynoxy-Palladium Interactions and C-H Activation.

    PubMed

    Minami, Yasunori; Hiyama, Tamejiro

    2016-01-19

    Organic synthesis based on straightforward transformations is essential for environmentally benign manufacturing for the invention of novel pharmaceuticals, agrochemicals, and organoelectronic materials in order to ultimately realize a sustainable society. Metal-catalyzed C-H bond-cleaving functionalization has become a promising method for achieving the above goal. For site-selective C-H bond cleavage, so-called directing groups, i.e., ligands attached to substrates, are employed. Commonly utilized directing groups are carbonyls, imines, carboxyls, amides, and pyridyls, which σ-donate electron pairs to metals. On the other hand, unsaturated substrates such as alkenes and alkynes, which participate largely as reactants in organic synthesis, are prepared readily by a wide variety of synthetic transformations and are also employed as reactants in organometallic chemistry. Moreover, such unsaturated groups form complexes with some metals by ligation of their p orbitals via donation and back-donation. However, the use of unsaturated bonds as directing groups has not been studied extensively. We have been involved in the development of methods for the cleavage of C-H bonds by means of transition-metal catalysts to achieve new carbon-carbon bond-forming reactions and incidentally came to focus on the alkynoxy group (-OC≡C-), which shows a ketene-like resonance structure. We expected the alkynoxy group to interact electrophilically with a low-valent transition-metal complex in order to cleave adjacent C-H bonds. In this Account, we summarize our recent achievements on C-H activation based on interactions of palladium with the alkynoxy group in alkynyl aryl ethers. The alkynoxy group plays two roles in the transformation: as a directing group for adjacent C-H bond activation and as an acceptor for the carbon and hydrogen fragments. A typical example is palladium-catalyzed ortho-C-H bond activation in alkynoxyarenes followed by sequential insertion/annulation with

  12. Stereoselective intermolecular C-H amination reactions.

    PubMed

    Lebel, Hélène; Trudel, Carl; Spitz, Cédric

    2012-08-14

    A novel chiral N-mesyloxycarbamate to perform rhodium-catalyzed stereoselective C-H amination reactions is reported. Chiral benzylic and propargylic amines are produced in good yields and selectivities using ethyl acetate as solvent. The corresponding free amines are easily obtained by cleavage of the chiral reagent, which could also be recovered. PMID:22751570

  13. Arene-metal π-complexation as a traceless reactivity enhancer for C-H arylation.

    PubMed

    Ricci, Paolo; Krämer, Katrina; Cambeiro, Xacobe C; Larrosa, Igor

    2013-09-11

    Current approaches to facilitate C-H arylation of arenes involve the use of either strongly electron-withdrawing substituents or directing groups. Both approaches require structural modification of the arene, limiting their generality. We present a new approach where C-H arylation is made possible without altering the connectivity of the arene via π-complexation of a Cr(CO)3 unit, greatly enhancing the reactivity of the aromatic C-H bonds. We apply this approach to monofluorobenzenes, highly unreactive arenes, which upon complexation become nearly as reactive as pentafluorobenzene itself in their couplings with iodoarenes. DFT calculations indicate that C-H activation via a concerted metalation-deprotonation transition state is facilitated by the predisposition of C-H bonds in (Ar-H)Cr(CO)3 to bend out of the aromatic plane. PMID:23962336

  14. Manganese Catalyzed C-H Halogenation.

    PubMed

    Liu, Wei; Groves, John T

    2015-06-16

    The remarkable aliphatic C-H hydroxylations catalyzed by the heme-containing enzyme, cytochrome P450, have attracted sustained attention for more than four decades. The effectiveness of P450 enzymes as highly selective biocatalysts for a wide range of oxygenation reactions of complex substrates has driven chemists to develop synthetic metalloporphyrin model compounds that mimic P450 reactivity. Among various known metalloporphyrins, manganese derivatives have received considerable attention since they have been shown to be versatile and powerful mediators for alkane hydroxylation and olefin epoxidation. Mechanistic studies have shown that the key intermediates of the manganese porphyrin-catalyzed oxygenation reactions include oxo- and dioxomanganese(V) species that transfer an oxygen atom to the substrate through a hydrogen abstraction/oxygen recombination pathway known as the oxygen rebound mechanism. Application of manganese porphyrins has been largely restricted to catalysis of oxygenation reactions until recently, however, due to ultrafast oxygen transfer rates. In this Account, we discuss recently developed carbon-halogen bond formation, including fluorination reactions catalyzed by manganese porphyrins and related salen species. We found that biphasic sodium hypochlorite/manganese porphyrin systems can efficiently and selectively convert even unactivated aliphatic C-H bonds to C-Cl bonds. An understanding of this novel reactivity derived from results obtained for the oxidation of the mechanistically diagnostic substrate and radical clock, norcarane. Significantly, the oxygen rebound rate in Mn-mediated hydroxylation is highly correlated with the nature of the trans-axial ligands bound to the manganese center (L-Mn(V)═O). Based on the ability of fluoride ion to decelerate the oxygen rebound step, we envisaged that a relatively long-lived substrate radical could be trapped by a Mn-F fluorine source, effecting carbon-fluorine bond formation. Indeed, this idea

  15. Cobalt-Catalyzed Oxidative C-H/C-H Cross-Coupling between Two Heteroarenes.

    PubMed

    Tan, Guangying; He, Shuang; Huang, Xiaolei; Liao, Xingrong; Cheng, Yangyang; You, Jingsong

    2016-08-22

    The first example of cobalt-catalyzed oxidative C-H/C-H cross-coupling between two heteroarenes is reported, which exhibits a broad substrate scope and a high tolerance level for sensitive functional groups. When the amount of Co(OAc)2 ⋅4 H2 O is reduced from 6.0 to 0.5 mol %, an excellent yield is still obtained at an elevated temperature with a prolonged reaction time. The method can be extended to the reaction between an arene and a heteroarene. It is worth noting that the Ag2 CO3 oxidant is renewable. Preliminary mechanistic studies by radical trapping experiments, hydrogen/deuterium exchange experiments, kinetic isotope effect, electron paramagnetic resonance (EPR), and high resolution mass spectrometry (HRMS) suggest that a single electron transfer (SET) pathway is operative, which is distinctly different from the dual C-H bond activation pathway that the well-described oxidative C-H/C-H cross-coupling reactions between two heteroarenes typically undergo. PMID:27460406

  16. Approximate thermochemical tables for some C-H and C-H-O species

    NASA Technical Reports Server (NTRS)

    Bahn, G. S.

    1973-01-01

    Approximate thermochemical tables are presented for some C-H and C-H-O species and for some ionized species, supplementing the JANAF Thermochemical Tables for application to finite-chemical-kinetics calculations. The approximate tables were prepared by interpolation and extrapolation of limited available data, especially by interpolations over chemical families of species. Original estimations have been smoothed by use of a modification for the CDC-6600 computer of the Lewis Research Center PACl Program which was originally prepared for the IBM-7094 computer Summary graphs for various families show reasonably consistent curvefit values, anchored by properties of existing species in the JANAF tables.

  17. Asparaginyl endopeptidase cleaves TDP-43 in brain.

    PubMed

    Herskowitz, Jeremy H; Gozal, Yair M; Duong, Duc M; Dammer, Eric B; Gearing, Marla; Ye, Keqiang; Lah, James J; Peng, Junmin; Levey, Allan I; Seyfried, Nicholas T

    2012-08-01

    TAR DNA-binding protein 43 (TDP-43) is a nuclear protein involved in RNA splicing and a major protein component in ubiquitin-positive, tau-negative inclusions of frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Under disease conditions, TDP-43 redistributes to the cytoplasm where it can be phosphorylated, ubiquitinated, and proteolytically cleaved. Enzymes responsible for TDP-43 proteolytic processing in brain remain largely unreported. Using a MS approach, we identified two truncated TDP-43 peptides, terminating C-terminal to asparagines 291 (N291) and 306 (N306). The only documented mammalian enzyme capable of cleaving C-terminal to asparagine is asparaginyl endopeptidase (AEP). TDP-43-immunoreactive fragments (~35 and 32 kDa) predicted to be generated by AEP cleavage at N291 and N306 were observed by Western blot analyses of postmortem frontotemporal lobar degeneration brain tissue and cultured human cells over-expressing TDP-43. Studies in vitro determined that AEP can directly cleave TDP-43 at seven sites, including N291 and N306. Western blots of brain homogenates isolated from AEP-null mice and wild-type littermate controls revealed that TDP-43 proteolytic fragments were substantially reduced in the absence of AEP in vivo. Taken together, we conclude that TDP-43 is cleaved by AEP in brain. Moreover, these data highlight the utility of combining proteomic strategies in vitro and in vivo to provide insight into TDP-43 biology that will fuel the design of more detailed models of disease pathogenesis. PMID:22718532

  18. Optimized catalytic DNA-cleaving ribozymes

    NASA Technical Reports Server (NTRS)

    Joyce, Gerald F. (Inventor)

    1996-01-01

    The present invention discloses nucleic acid enzymes capable of cleaving nucleic acid molecules, including single-stranded DNA, in a site-specific manner under physiologic conditions, as well as compositions including same. The present invention also discloses methods of making and using the disclosed enzymes and compositions.

  19. Cleaved-edge-overgrowth nanogap electrodes

    NASA Astrophysics Data System (ADS)

    Luber, Sebastian M.; Bichler, Max; Abstreiter, Gerhard; Tornow, Marc

    2011-02-01

    We present a method to fabricate multiple metal nanogap electrodes of tailored width and distance in parallel, on the cleaved plane of a GaAs/AlGaAs heterostructure. The three-dimensional patterned structures are obtained by a combination of molecular-beam-epitaxial regrowth on a crystal facet, using the cleaved-edge-overgrowth (CEO) method, and subsequent wet selective etching and metallization steps. SEM and AFM studies reveal smooth and co-planar electrodes of width and distance of the order of 10 nm. Preliminary electrical characterization indicates electrical gap insulation in the 100 MΩ range with kΩ lead resistance. We propose our methodology to realize multiple electrode geometries that would allow investigation of the electrical conductivity of complex nanoscale objects such as branched organic molecules.

  20. Iron-Catalyzed C-H Functionalization Processes.

    PubMed

    Cera, Gianpiero; Ackermann, Lutz

    2016-10-01

    Iron-catalyzed C-H activation has recently emerged as an increasingly powerful tool for the step-economical transformation of unreactive C-H bonds. Particularly, the recent development of low-valent iron catalysis has set the stage for novel C-H activation strategies via chelation assistance. The low-cost, natural abundance, and low toxicity of iron prompted its very recent application in organometallic C-H activation catalysis. An overview of the use of iron catalysis in C-H activation processes is summarized herein up to May 2016. PMID:27573499

  1. Oxidative addition of C--H bonds in organic molecules to transition metal centers

    SciTech Connect

    Bergman, R.G.

    1989-04-01

    Alkanes are among the most chemically inert organic molecules. They are reactive toward a limited range of reagents, such as highly energetic free radicals and strongly electrophilic and oxidizing species. This low reactivity is a consequence of the C--H bond energies in most saturated hydrocarbons. These values range from 90 to 98 kcal/mole for primary and secondary C--H bonds; in methane, the main constituent of natural gas, the C--H bond energy is 104 kcal/mole. This makes methane one of the most common but least reactive organic molecules in nature. This report briefly discusses the search for metal complexes capable of undergoing the C--H oxidative addition process allowing alkane chemistry to be more selective than that available using free radical reagents. 14 refs.

  2. Catalytic asymmetric benzylic C-H activation by means of carbenoid-induced C-H insertions.

    PubMed

    Davies, Huw M L; Jin, Qihui; Ren, Pingda; Kovalevsky, Andrey Yu

    2002-06-14

    Tetrakis[N-[4-dodecylphenyl)sulfonyl]-(S)-prolinate]dirhodium [Rh(2)(S-DOSP)(4)]-catalyzed decomposition of methyl aryldiazoacetates in the presence of substituted ethylbenzenes results in benzylic C-H activation by means of a rhodium-carbenoid-induced C-H insertion. A Hammet study showed that positive charge buildup occurred on the benzylic carbon in the transition state of the C-H activation step. C-H activation of toluene and isopropylbenzene is possible, but a competing double cyclopropanation occurs with these substrates. The C-H activation is highly regioselective and enantioselective, and in certain cases, moderate diastereoselectivity is also possible. PMID:12054951

  3. The nature of the air-cleaved mica surface

    NASA Astrophysics Data System (ADS)

    Christenson, Hugo K.; Thomson, Neil H.

    2016-06-01

    The accepted image of muscovite mica is that of an inert and atomically smooth surface, easily prepared by cleavage in an ambient atmosphere. Consequently, mica is extensively used a model substrate in many fundamental studies of surface phenomena and as a substrate for AFM imaging of biomolecules. In this review we present evidence from the literature that the above picture is not quite correct. The mica used in experimental work is almost invariably cleaved in laboratory air, where a reaction between the mica surface, atmospheric CO2 and water occurs immediately after cleavage. The evidence suggests very strongly that as a result the mica surface becomes covered by up to one formula unit of K2CO3 per nm2, which is mobile under humid conditions, and crystallises under drier conditions. The properties of mica in air or water vapour cannot be fully understood without reference to the surface K2CO3, and many studies of the structure of adsorbed water on mica surfaces may need to be revisited. With this new insight, however, the air-cleaved mica should provide exciting opportunities to study phenomena such as two-dimensional ion diffusion, electrolyte effects on surface conductivity, and two-dimensional crystal nucleation.

  4. Double C-H amination by consecutive SET oxidations.

    PubMed

    Evoniuk, Christopher J; Hill, Sean P; Hanson, Kenneth; Alabugin, Igor V

    2016-06-01

    A new method for intramolecular C-H oxidative amination is based on a FeCl3-mediated oxidative reaction of anilines with activated sp(3) C-H bonds. The amino group plays multiple roles in the reaction cascade: (1) as the activating group in single-electron-transfer (SET) oxidation process, (2) as a directing group in benzylic/allylic C-H activation at a remote position, and (3) internal nucleophile trapping reactive intermediates formed from the C-H activation steps. These multielectron oxidation reactions proceed with catalytic amounts of Fe(iii) and inexpensive reagents. PMID:27170275

  5. Pd/Norbornene: A Winning Combination for Selective Aromatic Functionalization via C-H Bond Activation.

    PubMed

    Della Ca', Nicola; Fontana, Marco; Motti, Elena; Catellani, Marta

    2016-07-19

    Direct C-H bond activation is an important reaction in synthetic organic chemistry. This methodology has the potential to simplify reactions by avoiding the use of prefunctionalized reagents. However, selectivity, especially site selectivity, remains challenging. Sequential reactions, in which different molecules or groups are combined in an ordered sequence, represent a powerful tool for the construction of complex molecules in a single operation. We have discovered and developed a synthetic methodology that combines selective C-H bond activation with sequential reactions. This procedure, which is now known as the "Catellani reaction", enables the selective functionalization of both the ortho and ipso positions of aryl halides. The desired molecules are obtained with high selectivity from a pool of simple precursors. These molecules are assembled under the control of a palladacycle, which is formed through the joint action of a metal (Pd) and an olefin such as norbornene. These two species act cooperatively with an aryl halide to construct the palladacycle, which is formed through ortho-C-H activation of the original aryl halide. The resulting complex acts as a scaffold to direct the reaction (via Pd(IV)) of other species, such as alkyl or aryl halides and amination or acylation agents, toward the sp(2) C-Pd bond. At the end of this process, because of steric hindrance, the scaffold is dismantled by norbornene extrusion. Pd(0) is cleaved from the organic product through C-C, C-H, C-N, C-O, or C-B coupling, in agreement with the well-known reactivity of aryl-Pd complexes. The cycle involves Pd(0), Pd(II), and Pd(IV) species. In particular, our discovery relates to alkylation and arylation reactions. Recently, remarkable progress has been made in the following areas: (a) the installation of an amino or an acyl group at the ortho position of aryl halides, (b) the formation of a C-B bond at the ipso position, (c) the achievement of meta-C-H bond activation of aryl

  6. Mild metal-catalyzed C-H activation: examples and concepts.

    PubMed

    Gensch, T; Hopkinson, M N; Glorius, F; Wencel-Delord, J

    2016-05-21

    Organic reactions that involve the direct functionalization of non-activated C-H bonds represent an attractive class of transformations which maximize atom- and step-economy, and simplify chemical synthesis. Due to the high stability of C-H bonds, these processes, however, have most often required harsh reaction conditions, which has drastically limited their use as tools for the synthesis of complex organic molecules. Following the increased understanding of mechanistic aspects of C-H activation gained over recent years, great strides have been taken to design and develop new protocols that proceed efficiently under mild conditions and duly benefit from improved functional group tolerance and selectivity. In this review, we present the current state of the art in this field and detail C-H activation transformations reported since 2011 that proceed either at or below ambient temperature, in the absence of strongly acidic or basic additives or without strong oxidants. Furthermore, by identifying and discussing the major strategies that have led to these improvements, we hope that this review will serve as a useful conceptual overview and inspire the next generation of mild C-H transformations. PMID:27072661

  7. Endonuclease V cleaves at inosines in RNA.

    PubMed

    Vik, Erik Sebastian; Nawaz, Meh Sameen; Strøm Andersen, Pernille; Fladeby, Cathrine; Bjørås, Magnar; Dalhus, Bjørn; Alseth, Ingrun

    2013-01-01

    Endonuclease V orthologues are highly conserved proteins found in all kingdoms of life. While the prokaryotic enzymes are DNA repair proteins for removal of deaminated adenosine (inosine) from the genome, no clear role for the eukaryotic counterparts has hitherto been described. Here we report that human endonuclease V (ENDOV) and also Escherichia coli endonuclease V are highly active ribonucleases specific for inosine in RNA. Inosines are normal residues in certain RNAs introduced by specific deaminases. Adenosine-to-inosine editing is essential for proper function of these transcripts and defects are linked to various human disease. Here we show that human ENDOV cleaves an RNA substrate containing inosine in a position corresponding to a biologically important site for deamination in the Gabra-3 transcript of the GABA(A) neurotransmitter. Further, human ENDOV specifically incises transfer RNAs with inosine in the wobble position. This previously unknown RNA incision activity may suggest a role for endonuclease V in normal RNA metabolism. PMID:23912683

  8. Endonuclease V cleaves at inosines in RNA

    PubMed Central

    Sebastian Vik, Erik; Sameen Nawaz, Meh; Strøm Andersen, Pernille; Fladeby, Cathrine; Bjørås, Magnar; Dalhus, Bjørn; Alseth, Ingrun

    2013-01-01

    Endonuclease V orthologues are highly conserved proteins found in all kingdoms of life. While the prokaryotic enzymes are DNA repair proteins for removal of deaminated adenosine (inosine) from the genome, no clear role for the eukaryotic counterparts has hitherto been described. Here we report that human endonuclease V (ENDOV) and also Escherichia coli endonuclease V are highly active ribonucleases specific for inosine in RNA. Inosines are normal residues in certain RNAs introduced by specific deaminases. Adenosine-to-inosine editing is essential for proper function of these transcripts and defects are linked to various human disease. Here we show that human ENDOV cleaves an RNA substrate containing inosine in a position corresponding to a biologically important site for deamination in the Gabra-3 transcript of the GABAA neurotransmitter. Further, human ENDOV specifically incises transfer RNAs with inosine in the wobble position. This previously unknown RNA incision activity may suggest a role for endonuclease V in normal RNA metabolism. PMID:23912683

  9. Manganese Porphyrins Catalyze Selective C-H Bond Halogenations

    SciTech Connect

    Liu, Wei; Groves, John T.

    2010-08-31

    We report a manganese porphyrin mediated aliphatic C-H bond chlorination using sodium hypochlorite as the chlorine source. In the presence of catalytic amounts of phase transfer catalyst and manganese porphyrin Mn(TPP)Cl 1, reaction of sodium hypochlorite with different unactivated alkanes afforded alkyl chlorides as the major products with only trace amounts of oxygenation products. Substrates with strong C-H bonds, such as neopentane (BDE =~100 kcal/mol) can be also chlorinated with moderate yield. Chlorination of a diagnostic substrate, norcarane, afforded rearranged products indicating a long-lived carbon radical intermediate. Moreover, regioselective chlorination was achieved by using a hindered catalyst, Mn(TMP)Cl, 2. Chlorination of trans-decalin with 2 provided 95% selectivity for methylene-chlorinated products as well as a preference for the C2 position. This novel chlorination system was also applied to complex substrates. With 5α-cholestane as the substrate, we observed chlorination only at the C2 and C3 positions in a net 55% yield, corresponding to the least sterically hindered methylene positions in the A-ring. Similarly, chlorination of sclareolide afforded the equatorial C2 chloride in a 42% isolated yield. Regarding the mechanism, reaction of sodium hypochlorite with the MnIII porphyrin is expected to afford a reactive MnV=O complex that abstracts a hydrogen atom from the substrate, resulting in a free alkyl radical and a MnIV—OH complex. We suggest that this carbon radical then reacts with a MnIV—OCl species, providing the alkyl chloride and regenerating the reactive MnV=O complex. The regioselectivity and the preference for CH2 groups can be attributed to nonbonded interactions between the alkyl groups on the substrates and the aryl groups of the manganese porphyrin. The results are indicative of a bent [Mnv=O---H---C] geometry due to the C—H approach to the Mn

  10. Nickel-Catalyzed Aromatic C-H Functionalization.

    PubMed

    Yamaguchi, Junichiro; Muto, Kei; Itami, Kenichiro

    2016-08-01

    Catalytic C-H functionalization using transition metals has received significant interest from organic chemists because it provides a new strategy to construct carbon-carbon bonds and carbon-heteroatom bonds in highly functionalized, complex molecules without pre-functionalization. Recently, inexpensive catalysts based on transition metals such as copper, iron, cobalt, and nickel have seen more use in the laboratory. This review describes recent progress in nickel-catalyzed aromatic C-H functionalization reactions classified by reaction types and reaction partners. Furthermore, some reaction mechanisms are described and cutting-edge syntheses of natural products and pharmaceuticals using nickel-catalyzed aromatic C-H functionalization are presented. PMID:27573407

  11. Rhodium-Catalyzed Intramolecular C-H Silylation by Silacyclobutanes.

    PubMed

    Zhang, Qing-Wei; An, Kun; Liu, Li-Chuan; Guo, Shuangxi; Jiang, Chenran; Guo, Huifang; He, Wei

    2016-05-17

    Silacyclobutane was discovered to be an efficient C-H bond silylation reagent. Under the catalysis of Rh(I) /TMS-segphos, silacyclobutane undergoes sequential C-Si/C-H bond activations, affording a series of π-conjugated siloles in high yields and regioselectivities. The catalytic cycle was proposed to involve a rarely documented endocyclic β-hydride elimination of five-membered metallacycles, which after reductive elimination gave rise to a Si-Rh(I) species that is capable of C-H activation. PMID:27073004

  12. Oxidative esterification via photocatalytic C-H activation

    EPA Science Inventory

    Direct oxidative esterification of alcohol via photocatalytic C-H activation has been developed using VO@g-C3N4 catalyst; an expeditious esterification of alcohols occurs under neutral conditions using visible light as the source of energy.

  13. Gold(I)-mediated C-H activation of arenes.

    PubMed

    Lu, Pengfei; Boorman, Tanya C; Slawin, Alexandra M Z; Larrosa, Igor

    2010-04-28

    We demonstrate the first Au(I)-mediated C-H activation of arenes. Au(I) salts undergo C-H activation with electron-poor arenes, in stark contrast to Au(III) salts, which activate electron-rich arenes. This operationally simple and highly regioselective process occurs under very mild conditions and gives access to a variety of Au(I)-arene complexes in excellent yields. PMID:20364835

  14. Copper-catalyzed etherification of arene C-H bonds.

    PubMed

    Roane, James; Daugulis, Olafs

    2013-11-15

    A method for direct, auxiliary-assisted alkoxylation and phenoxylation of β-sp(2) C-H bonds of benzoic acid derivatives and γ-sp(2) C-H bonds of amine derivatives is reported. The reaction employs (CuOH)2CO3 catalyst, air as an oxidant, phenol or alcohol coupling partner, DMF, pyridine, or DMPU solvent, and K2CO3, tetramethylguanidine, or K3PO4 base at 70-130 °C. PMID:24180517

  15. Heterocycle Synthesis via Direct C-H/N-H Coupling

    PubMed Central

    Nadres, Enrico T.; Daugulis, Olafs

    2012-01-01

    A method for five- and six-membered heterocycle formation by palladium-catalyzed C-H/N-H coupling is presented. The method employs a picolinamide directing group, PhI(OAc)2 oxidant, and toluene solvent at 80–120 °C. Cyclization is effective for sp2 as well as aliphatic and benzylic sp3 C-H bonds. PMID:22206416

  16. Hydrogen bond-like equatorial C-H⋯O interactions in aqueous 1,3-dioxane: A combined high-pressure infrared and Raman spectroscopy study

    NASA Astrophysics Data System (ADS)

    Chang, Hai-Chou; Jiang, Jyh-Chiang; Chuang, Ching-Wei; Lin, Jui-San; Lai, Wen-Wei; Yang, Yu-Chuan; Lin, Sheng Hsien

    2005-07-01

    Our results demonstrate that the equatorial C-H groups of 1,3-dioxane form hydrogen-bond-like C-H⋯O interactions more readily than do the axial C-H groups. The peak frequency of the strong axial C-H stretch band of 1,3-dioxane in a dilute D 2O solution possesses an unusual non-monotonic pressure dependence, which indicates enhanced C-H⋯O hydrogen bond formation at high pressure. We performed density functional theory calculations to predict the relative energies and total interaction energies of 1,3-dioxane/(water) n clusters and found that the equatorial C-H groups are more favorable sites for hydrogen bonding than are the axial C-H groups.

  17. Scalable and sustainable electrochemical allylic C-H oxidation.

    PubMed

    Horn, Evan J; Rosen, Brandon R; Chen, Yong; Tang, Jiaze; Chen, Ke; Eastgate, Martin D; Baran, Phil S

    2016-05-01

    New methods and strategies for the direct functionalization of C-H bonds are beginning to reshape the field of retrosynthetic analysis, affecting the synthesis of natural products, medicines and materials. The oxidation of allylic systems has played a prominent role in this context as possibly the most widely applied C-H functionalization, owing to the utility of enones and allylic alcohols as versatile intermediates, and their prevalence in natural and unnatural materials. Allylic oxidations have featured in hundreds of syntheses, including some natural product syntheses regarded as "classics". Despite many attempts to improve the efficiency and practicality of this transformation, the majority of conditions still use highly toxic reagents (based around toxic elements such as chromium or selenium) or expensive catalysts (such as palladium or rhodium). These requirements are problematic in industrial settings; currently, no scalable and sustainable solution to allylic oxidation exists. This oxidation strategy is therefore rarely used for large-scale synthetic applications, limiting the adoption of this retrosynthetic strategy by industrial scientists. Here we describe an electrochemical C-H oxidation strategy that exhibits broad substrate scope, operational simplicity and high chemoselectivity. It uses inexpensive and readily available materials, and represents a scalable allylic C-H oxidation (demonstrated on 100 grams), enabling the adoption of this C-H oxidation strategy in large-scale industrial settings without substantial environmental impact. PMID:27096371

  18. Cupric-Superoxo Mediated Inter-Molecular C-H Activation Chemistry

    PubMed Central

    Peterson, Ryan L.; Himes, Richard A.; Kotani, Hiroaki; Suenobu, Tomoyoshi; Tian, Li; Siegler, Maxime A.; Solomon, Edward I.; Fukuzumi, Shunichi; Karlin, Kenneth D.

    2011-01-01

    A new cupric-superoxo complex [LCuII(O2•−)]+, which possesses particularly strong O–O and Cu–O bonding, is capable of intermolecular C-H activation of the NADH analogue 1-benzyl-1,4-dihydronicotinamide (BNAH). Kinetic studies indicate a first-order dependence on both the Cu-complex and BNAH with a deuterium kinetic isotope effect (KIE) of 12.1, similar to that observed for certain copper monooxygenases. PMID:21265534

  19. Activation of the C-H bond by metal complexes

    NASA Astrophysics Data System (ADS)

    Shilov, Aleksandr E.; Shul'pin, Georgiy B.

    1990-09-01

    Reactions involving the cleavage of C-H bonds by metal complexes in saturated and aromatic hydrocarbons and also in other compounds are examined. Some of these processes occur with formation of a carbon-metal bond, whilst in others the interaction of the complexes with the hydrocarbon takes place without direct contact between the metal atom and the C-H bonds. Metal compounds are widely used as initiators of the liquid-phase oxidation of hydrocarbons at relatively low temperatures. There is a prospect of creating new technologies for the chemical processing of petroleum and gas hydrocarbons, whereby they can be converted into valuable products, for example, into alcohols, ketones, and carboxylic acids, on the basis of processes involving metal complexes. The study of the metal complex activation of the C-H bond also makes it possible to understand and model the metalloenzyme-catalysed hydrocarbon oxidation reactions in the living cell. The bibliography includes 340 references.

  20. C-H bond activation by f-block complexes.

    PubMed

    Arnold, Polly L; McMullon, Max W; Rieb, Julia; Kühn, Fritz E

    2015-01-01

    Most homogeneous catalysis relies on the design of metal complexes to trap and convert substrates or small molecules to value-added products. Organometallic lanthanide compounds first gave a tantalizing glimpse of their potential for catalytic C-H bond transformations with the selective cleavage of one C-H bond in methane by bis(permethylcyclopentadienyl)lanthanide methyl [(η(5) -C5 Me5 )2 Ln(CH3 )] complexes some 25 years ago. Since then, numerous metal complexes from across the periodic table have been shown to selectively activate hydrocarbon C-H bonds, but the challenges of closing catalytic cycles still remain; many f-block complexes show great potential in this important area of chemistry. PMID:25384554

  1. Sequential Regioselective C-H Functionalization of Thiophenes.

    PubMed

    Daniels, Matthew H; Armand, Jeremy R; Tan, Kian L

    2016-07-15

    Herein, the sequential functionalization of 5-membered ring heterocycles is disclosed. By employing a pH sensitive directing group both directed and nondirected C-H activation pathways are available, providing access to 2,3,4- and 2,4,5-substituted thiophenes. The C-H arylation was performed in water, and using a surfactant greatly improved the yield and mass recovery. The use of a directing group with an on/off switch offers a potentially powerful means of generating diversity around medicinally relevant cores. PMID:27388746

  2. Elaboration of copper-oxygen mediated C-H activation chemistry in consideration of future fuel and feedstock generation.

    PubMed

    Lee, Jung Yoon; Karlin, Kenneth D

    2015-04-01

    To contribute solutions to current energy concerns, improvements in the efficiency of dioxygen mediated C-H bond cleavage chemistry, for example, selective oxidation of methane to methanol, could minimize losses in natural gas usage or produce feedstocks for fuels. Oxidative C-H activation is also a component of polysaccharide degradation, potentially affording alternative biofuels from abundant biomass. Thus, an understanding of active-site chemistry in copper monooxygenases, those activating strong C-H bonds is briefly reviewed. Then, recent advances in the synthesis-generation and study of various copper-oxygen intermediates are highlighted. Of special interest are cupric-superoxide, Cu-hydroperoxo and Cu-oxy complexes. Such investigations can contribute to an enhanced future application of C-H oxidation or oxygenation processes using air, as concerning societal energy goals. PMID:25756327

  3. Enzyme catalysis: C-H activation is a Reiske business

    NASA Astrophysics Data System (ADS)

    Bruner, Steven D.

    2011-05-01

    Enzymes that selectively oxidize unactivated C-H bonds are capable of constructing complex molecules with high efficiency. A new member of this enzyme family is RedG, a Reiske-type oxygenase that catalyses chemically challenging cyclizations in the biosynthesis of prodiginine natural products.

  4. Dehydrogenation processes via C-H activation within alkylphosphines.

    PubMed

    Grellier, Mary; Sabo-Etienne, Sylviane

    2012-01-01

    Phosphines are commonly used in organometallic chemistry and are present in a wide variety of catalytic systems. This feature article highlights the advances made in dehydrogenation processes occurring within alkylphosphines, with the aim of further developing catalytic processes involving C-H activation together with potential applications in the field of hydrogen storage. PMID:21956347

  5. Copper-catalyzed direct C-H fluoroalkenylation of heteroarenes.

    PubMed

    Rousée, Kevin; Schneider, Cédric; Bouillon, Jean-Philippe; Levacher, Vincent; Hoarau, Christophe; Couve-Bonnaire, Samuel; Pannecoucke, Xavier

    2016-01-01

    Copper-catalyzed direct C-H fluoroalkenylation of heterocycles using various gem-bromofluoroalkenes as electrophiles is reported. This efficient method offers step-economical, low-cost and stereocontrolled access to relevant heteroarylated monofluoroalkenes. The synthesis of fluorinated analogues of biomolecules and therapeutic agents for the treatment of Duchenne muscular dystrophy as application is reported. PMID:26603641

  6. Ag-catalyzed C-H/C-C bond functionalization.

    PubMed

    Zheng, Qing-Zhong; Jiao, Ning

    2016-08-21

    Silver, known and utilized since ancient times, is a coinage metal, which has been widely used for various organic transformations in the past few decades. Currently, the silver-catalyzed reaction is one of the frontier areas in organic chemistry, and the progress of research in this field is very rapid. Compared with other transition metals, silver has long been believed to have low catalytic efficiency, and most commonly, it is used as either a cocatalyst or a Lewis acid. Interestingly, the discovery of Ag-catalysis has been significantly improved in recent years. Especially, Ag(i) has been demonstrated as an important and versatile catalyst for a variety of organic transformations. However, so far, there has been no systematic review on Ag-catalyzed C-H/C-C bond functionalization. In this review, we will focus on the development of Ag-catalyzed C-H/C-C bond functionalization and the corresponding mechanism. PMID:27056573

  7. Carbon stars with alpha-C:H emission

    NASA Technical Reports Server (NTRS)

    Gerbault, Florence; Goebel, John H.

    1989-01-01

    Many carbon stars in the IRS low resolution spectra (LRS) catalog were found which display emission spectra that compare favorable with the absorption spectrum of alpha-C:H. These stars have largely been classified as 4X in the LRS which has led to their interpretation by others in terms of displaying a mixture of the UIRF's 8.6 micron band and SiC at 11.5 microns. It was also found that many of these stars have a spectral upturn at 20+ microns which resembles the MgS band seen in carbon stars and planetary nebulae. It was concluded that this group of carbon stars will evolve into planetary nebulae like NGC 7027 and IC 418. In the presence of hard ultraviolet radiation the UIRF's will light up and be displayed as narrow emission bands on top of the broad alpha-C:H emission bands.

  8. Copper-catalyzed olefinic C-H difluoroacetylation of enamides.

    PubMed

    Caillot, Gilles; Dufour, Jérémy; Belhomme, Marie-Charlotte; Poisson, Thomas; Grimaud, Laurence; Pannecoucke, Xavier; Gillaizeau, Isabelle

    2014-06-01

    Copper-catalyzed olefinic difluoroacetylation of enamides via direct C-H bond functionalization using BrCF2CO2Et is reported for the first time. It constitutes an efficient radical-free method for the regioselective synthesis of β-difluoroester substituted enamides which exhibits broad substrate scope, and thus demonstrates its potent application in a late stage fluorination strategy. PMID:24760345

  9. Carbon dioxide utilization via carbonate-promoted C-H carboxylation

    NASA Astrophysics Data System (ADS)

    Banerjee, Aanindeeta; Dick, Graham R.; Yoshino, Tatsuhiko; Kanan, Matthew W.

    2016-03-01

    Using carbon dioxide (CO2) as a feedstock for commodity synthesis is an attractive means of reducing greenhouse gas emissions and a possible stepping-stone towards renewable synthetic fuels. A major impediment to synthesizing compounds from CO2 is the difficulty of forming carbon-carbon (C-C) bonds efficiently: although CO2 reacts readily with carbon-centred nucleophiles, generating these intermediates requires high-energy reagents (such as highly reducing metals or strong organic bases), carbon-heteroatom bonds or relatively acidic carbon-hydrogen (C-H) bonds. These requirements negate the environmental benefit of using CO2 as a substrate and limit the chemistry to low-volume targets. Here we show that intermediate-temperature (200 to 350 degrees Celsius) molten salts containing caesium or potassium cations enable carbonate ions (CO32-) to deprotonate very weakly acidic C-H bonds (pKa > 40), generating carbon-centred nucleophiles that react with CO2 to form carboxylates. To illustrate a potential application, we use C-H carboxylation followed by protonation to convert 2-furoic acid into furan-2,5-dicarboxylic acid (FDCA)—a highly desirable bio-based feedstock with numerous applications, including the synthesis of polyethylene furandicarboxylate (PEF), which is a potential large-scale substitute for petroleum-derived polyethylene terephthalate (PET). Since 2-furoic acid can readily be made from lignocellulose, CO32--promoted C-H carboxylation thus reveals a way to transform inedible biomass and CO2 into a valuable feedstock chemical. Our results provide a new strategy for using CO2 in the synthesis of multi-carbon compounds.

  10. Carbon dioxide utilization via carbonate-promoted C-H carboxylation.

    PubMed

    Banerjee, Aanindeeta; Dick, Graham R; Yoshino, Tatsuhiko; Kanan, Matthew W

    2016-03-10

    Using carbon dioxide (CO2) as a feedstock for commodity synthesis is an attractive means of reducing greenhouse gas emissions and a possible stepping-stone towards renewable synthetic fuels. A major impediment to synthesizing compounds from CO2 is the difficulty of forming carbon-carbon (C-C) bonds efficiently: although CO2 reacts readily with carbon-centred nucleophiles, generating these intermediates requires high-energy reagents (such as highly reducing metals or strong organic bases), carbon-heteroatom bonds or relatively acidic carbon-hydrogen (C-H) bonds. These requirements negate the environmental benefit of using CO2 as a substrate and limit the chemistry to low-volume targets. Here we show that intermediate-temperature (200 to 350 degrees Celsius) molten salts containing caesium or potassium cations enable carbonate ions (CO3(2-)) to deprotonate very weakly acidic C-H bonds (pKa > 40), generating carbon-centred nucleophiles that react with CO2 to form carboxylates. To illustrate a potential application, we use C-H carboxylation followed by protonation to convert 2-furoic acid into furan-2,5-dicarboxylic acid (FDCA)--a highly desirable bio-based feedstock with numerous applications, including the synthesis of polyethylene furandicarboxylate (PEF), which is a potential large-scale substitute for petroleum-derived polyethylene terephthalate (PET). Since 2-furoic acid can readily be made from lignocellulose, CO3(2-)-promoted C-H carboxylation thus reveals a way to transform inedible biomass and CO2 into a valuable feedstock chemical. Our results provide a new strategy for using CO2 in the synthesis of multi-carbon compounds. PMID:26961655

  11. Enantioselective C-H carbene insertions with homogeneous and immobilized copper complexes.

    PubMed

    Fraile, José M; López-Ram-de-Viu, Pilar; Mayoral, José A; Roldán, Marta; Santafé-Valero, Jorge

    2011-09-01

    The efficiency of chiral bis(oxazoline)- and azabis(oxazoline)-copper complexes in the enantioselective carbene insertion into C-H bonds of cyclic ethers in homogeneous phase strongly depends on the structure of the substrate. The immobilization on laponite clay by electrostatic interactions not only allows the recovery and reuse of the heterogeneous catalysts, but in some cases also improves enantioselectivity and overall chemoselectivity, making possible reactions that do not take place or lead to low yields in solution, even with the commonly used Rh(2)[S-DOSP](4) catalyst. PMID:21750830

  12. Seeing the B-A-C-H motif

    NASA Astrophysics Data System (ADS)

    Catravas, Palmyra

    2005-09-01

    Musical compositions can be thought of as complex, multidimensional data sets. Compositions based on the B-A-C-H motif (a four-note motif of the pitches of the last name of Johann Sebastian Bach) span several centuries of evolving compositional styles and provide an intriguing set for analysis since they contain a common feature, the motif, buried in dissimilar contexts. We will present analyses which highlight the content of this unusual set of pieces, with emphasis on visual display of information.

  13. Direct C-H Trifluoromethylation of Glycals by Photoredox Catalysis.

    PubMed

    Wang, Bang; Xiong, De-Cai; Ye, Xin-Shan

    2015-11-20

    A mild, efficient, and practical transformation for the direct C-H trifluoromethylation of glycals under visible light has been reported for the first time. This reaction employed fac-Ir(3+)(ppy)3 as the photocatalyst, Umemoto's reagent as the CF3 source, and a household blue LED or sunlight as the light source. Glycals bearing both electron-withdrawing and -donating protective groups performed this reaction smoothly. This visible light-mediated trifluoromethylation reaction was highlighted by the trifluoromethylation of the biologically important Neu2en moiety. PMID:26562610

  14. RNA-Cleaving DNA Enzymes with Altered Regio- or Enantioselectivity

    NASA Technical Reports Server (NTRS)

    Ordoukhanian, Phillip; Joyce, Gerald F.

    2002-01-01

    In vitro evolution methods were used to obtain DNA enzymes that cleave either a 2',5' - phosphodiester following a wibonucleotide or a 3',5' -phosphodiester following an L-ribonucleotide. Both enzymes can operate in an intermolecular reaction format with multiple turnover. The DNA enzyme that cleaves a 2',5' -phosphodiester exhibits a k(sub cat) of approx. 0.01/ min and catalytic efficiency, k(sub cat)/k(sub m) of approx. 10(exp 5)/ M min. The enzyme that cleaves an L-ribonudeotide is about 10-fold slower and has a catalytic efficiency of approx. 4 x 10(exp 5)/ M min. Both enzymes require a divalent metal cation for their activity and have optimal catalytic rate at pH 7-8 and 35-50 C. In a comparison of each enzyme s activity with either its corresponding substrate that contains an unnatural ribonudeotide or a substrate that instead contains a standard ribonucleotide, the 2',5' -phosphodiester-deaving DNA enzyme exhibited a regioselectivity of 6000- fold, while the L-ribonucleotide-cleaving DNA enzyme exhibited an enantioselectivity of 50-fold. These molecules demonstrate how in vitro evolution can be used to obtain regio- and enantioselective catalysts that exhibit specificities for nonnatural analogues of biological compounds.

  15. Molecular Dynamics of Dimethyldioxirane C-H Oxidation.

    PubMed

    Yang, Zhongyue; Yu, Peiyuan; Houk, K N

    2016-03-30

    We report molecular dynamics simulations of the reaction of dimethyldioxirane (DMDO) with isobutane. The reaction involves hydrogen atom abstraction in the transition state, and trajectories branch to the oxygen rebound pathway, which gives tert-butanol and acetone, or a separated radical pair. In the gas phase, only 10% of the reactive trajectories undergo the oxygen rebound pathway, but this increases to 90% in simulations in an implicit acetone solvent (SMD) because the oxygen rebound becomes barrierless in solution. Short-lived diradical species were observed in the oxygen rebound trajectories. The time gap between C-H bond-breaking and C-O bond formation ranges from 30 to 150 fs, close to the <200 fs lifetime of radical pairs from DMDO hydroxylation of trans-1-phenyl-2-ethylcyclopropane measured by Newcomb. PMID:26964643

  16. Dirhodium-catalyzed C-H arene amination using hydroxylamines.

    PubMed

    Paudyal, Mahesh P; Adebesin, Adeniyi Michael; Burt, Scott R; Ess, Daniel H; Ma, Zhiwei; Kürti, László; Falck, John R

    2016-09-01

    Primary and N-alkyl arylamine motifs are key functional groups in pharmaceuticals, agrochemicals, and functional materials, as well as in bioactive natural products. However, there is a dearth of generally applicable methods for the direct replacement of aryl hydrogens with NH2/NH(alkyl) moieties. Here, we present a mild dirhodium-catalyzed C-H amination for conversion of structurally diverse monocyclic and fused aromatics to the corresponding primary and N-alkyl arylamines using NH2/NH(alkyl)-O-(sulfonyl)hydroxylamines as aminating agents; the relatively weak RSO2O-N bond functions as an internal oxidant. The methodology is operationally simple, scalable, and fast at or below ambient temperature, furnishing arylamines in moderate-to-good yields and with good regioselectivity. It can be readily extended to the synthesis of fused N-heterocycles. PMID:27609890

  17. Aerobic Linear Allylic C-H Amination: Overcoming Benzoquinone Inhibition.

    PubMed

    Pattillo, Christopher C; Strambeanu, Iulia I; Calleja, Pilar; Vermeulen, Nicolaas A; Mizuno, Tomokazu; White, M Christina

    2016-02-01

    An efficient aerobic linear allylic C-H amination reaction is reported under palladium(II)/bis-sulfoxide/Brønsted base catalysis. The reaction operates under preparative, operationally simple conditions (1 equiv of olefin, 1 atm O2 or air) with reduced Pd(II)/bis-sulfoxide catalyst loadings while providing higher turnovers and product yields than systems employing stoichiometric benzoquinone (BQ) as the terminal oxidant. Pd(II)/BQ π-acidic interactions have been invoked in various catalytic processes and are often considered beneficial in promoting reductive functionalizations. When such electrophilic activation for functionalization is not needed, however, BQ at high concentrations may compete with crucial ligand (bis-sulfoxide) binding and inhibit catalysis. Kinetic studies reveal an inverse relationship between the reaction rate and the concentration of BQ, suggesting that BQ is acting as a ligand for Pd(II) which results in an inhibitory effect on catalysis. PMID:26730458

  18. Growth mechanism and composition of ultrasmooth a-C:H:Si films grown from energetic ions for superlubricity

    SciTech Connect

    Chen, Xinchun Kato, Takahisa

    2014-01-28

    Growth mechanism and ion energy dependence of composition of ultrasmooth a-C:H:Si films grown from ionization of tetramethylsilane (TMS) and toluene mixture at a fixed gas ratio have been investigated by varying the applied bias voltage. The dynamic scaling theory is employed to evaluate the roughness evolution of a-C:H:Si films, and to extract roughness and growth exponents of α ∼ 0.51 and β ∼ 0, respectively. The atomically smooth surface of a-C:H:Si films with Ra ∼ 0.1 nm is thermally activated by the energetic ion-impact induced subsurface “polishing” process for ion dominated deposition. The ion energy (bias voltage) plays a paramount role in determining the hydrogen incorporation, bonding structure and final stoichiometry of a-C:H:Si films. The hydrogen content in the films measured by ERDA gradually decreases from 36.7 to 17.3 at. % with increasing the bias voltage from 0.25 to 3.5 kV, while the carbon content in the films increases correspondingly from 52.5 to 70.1 at. %. The Si content is kept almost constant at ∼9–10 at. %. Depending on the ion-surface interactions, the bonding structure of a-C:H:Si films grown in different ion energy regions evolves from chain-developed polymer-like to cross-linked diamond-like to sp{sup 2}-bonded a–C as revealed by XPS, Raman, and FTIR analysis. Such a structural evolution is reflected in their measured nanomechanical properties such as hardness, modulus, and compressive stress. An enhanced viscoplastic behavior (i.e., viscoplastic exponent of ∼0.06) is observed for polymeric a-C:H:Si films. A hydrogen content threshold (H > 20 at. %) exists for the as-grown a-C:H:Si films to exhibit superlow friction in dry N{sub 2} atmosphere. An extremely low friction coefficient of ∼0.001 can be obtained for polymer-like a-C:H:Si film. These near-frictionless a-C:H:Si films are strongly promising for applications in industrial lubricating systems.

  19. Growth mechanism and composition of ultrasmooth a-C:H:Si films grown from energetic ions for superlubricity

    NASA Astrophysics Data System (ADS)

    Chen, Xinchun; Kato, Takahisa

    2014-01-01

    Growth mechanism and ion energy dependence of composition of ultrasmooth a-C:H:Si films grown from ionization of tetramethylsilane (TMS) and toluene mixture at a fixed gas ratio have been investigated by varying the applied bias voltage. The dynamic scaling theory is employed to evaluate the roughness evolution of a-C:H:Si films, and to extract roughness and growth exponents of α ˜ 0.51 and β ˜ 0, respectively. The atomically smooth surface of a-C:H:Si films with Ra ˜ 0.1 nm is thermally activated by the energetic ion-impact induced subsurface "polishing" process for ion dominated deposition. The ion energy (bias voltage) plays a paramount role in determining the hydrogen incorporation, bonding structure and final stoichiometry of a-C:H:Si films. The hydrogen content in the films measured by ERDA gradually decreases from 36.7 to 17.3 at. % with increasing the bias voltage from 0.25 to 3.5 kV, while the carbon content in the films increases correspondingly from 52.5 to 70.1 at. %. The Si content is kept almost constant at ˜9-10 at. %. Depending on the ion-surface interactions, the bonding structure of a-C:H:Si films grown in different ion energy regions evolves from chain-developed polymer-like to cross-linked diamond-like to sp2-bonded a-C as revealed by XPS, Raman, and FTIR analysis. Such a structural evolution is reflected in their measured nanomechanical properties such as hardness, modulus, and compressive stress. An enhanced viscoplastic behavior (i.e., viscoplastic exponent of ˜0.06) is observed for polymeric a-C:H:Si films. A hydrogen content threshold (H > 20 at. %) exists for the as-grown a-C:H:Si films to exhibit superlow friction in dry N2 atmosphere. An extremely low friction coefficient of ˜0.001 can be obtained for polymer-like a-C:H:Si film. These near-frictionless a-C:H:Si films are strongly promising for applications in industrial lubricating systems.

  20. Alcohols as alkylating agents in heteroarene C-H functionalization

    NASA Astrophysics Data System (ADS)

    Jin, Jian; MacMillan, David W. C.

    2015-09-01

    Redox processes and radical intermediates are found in many biochemical processes, including deoxyribonucleotide synthesis and oxidative DNA damage. One of the core principles underlying DNA biosynthesis is the radical-mediated elimination of H2O to deoxygenate ribonucleotides, an example of `spin-centre shift', during which an alcohol C-O bond is cleaved, resulting in a carbon-centred radical intermediate. Although spin-centre shift is a well-understood biochemical process, it is underused by the synthetic organic chemistry community. We wondered whether it would be possible to take advantage of this naturally occurring process to accomplish mild, non-traditional alkylation reactions using alcohols as radical precursors. Because conventional radical-based alkylation methods require the use of stoichiometric oxidants, increased temperatures or peroxides, a mild protocol using simple and abundant alkylating agents would have considerable use in the synthesis of diversely functionalized pharmacophores. Here we describe the development of a dual catalytic alkylation of heteroarenes, using alcohols as mild alkylating reagents. This method represents the first, to our knowledge, broadly applicable use of unactivated alcohols as latent alkylating reagents, achieved via the successful merger of photoredox and hydrogen atom transfer catalysis. The value of this multi-catalytic protocol has been demonstrated through the late-stage functionalization of the medicinal agents, fasudil and milrinone.

  1. Alcohols as alkylating agents in heteroarene C-H functionalization.

    PubMed

    Jin, Jian; MacMillan, David W C

    2015-09-01

    Redox processes and radical intermediates are found in many biochemical processes, including deoxyribonucleotide synthesis and oxidative DNA damage. One of the core principles underlying DNA biosynthesis is the radical-mediated elimination of H2O to deoxygenate ribonucleotides, an example of 'spin-centre shift', during which an alcohol C-O bond is cleaved, resulting in a carbon-centred radical intermediate. Although spin-centre shift is a well-understood biochemical process, it is underused by the synthetic organic chemistry community. We wondered whether it would be possible to take advantage of this naturally occurring process to accomplish mild, non-traditional alkylation reactions using alcohols as radical precursors. Because conventional radical-based alkylation methods require the use of stoichiometric oxidants, increased temperatures or peroxides, a mild protocol using simple and abundant alkylating agents would have considerable use in the synthesis of diversely functionalized pharmacophores. Here we describe the development of a dual catalytic alkylation of heteroarenes, using alcohols as mild alkylating reagents. This method represents the first, to our knowledge, broadly applicable use of unactivated alcohols as latent alkylating reagents, achieved via the successful merger of photoredox and hydrogen atom transfer catalysis. The value of this multi-catalytic protocol has been demonstrated through the late-stage functionalization of the medicinal agents, fasudil and milrinone. PMID:26308895

  2. Biochemical analysis of hatchet self-cleaving ribozymes

    PubMed Central

    Li, Sanshu; Lünse, Christina E.; Harris, Kimberly A.; Breaker, Ronald R.

    2015-01-01

    Hatchet RNAs are members of a novel self-cleaving ribozyme class that was recently discovered by using a bioinformatics search strategy. The consensus sequence and secondary structure of this class includes 13 highly conserved and numerous other modestly conserved nucleotides interspersed among bulges linking four base-paired substructures. A representative hatchet ribozyme from a metagenomic source requires divalent ions such as Mg2+ to promote RNA strand scission with a maximum rate constant of ∼4 min−1. As with all other small self-cleaving ribozymes discovered to date, hatchet ribozymes employ a general mechanism for catalysis involving the nucleophilic attack of a ribose 2′-oxygen atom on an adjacent phosphorus center. Kinetic characteristics of the reaction demonstrate that members of this ribozyme class have an essential requirement for divalent metal ions and that they might have a complex active site that employs multiple catalytic strategies to accelerate RNA cleavage by internal phosphoester transfer. PMID:26385510

  3. Cleaved thin-film probes for scanning tunneling microscopy.

    PubMed

    Siahaan, T; Kurnosikov, O; Barcones, B; Swagten, H J M; Koopmans, B

    2016-01-22

    We introduce an alternative type of probe for scanning tunneling microscopy (STM). Instead of using a needle-like tip made from a piece of metallic wire, a sharp-edged cleaved insulating substrate, which is initially covered by a thin conductive film, is used. The sharp tip is formed at the intersection of the two cleaved sides. Using this approach a variety of materials for STM probes can be used, and functionalization of STM probes is possible. The working principle of different probes made of metallic (Pt, Co, and CoB), indium-tin oxide, as well as Cu/Pt and Co/Pt multilayer films are demonstrated by STM imaging of clean Cu(001) and Cu(111) surfaces as well as the epitaxial Co clusters on Cu(111). PMID:26636763

  4. Crystal structure of a soluble cleaved HIV-1 envelope trimer.

    PubMed

    Julien, Jean-Philippe; Cupo, Albert; Sok, Devin; Stanfield, Robyn L; Lyumkis, Dmitry; Deller, Marc C; Klasse, Per-Johan; Burton, Dennis R; Sanders, Rogier W; Moore, John P; Ward, Andrew B; Wilson, Ian A

    2013-12-20

    HIV-1 entry into CD4(+) target cells is mediated by cleaved envelope glycoprotein (Env) trimers that have been challenging to characterize structurally. Here, we describe the crystal structure at 4.7 angstroms of a soluble, cleaved Env trimer that is stabilized and antigenically near-native (termed the BG505 SOSIP.664 gp140 trimer) in complex with a potent broadly neutralizing antibody, PGT122. The structure shows a prefusion state of gp41, the interaction between the component gp120 and gp41 subunits, and how a close association between the gp120 V1/V2/V3 loops stabilizes the trimer apex around the threefold axis. The complete epitope of PGT122 on the trimer involves gp120 V1, V3, and several surrounding glycans. This trimer structure advances our understanding of how Env functions and is presented to the immune system, and provides a blueprint for structure-based vaccine design. PMID:24179159

  5. T. thermophila group I introns that cleave amide bonds

    NASA Technical Reports Server (NTRS)

    Joyce, Gerald F. (Inventor)

    1997-01-01

    The present invention relates to nucleic acid enzymes or enzymatic RNA molecules that are capable of cleaving a variety of bonds, including phosphodiester bonds and amide bonds, in a variety of substrates. Thus, the disclosed enzymatic RNA molecules are capable of functioning as nucleases and/or peptidases. The present invention also relates to compositions containing the disclosed enzymatic RNA molecule and to methods of making, selecting, and using such enzymes and compositions.

  6. Dengue Virus Impairs Mitochondrial Fusion by Cleaving Mitofusins

    PubMed Central

    Yu, Chia-Yi; Liang, Jian-Jong; Li, Jin-Kun; Lee, Yi-Ling; Chang, Bi-Lan; Su, Chan-I; Huang, Wei-Jheng; Lai, Michael M. C.; Lin, Yi-Ling

    2015-01-01

    Mitochondria are highly dynamic subcellular organelles participating in many signaling pathways such as antiviral innate immunity and cell death cascades. Here we found that mitochondrial fusion was impaired in dengue virus (DENV) infected cells. Two mitofusins (MFN1 and MFN2), which mediate mitochondrial fusion and participate in the proper function of mitochondria, were cleaved by DENV protease NS2B3. By knockdown and overexpression approaches, these two MFNs showed diverse functions in DENV infection. MFN1 was required for efficient antiviral retinoic acid-inducible gene I–like receptor signaling to suppress DENV replication, while MFN2 participated in maintaining mitochondrial membrane potential (MMP) to attenuate DENV-induced cell death. Cleaving MFN1 and MFN2 by DENV protease suppressed mitochondrial fusion and deteriorated DENV-induced cytopathic effects through subverting interferon production and facilitating MMP disruption. Thus, MFNs participate in host defense against DENV infection by promoting the antiviral response and cell survival, and DENV regulates mitochondrial morphology by cleaving MFNs to manipulate the outcome of infection. PMID:26717518

  7. Enantioselective Intermolecular C-H Functionalization of Allylic and Benzylic sp(3) C-H Bonds Using N-Sulfonyl-1,2,3-triazoles.

    PubMed

    Kubiak, Robert W; Mighion, Jeffrey D; Wilkerson-Hill, Sidney M; Alford, Joshua S; Yoshidomi, Tetsushi; Davies, Huw M L

    2016-07-01

    The enantioselective intermolecular sp(3) C-H functionalization at the allylic and benzylic positions was achieved using rhodium-catalyzed reactions with 4-phenyl-N-(methanesulfonyl)-1,2,3-triazole. The optimum dirhodium tetracarboxylate catalyst for these reactions was Rh2(S-NTTL)4. The rhodium-bound α-imino carbene intermediates preferentially reacted with tertiary over primary C-H bonds in good yields and moderate levels of enantioselectivity (66-82% ee). This work demonstrates that N-sulfonyltriazoles can be applied to the effective C-H functionalization at sp(3) C-H bonds of substrates containing additional functionality. PMID:27333162

  8. Biocompatible Silver-containing a-C:H and a-C coatings: AComparative Study

    SciTech Connect

    Endrino, Jose Luis; Allen, Matthew; Escobar Galindo, Ramon; Zhang, Hanshen; Anders, Andre; Albella, Jose Maria

    2007-04-01

    Hydrogenated diamond-like-carbon (a-C:H) and hydrogen-free amorphous carbon (a-C) coatings are known to be biocompatible and have good chemical inertness. For this reason, both of these materials are strong candidates to be used as a matrix that embeds metallic elements with antimicrobial effect. In this comparative study, we have incorporated silver into diamond-like carbon (DLC) coatings by plasma based ion implantation and deposition (PBII&D) using methane (CH4) plasma and simultaneously depositing Ag from a pulsed cathodic arc source. In addition, we have grown amorphous carbon - silver composite coatings using a dual-cathode pulsed filtered cathodic-arc (FCA) source. The silver atomic content of the deposited samples was analyzed using glow discharge optical spectroscopy (GDOES). In both cases, the arc pulse frequency of the silver cathode was adjusted in order to obtain samples with approximately 5 at.% of Ag. Surface hardness of the deposited films was analyzed using the nanoindentation technique. Cell viability for both a-C:H/Ag and a-C:/Ag samples deposited on 24-well tissue culture plates has been evaluated.

  9. C-H Bond Oxidation Catalyzed by an Imine-Based Iron Complex: A Mechanistic Insight.

    PubMed

    Olivo, Giorgio; Nardi, Martina; Vìdal, Diego; Barbieri, Alessia; Lapi, Andrea; Gómez, Laura; Lanzalunga, Osvaldo; Costas, Miquel; Di Stefano, Stefano

    2015-11-01

    A family of imine-based nonheme iron(II) complexes (LX)2Fe(OTf)2 has been prepared, characterized, and employed as C-H oxidation catalysts. Ligands LX (X = 1, 2, 3, and 4) stand for tridentate imine ligands resulting from spontaneous condensation of 2-pycolyl-amine and 4-substituted-2-picolyl aldehydes. Fast and quantitative formation of the complex occurs just upon mixing aldehyde, amine, and Fe(OTf)2 in a 2:2:1 ratio in acetonitrile solution. The solid-state structures of (L1)2Fe(OTf)(ClO4) and (L3)2Fe(OTf)2 are reported, showing a low-spin octahedral iron center, with the ligands arranged in a meridional fashion. (1)H NMR analyses indicate that the solid-state structure and spin state is retained in solution. These analyses also show the presence of an amine-imine tautomeric equilibrium. (LX)2Fe(OTf)2 efficiently catalyze the oxidation of alkyl C-H bonds employing H2O2 as a terminal oxidant. Manipulation of the electronic properties of the imine ligand has only a minor impact on efficiency and selectivity of the oxidative process. A mechanistic study is presented, providing evidence that C-H oxidations are metal-based. Reactions occur with stereoretention at the hydroxylated carbon and selectively at tertiary over secondary C-H bonds. Isotopic labeling analyses show that H2O2 is the dominant origin of the oxygen atoms inserted in the oxygenated product. Experimental evidence is provided that reactions involve initial oxidation of the complexes to the ferric state, and it is proposed that a ligand arm dissociates to enable hydrogen peroxide binding and activation. Selectivity patterns and isotopic labeling studies strongly suggest that activation of hydrogen peroxide occurs by heterolytic O-O cleavage, without the assistance of a cis-binding water or alkyl carboxylic acid. The sum of these observations provides sound evidence that controlled activation of H2O2 at (LX)2Fe(OTf)2 differs from that occurring in biomimetic iron catalysts described to date. PMID

  10. Cell-cell interactions determine the dorsoventral axis in embryos of an equally cleaving opisthobranch mollusc.

    PubMed

    Boring, L

    1989-11-01

    Dorsoventral polarity in molluscan embryos can arise by two distinct mechanisms, where the mechanism employed is strongly correlated with the cleavage pattern of the early embryo. In species with unequal cleavage, the dorsal lineage, or "D quadrant", is determined in a cell-autonomous manner by the inheritance of cytoplasmic determinants. However, in gastropod molluscs with equal cleavage, cell-cell interactions are required to specify the fate of the dorsal blastomere. During the fifth cleavage interval in equally cleaving embryos, one of the vegetal macromeres makes exclusive contacts with the animal micromeres, and this macromere will give rise to the mesodermal precursor cell at the next division, thereby identifying the dorsal quadrant. This study examines D-quadrant determination in an equally cleaving species from a group of previously uninvestigated gastropods, the subclass Opisthobranchia. Blastomere ablation experiments were performed on embryos of Haminoea callidegenita to (i) determine the developmental potential of macromeres before and after fifth cleavage, and (ii) examine the role of micromere-macromere interactions in the establishment of bilateral symmetry. The results suggest that the macromeres are developmentally equivalent prior to fifth cleavage, but become nonequivalent soon afterward. The dorsoventral axis corresponds to the displacement of the micromeres over one macromere early in the fifth cleavage interval. This unusual cellular topology is hypothesized to result from constraints imposed on micromere-macromere interactions in an embryo that develops from a large egg and forms a stereoblastula (no cleavage cavity). Ablation of the entire first quarter of micromeres results in embryos which remain radially symmetrical in the vegetal hemisphere, indicating that micromere-macromere interactions are required for the elaboration of bilateral symmetry properties. Therefore, inductive interactions between cells may represent a general strategy

  11. Molecular dynamics simulation of liquid methanol. II. Unified assignment of infrared, raman, and sum frequency generation vibrational spectra in methyl C-H stretching region

    NASA Astrophysics Data System (ADS)

    Ishiyama, Tatsuya; Sokolov, Vladimir V.; Morita, Akihiro

    2011-01-01

    Vibrational spectra of methyl C-H stretching region are notoriously complicated, and thus a theoretical method of systematic assignment is strongly called for in condensed phase. Here we develop a unified analysis method of the vibrational spectra, such as infrared (IR), polarized and depolarized Raman, and ssp polarized sum frequency generation (SFG), by flexible and polarizable molecular dynamics simulation. The molecular model for methanol has been developed by charge response kernel model to allow for analyzing the methyl C-H stretching vibrations. The complicated spectral structure by the Fermi resonance has been unraveled by empirically shifting potential parameters, which provides clear information on the coupling mechanism. The analysis confirmed that for the IR, polarized Raman, and SFG spectra, two-band structure at about 2830 and 2950 cm^{-1} results from the Fermi resonance splitting of the methyl C-H symmetric stretching and bending overtones. In the IR spectrum, the latter, higher-frequency band is overlapped with prominent asymmetric C-H stretching bands. In the depolarized Raman spectrum, the high frequency band at about 2980 cm^{-1} is assigned to the asymmetric C-H stretching mode. In the SFG spectrum, the two bands of the splitted symmetric C-H stretching mode have negative amplitudes of imaginary nonlinear susceptibility χ ^{(2)}, while the higher-frequency band is partly cancelled by positive imaginary components of asymmetric C-H stretching modes.

  12. Molecular dynamics simulation of liquid methanol. II. Unified assignment of infrared, Raman, and sum frequency generation vibrational spectra in methyl C-H stretching region.

    PubMed

    Ishiyama, Tatsuya; Sokolov, Vladimir V; Morita, Akihiro

    2011-01-14

    Vibrational spectra of methyl C-H stretching region are notoriously complicated, and thus a theoretical method of systematic assignment is strongly called for in condensed phase. Here we develop a unified analysis method of the vibrational spectra, such as infrared (IR), polarized and depolarized Raman, and ssp polarized sum frequency generation (SFG), by flexible and polarizable molecular dynamics simulation. The molecular model for methanol has been developed by charge response kernel model to allow for analyzing the methyl C-H stretching vibrations. The complicated spectral structure by the Fermi resonance has been unraveled by empirically shifting potential parameters, which provides clear information on the coupling mechanism. The analysis confirmed that for the IR, polarized Raman, and SFG spectra, two-band structure at about 2830 and 2950 cm(-1) results from the Fermi resonance splitting of the methyl C-H symmetric stretching and bending overtones. In the IR spectrum, the latter, higher-frequency band is overlapped with prominent asymmetric C-H stretching bands. In the depolarized Raman spectrum, the high frequency band at about 2980 cm(-1) is assigned to the asymmetric C-H stretching mode. In the SFG spectrum, the two bands of the splitted symmetric C-H stretching mode have negative amplitudes of imaginary nonlinear susceptibility χ(2), while the higher-frequency band is partly cancelled by positive imaginary components of asymmetric C-H stretching modes. PMID:21241123

  13. Comparative study of properties between a-GeC:H and a-SiC:H films prepared by radio-frequency reactive sputtering in methane

    NASA Astrophysics Data System (ADS)

    Saito, N.; Yamaguchi, T.; Nakaaki, I.

    1995-09-01

    Hydrogenated amorphous germanium-carbon (a-GeC:H) and silicon-carbon (a-SiC:H) films were deposited by reactive magnetron sputtering of Ge and Si targets in a methane argon gas mixture. The effect of rf power on the structural, optical, and electrical properties of the films was investigated. The carbon content in a-SiC:H films is larger than in a-GeC:H for the same deposition condition, and it decreases with increasing rf power. The intensity of the carbon-related bonds, the optical band gap, and the activation energy of dc conductivity of both films decreases with decreasing carbon content. The temperature dependence of dc conductivity of a-SiC:H exhibits activated-type conduction, whereas hopping conduction is predominant in a-GeC:H. Hydrogen concentration and H bonding ratio are examined, indicating that the termination of the dangling bond by hydrogen is more effective in a a-SiC:H films than a-GeC:H films.

  14. Copper-mediated C-H(sp²)/C-H(sp³) coupling of benzoic acid derivatives with ethyl cyanoacetate: an expedient route to an isoquinolinone scaffold.

    PubMed

    Zhu, Wei; Zhang, Dengyou; Yang, Nan; Liu, Hong

    2014-09-21

    A facile, copper-mediated, direct C-H(sp(2))/C-H(sp(3)) bond coupling of benzoic acid derivatives with ethyl cyanoacetate by the deployment of an 8-aminoquinoline moiety as a bidentate directing group is disclosed. Such a unique transformation provides a new strategy for the construction of an isoquinolinone scaffold as one of the privileged cores. PMID:25074033

  15. Surface structure of cleaved (001) USb2 single crystal surface

    SciTech Connect

    Chen, Shao-ping

    2008-01-01

    We have achieved what we believe to be the first atomic resolution scanning tunneling microscopy (STM) images for a uranium compound USb2 taken at room temperature. The a, b, and c lattice parameters in the images confirm that the tetragonal USb2 crystals cleave on the (001) basal plane as expected. Our calculations indicate a symmetric cut between Sb planes to be the most favorable cleavage plane and U atoms to be responsible for most of the density of states measured by STM. Since the spacing between Sb atoms and between U atoms is the same, STM topography alone cannot unambiguously identify the surface atom species.

  16. Optical fiber alignment using cleaved-edge diffracted light

    NASA Astrophysics Data System (ADS)

    Brun, Louis C.; Bergeron, Patrick; Duguay, Michel A.; Ouellette, Francois; Tetu, Michel

    1993-08-01

    We describe a simple technique for aligning optical fibers prior to fusion splicing. The technique relies on the fact that well-cleaved fiber ends have extremely sharp edges. By making the narrow pencil of light emerging from one fiber scan laterally over the entrance face of a second fiber, and by monitoring the light diffracted past its sharp edges, we can locate precisely the geometric center of the output fiber. With this technique, we have aligned fiber cores with a mean lateral offset of 0.81 micrometers , the major part of this offset caused by the eccentricity of the core relative to the cladding's circular perimeter.

  17. Evolving optical second-harmonic anisotropy at the cleaved Bi2Se3 surface

    NASA Astrophysics Data System (ADS)

    An, Yong; Green, Avery; Diebold, Alain

    Bismuth selenide (Bi2Se3) is a centrosymmetric topological insulator with conducting surface states. The surface states have been studied by various electrical and optical techniques in air, but ambience effects and surface aging have not been adequately addressed. Optical second-harmonic generation (SHG) is a suitable probe for the Bi2Se3 surface because SHG arises from symmetry breaking at the surface and thus should detect surface states preferentially over bulk states. However, a strong time dependence of SHG is often observed, hampering the detection and investigation of the surface states. Here we find a new phenomenon in which the major and minor intensity lobes of a measured rotational-anisotropy SHG pattern from a cleaved Bi2Se3 (111) surface can significantly change with time and eventually switch their amplitudes. This switching provides a means for tracking the progress of surface oxidation inside a quintuple layer of Bi2Se3. We also perform pump-probe SHG experiments, comparatively on freshly cleaved and oxidized Bi2Se3 surfaces, to study charge dynamics at the oxide/Bi2Se3 interface and to detect spin polarization of photoexcited surface states in the Bi2Se3 topological insulator. This work was supported by the SRC NRI Institute for Nanoelectronics Discovery and Exploration (INDEX).

  18. Characterization of two alkyl hydroperoxide reductase C homologs alkyl hydroperoxide reductase C_H1 and alkyl hydroperoxide reductase C_H2 in Bacillus subtilis

    PubMed Central

    Cha, Mee-Kyung; Bae, Yoo-Jeen; Kim, Kyu-Jeong; Park, Byung-Joon; Kim, Il-Han

    2015-01-01

    AIM: To identify alkyl hydroperoxide reductase subunit C (AhpC) homologs in Bacillus subtilis (B. subtilis) and to characterize their structural and biochemical properties. AhpC is responsible for the detoxification of reactive oxygen species in bacteria. METHODS: Two AhpC homologs (AhpC_H1 and AhpC_H2) were identified by searching the B. subtilis database; these were then cloned and expressed in Escherichia coli. AhpC mutants carrying substitutions of catalytically important Cys residues (C37S, C47S, C166S, C37/47S, C37/166S, C47/166S, and C37/47/166S for AhpC_H1; C52S, C169S, and C52/169S for AhpC_H2) were obtained by site-directed mutagenesis and purified, and their structure-function relationship was analyzed. The B. subtilis ahpC genes were disrupted by the short flanking homology method, and the phenotypes of the resulting AhpC-deficient bacteria were examined. RESULTS: Comparative characterization of AhpC homologs indicates that AhpC_H1 contains an extra C37, which forms a disulfide bond with the peroxidatic C47, and behaves like an atypical 2-Cys AhpC, while AhpC_H2 functions like a typical 2-Cys AhpC. Tryptic digestion analysis demonstrated the presence of intramolecular Cys37-Cys47 linkage, which could be reduced by thioredoxin, resulting in the association of the dimer into higher-molecular-mass complexes. Peroxidase activity analysis of Cys→Ser mutants indicated that three Cys residues were involved in the catalysis. AhpC_H1 was resistant to inactivation by peroxide substrates, but had lower activity at physiological H2O2 concentrations compared to AhpC_H2, suggesting that in B. subtilis, the enzymes may be physiologically functional at different substrate concentrations. The exposure to organic peroxides induced AhpC_H1 expression, while AhpC_H1-deficient mutants exhibited growth retardation in the stationary phase, suggesting the role of AhpC_H1 as an antioxidant scavenger of lipid hydroperoxides and a stress-response factor in B. subtilis

  19. Transition-Metal-Catalyzed Redox-Neutral and Redox-Green C-H Bond Functionalization.

    PubMed

    Wang, Hongli; Huang, Hanmin

    2016-08-01

    Transition-metal-catalyzed C-H bond functionalization has become one of the most promising strategies to prepare complex molecules from simple precursors. However, the utilization of environmentally unfriendly oxidants in the oxidative C-H bond functionalization reactions reduces their potential applications in organic synthesis. This account describes our recent efforts in the development of a redox-neutral C-H bond functionalization strategy for direct addition of inert C-H bonds to unsaturated double bonds and a redox-green C-H bond functionalization strategy for realization of oxidative C-H functionalization with O2 as the sole oxidant, aiming to circumvent the problems posed by utilizing environmentally unfriendly oxidants. In principle, these redox-neutral and redox-green strategies pave the way for establishing new environmentally benign transition-metal-catalyzed C-H bond functionalization strategies. PMID:27258190

  20. Cleaving yeast and Escherichia coli genomes at a single site

    SciTech Connect

    Koob, M.; Szybalski, W. )

    1990-10-12

    The 15-megabase pair Saccharomyces cerevisiae and the 4.7-megabase pair Escherichia coli genomes were completely cleaved at a single predetermined site by means of the Achilles' heel cleavage (AC) procedure. The symmetric lac operator (lacO{sub s}) was introduced into the circular Escherichia coli genome and into one of the 16 yeast chromosomes. Intact chromosomes from the resulting strains were prepared in agarose microbeads and methylated with Hha I (5{prime}-GCGC) methyltransferase (M{center dot}Hha I) in the presence of lac repressor (LacI). All Hae II sites ({prime}-{sub G}{sup A}GCGC{sub C}{sup T}) with the exception of the one in lacO{sub s}, which was protected by LacI, were modified and thus no longer recognized by Hae II. After inactivation of M{center dot}Hha I and LacI, Hae II was used to completely cleave the chromosomes specifically at the inserted lacO{sub s}. These experiments demonstrate the feasibility of using the AC approach to efficiently extend the specificity of naturally occurring restriction enzymes and create new tools for the mapping and precise molecular dissection of multimegabase genomes.

  1. Biochemical analysis of pistol self-cleaving ribozymes

    PubMed Central

    Harris, Kimberly A.; Lünse, Christina E.; Li, Sanshu; Brewer, Kenneth I.; Breaker, Ronald R.

    2015-01-01

    Pistol RNAs are members of a distinct class of self-cleaving ribozymes that was recently discovered by using a bioinformatics search strategy. Several hundred pistol ribozymes share a consensus sequence including 10 highly conserved nucleotides and many other modestly conserved nucleotides associated with specific secondary structure features, including three base-paired stems and a pseudoknot. A representative pistol ribozyme from the bacterium Lysinibacillus sphaericus was found to promote RNA strand scission with a rate constant of ∼10 min−1 under physiological Mg2+ and pH conditions. The reaction proceeds via the nucleophilic attack of a 2′-oxygen atom on the adjacent phosphorus center, and thus adheres to the same general catalytic mechanism of internal phosphoester transfer as found with all other classes of natural self-cleaving ribozymes discovered to date. Analyses of the kinetic characteristics and the metal ion requirements of the cleavage reaction reveal that members of this ribozyme class likely use several catalytic strategies to promote the rapid cleavage of RNA. PMID:26385507

  2. Biochemical analysis of pistol self-cleaving ribozymes.

    PubMed

    Harris, Kimberly A; Lünse, Christina E; Li, Sanshu; Brewer, Kenneth I; Breaker, Ronald R

    2015-11-01

    Pistol RNAs are members of a distinct class of self-cleaving ribozymes that was recently discovered by using a bioinformatics search strategy. Several hundred pistol ribozymes share a consensus sequence including 10 highly conserved nucleotides and many other modestly conserved nucleotides associated with specific secondary structure features, including three base-paired stems and a pseudoknot. A representative pistol ribozyme from the bacterium Lysinibacillus sphaericus was found to promote RNA strand scission with a rate constant of ∼10 min(-1) under physiological Mg(2+) and pH conditions. The reaction proceeds via the nucleophilic attack of a 2'-oxygen atom on the adjacent phosphorus center, and thus adheres to the same general catalytic mechanism of internal phosphoester transfer as found with all other classes of natural self-cleaving ribozymes discovered to date. Analyses of the kinetic characteristics and the metal ion requirements of the cleavage reaction reveal that members of this ribozyme class likely use several catalytic strategies to promote the rapid cleavage of RNA. PMID:26385507

  3. Crystal structure of cleaved vaspin (serpinA12).

    PubMed

    Pippel, Jan; Kuettner, E Bartholomeus; Ulbricht, David; Daberger, Jan; Schultz, Stephan; Heiker, John T; Sträter, Norbert

    2016-01-01

    The adipokine vaspin (serpinA12) is mainly expressed in white adipose tissue and exhibits various beneficial effects on obesity-related processes. Kallikrein 7 is the only known target protease of vaspin and is inhibited by the classical serpin inhibitory mechanism involving a cleavage of the reactive center loop between P1 (M378) and P1' (E379). Here, we present the X-ray structure of vaspin, cleaved between M378 and E379. We provide a comprehensive analysis of differences between the uncleaved and cleaved forms in the shutter, breach, and hinge regions with relation to common molecular features underlying the serpin inhibitory mode. Furthermore, we point out differences towards other serpins and provide novel data underlining the remarkable stability of vaspin. We speculate that the previously reported FKGx1Wx2x3 motif in the breach region may play a decisive role in determining the reactive center loop configuration in the native vaspin state and might contribute to the high thermostability of vaspin. Thus, this structure may provide a basis for future mutational studies. PMID:26529565

  4. Interplay of Tunneling, Two-State Reactivity, and Bell-Evans-Polanyi Effects in C-H Activation by Nonheme Fe(IV)O Oxidants.

    PubMed

    Mandal, Debasish; Shaik, Sason

    2016-02-24

    The study of C-H bond activation reactions by nonheme Fe(IV)O species with nine hydrocarbons shows that the kinetic isotope effect (KIE) involves strong tunneling and is a signature of the reactive spin states. Theory reproduces the observed spike-like appearance of plots of KIE(exp) against the C-H bond dissociation energy, and its origins are discussed. The experimentally observed Bell-Evans-Polanyi correlations, in the presence of strong tunneling, are reproduced, and the pattern is rationalized. PMID:26824716

  5. Thermal Dehydrogenation of Base-Stabilized B2H5(+) Complexes and Its Role in C-H Borylation.

    PubMed

    Prokofjevs, Aleksandrs

    2015-11-01

    Thermally induced dehydrogenation of the H-bridged cation L2B2H5(+) (L=Lewis base) is proposed to be the key step in the intramolecular C-H borylation of tertiary amine boranes activated with catalytic amounts of strong "hydridophiles". Loss of H2 from L2B2H5(+) generates the highly reactive cation L2B2H3(+), which in its sp(2)-sp(3) diborane(4) form then undergoes either an intramolecular C-H insertion with B-B bond cleavage, or captures BH3 to produce L2B3H6(+). The effect of the counterion stability on the outcome of the reaction is illustrated by formation of LBH2C6F5 complexes through disproportionation of L2B2H5(+) HB(C6F5)3(-) . PMID:26377358

  6. A recombinant RNA bacteriophage system to identify functionally important nucleotides in a self-cleaving ribozyme

    PubMed Central

    2014-01-01

    Background RNA bacteriophages like Qbeta and MS2 are well known for their high mutation rate, short infection cycle and strong selection against foreign inserts. The hammerhead ribozyme (HHRz) is a small self-cleaving RNA molecule whose active residues have previously been identified by mutational analysis of each individual base. Here the functionally important bases of HHRz were determined in a single screening experiment by inserting the HHRz into the genome of MS2. Findings The minimal HHRz of satellite Tobacco ringspot virus was cloned into the genome of RNA bacteriophage MS2. Sequence analysis of the surviving phages revealed that the majority had acquired single base-substitutions that apparently inactivated the HHRz. The positions of these substitutions exactly matched that of the previously determined core residues of the HHRz. Conclusions Natural selection against a ribozyme in the genome of MS2 can be used to quickly identify nucleotides required for self-cleavage. PMID:24946926

  7. An Efficient Lanthanide-Dependent DNAzyme Cleaving 2'-5'-Linked RNA.

    PubMed

    Zhou, Wenhu; Ding, Jinsong; Liu, Juewen

    2016-05-17

    RNA can form two types of linkage. In addition to the predominant 3'-5' linkage, 2'-5'-linked RNA is also important in biology, medicine, and prebiotic studies. Here, in vitro selection was used to isolate a DNAzyme that specifically cleaves 2'-5' RNA by using Ce(3+) as the metal cofactor, but leaves the 3'-5' counterpart intact. This Ce5 DNAzyme requires trivalent light lanthanide ions and shows a rate of 0.16 min(-1) in the presence of 10 μm Ce(3+) ; the activity decreases with heavier lanthanide ions. This is the fastest DNAzyme reported for this reaction, and it might enable applications in chemical biology. As a proof-of-concept, using this DNAzyme, the reactions between phosphorothioate-modified RNA and strongly thiophilic metals (Hg(2+) and Tl(3+) ) were studied as a function of pH. PMID:26957420

  8. The Stabilized Cation Pool Method: Metal- and Oxidant-Free Benzylic C-H/Aromatic C-H Cross-Coupling.

    PubMed

    Hayashi, Ryutaro; Shimizu, Akihiro; Yoshida, Jun-Ichi

    2016-07-13

    Electrochemical oxidation of toluene derivatives in the presence of a sulfilimine gave benzylaminosulfonium ions as stabilized benzyl cation pools, which reacted with subsequently added aromatic nucleophiles to give the corresponding cross-coupling products. The transformation serves as a powerful metal- and chemical-oxidant-free method for benzylic C-H/aromatic C-H cross-coupling. The method has been successfully applied to synthesis of TP27, an inhibitor of PTPase. PMID:27341676

  9. Chemistry and Biology of Self-Cleaving Ribozymes.

    PubMed

    Jimenez, Randi M; Polanco, Julio A; Lupták, Andrej

    2015-11-01

    Self-cleaving ribozymes were discovered 30 years ago, but their biological distribution and catalytic mechanisms are only beginning to be defined. Each ribozyme family is defined by a distinct structure, with unique active sites accelerating the same transesterification reaction across the families. Biochemical studies show that general acid-base catalysis is the most common mechanism of self-cleavage, but metal ions and metabolites can be used as cofactors. Ribozymes have been discovered in highly diverse genomic contexts throughout nature, from viroids to vertebrates. Their biological roles include self-scission during rolling-circle replication of RNA genomes, co-transcriptional processing of retrotransposons, and metabolite-dependent gene expression regulation in bacteria. Other examples, including highly conserved mammalian ribozymes, suggest that many new biological roles are yet to be discovered. PMID:26481500

  10. Ring-Cleaving Dioxygenases with a Cupin Fold

    PubMed Central

    2012-01-01

    Ring-cleaving dioxygenases catalyze key reactions in the aerobic microbial degradation of aromatic compounds. Many pathways converge to catecholic intermediates, which are subject to ortho or meta cleavage by intradiol or extradiol dioxygenases, respectively. However, a number of degradation pathways proceed via noncatecholic hydroxy-substituted aromatic carboxylic acids like gentisate, salicylate, 1-hydroxy-2-naphthoate, or aminohydroxybenzoates. The ring-cleaving dioxygenases active toward these compounds belong to the cupin superfamily, which is characterized by a six-stranded β-barrel fold and conserved amino acid motifs that provide the 3His or 2- or 3His-1Glu ligand environment of a divalent metal ion. Most cupin-type ring cleavage dioxygenases use an FeII center for catalysis, and the proposed mechanism is very similar to that of the canonical (type I) extradiol dioxygenases. The metal ion is presumed to act as an electron conduit for single electron transfer from the metal-bound substrate anion to O2, resulting in activation of both substrates to radical species. The family of cupin-type dioxygenases also involves quercetinase (flavonol 2,4-dioxygenase), which opens up two C-C bonds of the heterocyclic ring of quercetin, a wide-spread plant flavonol. Remarkably, bacterial quercetinases are capable of using different divalent metal ions for catalysis, suggesting that the redox properties of the metal are relatively unimportant for the catalytic reaction. The major role of the active-site metal ion could be to correctly position the substrate and to stabilize transition states and intermediates rather than to mediate electron transfer. The tentative hypothesis that quercetinase catalysis involves direct electron transfer from metal-bound flavonolate to O2 is supported by model chemistry. PMID:22287012

  11. Substrate recognition mechanism of VAMP/synaptobrevin-cleaving clostridial neurotoxins.

    PubMed

    Sikorra, Stefan; Henke, Tina; Galli, Thierry; Binz, Thomas

    2008-07-25

    Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) inhibit neurotransmitter release by proteolyzing a single peptide bond in one of the three soluble N-ethylmaleimide-sensitive factor attachment protein receptors SNAP-25, syntaxin, and vesicle-associated membrane protein (VAMP)/synaptobrevin. TeNT and BoNT/B, D, F, and G of the seven known BoNTs cleave the synaptic vesicle protein VAMP/synaptobrevin. Except for BoNT/B and TeNT, they cleave unique peptide bonds, and prior work suggested that different substrate segments are required for the interaction of each toxin. Although the mode of SNAP-25 cleavage by BoNT/A and E has recently been studied in detail, the mechanism of VAMP/synaptobrevin proteolysis is fragmentary. Here, we report the determination of all substrate residues that are involved in the interaction with BoNT/B, D, and F and TeNT by means of systematic mutagenesis of VAMP/synaptobrevin. For each of the toxins, three or more residues clustered at an N-terminal site remote from the respective scissile bond are identified that affect solely substrate binding. These exosites exhibit different sizes and distances to the scissile peptide bonds for each neurotoxin. Substrate segments C-terminal of the cleavage site (P4-P4') do not play a role in the catalytic process. Mutation of residues in the proximity of the scissile bond exclusively affects the turnover number; however, the importance of individual positions at the cleavage sites varied for each toxin. The data show that, similar to the SNAP-25 proteolyzing BoNT/A and E, VAMP/synaptobrevin-specific clostridial neurotoxins also initiate substrate interaction, employing an exosite located N-terminal of the scissile peptide bond. PMID:18511418

  12. An Iminium Salt Organocatalyst for Selective Aliphatic C-H Hydroxylation.

    PubMed

    Wang, Daoyong; Shuler, William G; Pierce, Conor J; Hilinski, Michael K

    2016-08-01

    The first examples of catalysis of aliphatic C-H hydroxylation by an iminium salt are presented. The method allows the selective organocatalytic hydroxylation of unactivated 3° C-H bonds at room temperature using hydrogen peroxide as the terminal oxidant. Hydroxylation of an unactivated 2° C-H bond is also demonstrated. Furthermore, improved functional group compatibility over other catalytic methods is reported in the form of selectivity for aliphatic C-H hydroxylation over alcohol oxidation. On the basis of initial mechanistic studies, an oxaziridinium species is proposed as the active oxidant. PMID:27391543

  13. Importance of C-H-donor and C-H-anion contact interactions for the crystal packing, the lattice softness and the superconducting transition temperatures of organic conducting salts

    SciTech Connect

    Whangbo, M.-H.; Novoa, J.J.; Jung, D. . Dept. of Chemistry); Williams, J.M.; Kinj, A.M.; Wang, H.H.; Geiser, U.; Beno, M.A.; Carlson, K.D. )

    1990-01-01

    The organic donor molecule BEDT-TTF and its analogs 2--4 have yielded a number of ambient-pressure superconducting salts. What structural and electronic factors govern the magnitudes of their superconducting transition temperature {Tc} has been a topic of intense studies. Examination of the band electronic structures of closely related superconducting salts shows, that the magnitudes of their {Tc}'s are primarily determined by the softness of their crystal lattices. The crystal packing and the lattice softness of organic donor salts are strongly influenced by the donor{hor ellipsis}donor and donor{hor ellipsis}anion contact interactions involving the donor-molecule C-H bonds. In the present work, we briefly review the electronic structures of some representative organic salt superconductors and discuss the softness of their crytsal lattices on the basis of the interaction energies calculated for the C-H{hor ellipsis}donor and C-H{hor ellipsis}anion contact interactions. 34 refs., 14 figs., 8 tabs.

  14. Palladium/copper-catalyzed oxidative C-H alkenylation/N-dealkylative carbonylation of tertiary anilines.

    PubMed

    Shi, Renyi; Lu, Lijun; Zhang, Hua; Chen, Borui; Sha, Yuchen; Liu, Chao; Lei, Aiwen

    2013-09-27

    C-H/C-N activation: The first palladium/copper-catalyzed aerobic oxidative C-H alkenylation/N-dealkylative carbonylation of tertiary anilines has been developed. Various functional groups were tolerated and acrylic ester could also be suitable substrates. This transformation provided efficient and straightforward synthesis of biologically active 3-methyleneindolin-2-one derivatives from cheap and simple substrates. PMID:23946242

  15. Trifluoromethylallylation of Heterocyclic C-H Bonds with Allylic Carbonates under Rhodium Catalysis.

    PubMed

    Choi, Miji; Park, Jihye; Sharma, Satyasheel; Jo, Hyeim; Han, Sangil; Jeon, Mijin; Mishra, Neeraj Kumar; Han, Sang Hoon; Lee, Jong Suk; Kim, In Su

    2016-06-01

    The rhodium(III)-catalyzed γ-trifluoromethylallylation of various heterocyclic C-H bonds with CF3-substituted allylic carbonates is described. These reactions provide direct access to linear CF3-containing allyl frameworks with complete trans-selectivity via C-H bond activation followed by a formal SN-type reaction pathway. PMID:27187625

  16. Synthesis of aza-fused polycyclic quinolines via double C-H bond activation.

    PubMed

    Huang, Ji-Rong; Dong, Lin; Han, Bo; Peng, Cheng; Chen, Ying-Chun

    2012-07-16

    Simple but efficient: Aza-fused polycyclic quinolines were efficiently assembled through rhodium(III)-based direct double C-H activation of N-aryl azoles followed by cyclization with alkynes without heteroatom-assisted chelation. Copper(II) acetate, aside from acting as an oxidant, could also play an important role in the C-H activation process. PMID:22715023

  17. A Highly Selective Vanadium Catalyst for Benzylic C-H Oxidation.

    PubMed

    Xia, Ji-Bao; Cormier, Kevin W; Chen, Chuo

    2012-01-01

    Vanadium complexes have been used extensively to catalyze olefin and alcohol oxidation. However, their application in C-H oxidation has not been well-studied. We report herein that commercially available Cp(2)VCl(2) catalyzes benzylic C-H oxidation selectively and effectively, giving no aromatic oxidation products. PMID:22712051

  18. Ruthenium-Catalyzed C-H Alkynylation of Aromatic Amides with Hypervalent Iodine-Alkyne Reagents.

    PubMed

    Boobalan, Ramadoss; Gandeepan, Parthasarathy; Cheng, Chien-Hong

    2016-07-15

    An efficient C-H activation method for the ortho alkynylation of aromatic N-methoxyamides with hypervalent iodine-alkyne reagent using a ruthenium catalyst is described. The reaction proceeds under mild reaction conditions with broad substrate scope. A possible catalytic cycle involving a ruthenium carboxylate assisted C-H bond cleavage is proposed from the preliminary mechanistic evidence. PMID:27357724

  19. LRE Project Exchange. Ideas from Project P.A.T.C.H.

    ERIC Educational Resources Information Center

    Nessel, Paula A.

    1997-01-01

    Profiles "Civil Law Mini-Trials," an instructional activity developed by P.A.T.C.H. (Participatory Awareness Through Community Help). The Mini-Trials allow students to participate in mock civil cases including preparation, presentation of arguments, debriefing afterwards, and a discussion of the real case verdict. Discusses other P.A.T.C.H.…

  20. The C-H Dissociation Energy of C2H6

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Partridge, Harry; Langhoff, Stephen R. (Technical Monitor)

    1994-01-01

    The C-H bond energy in C2H6 is computed to be 99.76 +/- 0.35 kcal/mol, which is in excellent agreement with the most recent experimental values. The calculation of the C-H bond energy by direct dissociation and by an isodesmic reaction is discussed.

  1. Structure of cleaved (001) USb2 single crystal

    SciTech Connect

    Chen, Shao-ping; Hawley, Marilyn; Bauer, Eric D; Stockum, Phil B; Manoharan, Hari C

    2009-01-01

    We have achieved what we believe to be the first atomic resolution STM images for a uranium compound taken at room temperature. The a, b, and c lattice parameters in the images confirm that the USb{sub 2} crystals cleave on the (001) basal plane as expected. The a and b dimensions were equal, with the atoms arranged in a cubic pattern. Our calculations indicate a symmetric cut between Sb planes to be the most favorable cleavage plane and U atoms to be responsible for most of the DOS measured by STM. Some strange features observed in the STM will be discussed in conjunction with ab initio calculations. The purpose of this work is to demonstrate the power of scanning tunneling microscopy (STM) techniques combined with a theoretical underpinning to determine the surface atomic structure and properties of actinide materials, such as the quasi 2-dimensional uranium dipnictide USb{sub 2} single crystal, thereby contributing to the understanding of their surface structural and electronic properties. The members of this interesting UX{sub 2} (X=P, As, Sb, Bi) series of compounds display dual localized and itinerant 5f electron behavior within the same compound due to the hybridization of the 5f orbitals with the conduction band. With the exception of UO{sub 2}, which has to be studied at elevated temperature to generate enough carriers for STM imaging, STM techniques have not been applied successfully to the characterization of the surface atomic structure of any other single crystal actinide compound, to the best of our knowledge. However, STM has been used to a limited extent for the study of some cerium compounds. STM probes electronic properties at the atomic level and can directly provide information about the local density of filled and empty states (LDOS) states simultaneously. A STM topograph provides the local atomic arrangement and spacing of the atoms on the surface, local defect structures (e.g. steps, vacancies, and kink sites) and the presence of contaminants

  2. Surface-Controlled Mono/Diselective ortho C-H Bond Activation.

    PubMed

    Li, Qing; Yang, Biao; Lin, Haiping; Aghdassi, Nabi; Miao, Kangjian; Zhang, Junjie; Zhang, Haiming; Li, Youyong; Duhm, Steffen; Fan, Jian; Chi, Lifeng

    2016-03-01

    One of the most charming and challenging topics in organic chemistry is the selective C-H bond activation. The difficulty arises not only from the relatively large bond-dissociation enthalpy, but also from the poor reaction selectivity. In this work, Au(111) and Ag(111) surfaces were used to address ortho C-H functionalization and ortho-ortho couplings of phenol derivatives. More importantly, the competition between dehydrogenation and deoxygenation drove the diversity of reaction pathways of phenols on surfaces, that is, diselective ortho C-H bond activation on Au(111) surfaces and monoselective ortho C-H bond activation on Ag(111) surfaces. The mechanism of this unprecedented phenomenon was extensively explored by scanning tunneling microscopy, density function theory, and X-ray photoelectron spectroscopy. Our findings provide new pathways for surface-assisted organic synthesis via the mono/diselective C-H bond activation. PMID:26853936

  3. Integrated catalysis opens new arylation pathways via regiodivergent enzymatic C-H activation.

    PubMed

    Latham, Jonathan; Henry, Jean-Marc; Sharif, Humera H; Menon, Binuraj R K; Shepherd, Sarah A; Greaney, Michael F; Micklefield, Jason

    2016-01-01

    Despite major recent advances in C-H activation, discrimination between two similar, unactivated C-H positions is beyond the scope of current chemocatalytic methods. Here we demonstrate that integration of regioselective halogenase enzymes with Pd-catalysed cross-coupling chemistry, in one-pot reactions, successfully addresses this problem for the indole heterocycle. The resultant 'chemobio-transformation' delivers a range of functionally diverse arylated products that are impossible to access using separate enzymatic or chemocatalytic C-H activation, under mild, aqueous conditions. This use of different biocatalysts to select different C-H positions contrasts with the prevailing substrate-control approach to the area, and presents opportunities for new pathways in C-H activation chemistry. The issues of enzyme and transition metal compatibility are overcome through membrane compartmentalization, with the optimized process requiring no intermediate work-up or purification steps. PMID:27283121

  4. Double C-H functionalization in sequential order: direct synthesis of polycyclic compounds by a palladium-catalyzed C-H alkenylation-arylation cascade.

    PubMed

    Ohno, Hiroaki; Iuchi, Mutsumi; Kojima, Naoto; Yoshimitsu, Takehiko; Fujii, Nobutaka; Tanaka, Tetsuaki

    2012-04-23

    Palladium-catalyzed cascade C-H alkenylation and arylation provides convenient access to polycyclic aromatic compounds. Treatment of 3-bromoaniline derivatives bearing a bromocinnamyl group on the nitrogen atom with a catalytic amount of [Pd(OAc)(2)] and PCy(3)·HBF(4) in the presence of Cs(2)CO(3) in dioxane affords naphthalene-fused indole derivatives in good yields. This double cyclization reaction is also applicable to heterocyclic substrates, giving fused indoles containing a heteroaromatic ring such as dibenzofuran, dibenzothiophene, carbazole, indole, or benzofuran through heterocyclic C-H arylation. When using a 2,6-unsubstituted aniline derivative, the first C-H arylation preferentially proceeds at the more hindered position of the aniline ring. PMID:22422703

  5. Non-directed, carbonate-mediated C-H activation and aerobic C-H oxygenation with Cp*Ir catalysts.

    PubMed

    Kerr, M E; Ahmed, I; Gunay, A; Venditto, N J; Zhu, F; Ison, E A; Emmert, M H

    2016-06-14

    The effect of oxidatively stable L- and X-type additives on the activity of Cp*Ir catalyst precursors in the C-H activation of arenes has been studied. Turnover numbers for C-H activation of up to 65 can thus be achieved, as determined by H/D exchange in MeOH-D4. In particular, carbonate additives are found to enhance the C-H activation reactivity of Cp*Ir(H2O)3(OTf)2 () more significantly than L-type ligands investigated in this study. Based on these studies, Cp*Ir/carbonate systems are developed that catalyze the aerobic Csp(3)-H oxygenation of alkyl arenes, employing air as oxidant. PMID:26979568

  6. Universal binding energy relation for cleaved and structurally relaxed surfaces.

    PubMed

    Srirangarajan, Aarti; Datta, Aditi; Gandi, Appala Naidu; Ramamurty, U; Waghmare, U V

    2014-02-01

    The universal binding energy relation (UBER), derived earlier to describe the cohesion between two rigid atomic planes, does not accurately capture the cohesive properties when the cleaved surfaces are allowed to relax. We suggest a modified functional form of UBER that is analytical and at the same time accurately models the properties of surfaces relaxed during cleavage. We demonstrate the generality as well as the validity of this modified UBER through first-principles density functional theory calculations of cleavage in a number of crystal systems. Our results show that the total energies of all the relaxed surfaces lie on a single (universal) energy surface, that is given by the proposed functional form which contains an additional length-scale associated with structural relaxation. This functional form could be used in modelling the cohesive zones in crack growth simulation studies. We find that the cohesive law (stress-displacement relation) differs significantly in the case where cracked surfaces are allowed to relax, with lower peak stresses occurring at higher displacements. PMID:24356124

  7. Far-field radiation from a cleaved cylindrical dielectric waveguide

    SciTech Connect

    Cerjan, C.

    1996-07-09

    Angular spread in the far-field radiation pattern of a cleaved dielectric waveguide is determined from the modal structure at the surface of the waveguide using the Smythe vector integral formulation. Essential features: First, a mode exists in the fiber that has no wavelength cutoff--the so-called HE{sub 11} mode. This mode arises when non-azimuthal angular dependence of the incoming radiation is present. Second, the energy flow from this hybrid mode fills the fiber face and is not annularly shaped as opposed to the symmetric TE and TM modes. Third, the HE{sub 11} mode is not polarization dependent in contrast to the TE and TM modes. Fourth, for small differences in the refractive indices between the core and cladding regions, only the HE{sub 11} mode will be supported until the next modes appear around 3.33{lambda}. At this point, three new modes can propagate and the model structure of the radiation becomes more complicated. Fifth, the far-field radiation pattern will have negligibly small angular dependence in the phases of the vector fields when only the lowest mode is present; the amplitude has an overall angular dependent form factor. Furthermore, when other modes are present (above 3.33{lambda}), the phase of the vector fields will acquire an angular dependence.

  8. Atomically precise, coupled quantum dots fabricated by cleaved edge overgrowth

    NASA Astrophysics Data System (ADS)

    Wegscheider, W.; Schedelbeck, G.; Bichler, M.; Abstreiter, G.

    Recent progress in the fabrication of quantum dots by molecular beam epitaxy along three directions in space is reviewed. The optical properties of different sample structures consisting of individual quantum dots, pairs of coupled dots as well as of linear arrays of dots are studied by microscopic photoluminescence spectroscopy. The high degree of control over shape, composition and position of the 7×7×7 nm3 size GaAs quantum dots, which form at the intesection of three orthogonal quantum wells, allows a detailed investigation of the influence of coupling between almost identical zero-dimensional objects. In contrast to the inhomogeneously broadened quantum well and quantum wire signals originating from the complex twofold cleaved edge overgrowth structure, the photoluminescence spetrum of an individual quantum dot exhibits a single sharp line (full width at half maximum <70μeV) almost free of background signal. Microscopic photoluminescence excitation spectroscopy directly reveals the discreteness of the energy levels of the zero-dimensional structures and justifies the denomination "artificial atoms" for the quantum dots. It is further demonstrated that an "artifical molecule", characterized by the existence of bonding and antibonding states can be assembled from two of such "artificial atoms". The coupling strength between the "artificial atoms" is adjusted by the "interatomic" distance and is reflected in the energetic separation of the bonding and antibonding levels and the linewidths of the corresponding interband transitions.

  9. Synthesis, characterization and DNA cleaving studies of new organocobaloxime derivatives.

    PubMed

    Erdem-Tuncmen, Mukadder; Karipcin, Fatma; Ozmen, Ismail

    2013-01-01

    Dioxime ligand (H2L) was synthesized by condensation reaction between 4-biphenylchloroglyoxime and 4-chloroaniline. The metal complexes of the types, [Co(HL)2(i-Pr)Py], [CoL2(i-Pr)PyB2F4] and [CoL2(i-Pr)Py(Cu(phen))2](ClO4)2 [H2L = 4-(4-chlorophenylamino)biphenylglyoxime; phen = 1,10-phenanthroline; i-Pr = isopropyl; Py = pyridine] were synthesized and characterized by elemental analysis, FT-IR, 1H NMR and magnetic susceptibility, conductivity measurements. The results of elemental analyses, IR and NMR confirmed the stoichiometry of the complexes and the formation of ligand frameworks around the metal ions. The magnetic moment measurements of the complexes indicated that the complexes are diamagnetic (low-spin d6 octahedral) except trinuclear complex. Furthermore the interaction between the dioxime ligand and its complexes with DNA has also been investigated by agarose gel electrophoresis. The trinuclear Cu2Co complex with H2O2 as a cooxidant exhibited the strongest DNA cleaving activity. PMID:23841342

  10. Adsorption of alcohols and fatty acids onto hydrogenated (a-C:H) DLC coatings

    NASA Astrophysics Data System (ADS)

    Simič, R.; Kalin, M.; Kovač, J.; Jakša, G.

    2016-02-01

    Information about the interactions between lubricants and DLC coatings is scarce, despite there having been many studies over the years. In this investigation we used ToF-SIMS, XPS and contact-angle analyses to examine the adsorption ability and mechanisms with respect to two oiliness additives, i.e., hexadecanol and hexadecanoic acid, on an a-C:H coating. In addition, we analyzed the resistance of the adsorbed films to external influences like solvent cleaning. The results show that both molecules adsorb onto surface oxides and hydroxides present on the initial DLC surface and shield these structures with their hydrocarbon tails. This makes the surfaces less polar, which is manifested in a smaller polar component of the surface energy. We also showed that ultrasonic cleaning in heptane has no significant effect on the quantity of adsorbed molecules or on their chemical state. This not only shows the relatively strong adsorption of these molecules, but also provides useful information for future experimental work. Of the two examined molecules, the acid showed a greater adsorption ability than the alcohol, which explains some of the previously reported better tribological properties in the case of the acid with respect to the alcohol.

  11. A potential role of a substrate as a base for the deprotonation pathway in Rh-catalysed C-H amination of heteroarenes: DFT insights.

    PubMed

    Ajitha, Manjaly J; Huang, Kuo-Wei; Kwak, Jaesung; Kim, Hyun Jin; Chang, Sukbok; Jung, Yousung

    2016-05-10

    The possibility of direct introduction of a new functionality through C-H bond activation is an attractive strategy in covalent synthesis. Here, we investigated the mechanism of Rh-catalysed C-H amination of the heteroaryl substrate (2-phenylpyridine) using phenyl azide as a nitrogen source by density functional theory (DFT). For the deprotocyclometallation and protodecyclometallation processes of the title reaction, we propose a stepwise base-assisted mechanism (pathway I) instead of the previously reported concerted mechanism (pathway II). In the new mechanism proposed here, 2-phenylpyridine acts as a base in the initial deprotonation step (C-H bond cleavage) and transports the proton towards the final protonation step. In fact, the N-H bond of the strong conjugate acid (formed during the initial C-H bond cleavage) considered in pathway I (via) is more acidic than the C-H bond of the neutral substrate considered in pathway II (via). The higher activation barrier of mainly originates from the ring strain of the four-membered cyclic transition state. The vital role of the base, as disclosed here, can potentially have broader mechanistic implications for the development of reaction conditions of transition metal-catalysed reactions. PMID:27071025

  12. Resistance to anticancer drugs in NIH3T3 cells transfected with c-myc and/or c-H-ras genes.

    PubMed Central

    Niimi, S.; Nakagawa, K.; Yokota, J.; Tsunokawa, Y.; Nishio, K.; Terashima, Y.; Shibuya, M.; Terada, M.; Saijo, N.

    1991-01-01

    NIH3T3 cells transfected with c-H-ras and/or c-myc genes were examined for differences in drug sensitivity. The five transfectants used were N8, NIH3T3-nm-1, pT22-3-nm-2, pP1-4 and pT22-3. They were transfected with pKOneo alone, pKOneo and c-myc, pKOneo and c-myc plus activated c-H-ras, normal c-H-ras and activated c-H-ras genes, respectively. The IC50s of cisplatin, 4-hydroperoxycyclophosphamide, adriamycin, melphalan, and CPT-11 were significantly higher for NIH3T3-nm-1 abd pT22-3-nm-2 than for the parental NIH3T3 and N8 cells. Transfection with normal and activated C-H-ras oncogenes only led to increases in the IC50s of alkylating agents. There was no significant difference between the IC50s of N8 and those of NIH3T3 parental cells to any of these anticancer agents. These results strongly suggest that the expression of the c-myc gene plays a role in the acquisition of drug resistance. The c-myc gene may therefore provide us with an important clue in determining the mechanism of drug resistance. Images Figure 1 Figure 2 Figure 3 PMID:1997100

  13. Ni nanoparticle catalyzed growth of MWCNTs on Cu NPs @ a-C:H substrate

    NASA Astrophysics Data System (ADS)

    Ghodselahi, T.; Solaymani, S.; Akbarzadeh Pasha, M.; Vesaghi, M. A.

    2012-11-01

    NiCu NPs @ a-C:H thin films with different Cu content were prepared by co-deposition by RF-sputtering and RF-plasma enhanced chemical vapor deposition (RF-PECVD) from acetylene gas and Cu and Ni targets. The prepared samples were used as catalysts for growing multi-wall carbon nanotubes (MWCNTs) from liquid petroleum gas (LPG) at 825 °C by thermal chemical vapor deposition (TCVD). By addition of Cu NPs @ a-C:H thin layer as substrate for Ni NPs catalyst, the density of the grown CNTs is greatly enhanced in comparison to bare Si substrate. Furthermore the average diameter of the grown CNTs decreases by decreasing of Cu content of Cu NPs @ a-C:H thin layer. However Cu NPs @ a-C:H by itself has no catalytic property in MWCNTs growth. Morphology and electrical and optical properties of Cu NPs @ a-C:H thin layer is affected by Cu content and each of them is effective parameter on growth of MWCNTs based on Ni NPs catalyst. Moreover, adding of a low amount of Ni NPs doesn't vary optical, electrical and morphology properties of Cu NPs @ a-C:H thin layer but it has a profound effect on its catalytic activity. Finally the density and diameter of MWCNTs can be optimized by selection of the Cu NPs @ a-C:H thin layer as substrate of Ni NPs.

  14. Effective DNA binding and cleaving tendencies of malonic acid coupled transition metal complexes

    NASA Astrophysics Data System (ADS)

    Pravin, Narayanaperumal; Utthra, Ponnukalai Ponya; Kumaravel, Ganesan; Raman, Natarajan

    2016-11-01

    Eight transition metal complexes were designed to achieve maximum biological efficacy. They were characterized by elemental analysis and various other spectroscopic techniques. The monomeric complexes were found to espouse octahedral geometry and non-electrolytic nature. The DNA interaction propensity of the complexes with calf thymus DNA (CT-DNA), studied at physiological pH by spectrophotometric, spectrofluorometric, cyclic voltammetry, and viscometric techniques revealed intercalation as the possible binding mode. Fascinatingly, the complexes were found to exhibit greater binding strength than that of the free ligands. A strong hypochromism and a slight red shift were exhibited by complex 5 among the other complexes. The intrinsic binding constant values of all the complexes compared to cisplatin reveal that they are excellent metallonucleases than that of cisplatin. The complexes were also shown to reveal displacement of the ethidium bromide, a strong intercalator using fluorescence titrations. Gel electrophoresis was used to divulge the competence of the complexes in cleaving the supercoiled pBR322 plasmid DNA. From the results, it is concluded that the complexes, especially 5, are excellent chemical nucleases in the presence of H2O2. Furthermore, the in vitro antimicrobial screening of the complexes exposes that these complexes are excellent antimicrobial agents. Overall the effect of coligands is evident from the results of all the investigations.

  15. A General Strategy for the Nickel-Catalyzed C-H Alkylation of Anilines.

    PubMed

    Ruan, Zhixiong; Lackner, Sebastian; Ackermann, Lutz

    2016-02-24

    The C-H alkylation of aniline derivatives with both primary and secondary alkyl halides was achieved with a versatile nickel catalyst of a vicinal diamine ligand. Step-economic access to functionalized 2-pyrimidyl anilines, key structural motifs in anticancer drugs, is thus provided. The C-H functionalization proceeded through facile C-H activation and SET-type C-X bond cleavage with the assistance of a monodentate directing group, which could be removed in a traceless fashion. PMID:26822673

  16. Rhodium-catalyzed C-C coupling reactions via double C-H activation.

    PubMed

    Li, Shuai-Shuai; Qin, Liu; Dong, Lin

    2016-05-18

    Various rhodium-catalyzed double C-H activations are reviewed. These powerful strategies have been developed to construct C-C bonds, which might be widely embedded in complex aza-fused heterocycles, polycyclic skeletons and heterocyclic scaffolds. In particular, rhodium(iii) catalysis shows good selectivity and reactivity to functionalize the C-H bond, generating reactive organometallic intermediates in most of the coupling reactions. Generally, intermolecular, intramolecular and multi-component coupling reactions via double C-H activations with or without heteroatom-assisted chelation are discussed in this review. PMID:27099126

  17. Synthesis of Dihydropyridines and Pyridines from Imines and Alkynes via C-H Activation

    SciTech Connect

    Ellman, Jonathan A.; Colby, Denise; Bergman, Robert

    2007-11-20

    A convenient one-pot C-H alkenylation/electrocyclization/aromatization sequence has been developed for the synthesis of highly substituted pyridine derivatives from alkynes and {alpha},{beta}-unsaturated N-benzyl aldimines and ketimines that proceeds through dihydropyridine intermediates. A new class of ligands for C-H activation was developed, providing broader scope for the alkenylation step than could be achieved with previously reported ligands. Substantial information was obtained about the mechanism of the reaction. This included the isolation of a C-H activated complex and its structure determination by X-ray analysis; in addition, kinetic simulations using the Copasi software were employed to determine rate constants for this transformation, implicating facile C-H oxidative addition and slow reductive elimination steps.

  18. Manganese-catalyzed late-stage aliphatic C-H azidation.

    PubMed

    Huang, Xiongyi; Bergsten, Tova M; Groves, John T

    2015-04-29

    We report a manganese-catalyzed aliphatic C-H azidation reaction that can efficiently convert secondary, tertiary, and benzylic C-H bonds to the corresponding azides. The method utilizes aqueous sodium azide solution as the azide source and can be performed under air. Besides its operational simplicity, the potential of this method for late-stage functionalization has been demonstrated by successful azidation of various bioactive molecules with yields up to 74%, including the important drugs pregabalin, memantine, and the antimalarial artemisinin. Azidation of celestolide with a chiral manganese salen catalyst afforded the azide product in 70% ee, representing a Mn-catalyzed enantioselective aliphatic C-H azidation reaction. Considering the versatile roles of organic azides in modern chemistry and the ubiquity of aliphatic C-H bonds in organic molecules, we envision that this Mn-azidation method will find wide application in organic synthesis, drug discovery, and chemical biology. PMID:25871027

  19. Charge-transfer-directed radical substitution enables para-selective C-H functionalization.

    PubMed

    Boursalian, Gregory B; Ham, Won Seok; Mazzotti, Anthony R; Ritter, Tobias

    2016-08-01

    Efficient C-H functionalization requires selectivity for specific C-H bonds. Progress has been made for directed aromatic substitution reactions to achieve ortho and meta selectivity, but a general strategy for para-selective C-H functionalization has remained elusive. Herein we introduce a previously unappreciated concept that enables nearly complete para selectivity. We propose that radicals with high electron affinity elicit arene-to-radical charge transfer in the transition state of radical addition, which is the factor primarily responsible for high positional selectivity. We demonstrate with a simple theoretical tool that the selectivity is predictable and show the utility of the concept through a direct synthesis of aryl piperazines. Our results contradict the notion, widely held by organic chemists, that radical aromatic substitution reactions are inherently unselective. The concept of radical substitution directed by charge transfer could serve as the basis for the development of new, highly selective C-H functionalization reactions. PMID:27442288

  20. Cp*Co(III)-Catalyzed C-H Alkenylation/Annulation to Afford Spiro Indenyl Benzosultam.

    PubMed

    Liu, Hui; Li, Jie; Xiong, Miao; Jiang, Jijun; Wang, Jun

    2016-07-15

    Cp*Co(III)-catalyzed tandem inert C-H alkenylation/annulation of N-sulfonyl ketimines with alkynes is revealed. A series of spiro indenyl benzosultams were facilely prepared in good yields under mild reaction conditions. PMID:27341208

  1. Pd-Catalyzed C-H Bond Functionalization on the Indole and Pyrrole Nucleus

    NASA Astrophysics Data System (ADS)

    Beck, Elizabeth M.; Gaunt, Matthew J.

    This review details recent developments in the Pd-catalyzed C-H bond arylation and alkenylation of indoles and pyrroles, aromatic heterocycles that are frequently displayed in natural products and medicinal agents.

  2. Quantification of primary versus secondary C-H bond cleavage in alkane activation: Propane on Pt

    SciTech Connect

    Weinberg, W.H.; Sun, Yongkui )

    1991-08-02

    The trapping-mediated dissociative chemisorption of three isotopes of propane (C{sub 3}H{sub 8}, CH{sub 3}, CD{sub 2}CH{sub 3}, and C{sub 3}D{sub 8}) has been investigated on the Pt(110)-(1 {times} 2) surface, and both the apparent activation energies and the preexponential factors of the surface reaction rate coefficients have been measured. In addition, the probabilities of primary and secondary C-H bond cleavage for alkane activation on a surface were evaluated. The activation energy for primary C-H bond cleavage was 425 calories per mole greater than that of secondary C-H bond cleavage, and the two true activation energies that embody the single measured activation energy were determined for each of the three isotopes. Secondary C-H bond cleavage is also preferred on entropic grounds, and the magnitude of the effect was quantified.

  3. Synthesis of indoles and tryptophan derivatives via photoinduced nitrene C-H insertion.

    PubMed

    Junk, Lukas; Kazmaier, Uli

    2016-03-14

    Functionalized indoles and tryptophans can be obtained from stannylated alkenes and o-iodoanilines via Stille coupling. Subsequent azidation and photochemical nitrene generation results in the formation of the heterocyclic ring systems via C-H insertion. PMID:26869211

  4. C-H Coupling Reactions Directed by Sulfoxides: Teaching an Old Functional Group New Tricks.

    PubMed

    Pulis, Alexander P; Procter, David J

    2016-08-16

    Sulfoxides are classical functional groups for directing the stoichiometric metalation and functionalization of C-H bonds. In recent times, sulfoxides have been given a new lease on life owing to the development of modern synthetic methods that have arisen because of their unique reactivity. They have recently been used in catalytic C-H activation proceeding via coordination of an internal sulfoxide to a metal or through the action of an external sulfoxide ligand. Furthermore, sulfoxides are able to capture nucleophiles and electrophiles to give sulfonium salts, which subsequently enable the formation of C-C bonds at the expense of C-H bonds. This Review summarizes a renaissance period in the application of sulfoxides arising from their versatility in directing C-H functionalization. PMID:27409984

  5. Iridium-Catalyzed Branch-Selective Hydroarylation of Vinyl Ethers via C-H Bond Activation.

    PubMed

    Ebe, Yusuke; Nishimura, Takahiro

    2015-05-13

    Iridium-catalyzed hydroarylation of vinyl ethers via a directed C-H bond activation of aromatic compounds gave high yields of the corresponding addition products with high branch selectivity. PMID:25928127

  6. Trends in applying C-H oxidation to the total synthesis of natural products.

    PubMed

    Qiu, Yuanyou; Gao, Shuanhu

    2016-04-30

    Covering: 2006 to 2015C-H functionalization remains one of the frontier challenges in organic chemistry and drives quite an active area of research. It has recently been applied in various novel strategies for the synthesis of natural products. It can dramatically increase synthetic efficiency when incorporated into retrosynthetic analyses of complex natural products, making it an essential part of current trends in organic synthesis. In this Review, we focus on selected case studies of recent applications of C-H oxidation methodologies in which the C-H bond has been exploited effectively to construct C-O and C-N bonds in natural product syntheses. Examples of syntheses representing different types of C-H oxidation are discussed to illustrate the potential of this approach and inspire future applications. PMID:26847167

  7. A cooperative Pd-Cu system for direct C-H bond arylation.

    PubMed

    Lesieur, Mathieu; Lazreg, Faïma; Cazin, Catherine S J

    2014-08-18

    A novel and efficient method for C-H arylation using well-defined Pd- and Cu-NHC systems has been developed. This process promotes the challenging construction of C-C bonds from arenes or heteroarenes using aryl bromides and chlorides. Mechanistic studies show that [Cu(OH)(NHC)] plays a key role in the C-H activation and is involved in the transmetallation with the Pd-NHC co-catalyst. PMID:24976025

  8. Rhodium(II)-Catalyzed C-H Functionalization of Electron-Deficient Methyl Groups.

    PubMed

    Fu, Liangbing; Guptill, David M; Davies, Huw M L

    2016-05-11

    Enantioselective C-H functionalization of relatively electron-deficient methyl sites was achieved with the combination of 2,2,2-trichloroethyl aryldiazoacetates and tetrakis(triarylcyclopropanecarboxylate) dirhodium catalysts. The substrate scope of the transformation was relatively broad, and C-H functionalization products were furnished with excellent levels of enantioselectivity. As a strategic reaction, crotonate derivatives give 1,6-dicarbonyl compounds, which are useful for further diversification. PMID:27064173

  9. Copper-Catalyzed Oxidative C-H Amination of Tetrahydrofuran with Indole/Carbazole Derivatives.

    PubMed

    Yang, Qingjing; Choy, Pui Ying; Fu, Wai Chung; Fan, Baomin; Kwong, Fuk Yee

    2015-11-01

    A simple α-C-H amination of cyclic ether with indole/carbazole derivatives has been accomplished by employing copper(II) chloride/bipy as the catalyst system. In the presence of the di-tert-butyl peroxide oxidant, cyclic ethers such as tetrahydrofuran, 1,4-dioxane, and tetrahydropyran successfully undergo C-H/N-H cross dehydrogenative coupling (CDC) with various carbazole or indole derivatives in good-to-excellent yields. PMID:26485515

  10. Palladium-catalysed C-H activation of aliphatic amines to give strained nitrogen heterocycles

    NASA Astrophysics Data System (ADS)

    McNally, Andrew; Haffemayer, Benjamin; Collins, Beatrice S. L.; Gaunt, Matthew J.

    2014-06-01

    The development of new chemical transformations based on catalytic functionalization of unactivated C-H bonds has the potential to simplify the synthesis of complex molecules dramatically. Transition metal catalysis has emerged as a powerful tool with which to convert these unreactive bonds into carbon-carbon and carbon-heteroatom bonds, but the selective transformation of aliphatic C-H bonds is still a challenge. The most successful approaches involve a `directing group', which positions the metal catalyst near a particular C-H bond, so that the C-H functionalization step occurs via cyclometallation. Most directed aliphatic C-H activation processes proceed through a five-membered-ring cyclometallated intermediate. Considering the number of new reactions that have arisen from such intermediates, it seems likely that identification of distinct cyclometallation pathways would lead to the development of other useful chemical transformations. Here we report a palladium-catalysed C-H bond activation mode that proceeds through a four-membered-ring cyclopalladation pathway. The chemistry described here leads to the selective transformation of a methyl group that is adjacent to an unprotected secondary amine into a synthetically versatile nitrogen heterocycle. The scope of this previously unknown bond disconnection is highlighted through the development of C-H amination and carbonylation processes, leading to the synthesis of aziridines and β-lactams (respectively), and is suggestive of a generic C-H functionalization platform that could simplify the synthesis of aliphatic secondary amines, a class of small molecules that are particularly important features of many pharmaceutical agents.

  11. Propane σ-Complexes on PdO(101): Spectroscopic Evidence of the Selective Coordination and Activation of Primary C-H Bonds.

    PubMed

    Zhang, Feng; Pan, Li; Choi, Juhee; Mehar, Vikram; Diulus, John T; Asthagiri, Aravind; Weaver, Jason F

    2015-11-16

    Achieving selective C-H bond cleavage is critical for developing catalytic processes that transform small alkanes to value-added products. The present study clarifies the molecular-level origin for an exceptionally strong preference for propane to dissociate on the crystalline PdO(101) surface via primary C-H bond cleavage. Using reflection absorption infrared spectroscopy (RAIRS) and density functional theory (DFT) calculations, we show that adsorbed propane σ-complexes preferentially adopt geometries on PdO(101) in which only primary C-H bonds datively interact with the surface Pd atoms at low propane coverages and are thus activated under typical catalytic reaction conditions. We show that a propane molecule achieves maximum stability on PdO(101) by adopting a bidentate geometry in which a H-Pd dative bond forms at each CH3 group. These results demonstrate that structural registry between the molecule and surface can strongly influence the selectivity of a metal oxide surface in activating alkane C-H bonds. PMID:26420576

  12. Cyclopropenone (c-H2C3O): A New Interstellar Ring Molecule

    NASA Astrophysics Data System (ADS)

    Hollis, J. M.; Remijan, A. J.; Jewell, P. R.; Lovas, F. J.

    2005-12-01

    The 3-carbon keto-ring cyclopropenone (c-H2C3O) has been detected largely in absorption with the 100-m Green Bank Telescope (GBT) toward the star-forming region Sagittarius B2(N) by means of a number of rotational transitions between energy levels that have energies less than 10 K. Previous negative results from searches for interstellar c-H2C3O by other investigators attempting to detect rotational transitions that have energy levels ˜10 K or greater indicate no significant hot core component. Thus, we conclude that only the low energy levels of c-H2C3O are populated because the molecule state temperature is low, suggesting that c-H2C3O resides in a star-forming core halo region that has a widespread arcminute spatial scale. Toward Sagittarius B2(N), the GBT was also used to observe the previously-reported, spatially-ubiquitous, 3-carbon ring cyclopropenylidene (c-C3H2) which has a divalent carbon that makes it highly reactive in the laboratory. The presence of both c-C3H2 and c-H2C3O toward Sagittarius B2(N) suggests that gas-phase oxygen addition may account for the synthesis of c-H2C3O from c-C3H2. We also searched for but did not detect the three-carbon sugar glyceraldehyde (CH2OHCHOHCHO) .

  13. Cyclopropenone (c-H2C3O): A New Interstellar Ring Molecule

    NASA Astrophysics Data System (ADS)

    Hollis, J. M.; Remijan, Anthony J.; Jewell, P. R.; Lovas, F. J.

    2006-05-01

    The three-carbon keto ring cyclopropenone (c-H2C 3O) has been detected largely in absorption with the 100 m Green Bank Telescope (GBT) toward the star-forming region Sagittarius B2(N) by means of a number of rotational transitions between energy levels that have energies less than 10 K. Previous negative results from searches for interstellar c-H2C3O by other investigators attempting to detect rotational transitions that have energy levels ~10 K or greater indicate no significant hot core component. Thus, we conclude that only the low-energy levels of c-H2C3O are populated because the molecule state temperature is low, suggesting that c-H2C3O resides in a star-forming core halo region that has a widespread arcminute spatial scale. Toward Sagittarius B2(N), the GBT was also used to observe the previously reported, spatially ubiquitous, three-carbon ring cyclopropenylidene (c-C3H2 ), which has a divalent carbon that makes it highly reactive in the laboratory. The presence of both c-C3H2 and c-H2C3O toward Sagittarius B2(N) suggests that gas-phase oxygen addition may account for the synthesis of c-H 2C3O from c-C3H2. We also searched for but did not detect the three-carbon sugar glyceraldehyde (CH2OHCHOHCHO).

  14. Ligand Lone-Pair Influence on Hydrocarbon C-H Activation. A Computational Perspective

    SciTech Connect

    Ess, Daniel H.; Gunnoe, T. Brent; Cundari, Thomas R.; Goddard, William A.; Periana, Roy A.

    2010-12-03

    Mid to late transition metal complexes that break hydrocarbon C-H bonds by transferring the hydrogen to a heteroatom ligand while forming a metal-alkyl bond offer a promising strategy for C-H activation. Here we report a density functional (B3LYP, M06, and X3LYP) analysis of cis-(acac)2MX and TpM(L)X (M = Ir, Ru, Os, and Rh; acac = acetylacetonate, Tp = tris(pyrazolyl)borate; X = CH3, OH, OMe, NH2, and NMe2) systems for methane C-H bond activation reaction kinetics and thermodynamics. We address the importance of whether a ligand lone pair provides an intrinsic kinetic advantage through possible electronic dπ-pπ repulsions for M-OR and M-NR2 systems versus M-CH3 systems. This involves understanding the energetic impact of the X ligand group on ligand loss, C-H bond coordination, and C-H bond cleavage steps as well as understanding how the nucleophilicity of the ligand X group, the electrophilicity of the transition metal center, and cis-ligand stabilization effect influence each of these steps. We also explore how spectator ligands and second- versus third-row transition metal centers impact the energetics of each of these C-H activation steps.

  15. Pushing the limits of catalytic C-H amination in polyoxygenated cyclobutanes.

    PubMed

    Nocquet, Pierre-Antoine; Hensienne, Raphaël; Wencel-Delord, Joanna; Laigre, Eugénie; Sidelarbi, Khadidja; Becq, Frédéric; Norez, Caroline; Hazelard, Damien; Compain, Philippe

    2016-03-01

    A synthetic route to a new class of conformationally constrained iminosugars based on a 5-azaspiro[3.4]octane skeleton has been developed by way of Rh(ii)-catalyzed C(sp(3))-H amination. The pivotal stereocontrolled formation of the quaternary C-N bond by insertion into the C-H bonds of the cyclobutane ring was explored with a series of polyoxygenated substrates. In addition to anticipated regioselective issues induced by the high density of activated α-ethereal C-H bonds, this systematic study showed that cyclobutane C-H bonds were, in general, poorly reactive towards catalytic C-H amination. This was demonstrated inter alia by the unexpected formation of a oxathiazonane derivative, which constitutes a very rare example of the formation of a 9-membered ring by way of catalyzed C(sp(3))-H amination. A complete stereocontrol could be however achieved by activating the key insertion position as an allylic C-H bond in combination with reducing the electron density at the undesired C-H insertion sites by using electron-withdrawing protecting groups. Preliminary biological evaluations of the synthesized spiro-iminosugars were performed, which led to the identification of a new class of correctors of the defective F508del-CFTR gating involved in cystic fibrosis. PMID:26860404

  16. Biological actions of cleaved atrial natriuretic factor (ANF101-105/106-126) in conscious sheep.

    PubMed

    Charles, C J; Espiner, E A; Yandle, T G; Cameron, V A; Richards, A M

    1991-03-01

    Atrial natriuretic factor (ANF) cleaved between Cys105 and Phe106 is the primary metabolite of ANF and circulates in human plasma. Because the role of this metabolite in vivo and its possible interaction with intact ANF are unclear, we studied the biologic effects of a 2-h infusion of rat cleaved ANF101-105/106-126 (15 pmol/kg/min) or vehicle alone in six normal sheep. Infusions of cleaved ANF increased venous plasma levels of cleaved ANF from less than 5 to 260 pmol/L and induced a progressive and significant increase in plasma cyclic GMP (p = 0.025) without significantly affecting plasma ANF levels. These changes were associated with a small (nonsignificant) decrease in arterial pressure and a significant increase in heart rate (HR) and sympathetic nervous activity and were followed by activation of the renin-angiotensin-aldosterone (RAA) axis after infusions were terminated. Unlike ANF itself, cleaved ANF was not natriuretic and did not reduce plasma volume or right atrial pressure. Calculated metabolic clearance rate (MCR) (1.47 +/- 0.4 L/min) and disappearance rate of cleaved ANF from plasma (4.8 +/- 0.37 min) were similar to values reported previously for intact ANF in sheep. These studies show that cleaved ANF stimulates guanylate cyclase and alters hemodynamics and the RAA system in vivo. PMID:1711601

  17. Strong Interaction

    SciTech Connect

    Karsch, F.; Vogelsang, V.

    2009-09-29

    We will give here an overview of our theory of the strong interactions, Quantum Chromo Dynamics (QCD) and its properties. We will also briefly review the history of the study of the strong interactions, and the discoveries that ultimately led to the formulation of QCD. The strong force is one of the four known fundamental forces in nature, the others being the electromagnetic, the weak and the gravitational force. The strong force, usually referred to by scientists as the 'strong interaction', is relevant at the subatomic level, where it is responsible for the binding of protons and neutrons to atomic nuclei. To do this, it must overcome the electric repulsion between the protons in an atomic nucleus and be the most powerful force over distances of a few fm (1fm=1 femtometer=1 fermi=10{sup -15}m), the typical size of a nucleus. This property gave the strong force its name.

  18. Effect of C-H ⋯ S and C-H ⋯ Cl interactions on the conformational preference of inhibitors of TIBO family

    NASA Astrophysics Data System (ADS)

    Freitas, Renato F.; Galembeck, Sérgio E.

    2006-05-01

    he non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) are an important class of drugs employed in antiviral therapy. The coordinates of three inhibitors, derived from TIBO, tetrahydroimidazo-(4,5,1-1- jk)(1,4)-benzodi-azepin-2(1 H)-one (which belongs to the NNRTIs class), were taken from PDB database and the electronic structure were investigated by using the B3LYP/6-31+G(d,p) model. Results obtained by means of the natural bond orbital (NBO) and atoms in molecules (AIM) methods indicated the presence of weak hydrogen bonds of the C-H ⋯ S and C-H ⋯ Cl type, which are partially responsible for the conformational differences observed between the inhibitors 8 Cl-TIBO and 9 Cl-TIBO.

  19. Micro-ultrasonic cleaving of cell clusters by laser-generated focused ultrasound and its mechanisms

    PubMed Central

    Baac, Hyoung Won; Lee, Taehwa; Guo, L. Jay

    2013-01-01

    Laser-generated focused ultrasound (LGFU) is a unique modality that can produce single-pulsed cavitation and strong local disturbances on a tight focal spot (<100 μm). We utilize LGFU as a non-contact, non-thermal, high-precision tool to fractionate and cleave cell clusters cultured on glass substrates. Fractionation processes are investigated in detail, which confirms distinct cell behaviors in the focal center and the periphery of LGFU spot. For better understanding of local disturbances under LGFU, we use a high-speed laser-flash shadowgraphy technique and then fully visualize instantaneous microscopic processes from the ultrasound wave focusing to the micro-bubble collapse. Based on these visual evidences, we discuss possible mechanisms responsible for the focal and peripheral disruptions, such as a liquid jet-induced wall shear stress and shock emissions due to bubble collapse. The ultrasonic micro-fractionation is readily available for in vitro cell patterning and harvesting. Moreover, it is significant as a preliminary step towards high-precision surgery applications in future. PMID:24010006

  20. Delta-secretase cleaves amyloid precursor protein and regulates the pathogenesis in Alzheimer's disease

    PubMed Central

    Zhang, Zhentao; Song, Mingke; Liu, Xia; Su Kang, Seong; Duong, Duc M.; Seyfried, Nicholas T.; Cao, Xuebing; Cheng, Liming; Sun, Yi E.; Ping Yu, Shan; Jia, Jianping; Levey, Allan I.; Ye, Keqiang

    2015-01-01

    The age-dependent deposition of amyloid-β peptides, derived from amyloid precursor protein (APP), is a neuropathological hallmark of Alzheimer's disease (AD). Despite age being the greatest risk factor for AD, the molecular mechanisms linking ageing to APP processing are unknown. Here we show that asparagine endopeptidase (AEP), a pH-controlled cysteine proteinase, is activated during ageing and mediates APP proteolytic processing. AEP cleaves APP at N373 and N585 residues, selectively influencing the amyloidogenic fragmentation of APP. AEP is activated in normal mice in an age-dependent manner, and is strongly activated in 5XFAD transgenic mouse model and human AD brains. Deletion of AEP from 5XFAD or APP/PS1 mice decreases senile plaque formation, ameliorates synapse loss, elevates long-term potentiation and protects memory. Blockade of APP cleavage by AEP in mice alleviates pathological and behavioural deficits. Thus, AEP acts as a δ-secretase, contributing to the age-dependent pathogenic mechanisms in AD. PMID:26549211

  1. Topographic and electronic structure of cleaved SrTiO{sub 3}(001) surfaces

    SciTech Connect

    Sitaputra, Wattaka Skowronski, Marek; Feenstra, Randall M.

    2015-05-15

    The topographic and electronic structure of cleaved SrTiO{sub 3}(001) surfaces were studied, employing samples that either had or had not been coated with Ti on their outer surfaces prior to fracture. In both cases, SrO- and TiO{sub 2}-terminated terraces were present on the cleavage surface, enabling in situ studies on either termination. However, the samples coated with Ti prior to fracture were found to yield a rougher morphology on TiO{sub 2}-terminated terraces as well as a higher density of oxygen vacancies during an annealing (outgassing) step following the coating. The higher density of oxygen vacancies in the bulk of the Ti-coated samples also provides higher conductivity, which, in turn, improves a sensitivity of the spectroscopy and reduces the effect of tip-induced band bending. Nonetheless, similar spectral features, unique to each termination, were observed for samples both with and without the Ti coating. Notably, with moderate-temperature annealing following fracture, a strong discrete peak in the conductance spectra, arising from oxygen vacancies, was observed on the SrO-terminated terraces. This peak appears at slightly different voltages for coated and uncoated samples, signifying a possible effect of tip-induced band bending.

  2. Beta-secretase-cleaved amyloid precursor protein in Alzheimer brain: a morphologic study.

    PubMed

    Sennvik, Kristina; Bogdanovic, N; Volkmann, Inga; Fastbom, J; Benedikz, E

    2004-01-01

    beta-amyloid (Abeta) is the main constituent of senile plaques seen in Alzheimer's disease. Abeta is derived from the amyloid precursor protein (APP) via proteolytic cleavage by proteases beta- and gamma-secretase. In this study, we examined content and localization of beta-secretase-cleaved APP (beta-sAPP) in brain tissue sections from the frontal, temporal and occipital lobe. Strong granular beta-sAPP staining was found throughout the gray matter of all three areas, while white matter staining was considerably weaker. beta-sAPP was found to be localized in astrocytes and in axons. We found the beta-sAPP immunostaining to be stronger and more extensive in gray matter in Alzheimer disease (AD) cases than controls. The axonal beta-sAPP staining was patchy and unevenly distributed for the AD cases, indicating impaired axonal transport. beta-sAPP was also found surrounding senile plaques and cerebral blood vessels. The results presented here show altered beta-sAPP staining in the AD brain, suggestive of abnormal processing and transport of APP. PMID:15090268

  3. Delta-secretase cleaves amyloid precursor protein and regulates the pathogenesis in Alzheimer's disease.

    PubMed

    Zhang, Zhentao; Song, Mingke; Liu, Xia; Su Kang, Seong; Duong, Duc M; Seyfried, Nicholas T; Cao, Xuebing; Cheng, Liming; Sun, Yi E; Ping Yu, Shan; Jia, Jianping; Levey, Allan I; Ye, Keqiang

    2015-01-01

    The age-dependent deposition of amyloid-β peptides, derived from amyloid precursor protein (APP), is a neuropathological hallmark of Alzheimer's disease (AD). Despite age being the greatest risk factor for AD, the molecular mechanisms linking ageing to APP processing are unknown. Here we show that asparagine endopeptidase (AEP), a pH-controlled cysteine proteinase, is activated during ageing and mediates APP proteolytic processing. AEP cleaves APP at N373 and N585 residues, selectively influencing the amyloidogenic fragmentation of APP. AEP is activated in normal mice in an age-dependent manner, and is strongly activated in 5XFAD transgenic mouse model and human AD brains. Deletion of AEP from 5XFAD or APP/PS1 mice decreases senile plaque formation, ameliorates synapse loss, elevates long-term potentiation and protects memory. Blockade of APP cleavage by AEP in mice alleviates pathological and behavioural deficits. Thus, AEP acts as a δ-secretase, contributing to the age-dependent pathogenic mechanisms in AD. PMID:26549211

  4. Dependence of 20-nm C/H CD windows on critical process parameters

    NASA Astrophysics Data System (ADS)

    Chen, Wei-Su; Gu, Pei-Yi; Tsai, Ming-Jinn

    2010-04-01

    20 nm contact hole (C/H) patterning is applicable for sub-22 nm technology node applications. Dependence of C/H CD window on critical process parameters is important for process stability and repeatability. Post applied baking (PAB) condition, resist thickness, develop time, and dry etch rate are considered to be the most important process parameters for e-beam chain scission resist ZEP520A C/H patterning. In this paper, PAB temperatures (TPAB) are investigated at temperatures between lower than glass transition temperature (TG) and much higher than TF. Effects of these process parameters on 20 nm +/-10% C/H CD window for various pattern densities and e-beam doses are studied. The critical process parameters are determined by their effects on CD window size, C/H sidewall profile, proximity effect immunity, ΔCD/ΔDose slope, and etch selectivity. Experimental results are summarized below. Thinnest ZEP520A film has the largest 20nm +/-10% CD window on D-D plot for various L/S ratios and doses. The dosage window of smaller C/H CD is larger. The proximity effect is negligible for 50 nm ZEP520A baked at 200°C/300 sec. No apparent effect is found in CD window on D-D plot for develop time as short as 30 sec. PAB condition is most critical than the other process parameters in determining resist density and polymerization which affect e-beam scattering and chain scission in resist film and therefore affects CD resolution and window. PAB condition of 140°C/60 sec is most desirable in terms of CD window on D-D plot, C/H sidewall profile, dry etch rate and proximity effect.

  5. An ion-gating multinanochannel system based on a copper-responsive self-cleaving DNAzyme.

    PubMed

    Chen, Yang; Zhou, Di; Meng, Zheyi; Zhai, Jin

    2016-08-21

    We developed an ion-gating nanochannel composite system by immobilizing a Cu(2+)-responsive self-cleaving DNAzyme into PET conical multinanochannels, which could control the ion transport by regulating the surface charge density of the channels. PMID:27443504

  6. Type II restriction endonucleases cleave single-stranded DNAs in general.

    PubMed Central

    Nishigaki, K; Kaneko, Y; Wakuda, H; Husimi, Y; Tanaka, T

    1985-01-01

    Restriction endonucleases (13 out of 18 species used for the test) were certified to cleave single-stranded(ss)DNA. Such enzymes as AvaII, HaeII, DdeI, AluI, Sau3AI, AccII,TthHB8I and HapII were newly reported to cleave ssDNA. A model to account for the cleavage of ssDNA by restriction enzymes was proposed with supportive data. The essential part of the model was that restriction enzymes preferentially cleave transiently formed secondary structures (called canonical structures) in ssDNA composed of two recognition sequences with two fold rotational symmetry. This means that a restriction enzyme can cleave ssDNAs in general so far as the DNAs have the sequences of restriction sites for the enzyme, and that the rate of cleavage depends on the stabilities of canonical structures. Images PMID:2994012

  7. Transition metal-free intramolecular regioselective couplings of aliphatic and aromatic C-H bonds.

    PubMed

    Tian, Hua; Yang, Haijun; Zhu, Changjin; Fu, Hua

    2016-01-01

    Cross-dehydrogenative couplings of two different C-H bonds have emerged as an attractive goal in organic synthesis. However, achieving regioselective C-H activation is a great challenge because C-H bonds are ubiquitous in organic compounds. Actually, the regioselective couplings promoted by enzymes are a common occurrence in nature. Herein, we have developed simple, efficient and general transition metal-free intramolecular couplings of alphatic and aromatic C-H bonds. The protocol uses readily available aryl triazene as the radical initiator, cheap K2S2O8 as the oxidant, and the couplings were performed well with excellent tolerance of functional groups. Interestingly, α-carbon configuration of some amino acid residues in the substrates was kept after the reactions, and the couplings for substrates with substituted phenylalanine residues exhibited complete β-carbon diastereoselectivity for induction of the chiral α-carbon. Therefore, the present study should provide a novel strategy for regioselective cross-dehydrogenative couplings of two different C-H bonds. PMID:26822836

  8. Transition metal-free intramolecular regioselective couplings of aliphatic and aromatic C-H bonds

    PubMed Central

    Tian, Hua; Yang, Haijun; Zhu, Changjin; Fu, Hua

    2016-01-01

    Cross-dehydrogenative couplings of two different C-H bonds have emerged as an attractive goal in organic synthesis. However, achieving regioselective C-H activation is a great challenge because C-H bonds are ubiquitous in organic compounds. Actually, the regioselective couplings promoted by enzymes are a common occurrence in nature. Herein, we have developed simple, efficient and general transition metal-free intramolecular couplings of alphatic and aromatic C-H bonds. The protocol uses readily available aryl triazene as the radical initiator, cheap K2S2O8 as the oxidant, and the couplings were performed well with excellent tolerance of functional groups. Interestingly, α-carbon configuration of some amino acid residues in the substrates was kept after the reactions, and the couplings for substrates with substituted phenylalanine residues exhibited complete β-carbon diastereoselectivity for induction of the chiral α-carbon. Therefore, the present study should provide a novel strategy for regioselective cross-dehydrogenative couplings of two different C-H bonds. PMID:26822836

  9. A Simple and Versatile Amide Directing Group for C-H Functionalizations.

    PubMed

    Zhu, Ru-Yi; Farmer, Marcus E; Chen, Yan-Qiao; Yu, Jin-Quan

    2016-08-26

    Achieving selective C-H activation at a single and strategic site in the presence of multiple C-H bonds can provide a powerful and generally useful retrosynthetic disconnection. In this context, a directing group serves as a compass to guide the transition metal to C-H bonds by using distance and geometry as powerful recognition parameters to distinguish between proximal and distal C-H bonds. However, the installation and removal of directing groups is a practical drawback. To improve the utility of this approach, one can seek solutions in three directions: 1) Simplifying the directing group, 2) using common functional groups or protecting groups as directing groups, and 3) attaching the directing group to substrates via a transient covalent bond to render the directing group catalytic. This Review describes the rational development of an extremely simple and yet broadly applicable directing group for Pd(II) , Rh(III) , and Ru(II) catalysts, namely the N-methoxy amide (CONHOMe) moiety. Through collective efforts in the community, a wide range of C-H activation transformations using this type of simple directing group have been developed. PMID:27479708

  10. Site-selective and stereoselective functionalization of unactivated C-H bonds.

    PubMed

    Liao, Kuangbiao; Negretti, Solymar; Musaev, Djamaladdin G; Bacsa, John; Davies, Huw M L

    2016-05-12

    The laboratory synthesis of complex organic molecules relies heavily on the introduction and manipulation of functional groups, such as carbon-oxygen or carbon-halogen bonds; carbon-hydrogen bonds are far less reactive and harder to functionalize selectively. The idea of C-H functionalization, in which C-H bonds are modified at will instead of the functional groups, represents a paradigm shift in the standard logic of organic synthesis. For this approach to be generally useful, effective strategies for site-selective C-H functionalization need to be developed. The most practical solutions to the site-selectivity problem rely on either intramolecular reactions or the use of directing groups within the substrate. A challenging, but potentially more flexible approach, would be to use catalyst control to determine which site in a particular substrate would be functionalized. Here we describe the use of dirhodium catalysts to achieve highly site-selective, diastereoselective and enantioselective C-H functionalization of n-alkanes and terminally substituted n-alkyl compounds. The reactions proceed in high yield, and functional groups such as halides, silanes and esters are compatible with this chemistry. These studies demonstrate that high site selectivity is possible in C-H functionalization reactions without the need for a directing or anchoring group present in the molecule. PMID:27172046

  11. Improved fabrication of HgI/sub 2/ nuclear radiation detectors by machine-cleaving

    SciTech Connect

    Levi, A.; Burger, A.; Schieber, M.; Vandenberg, L.; Yellon, W.B.; Alkire, R.W.

    1982-01-01

    The perfection of machine-cleaved sections from HgI/sub 2/ bulk crystals was examined. The perfection of the machine-cleaved sections as established by gamma diffraction rocking curves was found to be much better than the perfection of hand-cleaved sections or as grown thin platelets, reaching a perfection similar to that of the wire-sawn sections of HgI/sub 2/. A correlation between the perfection and the thickness of the machine-cleaved section was also found, i.e., the thicker the cleaved-section the more perfect it is. The reproducibility of the fabrication was significantly improved by using machine cleaving in the process of fabrication. Large single crystals of HgI/sub 2/ weighing 20 to 200 g, can be grown from the vapor phase using the TOM Technique. In order to fabricate nuclear radiation detectors from these single crystals, thin sections of about 0.4 to 0.8 mm thickness have to be prepared. Up till now, the state-of-the-art of fabricating HgI/sub 2/ nuclear radiation detectors involved two methods to get thin sections from the large single crystals: (1) hand-cleaving using a razor-blade and (2) solution wire sawing. The chemical wire sawing method involves a loss of about 50% of the crystal volume and is usually followed by a chemical polishing process which involves a significant loss of volume of the original volume. This procedure is complicated and wasteful. The traditional fabrication method, i.e., hand-cleaving followed by rapid nonselective chemical etching, is simpler and less wasteful.

  12. Stop-cleaved InGaAsP laser monolithically integrated with a monitoring detector

    SciTech Connect

    Antreasyan, A.; Chen, C.Y.; Napholtz, S.G.; Wilt, D.P.

    1985-11-01

    We report the monolithic fabrication of a stop-cleaved laser with a monitoring detector. Stop-cleaved, double channel planar buried heterostructure lasers with threshold currents of 57 mA have been obtained emitting at 1.3-..mu..m wavelength. For the monitoring detector on the same substrate we have estimated a quantum efficiency of 31% from the measured responsivity of 14.4 ..mu..A/mW and the theoretical diffraction coupling efficiency.

  13. Etching of deep grooves for the precise positioning of cleaves in semiconductor lasers

    SciTech Connect

    Bowers, J.E.; Hemenway, B.R.; Wilt, D.P.

    1985-03-01

    Photoelectrochemical etching of InP is used to etch deep (80 ..mu..m), narrow (20 ..mu..m) grooves. The grooves are used to precisely position cleaves in semiconductor lasers and to demonstrate the first wafer processing of long/short cleaved-coupled-cavity (C/sup 3/) lasers. Large numbers of low threshold C/sup 3/ lasers wth very similar cavity lengths were obtained.

  14. Experimental and Metabolic Modeling Evidence for a Folate-Cleaving Side-Activity of Ketopantoate Hydroxymethyltransferase (PanB)

    PubMed Central

    Thiaville, Jennifer J.; Frelin, Océane; García-Salinas, Carolina; Harrison, Katherine; Hasnain, Ghulam; Horenstein, Nicole A.; Díaz de la Garza, Rocio I.; Henry, Christopher S.; Hanson, Andrew D.; de Crécy-Lagard, Valérie

    2016-01-01

    Tetrahydrofolate (THF) and its one-carbon derivatives, collectively termed folates, are essential cofactors, but are inherently unstable. While it is clear that chemical oxidation can cleave folates or damage their pterin precursors, very little is known about enzymatic damage to these molecules or about whether the folate biosynthesis pathway responds adaptively to damage to its end-products. The presence of a duplication of the gene encoding the folate biosynthesis enzyme 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (FolK) in many sequenced bacterial genomes combined with a strong chromosomal clustering of the folK gene with panB, encoding the 5,10-methylene-THF-dependent enzyme ketopantoate hydroxymethyltransferase, led us to infer that PanB has a side activity that cleaves 5,10-methylene-THF, yielding a pterin product that is recycled by FolK. Genetic and metabolic analyses of Escherichia coli strains showed that overexpression of PanB leads to accumulation of the likely folate cleavage product 6-hydroxymethylpterin and other pterins in cells and medium, and—unexpectedly—to a 46% increase in total folate content. In silico modeling of the folate biosynthesis pathway showed that these observations are consistent with the in vivo cleavage of 5,10-methylene-THF by a side-activity of PanB, with FolK-mediated recycling of the pterin cleavage product, and with regulation of folate biosynthesis by folates or their damage products. PMID:27065985

  15. Nanocrystalline SiC formed by annealing of a-SiC:H on Si substrates: A study of dopant interdiffusion

    SciTech Connect

    Schnabel, Manuel; Weiss, Charlotte; Löper, Philipp; Janz, Stefan; Canino, Mariaconcetta; Summonte, Caterina; Wilshaw, Peter R.

    2014-07-14

    Nanocrystalline silicon carbide (nc-SiC) is an interesting material for electronics applications, both in its own right and as a host matrix for silicon quantum dots. When synthesized by annealing of a-SiC:H on Si substrates, interdiffusion of dopants occurs if either the a-SiC:H or the Si substrate is doped. Annealing a-SiC:H on highly boron-doped substrates at 1100 °C leads to a fairly homogeneous doping level of ≥4 × 10{sup 19} cm{sup −3} throughout the nc-SiC film. An unexpected anomaly in secondary ion mass spectroscopy quantification is observed and a method to circumvent it is shown. The nanostructure of the nc-SiC is only weakly affected as most of the diffusion occurs after the onset of crystallization. Annealing of doped a-SiC:H on Si substrates at 1100 °C leads to strong free carrier absorption at infrared wavelengths. This is demonstrated to originate from dopants that have diffused from the a-SiC:H to the Si substrate, and a method is developed to extract from it the doping profile in the Si substrate. The detection limit of this method is estimated to be ≤6 × 10{sup 13} cm{sup −2}. Doping levels of (0.5–3.5) × 10{sup 19} cm{sup −3} are induced at the Si substrate surface by both boron and phosphorus-doped a–SiC:H. When the Si substrate is doped opposite to the a-SiC:H p–n junctions are induced at a depth of 0.9–1.4 μm within the Si substrate for substrate resistivities of 1–10 Ω cm. Implications for different solar cell architectures are discussed. Dopant diffusion can be strongly reduced by lowering the annealing temperature to 1000 °C, albeit at the expense of reduced crystallinity.

  16. N-Acyl Amino Acid Ligands for Ruthenium(II)-Catalyzed meta-C-H tert-Alkylation with Removable Auxiliaries.

    PubMed

    Li, Jie; Warratz, Svenja; Zell, Daniel; De Sarkar, Suman; Ishikawa, Eloisa Eriko; Ackermann, Lutz

    2015-11-01

    Acylated amino acid ligands enabled ruthenium(II)-catalyzed C-H functionalizations with excellent levels of meta-selectivity. The outstanding catalytic activity of the ruthenium(II) complexes derived from monoprotected amino acids (MPAA) set the stage for the first ruthenium-catalyzed meta-functionalizations with removable directing groups. Thereby, meta-alkylated anilines could be accessed, which are difficult to prepare by other means of direct aniline functionalizations. The robust nature of the versatile ruthenium(II)-MPAA was reflected by challenging remote C-H transformations with tertiary alkyl halides on aniline derivatives as well as on pyridyl-, pyrimidyl-, and pyrazolyl-substituted arenes. Detailed mechanistic studies provided strong support for an initial reversible C-H ruthenation, followed by a SET-type C-Hal activation through homolytic bond cleavage. Kinetic analyses confirmed this hypothesis through an unusual second-order dependence of the reaction rate on the ruthenium catalyst concentration. Overall, this report highlights the exceptional catalytic activity of ruthenium complexes derived from acylated amino acids, which should prove instrumental for C-H activation chemistry beyond remote functionalization. PMID:26418891

  17. Facile P-C/C-H Bond-Cleavage Reactivity of Nickel Bis(diphosphine) Complexes.

    PubMed

    Zhang, Shaoguang; Li, Haixia; Appel, Aaron M; Hall, Michael B; Bullock, R Morris

    2016-07-01

    Unusual cleavage of P-C and C-H bonds of the P2 N2 ligand, in heteroleptic [Ni(P2 N2 )(diphosphine)](2+) complexes under mild conditions, results in the formation of an iminium formyl nickelate featuring a C,P,P-tridentate coordination mode. The structures of both the heteroleptic [Ni(P2 N2 )(diphosphine)](2+) complexes and the resulting iminium formyl nickelate have been characterized by NMR spectroscopy and single-crystal X-ray diffraction analysis. Density functional theory (DFT) calculations were employed to investigate the mechanism of the P-C/C-H bond cleavage, which involves C-H bond cleavage, hydride rotation, Ni-C/P-H bond formation, and P-C bond cleavage. PMID:27189413

  18. Ligand-Promoted Meta-C-H Arylation of Anilines, Phenols, and Heterocycles.

    PubMed

    Wang, Peng; Farmer, Marcus E; Huo, Xing; Jain, Pankaj; Shen, Peng-Xiang; Ishoey, Mette; Bradner, James E; Wisniewski, Steven R; Eastgate, Martin D; Yu, Jin-Quan

    2016-07-27

    Here we report the development of a versatile 3-acetylamino-2-hydroxypyridine class of ligands that promote meta-C-H arylation of anilines, heterocyclic aromatic amines, phenols, and 2-benzyl heterocycles using norbornene as a transient mediator. More than 120 examples are presented, demonstrating this ligand scaffold enables a wide substrate and coupling partner scope. Meta-C-H arylation with heterocyclic aryl iodides as coupling partners is also realized for the first time using this ligand. The utility for this transformation for drug discovery is showcased by allowing the meta-C-H arylation of a lenalidomide derivative. The first steps toward a silver-free protocol for this reaction are also demonstrated. PMID:27384126

  19. Interpreting CARS images of tissue within the C-H-stretching region.

    PubMed

    Meyer, Tobias; Bergner, Norbert; Medyukhina, Anna; Dietzek, Benjamin; Krafft, Christoph; Romeike, Bernd F M; Reichart, Rupert; Kalff, Rolf; Popp, Jürgen

    2012-10-01

    Single band coherent anti-Stokes Raman scattering (CARS) microscopy is one of the fastest implementation of nonlinear vibrational imaging allowing for video-rate image acquisition of tissue. This is due to the large Raman signal in the C-H-stretching region. However, the chemical specificity of such images is conventionally assumed to be low. Nonetheless, CARS imaging within the C-H-stretching region enables detection of single cells and nuclei, which allows for histopathologic grading of tissue. Relevant information such as nucleus to cytoplasm ratio, cell density, nucleus size and shape is extracted from CARS images by innovative image processing procedures. In this contribution CARS image contrast within the C-H-stretching region is interpreted by direct comparison with Raman imaging and correlated to the tissue composition justifying the use of CARS imaging in this wavenumber region for biomedical applications. PMID:22815249

  20. A steric tethering approach enables palladium-catalysed C-H activation of primary amino alcohols

    NASA Astrophysics Data System (ADS)

    Calleja, Jonas; Pla, Daniel; Gorman, Timothy W.; Domingo, Victoriano; Haffemayer, Benjamin; Gaunt, Matthew J.

    2015-12-01

    Aliphatic primary amines are a class of chemical feedstock essential to the synthesis of higher-order nitrogen-containing molecules, commonly found in biologically active compounds and pharmaceutical agents. New methods for the construction of complex amines remain a continuous challenge to synthetic chemists. Here, we outline a general palladium-catalysed strategy for the functionalization of aliphatic C-H bonds within amino alcohols, an important class of small molecule. Central to this strategy is the temporary conversion of catalytically incompatible primary amino alcohols into hindered secondary amines that are capable of undergoing a sterically promoted palladium-catalysed C-H activation. Furthermore, a hydrogen bond between amine and catalyst intensifies interactions around the palladium and orients the aliphatic amine substituents in an ideal geometry for C-H activation. This catalytic method directly transforms simple, easily accessible amines into highly substituted, functionally concentrated and structurally diverse products, and can streamline the synthesis of biologically important amine-containing molecules.

  1. Copper-catalyzed aerobic oxidative C-H functionalizations: trends and mechanistic insights.

    PubMed

    Wendlandt, Alison E; Suess, Alison M; Stahl, Shannon S

    2011-11-18

    The selective oxidation of C-H bonds and the use of O(2) as a stoichiometric oxidant represent two prominent challenges in organic chemistry. Copper(II) is a versatile oxidant, capable of promoting a wide range of oxidative coupling reactions initiated by single-electron transfer (SET) from electron-rich organic molecules. Many of these reactions can be rendered catalytic in Cu by employing molecular oxygen as a stoichiometric oxidant to regenerate the active copper(II) catalyst. Meanwhile, numerous other recently reported Cu-catalyzed C-H oxidation reactions feature substrates that are electron-deficient or appear unlikely to undergo single-electron transfer to copper(II). In some of these cases, evidence has been obtained for the involvement of organocopper(III) intermediates in the reaction mechanism. Organometallic C-H oxidation reactions of this type represent important new opportunities for the field of Cu-catalyzed aerobic oxidations. PMID:22034061

  2. Transition metal-catalyzed ketone-directed or mediated C-H functionalization.

    PubMed

    Huang, Zhongxing; Lim, Hee Nam; Mo, Fanyang; Young, Michael C; Dong, Guangbin

    2015-11-01

    Transition metal-catalyzed C-H functionalization has evolved into a prominent and indispensable tool in organic synthesis. While nitrogen, phosphorus and sulfur-based functional groups (FGs) are widely employed as effective directing groups (DGs) to control the site-selectivity of C-H activation, the use of common FGs (e.g. ketone, alcohol and amine) as DGs has been continuously pursued. Ketones are an especially attractive choice of DGs and substrates due to their prevalence in various molecules and versatile reactivity as synthetic intermediates. Over the last two decades, transition metal-catalyzed C-H functionalization that is directed or mediated by ketones has experienced vigorous growth. This review summarizes these advancements into three major categories: use of ketone carbonyls as DGs, direct β-functionalization, and α-alkylation/alkenylation with unactivated olefins and alkynes. Each of these subsections is discussed from the perspective of strategic design and reaction discovery. PMID:26185960

  3. Erosion of a-C:H films under interaction with nitrous oxide afterglow discharge

    NASA Astrophysics Data System (ADS)

    Zalavutdinov, R. Kh.; Gorodetsky, A. E.; Bukhovets, V. L.; Zakharov, A. P.; Mazul, I. V.

    2009-06-01

    Hydrocarbon film removal using chemically active oxygen formed in a direct current glow discharge with a hollow cathode in nitrous oxide was investigated. In the afterglow region sufficiently fast removal of a-C:H films about 500 nm thick during about 8 h was achieved at N 2O pressure of 12 Pa and 370 K. The erosion rate in the afterglow region was directly proportional to the initial pressure and increased two orders of magnitude at temperature rising from 300 to 500 K. The products of a-C:H film plasmolysis were CO, CO 2, H 2O, and H 2. After removal of a-C:H films previously deposited on stainless steel, molybdenum or tungsten 3-30 nm thick oxide films were formed on the substrates. Reactions of oxygen ion neutralization and atomic oxygen recombination suppressed further oxidation of the materials.

  4. The direct arylation of allylic sp3 C-H bonds via organic and photoredox catalysis

    NASA Astrophysics Data System (ADS)

    Cuthbertson, James D.; MacMillan, David W. C.

    2015-03-01

    The direct functionalization of unactivated sp3 C-H bonds is still one of the most challenging problems facing synthetic organic chemists. The appeal of such transformations derives from their capacity to facilitate the construction of complex organic molecules via the coupling of simple and otherwise inert building blocks, without introducing extraneous functional groups. Despite notable recent efforts, the establishment of general and mild strategies for the engagement of sp3 C-H bonds in C-C bond forming reactions has proved difficult. Within this context, the discovery of chemical transformations that are able to directly functionalize allylic methyl, methylene and methine carbons in a catalytic manner is a priority. Although protocols for direct oxidation and amination of allylic C-H bonds (that is, C-H bonds where an adjacent carbon is involved in a C = C bond) have become widely established, the engagement of allylic substrates in C-C bond forming reactions has thus far required the use of pre-functionalized coupling partners. In particular, the direct arylation of non-functionalized allylic systems would enable access to a series of known pharmacophores (molecular features responsible for a drug's action), though a general solution to this long-standing challenge remains elusive. Here we report the use of both photoredox and organic catalysis to accomplish a mild, broadly effective direct allylic C-H arylation. This C-C bond forming reaction readily accommodates a broad range of alkene and electron-deficient arene reactants, and has been used in the direct arylation of benzylic C-H bonds.

  5. The direct arylation of allylic sp(3) C-H bonds via organic and photoredox catalysis.

    PubMed

    Cuthbertson, James D; MacMillan, David W C

    2015-03-01

    The direct functionalization of unactivated sp(3) C-H bonds is still one of the most challenging problems facing synthetic organic chemists. The appeal of such transformations derives from their capacity to facilitate the construction of complex organic molecules via the coupling of simple and otherwise inert building blocks, without introducing extraneous functional groups. Despite notable recent efforts, the establishment of general and mild strategies for the engagement of sp(3) C-H bonds in C-C bond forming reactions has proved difficult. Within this context, the discovery of chemical transformations that are able to directly functionalize allylic methyl, methylene and methine carbons in a catalytic manner is a priority. Although protocols for direct oxidation and amination of allylic C-H bonds (that is, C-H bonds where an adjacent carbon is involved in a C = C bond) have become widely established, the engagement of allylic substrates in C-C bond forming reactions has thus far required the use of pre-functionalized coupling partners. In particular, the direct arylation of non-functionalized allylic systems would enable access to a series of known pharmacophores (molecular features responsible for a drug's action), though a general solution to this long-standing challenge remains elusive. Here we report the use of both photoredox and organic catalysis to accomplish a mild, broadly effective direct allylic C-H arylation. This C-C bond forming reaction readily accommodates a broad range of alkene and electron-deficient arene reactants, and has been used in the direct arylation of benzylic C-H bonds. PMID:25739630

  6. Synthesis of a Benzodiazepine-derived Rhodium NHC Complex by C-H Bond Activation

    SciTech Connect

    Bergman, Roberg G.; Gribble, Jr., Michael W.; Ellman, Jonathan A.

    2008-01-30

    The synthesis and characterization of a Rh(I)-NHC complex generated by C-H activation of 1,4-benzodiazepine heterocycle are reported. This complex constitutes a rare example of a carbene tautomer of a 1,4-benzodiazepine aldimine stabilized by transition metal coordination and demonstrates the ability of the catalytically relevant RhCl(PCy{sub 3}){sub 2} fragment to induce NHC-forming tautomerization of heterocycles possessing a single carbene-stabilizing heteroatom. Implications for the synthesis of benzodiazepines and related pharmacophores via C-H functionalization are discussed.

  7. Binuclear Aromatic C-H Bond Activation at a Dirhenium Site.

    PubMed

    Adams, Richard D; Rassolov, Vitaly; Wong, Yuen Onn

    2016-01-22

    The electronically unsaturated dirhenium complex [Re2(CO)8(μ-H)(μ-Ph)] (1) has been found to exhibit aromatic C-H activation upon reaction with N,N-diethylaniline, naphthalene, and even [D6]benzene to yield the compounds [Re2(CO)8(μ-H)(μ-η(1)-NEt2C6H4)] (2), [Re2(CO)8(μ-H)(μ-η(2)-1,2-C10H7)] (3), and [D6]-1, respectively, in good yields. The mechanism has been elucidated by using DFT computational analyses, and involves a binuclear C-H bond-activation process. PMID:26643854

  8. Rhodium catalyzed chelation-assisted C-H bond functionalization reactions

    PubMed Central

    Colby, Denise A.; Tsai, Andy S.; Bergman, Robert G.; Ellman, Jonathan A.

    2011-01-01

    Conspectus Over the last several decades, researchers have achieved remarkable progress in the field of organometallic chemistry. The development of metal-catalyzed cross-coupling reactions represents a paradigm shift in chemical synthesis, and today synthetic chemists can readily access carbon-carbon and carbon-heteroatom bonds from a vast array of starting compounds. Although we cannot understate the importance of these methods, the required pre-functionalization to carry out these reactions adds cost and reduces the availability of the starting reagents. The use of C-H bond activation in lieu of pre-functionalization has presented a tantalizing alternative to classical cross-coupling reactions. Researchers have met the challenges of selectivity and reactivity associated with the development of C-H bond functionalization reactions with an explosion of creative advances in substrate and catalyst design. Literature reports on selectivity based on steric effects, acidity, and electronic and directing group effects are now numerous. Our group has developed an array of C-H bond functionalization reactions that take advantage of a chelating directing group, and this Account surveys our progress in this area. The use of chelation control in C-H bond functionalization offers several advantages with respect to substrate scope and application to total synthesis. The predictability and decreased dependence on the inherent stereoelectronics of the substrate generally result in selective and high yielding transformations with broad applicability. The nature of the chelating moiety can be chosen to serve as a functional handle in subsequent elaborations. Our work began with the use of Rh(I) catalysts in intramolecular aromatic C-H annulations, which we further developed to include enantioselective transformations. The application of this chemistry to the simple olefinic C-H bonds found in α,β-unsaturated imines allowed access to highly substituted olefins, pyridines, and

  9. C-H Polyaddition of Dimethoxyarenes to Unconjugated Dienes by Rare Earth Catalysts.

    PubMed

    Shi, Xiaochao; Nishiura, Masayoshi; Hou, Zhaomin

    2016-05-18

    The C-H polyaddition of dimethoxyarenes such as 1,4-dimethoxybenzene and 4,4'-dimethoxybiphenyl to unconjugated dienes such as norbornadiene and 1,4-divinylbenzene has been achieved for the first time by using cationic half-sandwich rare earth alkyl catalysts. This protocol afforded novel polymer materials consisting of dimethoxyarene moieties and nonpolar hydrocarbon structure motifs (cyclic, linear, and aromatic) in perfectly alternating sequences that are otherwise difficult to make. The reaction proceeded via C═C double bond insertion into a C-H bond ortho to each of the two methoxy groups in a step-growth polymerization fashion. PMID:27149275

  10. Activation of C-H bonds and functionalization of hydrocarbons of the adamantane series. Review

    SciTech Connect

    Bagrii, Ye.I.; Karaulova, Ye.N.

    1993-12-31

    The highly symmetrical compact structure of an adamantane molecule gives its derivatives unusual properties. This governs the use of compounds with an adamantane fragment both for scientific research and in industry, and in particular in medicine. Importants ways of producing functional derivatives of adamantane without changing its carbon skeleton are processes occurring via the activation of the C-H bond. Detailed information concerning these reactions was given in an earlier monograph, which dealt with research published mainly before 1986. In the present review an examination is made of later investigations of C-H bond activation in adamantane, including research using biological and biomimetic methods of activation.

  11. A Versatile, Traceless C-H Activation-Based Approach for the Synthesis of Heterocycles.

    PubMed

    Zhou, Shuguang; Wang, Jinhu; Zhang, Feifei; Song, Chao; Zhu, Jin

    2016-05-20

    A versatile, traceless C-H activation-based approach for the synthesis of diversified heterocycles is reported. Rh(III)-catalyzed, N-amino-directed C-H alkenylation generates either olefination products or indoles (in situ annulation) in an atom- and step-economic manner at room temperature. The remarkable reactivity endowed by this directing group enables scale-up of the reaction to a 10 g scale at a very low catalyst loading (0.01 mol %/0.1 mol %). Ex situ annulation of olefination product provides entry into an array of heterocycles. PMID:27135982

  12. Iron-Catalyzed Oxyfunctionalization of Aliphatic Amines at Remote Benzylic C-H Sites.

    PubMed

    Mbofana, Curren T; Chong, Eugene; Lawniczak, James; Sanford, Melanie S

    2016-09-01

    We report the development of an iron-catalyzed method for the selective oxyfunctionalization of benzylic C(sp(3))-H bonds in aliphatic amine substrates. This transformation is selective for benzylic C-H bonds that are remote (i.e., at least three carbons) from the amine functional group. High site selectivity is achieved by in situ protonation of the amine with trifluoroacetic acid, which deactivates more traditionally reactive C-H sites that are α to nitrogen. The scope and synthetic utility of this method are demonstrated via the synthesis and derivatization of a variety of amine-containing, biologically active molecules. PMID:27529646

  13. Development of a Direct Photocatalytic C-H Fluorination for the Preparative Synthesis of Odanacatib.

    PubMed

    Halperin, Shira D; Kwon, Daniel; Holmes, Michael; Regalado, Erik L; Campeau, Louis-Charles; DiRocco, Daniel A; Britton, Robert

    2015-11-01

    Late-stage C-H fluorination is an appealing reaction for medicinal chemistry. However, the application of this strategy to process research appears less attractive due to the formation and necessary purification of mixtures of organofluorines. Here we demonstrate that γ-fluoroleucine methyl ester, an intermediate critical to the large-scale synthesis of odanacatib, can be accessed directly from leucine methyl ester using a combination of the decatungstate photocatalyst and N-fluorobenzenesulfonimide in flow. This efficient C-H fluorination reaction compares favorably with several generations of classical γ-fluoroleucine process syntheses. PMID:26484983

  14. Donor-Acceptor-Donor Thienopyrazines via Pd-Catalyzed C-H Activation as NIR Fluorescent Materials.

    PubMed

    McNamara, Louis E; Liyanage, Nalaka; Peddapuram, Adithya; Murphy, J Scott; Delcamp, Jared H; Hammer, Nathan I

    2016-01-01

    A series of thienopyrazine-based donor-acceptor-donor (D-A-D) near-infrared (NIR) fluorescent compounds were synthesized through a rapid, palladium-catalyzed C-H activation route. The dyes were studied through computational analysis, electrochemical properties analysis, and characterization of their photophysical properties. Large Stokes shifts of approximately 175 nm were observed, which led to near-infrared emission. Computational evaluation shows that the origin of this large Stokes shift is a significant molecular reorganization particularly about the D-A bond. The series exhibits quantum yields of up to φ = >4%, with emission maxima ranging from 725 to 820 nm. The emission is strong in solution, in thin films, and also in isolation at the single-molecule level. Their stable emission at the single-molecule level makes these compounds good candidates for single-molecule photon sources in the near-infrared. PMID:26599501

  15. Matrilysin-1 (MMP7) cleaves galectin-3 and inhibits wound healing in intestinal epithelial cells

    PubMed Central

    Puthenedam, Manjula; Wu, Feng; Shetye, Alysha; Michaels, Alex; Rhee, Ki-Jong; Kwon, John H

    2010-01-01

    Background Galectin-3 is an animal lectin that has been implicated in wound healing and is decreased in inflammatory bowel disease (IBD). Matrix metalloproteinase-7 (MMP7) also known as matrilysin-1, a protease shown to cleave extracellular matrix proteins, is highly expressed in IBD tissues, especially at the leading edge of gastrointestinal ulcers. The ability of MMP7 to cleave galectin-3 and influence wound healing has not been reported previously. Aim To determine whether MMP7 cleaves galectin-3 and modulates wound healing in intestinal epithelial cells. Methods The cleaved fragments of galectin-3 were identified by N-terminal sequencing and mass spectrometry. Western blotting was used to detect the cleaved galectin-3 products in a colonic epithelial cell line (T84 cells). Cell migration was studied by in vitro scratch method. Results We demonstrate for the first time that MMP7 cleaves galectin-3 in vitro, resulting in three cleaved fragments (20.2 kDa, 18.9 kDa and 15.5 kDa). Exogenous treatment of T84 cells with recombinant MMP7 resulted in the appearance of secreted galectin-3 cleavage fragments in the supernatant. MMP7 inhibited cell migration and resulted in wound retraction and the addition of MMP7 to galectin-3 abrogated the wound healing and cell migration induced by galectin-3. Conclusions We have demonstrated that galectin-3 is a substrate for MMP7. Cleavage of galectin-3 may be one mechanism by which MMP7 inhibits wound healing. This study has significance in understanding delayed wound healing in chronic intestinal diseases like intestinal ulcers and IBD where MMP7 protein expression is elevated with a decreased galectin-3 protein expression. PMID:20812334

  16. Repetitive synthetic method for o,o,p-oligophenylenes using C-H arylation.

    PubMed

    Manabe, Kei; Kimura, Takeshi

    2013-01-18

    A synthetic method for the preparation of o,o,p-oligophenylenes has been developed. It involves Miura's C-H arylation of 2-biphenols with aryl nonaflates as the key step. Oligophenylenes with defined lengths are successfully synthesized using this method. PMID:23289430

  17. Direct C-H alkylation and indole formation of anilines with diazo compounds under rhodium catalysis.

    PubMed

    Mishra, Neeraj Kumar; Choi, Miji; Jo, Hyeim; Oh, Yongguk; Sharma, Satyasheel; Han, Sang Hoon; Jeong, Taejoo; Han, Sangil; Lee, Seok-Yong; Kim, In Su

    2015-12-18

    The rhodium(III)-catalyzed direct functionalization of aniline C-H bonds with α-diazo compounds is described. These transformations provide a facile construction of ortho-alkylated anilines with diazo malonates or highly substituted indoles with diazo acetoacetates. PMID:26458276

  18. Selective remote C-H sulfonylation of aminoquinolines with arylsulfonyl chlorides via copper catalysis.

    PubMed

    Liang, Hong-Wen; Jiang, Kun; Ding, Wei; Yuan, Yi; Shuai, Li; Chen, Ying-Chun; Wei, Ye

    2015-12-11

    Copper-catalysed direct C-H bond sulfonylation of aminoquinolines using commercially available and inexpensive arylsulfonyl chlorides as the sulfonylation reagents is described. The reactions took place exclusively at the C5-H position of the quinoline rings and tolerated a wide spectrum of functional groups. Moreover, synthetic transformations of the sulfonylated products led to useful compounds. PMID:26439889

  19. Copper-mediated ortho C-H sulfonylation of benzoic acid derivatives with sodium sulfinates.

    PubMed

    Liu, Jidan; Yu, Lin; Zhuang, Shaobo; Gui, Qingwen; Chen, Xiang; Wang, Wenduo; Tan, Ze

    2015-04-14

    Copper-mediated direct ortho C-H bond sulfonylation of benzoic acid derivatives with sodium sulfinates was achieved by employing an 8-aminoquinoline moiety as the bidentate directing group. Various aryl sulfones were synthesized in good yields with excellent regioselectivity. PMID:25766975

  20. Direct 2-acetoxylation of quinoline N-oxides via copper catalyzed C-H bond activation.

    PubMed

    Chen, Xuan; Zhu, Chongwei; Cui, Xiuling; Wu, Yangjie

    2013-08-01

    An efficient and direct 2-acetoxylation of quinoline N-oxides via copper(I) catalyzed C-H bond activation has been developed. This transformation was achieved using TBHP as an oxidant in the cross-dehydrogenative coupling (CDC) reaction of quinoline N-oxides with aldehydes, and provided a practical pathway to 2-acyloxyl quinolines. PMID:23793162

  1. Nonlinear effects in collision cascades and high energy shock waves during ta-C:H growth

    SciTech Connect

    Piazza, F.; Resto, O.; Morell, G.

    2007-07-01

    The surface topography of hydrogenated tetrahedral amorphous carbon (ta-C:H) is critical for various applications such as microelectromechanical devices, magnetic and optical storage devices, and medical implants. The surface topography of ta-C:H films deposited by distributed electron cyclotron resonance plasma from C{sub 2}H{sub 2} gas precursor was investigated. The effects of pressure, together with ion flux and energy, are studied by atomic force microscopy in relation to the structural evolution of the films. The results are compared with the predictions of the Edward-Wilkinson model [Proc. R. Soc. London, Ser. A 44, 1039 (1966)] recently proposed to account for ta-C:H growth and with previous interpretations based on hypersonic shock waves. The random hillocks observed on the smooth surfaces of ta-C:H films deposited at high pressure are thought to result from the interference of high energy shock waves triggered by C{sub 4}H{sub x}{sup +} ions that produce overlapping collision cascades and induce nonlinear effects.

  2. Palladium-catalysed transannular C-H functionalization of alicyclic amines.

    PubMed

    Topczewski, Joseph J; Cabrera, Pablo J; Saper, Noam I; Sanford, Melanie S

    2016-03-10

    Discovering pharmaceutical candidates is a resource-intensive enterprise that frequently requires the parallel synthesis of hundreds or even thousands of molecules. C-H bonds are present in almost all pharmaceutical agents. Consequently, the development of selective, rapid and efficient methods for converting these bonds into new chemical entities has the potential to streamline pharmaceutical development. Saturated nitrogen-containing heterocycles (alicyclic amines) feature prominently in pharmaceuticals, such as treatments for depression (paroxetine, amitifadine), diabetes (gliclazide), leukaemia (alvocidib), schizophrenia (risperidone, belaperidone), malaria (mefloquine) and nicotine addiction (cytisine, varenicline). However, existing methods for the C-H functionalization of saturated nitrogen heterocycles, particularly at sites remote to nitrogen, remain extremely limited. Here we report a transannular approach to selectively manipulate the C-H bonds of alicyclic amines at sites remote to nitrogen. Our reaction uses the boat conformation of the substrates to achieve palladium-catalysed amine-directed conversion of C-H bonds to C-C bonds on various alicyclic amine scaffolds. We demonstrate this approach by synthesizing new derivatives of several bioactive molecules, including varenicline. PMID:26886789

  3. Helium permeation through a-C:H films deposited on polymeric substrates

    NASA Astrophysics Data System (ADS)

    Valentini, L.; Bellachioma, M. C.; Lozzi, L.; Santucci, S.; Kenny, J. M.

    2002-09-01

    The influence of amorphous hydrogenated carbon a-C:H coatings on gas permeation through polymer films was investigated. Hydrogenated amorphous carbon (a-C:H) films were deposited, at room temperature, from a CH4/Ar plasma produced by a radio frequency glow discharge system at 13.56 MHz. Polyether-etherketone (PEEK) and polyetherimide foils with different thicknesses were used as substrates. The permeation of He was measured and the reduction of the permeability coefficient is correlated here to the composition and density of the a-C:H films. The density and film structure of the layers were analyzed using x-ray reflectivity and Raman spectroscopy of films deposited onto silicon reference samples. A less pronounced reduction of the permeability coefficients for hard, dense diamond-like layers is reported with respect to those obtained for soft, polymer-like layers on PEEK substrates. Surprisingly, the barrier efficacy of the coating decreases with an increase in a-C:H film density. This unexpected result is attributed to intrinsic stress and the corresponding formation of microcracks. The effect of nitrogen incorporation, which reduces film permeability, is investigated in terms of the stress relaxation mechanism promoted. copyright 2002 American Vacuum Society.

  4. The C-H bond dissociation enthalpies in fused N-heterocyclic compounds

    NASA Astrophysics Data System (ADS)

    Wang, Ying-Xing; Zheng, Wen-Rui; Ding, Lan-Lan

    2016-03-01

    The C-H bond dissociation enthalpies (BDEs) of the 26 N, O, S-containing mono-heterocyclic compounds were evaluated using the composite high-level ab initio methods G3 and G4. The C-H BDEs for 32 heterocyclic compounds were calculated using 8 types of density functional theory (DFT) methods. Comparing with the experimental values, the BMK method gave the lowest root mean square error (RMSE) of 7.2 kJ/mol. Therefore, the C-H BDEs of N-fused-heterocyclic compounds at different positions were investigated by the BMK method. By NBO analysis two linear relationships between the C-H BDEs of quinoline and isoquinoline with natural charges qC/ e in molecules and with natural charges qC/ e in radicals were found. The substituent effects on C(α)-H BDEs in N-fused-heterocyclic compounds were also discussed. It was found that there are two linear relationships between the C(α)-H BDEs of quinoline and isoquinoline derivatives with natural charges qC(α)/ e for the EDGs and CEGs substituents.

  5. Ruthenium(II)-Catalyzed Decarboxylative C-H Activation: Versatile Routes to meta-Alkenylated Arenes.

    PubMed

    Kumar, N Y Phani; Bechtoldt, Alexander; Raghuvanshi, Keshav; Ackermann, Lutz

    2016-06-01

    Ruthenium(II) bis(carboxylate)s proved highly effective for two decarboxylative C-H alkenylation strategies. The decarboxylation proceeded efficiently at rather low temperatures. The unique versatility of the decarboxylative ruthenium(II) catalysis is reflected in the oxidative olefinations with alkenes as well as the redox-neutral hydroarylations of alkynes. PMID:26996920

  6. Allylic and benzylic sp3 C-H oxidation in water.

    PubMed

    Ang, Wei Jie; Lam, Yulin

    2015-01-28

    A copper-catalyzed method for the oxidation of allylic and benzylic sp(3) C-H by aqueous tert-butyl hydroperoxide (T-Hydro) in water using a recyclable fluorous ligand has been developed. The reaction procedure is tolerant to additional functional groups and the fluorous ligand could be reused with little loss of catalytic activity. PMID:25412371

  7. Synthesis of Mesoionic Isoquinolines by Rhodium(III)-Catalyzed C-H Activation.

    PubMed

    Zhang, Wei; Wang, Cheng-Qi; Lin, Hui; Dong, Lin; Xu, Yan-Jun

    2016-01-18

    Hydroxyl-substituted benzaldimines underwent a Rh(III) -catalyzed C-H activation and annulation with alkynes to provide novel mesoionic isoquinoline derivatives in moderate to excellent yields using oxygen as an internal anion source. This simple and efficient approach has a broad substrate scope. PMID:26671527

  8. Copper-catalyzed phosphorylation of sp(2) C-H bonds.

    PubMed

    Wang, Shan; Guo, Rui; Wang, Gao; Chen, Shan-Yong; Yu, Xiao-Qi

    2014-10-28

    The phosphorylation of the ortho C-H bonds in benzamides containing an 8-aminoquinoline moiety as a bidentate directing group with H-phosphonates using copper as a catalyst under mild temperature conditions is described. This method shows high functional group compatibility and selectively gives mono-substituted products. PMID:25204577

  9. Copper-catalyzed aliphatic C-H amination with an amidine moiety.

    PubMed

    Chen, Hui; Sanjaya, Stephen; Wang, Yi-Feng; Chiba, Shunsuke

    2013-01-01

    A method for amination of aliphatic C-H bonds of N-alkylamidines is described that utilizes Cu(OAc)(2) as the catalyst in the presence of PhI(OAc)(2) and K(3)PO(4). The resulting products, dihydroimidazoles and tetrahydropyrimidines, could be converted into the corresponding diamines by hydride reduction. PMID:23252919

  10. The Importance of Both Similarities and Differences in Multicultural Counseling: Reaction to C. H. Patterson.

    ERIC Educational Resources Information Center

    Pederson, Paul

    1996-01-01

    Reacts to C. H. Patterson's article (this issue) concerning multicultural counseling. Asserts that there are problems with historical concepts of counseling, the definition of culture, and the practice of counseling in multicultural settings. A cultural-centered approach to counseling recognizes that the client has internalized patterns of…

  11. Time resolved infrared studies of C-H bond activation by organometallics

    SciTech Connect

    Asplund, M.C. |

    1998-06-01

    This work describes how step-scan Fourier Transform Infrared spectroscopy and visible and near infrared ultrafast lasers have been applied to the study of the photochemical activation of C-H bonds in organometallic systems, which allow for the selective breaking of C-H bonds in alkanes. The author has established the photochemical mechanism of C-H activation by Tp{sup *}Rh(CO){sub 2}(Tp{sup *} = HB-Pz{sup *}{sub 3}, Pz = 3,5-dimethylpyrazolyl) in alkane solution. The initially formed monocarbonyl forms a weak solvent complex, which undergoes a change in Tp{sup *} ligand connectivity. The final C-H bond breaking step occurs at different time scales depending on the structure of the alkane. In linear solvents, the time scale is <50 ns and cyclic alkanes is {approximately}200 ps. The reactivity of the Tp{sup *}Rh(CO){sub 2} system has also been studied in aromatic solvents. Here the reaction proceeds through two different pathways, with very different time scales. The first proceeds in a manner analogous to alkanes and takes <50 ns. The second proceeds through a Rh-C-C complex, and takes place on a time scale of 1.8 {micro}s.

  12. Efficient photolytic C-H bond functionalization of alkylbenzene with hypervalent iodine(iii) reagent.

    PubMed

    Sakamoto, Ryu; Inada, Tsubasa; Selvakumar, Sermadurai; Moteki, Shin A; Maruoka, Keiji

    2016-03-01

    A practical approach to radical C-H bond functionalization by the photolysis of a hypervalent iodine(iii) reagent is presented. The photolysis of [bis(trifluoroacetoxy)iodo]benzene (PIFA) leads to the generation of trifluoroacetoxy radicals, which allows the smooth transformation of various alkylbenzenes to the corresponding benzyl ester compounds under mild reaction conditions. PMID:26686276

  13. Palladium-catalyzed intramolecular C-H arylation of arenes using tosylates and mesylates as electrophiles.

    PubMed

    Nervig, Christine S; Waller, Peter J; Kalyani, Dipannita

    2012-09-21

    This paper describes a method for the palladium catalyzed intramolecular C-H arylation using tosylates and mesylates as electrophiles. The transformation is efficient for the synthesis of various heterocyclic motifs including furans, carbazoles, indoles, and lactams. Additionally, a protocol for the one-pot sequential tosylation/arylation of phenol derivatives is presented. PMID:22974229

  14. Palladium-catalysed transannular C-H functionalization of alicyclic amines

    NASA Astrophysics Data System (ADS)

    Topczewski, Joseph J.; Cabrera, Pablo J.; Saper, Noam I.; Sanford, Melanie S.

    2016-03-01

    Discovering pharmaceutical candidates is a resource-intensive enterprise that frequently requires the parallel synthesis of hundreds or even thousands of molecules. C-H bonds are present in almost all pharmaceutical agents. Consequently, the development of selective, rapid and efficient methods for converting these bonds into new chemical entities has the potential to streamline pharmaceutical development. Saturated nitrogen-containing heterocycles (alicyclic amines) feature prominently in pharmaceuticals, such as treatments for depression (paroxetine, amitifadine), diabetes (gliclazide), leukaemia (alvocidib), schizophrenia (risperidone, belaperidone), malaria (mefloquine) and nicotine addiction (cytisine, varenicline). However, existing methods for the C-H functionalization of saturated nitrogen heterocycles, particularly at sites remote to nitrogen, remain extremely limited. Here we report a transannular approach to selectively manipulate the C-H bonds of alicyclic amines at sites remote to nitrogen. Our reaction uses the boat conformation of the substrates to achieve palladium-catalysed amine-directed conversion of C-H bonds to C-C bonds on various alicyclic amine scaffolds. We demonstrate this approach by synthesizing new derivatives of several bioactive molecules, including varenicline.

  15. Metal-catalysed azidation of tertiary C-H bonds suitable for late-stage functionalization

    NASA Astrophysics Data System (ADS)

    Sharma, Ankit; Hartwig, John F.

    2015-01-01

    Many enzymes oxidize unactivated aliphatic C-H bonds selectively to form alcohols; however, biological systems do not possess enzymes that catalyse the analogous aminations of C-H bonds. The absence of such enzymes limits the discovery of potential medicinal candidates because nitrogen-containing groups are crucial to the biological activity of therapeutic agents and clinically useful natural products. In one prominent example illustrating the importance of incorporating nitrogen-based functionality, the conversion of the ketone of erythromycin to the -N(Me)CH2- group in azithromycin leads to a compound that can be dosed once daily with a shorter treatment time. For such reasons, synthetic chemists have sought catalysts that directly convert C-H bonds to C-N bonds. Most currently used catalysts for C-H bond amination are ill suited to the intermolecular functionalization of complex molecules because they require excess substrate or directing groups, harsh reaction conditions, weak or acidic C-H bonds, or reagents containing specialized groups on the nitrogen atom. Among C-H bond amination reactions, those forming a C-N bond at a tertiary alkyl group would be particularly valuable, because this linkage is difficult to form from ketones or alcohols that might be created in a biosynthetic pathway by oxidation. Here we report a mild, selective, iron-catalysed azidation of tertiary C-H bonds that occurs without excess of the valuable substrate. The reaction tolerates aqueous environments and is suitable for the functionalization of complex structures in the late stages of a multistep synthesis. Moreover, this azidation makes it possible to install a range of nitrogen-based functional groups, including those from Huisgen `click' cycloadditions and the Staudinger ligation. We anticipate that these reactions will create opportunities to modify natural products, their precursors and their derivatives to produce analogues that contain different polarity and charge as a

  16. The cleaved cytoplasmic tail of polycystin-1 regulates Src-dependent STAT3 activation.

    PubMed

    Talbot, Jeffrey J; Song, Xuewen; Wang, Xiaofang; Rinschen, Markus M; Doerr, Nicholas; LaRiviere, Wells B; Schermer, Bernhard; Pei, York P; Torres, Vicente E; Weimbs, Thomas

    2014-08-01

    Polycystin-1 (PC1) mutations result in proliferative renal cyst growth and progression to renal failure in autosomal dominant polycystic kidney disease (ADPKD). The transcription factor STAT3 (signal transducer and activator of transcription 3) was shown to be activated in cyst-lining cells in ADPKD and PKD mouse models and may drive renal cyst growth, but the mechanisms leading to persistent STAT3 activation are unknown. A proteolytic fragment of PC1 corresponding to the cytoplasmic tail, PC1-p30, is overexpressed in ADPKD. Here, we show that PC1-p30 interacts with the nonreceptor tyrosine kinase Src, resulting in Src-dependent activation of STAT3 by tyrosine phosphorylation. The PC1-p30-mediated activation of Src/STAT3 was independent of JAK family kinases and insensitive to the STAT3 inhibitor suppressor of cytokine signaling 3. Signaling by the EGF receptor (EGFR) or cAMP amplified the activation of Src/STAT3 by PC1-p30. Expression of PC1-p30 changed the cellular response to cAMP signaling. In the absence of PC1-p30, cAMP dampened EGFR- or IL-6-dependent activation of STAT3; in the presence of PC1-p30, cAMP amplified Src-dependent activation of STAT3. In the polycystic kidney (PCK) rat model, activation of STAT3 in renal cystic cells depended on vasopressin receptor 2 (V2R) signaling, which increased cAMP levels. Genetic inhibition of vasopressin expression or treatment with a pharmacologic V2R inhibitor strongly suppressed STAT3 activation and reduced renal cyst growth. These results suggest that PC1, via its cleaved cytoplasmic tail, integrates signaling inputs from EGFR and cAMP, resulting in Src-dependent activation of STAT3 and a proliferative response. PMID:24578126

  17. Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2.

    PubMed

    Hirayasu, Kouyuki; Saito, Fumiji; Suenaga, Tadahiro; Shida, Kyoko; Arase, Noriko; Oikawa, Keita; Yamaoka, Toshifumi; Murota, Hiroyuki; Chibana, Hiroji; Nakagawa, Ichiro; Kubori, Tomoko; Nagai, Hiroki; Nakamaru, Yuji; Katayama, Ichiro; Colonna, Marco; Arase, Hisashi

    2016-01-01

    Microbial proteases degrade a variety of host proteins(1-3). However, it has remained largely unknown why microorganisms have evolved to acquire such proteases and how the host responds to microbially degraded products. Here, we have found that immunoglobulins disrupted by microbial pathogens are specifically detected by leukocyte immunoglobulin-like receptor A2 (LILRA2), an orphan activating receptor expressed on human myeloid cells. Proteases from Mycoplasma hyorhinis, Legionella pneumophila, Streptococcus pneumonia and Candida albicans cleaved the N-terminus of immunoglobulins. Identification of the immunoglobulin-cleaving protease from L. pneumophila revealed that the protease is conserved across some bacteria including Vibrio spp. and Pseudomonas aeruginosa. These microbially cleaved immunoglobulins but not normal immunoglobulins stimulated human neutrophils via LILRA2. In addition, stimulation of primary monocytes via LILRA2 inhibited the growth of L. pneumophila. When mice were infected with L. pneumophila, immunoglobulins were cleaved and recognized by LILRA2. More importantly, cleaved immunoglobulins were detected in patients with bacterial infections and stimulated LILRA2-expressing cells. Our findings demonstrate that LILRA2 is a type of innate immune receptor in the host immune system that detects immunoglobulin abnormalities caused by microbial pathogens. PMID:27572839

  18. C--H...O hydrogen-bonding and C--H...pi interactions in 3-(4-fluorophenyl)-1,5,7-trimethyl-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidine-2,4-dione.

    PubMed

    Patel, Urmila H; Patel, Pinal D; Thakker, Neha

    2007-06-01

    In the title compound, C(16)H(14)FN(3)O(2), a diverse set of weak intermolecular C--H...pi, pi-pi and C--H...O interactions link the molecules into sheets. The C--H...O interactions generate centrosymmetric rings with a graph-set motif of R(2)(2)(14) and chains with a C(8) motif. PMID:17551197

  19. The Caspase-8 Homolog Dredd Cleaves Imd and Relish but Is Not Inhibited by p35*

    PubMed Central

    Kim, Chan-Hee; Paik, Donggi; Rus, Florentina; Silverman, Neal

    2014-01-01

    In Drosophila, the Imd pathway is activated by diaminopimelic acid-type peptidoglycan and triggers the humoral innate immune response, including the robust induction of antimicrobial peptide gene expression. Imd and Relish, two essential components of this pathway, are both endoproteolytically cleaved upon immune stimulation. Genetic analyses have shown that these cleavage events are dependent on the caspase-8 like Dredd, suggesting that Imd and Relish are direct substrates of Dredd. Among the seven Drosophila caspases, we find that Dredd uniquely promotes Imd and Relish processing, and purified recombinant Dredd cleaves Imd and Relish in vitro. In addition, interdomain cleavage of Dredd is not required for Imd or Relish processing and is not observed during immune stimulation. Baculovirus p35, a suicide substrate of executioner caspases, is not cleaved by purified Dredd in vitro. Consistent with this biochemistry but contrary to earlier reports, p35 does not interfere with Imd signaling in S2* cells or in vivo. PMID:24891502

  20. High-throughput assay and engineering of self-cleaving ribozymes by sequencing

    PubMed Central

    Kobori, Shungo; Nomura, Yoko; Miu, Anh; Yokobayashi, Yohei

    2015-01-01

    Self-cleaving ribozymes are found in all domains of life and are believed to play important roles in biology. Additionally, self-cleaving ribozymes have been the subject of extensive engineering efforts for applications in synthetic biology. These studies often involve laborious assays of multiple individual variants that are either designed rationally or discovered through selection or screening. However, these assays provide only a limited view of the large sequence space relevant to the ribozyme function. Here, we report a strategy that allows quantitative characterization of greater than 1000 ribozyme variants in a single experiment. We generated a library of predefined ribozyme variants that were converted to DNA and analyzed by high-throughput sequencing. By counting the number of cleaved and uncleaved reads of every variant in the library, we obtained a complete activity profile of the ribozyme pool which was used to both analyze and engineer allosteric ribozymes. PMID:25829176

  1. New classes of self-cleaving ribozymes revealed by comparative genomics analysis.

    PubMed

    Weinberg, Zasha; Kim, Peter B; Chen, Tony H; Li, Sanshu; Harris, Kimberly A; Lünse, Christina E; Breaker, Ronald R

    2015-08-01

    Enzymes made of RNA catalyze reactions that are essential for protein synthesis and RNA processing. However, such natural ribozymes are exceedingly rare, as evidenced by the fact that the discovery rate for new classes has dropped to one per decade from about one per year during the 1980s. Indeed, only 11 distinct ribozyme classes have been experimentally validated to date. Recently, we recognized that self-cleaving ribozymes frequently associate with certain types of genes from bacteria. Herein we exploited this association to identify divergent architectures for two previously known ribozyme classes and to discover additional noncoding RNA motifs that are self-cleaving RNA candidates. We identified three new self-cleaving classes, which we named twister sister, pistol and hatchet, from this collection, suggesting that even more ribozymes remain hidden in modern cells. PMID:26167874

  2. New classes of self-cleaving ribozymes revealed by comparative genomics analysis

    PubMed Central

    Weinberg, Zasha; Kim, Peter B.; Chen, Tony H.; Li, Sanshu; Harris, Kimberly A.; Lünse, Christina E.; Breaker, Ronald R.

    2015-01-01

    Enzymes made of RNA catalyze reactions that are essential for protein synthesis and RNA processing. However, such natural ribozymes are exceedingly rare, as evident by the fact that the discovery rate for new classes has dropped to one per decade from about one per year during the 1980s. Indeed, only 11 distinct ribozyme classes have been experimentally validated to date. Recently, we recognized that self-cleaving ribozymes frequently associate with certain types of genes from bacteria. Herein this synteny was exploited to identify divergent architectures for two previously known ribozyme classes and to discover additional noncoding RNA motifs that are self-cleaving RNA candidates. Three new self-cleaving classes, named twister sister, pistol and hatchet, have been identified from this collection, suggesting that even more ribozymes remain hidden in modern cells. PMID:26167874

  3. Deposition of a-C:H films on a nanotrench pattern by bipolar PBII&D

    NASA Astrophysics Data System (ADS)

    Hirata, Yuki; Nakahara, Yuya; Nagato, Keisuke; Choi, Junho

    2016-06-01

    In this study, hydrogenated amorphous carbon (a-C:H) films were deposited on a nanotrench pattern (300 nm pitch, aspect ratio: 2.0) by bipolar-type plasma based ion implantation and deposition technique (bipolar PBII&D), and the effects of bipolar pulse on the film properties were investigated. Moreover, the behaviour of ions and radicals surrounding the nanotrench was analyzed to clarify the coating mechanism and properties of the a-C:H films on the nanotrench. Further, thermal nanoimprint lithography was carried out using the nanotrench pattern coated with a-C:H films as the mold, and the mold release properties were evaluated. All nanotrench surfaces were successfully coated with the a-C:H films, but the film thickness on the top, sidewall, and bottom surfaces of the trench were not uniform. The surface roughness of the a-C:H films was found to decrease at a higher positive voltage; this happens due to the higher electron temperature around the nanotrench because of the surface migration of plasma particles arrived on the trench. The effects of the negative voltage on the behaviour of ions and radicals near the sidewall of the nanotrench are quite similar to those near the microtrench reported previously (Park et al 2014 J. Phys. D: Appl. Phys. 47 335306). However, the positive pulse voltage was also found to affect the behaviour of ions and radicals near the sidewall surface. The incident angles of ions on the sidewall surface increased with the positive pulse voltage because the energy of incoming ions on the trench decreases with increasing positive voltage. Moreover, the incident ion flux on the sidewall is affected by the positive voltage history. Further, the radical flux decreases with increasing positive voltage. It can be concluded that a higher positive voltage at a lower negative voltage condition is good to obtain better film properties and higher film thickness on the sidewall surface. Pattern transfer properties for the nanoimprint formed by

  4. Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura.

    PubMed

    Furlan, M; Robles, R; Solenthaler, M; Wassmer, M; Sandoz, P; Lämmle, B

    1997-05-01

    In patients with thrombotic thrombocytopenic purpura (TTP), excessive intravascular platelet aggregation has been associated with appearance in plasma of unusually large von Willebrand factor (vWF) multimers. These extremely adhesive vWF multimers may arise due to deficiency of a "depolymerase" cleaving vWF to smaller molecular forms, either by reducing the interdimeric disulfide bridges or by proteolytic degradation. We studied the activity of a recently described vWF-cleaving protease in four patients with chronic relapsing TTP. Diluted plasma samples of TTP patients were incubated with purified normal human vWF in the presence of a serine protease inhibitor, at low ionic strength, and in the presence of urea and barium ions. The extent of vWF degradation was assayed by electrophoresis in sodium dodecyl sulfate-agarose gels and immunoblotting. Four patients, that included two brothers, with chronic relapsing TTP displayed either substantially reduced levels or a complete absence of vWF-cleaving protease activity. In none of these patient plasmas was an inhibitor of or an antibody against the vWF-cleaving protease established. Our data suggest that the unusually large vWF multimers found in TTP patients may be caused by deficient vWF-cleaving protease activity. Deficiency of this protease may be inherited in an autosomal recessive manner and seems to predispose to chronic relapsing TTP. The assay of the vWF-cleaving protease activity may be used as a sensitive diagnostic tool for identification of subjects with a latent TTP tendency. PMID:9129011

  5. Low-threshold, high quantum efficiency stop-cleaved InGaAsP semiconductor lasers

    SciTech Connect

    Antreasyan, A.; Chen, C.Y.; Napholtz, S.G.; Wilt, D.P.

    1985-08-15

    InGaAsP double-channel--planar-buried-heterostructure lasers with stop-cleaved mirrors emitting at 1.3 ..mu..m have been fabricated. Threshold currents as low as 18 mA and differential quantum efficiencies as high as 39% have been obtained. Furthermore, we have achieved a yield greater than 50% in obtaining good quality facets utilizing the stop-cleaving technique. Our result represents one of the lowest threshold currents obtained so far at 1.3-..mu..m wavelength among the structures designed for monolithic optoelectronic integration.

  6. Monolithically integrated external feedback InGaAsP lasers using stop-cleaving technique

    SciTech Connect

    Antreasyan, A.; Chen, C.Y.; Napholtz, S.G.; Wilt, D.P.; Ostermayer, F.W.

    1986-02-15

    We have developed a monolithically integrated external feedback laser utilizing a pair of stop-cleaved double channel planar buried heterostructure lasers emitting at 1.3 ..mu..m. The external feedback is provided by the stop cleaved facet of the second cavity. A sidemode rejection ratio of 200 : 1 has been obtained with a laser having a 250-..mu..m cavity length and an external resonator length of 200 ..mu..m. Since both lasers are fabricated in a self-aligned structure, this device may prove to be a powerful scheme for injection locking to reduce dynamic linewidth.

  7. Cleaved-coupled-cavity lasers with large cavity length ratios for enhanced stability

    SciTech Connect

    Bowers, J.E.; Bjorkholm, J.E.; Burrus, C.A.; Coldren, L.A.; Hemenway, B.R.; Wilt, D.P.

    1984-05-01

    The fabrication and operation of the first cleaved-coupled-cavity (C/sup 3/) semiconductor lasers with large cavity length ratios are described. The internal cleaved facet is precisely positioned by photochemically etching a groove through most of the wafer. Single longitudinal mode operation is obtained over a temperature range of 21 /sup 0/C and over a current range of threshold to greater than four times threshold. Sidemode suppression of 100:1 was measured when the laser was modulated at 350 MHz with an extinction ratio greater than 10:1. These results are experimentally and theoretically compared to approximately equal length C/sup 3/ lasers.

  8. C-H\\ctdot O hydrogen bonding in a 4-fluorobenzoate multilayer induced by silver nanoparticles

    NASA Astrophysics Data System (ADS)

    Perry, Donald A.; Schiefer, Elizabeth M.; Cordova, James S.; Bonde, Ashley M.; Razer, Taylor M.; Primm, Katherine M.; Chen, Tsung Yen; Biris, Alexandru S.

    2011-08-01

    SERS, SEIRA, and DFT calculations showed silver nanoparticles can stimulate C-H⋯O hydrogen bonding in 4-fluorobenzoate ion/ n-heptane multilayers. SERS/DFT demonstrated that 4-fluorobenzoic acid (4FBA) adsorbed as a 4-fluorobenzoate (4FBT) monolayer on nanosilver. Ionization of 4FBA to 4FBT occurred in the multilayer when 4FBA was deposited in n-heptane onto nanosilver. Frequency shifts in SEIRA bands of 4FBT COO stretch and n-heptane CH bend modes illustrated a change in the degree of C-H⋯O hydrogen bonding as more 4FBT/ n-heptane was adsorbed to the multilayer. This work will influence many research areas such as sensors formed from thin organic layers on metal nanoparticles.

  9. Platinum containing amorphous hydrogenated carbon (a-C:H/Pt) thin films as selective solar absorbers

    NASA Astrophysics Data System (ADS)

    Lan, Yung-Hsiang; Brahma, Sanjaya; Tzeng, Y. H.; Ting, Jyh-Ming

    2014-10-01

    We have investigated a double-cermet structured thin film in which an a-C:H thin film was used as an anti-reflective (AR) layer and two platinum-containing amorphous hydrogenated carbon (a-C:H/Pt) thin films were used as the double cermet layers. A reactive co-sputter deposition method was used to prepare both the anti-reflective and cermet layers. Effects of the target power and heat treatment were studied. The obtained films were characterized using X-ray diffraction, scanning electron microscopy, high-resolution transmission electron microscopy. The optical absorptance and emittance of the as deposited and annealed films were determined using UV-vis-NIR spectroscopy. We show that the optical absorptance of the resulting double-cermet structured thin film is as high as 96% and remains to be 91% after heat treatment at 400 °C, indicating the thermal stability of the film.

  10. Aromatic C-H bond activation revealed by infrared multiphoton dissociation spectroscopy.

    PubMed

    Jašíková, Lucie; Hanikýřová, Eva; Schröder, Detlef; Roithová, Jana

    2012-04-01

    Metal-oxide cations are models of catalyst mediating the C-H bond activation of organic substrates. One of the most powerful reagents suggested in the gas phase is based on CuO(+) . Here, we describe the activation of the aromatic C-H bonds of phenanthroline in its complex with CuO(+) . The reaction sequence starts with a hydrogen atom abstraction by the oxygen atom from the 2-position of the phenanthroline ring, followed by OH migration to the ring. Using infrared multiphoton spectroscopy, it is shown that the reaction can be energetically facilitated by additional coordination of a water ligand to the copper ion. As the reaction is intramolecular, a spectroscopic characterization of the product is mandatory in order to unambiguously address the reaction mechanism. PMID:22689621

  11. Catalytic C-H bond functionalisation chemistry: the case for quasi-heterogeneous catalysis.

    PubMed

    Reay, Alan J; Fairlamb, Ian J S

    2015-11-25

    This feature article examines the potential of heterogeneous Pd species to mediate catalytic C-H bond functionalisation processes employing suitable substrates (e.g. aromatic/heteroaromatic compounds). A focus is placed on the reactivity of supported and non-supported Pd nanoparticle (PdNPs) catalysts, in addition to the re-appropriation of well-established heterogeneous Pd catalysts such as Pd/C. Where possible, reasonable comparisons are made between PdNPs and traditional 'homogeneous' Pd precatalyst sources (which form PdNPs). The involvement of higher order Pd species in traditional cross-coupling processes, such as Mizoroki-Heck, Sonogashira and Suzuki-Miyaura reactions, allows the exemplification of potential future topics for study in the area of catalytic C-H bond functionalisation processes. PMID:26439875

  12. Aromatic Cyanoalkylation through Double C-H Activation Mediated by Ni(III).

    PubMed

    Zhou, Wen; Zheng, Shuai; Schultz, Jason W; Rath, Nigam P; Mirica, Liviu M

    2016-05-11

    Herein we report an atom- and step-economic aromatic cyanoalkylation reaction that employs nitriles as building blocks and proceeds through Csp(2)-H and Csp(3)-H bond activation steps mediated by Ni(III). In addition to cyanomethylation with MeCN, regioselective α-cyanoalkylation was observed with various nitrile substrates to generate secondary and tertiary nitriles. Importantly, to the best of our knowledge these are the first examples of C-H bond activation reactions occurring at a Ni(III) center, which may exhibit different reactivity and selectivity profiles than those corresponding to analogous Ni(II) centers. These studies provide guiding principles to design catalytic C-H activation and functionalization reactions involving high-valent Ni species. PMID:27120207

  13. Copper-catalyzed oxaziridine-mediated oxidation of C-H bonds.

    PubMed

    Motiwala, Hashim F; Gülgeze, Belgin; Aubé, Jeffrey

    2012-08-17

    The highly regio- and chemoselective oxidation of activated C-H bonds has been observed via copper-catalyzed reactions of oxaziridines. The oxidation proceeded with a variety of substrates, primarily comprising allylic and benzylic examples, as well as one example of an otherwise unactivated tertiary C-H bond. The mechanism of the reaction is proposed to involve single-electron transfer to the oxaziridines to generate a copper-bound radical anion, followed by hydrogen atom abstraction and collapse to products, with regeneration of the catalyst by a final single-electron transfer event. The involvement of allylic radical intermediates was supported by a radical-trapping experiment with TEMPO. PMID:22830300

  14. C-H complex defects and their influence in ZnO single crystal

    NASA Astrophysics Data System (ADS)

    Xie, Hui; Zhao, You-Wen; Liu, Tong; Dong, Zhi-Yuan; Yang, Jun; Liu, Jing-Ming

    2015-10-01

    Infrared absorption local vibration mode (LVM) spectroscopy is used to study hydrogen related defects in n-type ZnO single crystal grown by a closed chemical vapor transport (CVT) method under Zn-rich growth conditions, in which carbon is used as a transport agent. Two C-H complex related absorption peaks at 2850 cm-1 and 2919 cm-1 are detected in the sample. The formation of the C-H complex implies an effect of carbon donor passivation and formation suppression of H donor in ZnO. The influence of the complex defects on the electrical property of the CVT-ZnO is discussed based on Hall measurement results and residual impurity analysis. Project supported by the National Natural Science Foundation of China (Grant No. 61474104).

  15. Theoretical study of the C-H bond dissociation energy of C2H

    NASA Technical Reports Server (NTRS)

    Bauschlicher, Charles W., Jr.; Langhoff, Stephen R.

    1990-01-01

    A theoretical study of the convergence of the C-H bond dissociation energy D(0) in C2H with respect to both the one- and n-particle spaces is presented. The calculated C-H bond energies of C2H2 and C2H4, which are in excellent agreement with experiment, are used for calibration. The best estimate for D(0) of 112.4 + or - 2.0 kcal/mol is slightly below the recent experimental value of 116.3 + or - 2.6 kcal/mol, but substantially above a previous theoretical estimate of 102 kcal/mol. The remaining discrepancy with experiment may reflect primarily the uncertainty in the experimental D(0) value of C2 required in the analysis.

  16. BORON CATALYSIS. Metal-free catalytic C-H bond activation and borylation of heteroarenes.

    PubMed

    Légaré, Marc-André; Courtemanche, Marc-André; Rochette, Étienne; Fontaine, Frédéric-Georges

    2015-07-31

    Transition metal complexes are efficient catalysts for the C-H bond functionalization of heteroarenes to generate useful products for the pharmaceutical and agricultural industries. However, the costly need to remove potentially toxic trace metals from the end products has prompted great interest in developing metal-free catalysts that can mimic metallic systems. We demonstrated that the borane (1-TMP-2-BH2-C6H4)2 (TMP, 2,2,6,6-tetramethylpiperidine) can activate the C-H bonds of heteroarenes and catalyze the borylation of furans, pyrroles, and electron-rich thiophenes. The selectivities complement those observed with most transition metal catalysts reported for this transformation. PMID:26228143

  17. C-H activation of cycloalkenes by dimetallynes (M = Ge, Sn) under ambient conditions.

    PubMed

    Summerscales, Owen T; Fettinger, James C; Power, Philip P

    2011-08-10

    Treatment of the dimetallynes Ar'EEAr' [E = Ge, Sn; Ar' = C(6)H(3)-2,6-(C(6)H(3)-2,6-iPr(2))(2)] with a cyclic olefin-cyclopentadiene (CpH), cyclopentene, 1,4-cyclohexadiene (CHD), or cyclohexene-showed that, with the exception of cyclohexene, they react readily, affording C-H activation at room temperature. Reaction of the digermyne and distannyne with CpH gave the cyclopentadienyl anion, which is bound in a π-fashion to a mononuclear group 14 element center, along with evolution of hydrogen gas. Unusually, the digermyne also reacted with cyclopentene to give the same dehydroaromatization product, formed from triple C-H activation/dehydrogenation. It also was found to react with CHD to give a mixture of (Ar'GeH)(2), benzene, and a new 7-germanorbornadiene species bound to a cyclohex-2-enyl fragment. PMID:21749107

  18. Palladium-Catalyzed Allylic C-H Bond Functionalization of Olefins

    NASA Astrophysics Data System (ADS)

    Liu, Guosheng; Wu, Yichen

    Transition metal-mediated carbon-hydrogen bond cleavage and functionalization is a mechanistically interesting and synthetically attractive process. One of the important cases is the removal of a allylic hydrogen from an olefin by a PdII salt to yield a π-allylpalladium complex, followed by nucleophilic attack to efficient produce allylic derivatives. In contrast to the well-known allylic acetoxylation of cyclohexene, the reaction of open-chain olefins is fairly poor until recent several years. Some palladium catalytic systems have been reported to achieve allylic C-H functionalization, including acetoxylation, amination and alkylation of terminal alkenes. In the most of cases, ligand is crucial to the success of the transformation. This review surveys the recent development of palladium-catalyzed allylic C-H functionalziation of alkenes. These results promise a significant increase in the scope of olefin transformation.

  19. A Palladium(II)-Catalyzed C-H Activation Cascade Sequence for Polyheterocycle Formation.

    PubMed

    Cooper, Stephen P; Booker-Milburn, Kevin I

    2015-05-26

    Polyheterocycles are found in many natural products and are useful moieties in functional materials and drug design. As part of a program towards the synthesis of Stemona alkaloids, a novel palladium(II)-catalyzed C-H activation strategy for the construction of such systems has been developed. Starting from simple 1,3-dienyl-substituted heterocycles, a large range of polycyclic systems containing pyrrole, indole, furan and thiophene moieties can be synthesized in a single step. PMID:25872492

  20. Recent advances in copper-catalyzed C-H bond amidation.

    PubMed

    Wan, Jie-Ping; Jing, Yanfeng

    2015-01-01

    Copper catalysis has been known as a powerful tool for its ubiquitous application in organic synthesis. One of the fundamental utilities of copper catalysis is in the C-N bond formation by using carbon sources and nitrogen functional groups such as amides. In this review, the recent progress in the amidation reactions employing copper-catalyzed C-H amidation is summarized. PMID:26664644

  1. Boron-Catalyzed Aromatic C-H Bond Silylation with Hydrosilanes.

    PubMed

    Ma, Yuanhong; Wang, Baoli; Zhang, Liang; Hou, Zhaomin

    2016-03-23

    Metal-free catalytic C-H silylation of a series of aromatic compounds such as N,N-disubstituted anilines with various hydrosilanes has been achieved for the first time using commercially available B(C6F5)3 as a catalyst. This protocol features simple and neutral reaction conditions, high regioselectivity, wide substrate scope (up to 40 examples), Si-Cl bond compatibility, and no requirement for a hydrogen acceptor. PMID:26959863

  2. Facile C-H alkylation in water: enabling defect-free materials for optoelectronic devices.

    PubMed

    Saikia, Gunin; Iyer, Parameswar K

    2010-04-16

    A facile method for the alkylation of fluorene achieved via direct C-H alkylation under aqueous conditions is reported, wherein the formation of fluorenone is inhibited, resulting in the exclusive formation of the desired dialkyl-substituted fluorene monomer. As a proof of concept, this method has also been successfully extended to perform N-alkylation of carbazole, diphenylamine, and N,N-dialkylation of aniline in high yields. PMID:20297790

  3. Copper(I)-catalyzed alkylation of polyfluoroarenes through Direct C-H bond functionalization.

    PubMed

    Xu, Shuai; Wu, Guojiao; Ye, Fei; Wang, Xi; Li, Huan; Zhao, Xia; Zhang, Yan; Wang, Jianbo

    2015-04-01

    The copper(I)-catalyzed alkylation of electron-deficient polyfluoroarenes with N-tosylhydrazones and diazo compounds has been developed. This reaction uses readily available starting materials and is operationally simple, thus representing a practical method for the construction of C(sp(2) )-C(sp(3) ) bonds with polyfluoroarenes through direct C-H bond functionalization. Mechanistically, copper(I) carbene formation and subsequent migratory insertion are proposed as the key steps in the reaction pathway. PMID:25690761

  4. C-H bond halogenation catalyzed or mediated by copper: an overview.

    PubMed

    Hao, Wenyan; Liu, Yunyun

    2015-01-01

    Carbon-halogen (C-X) bonds are amongst the most fundamental groups in organic synthesis, they are frequently and widely employed in the synthesis of numerous organic products. The generation of a C-X bond, therefore, constitutes an issue of universal interest. Herein, the research advances on the copper-catalyzed and mediated C-X (X = F, Cl, Br, I) bond formation via direct C-H bond transformation is reviewed. PMID:26664634

  5. C-H Bond Functionalizations with Palladium(II): Intramolecular Oxidative Annulations of Arenes

    PubMed Central

    Ferreira, Eric M.; Zhang, Haiming

    2008-01-01

    Oxidative annulations for the synthesis of carbocycles were developed using a catalytic palladium(II) system. Indoles with pendant olefin tethers were oxidatively cyclized to form annulated products. Electron-rich aromatic systems were also investigated, culminating in the synthesis of benzofurans and dihydrobenzofurans by a similar protocol. These reactions were demonstrated to proceed by an initial C-H bond functionalization event, followed by olefin insertion and β-hydride elimination. PMID:18587498

  6. Deposition of a-C:H films on UHMWPE substrate and its wear-resistance

    NASA Astrophysics Data System (ADS)

    Xie, Dong; Liu, Hengjun; Deng, Xingrui; Leng, Y. X.; Huang, Nan

    2009-10-01

    In prosthetic hip replacements, ultrahigh molecular weight polyethylene (UHMWPE) wear debris is identified as the main factor limiting the lifetime of the artificial joints. Especially UHMWPE debris from the joint can induce tissue reactions and bone resorption that may lead to the joint loosening. The diamond like carbon (DLC) film has attracted a great deal of interest in recent years mainly because of its excellent tribological property, biocompatibility and chemically inert property. In order to improve the wear-resistance of UHMWPE, a-C:H films were deposited on UHMWPE substrate by electron cyclotron resonance microwave plasma chemical vapor deposition (ECR-PECVD) technology. During deposition, the working gases were argon and acetylene, the microwave power was set to 800 W, the biased pulsed voltage was set to -200 V (frequency 15 kHz, duty ratio 20%), the pressure in vacuum chamber was set to 0.5 Pa, and the process time was 60 min. The films were analysed by X-ray photoelectron spectroscopy (XPS), Raman spectroscopy, nano-indentation, anti-scratch and wear test. The results showed that a typical amorphous hydrogenated carbon (a-C:H) film was successfully deposited on UHMWPE with thickness up to 2 μm. The nano-hardness of the UHMWPE coated with a-C:H films, measured at an applied load of 200 μN, was increased from 10 MPa (untreated UHMWPE) to 139 MPa. The wear test was carried out using a ball (Ø 6 mm, SiC) on disk tribometer with an applied load of 1 N for 10000 cycles, and the results showed a reduction of worn cross-sectional area from 193 μm 2 of untreated UHMWPE to 26 μm 2 of DLC coated sample. In addition the influence of argon/acetylene gas flow ratio on the growth of a-C:H films was studied.

  7. Polynomial coefficients of thermochemical data for the C-H-O-N system

    NASA Technical Reports Server (NTRS)

    Wakelyn, N. T.; Mclain, A. G.

    1975-01-01

    Thermodynamic data are required input for the finite kinetics and equilibrium computer programs needed for modeling the combustion of hydrocarbons in the fields of energy and pollution research. Least squares determined coefficients of the curve-fitted thermodynamic data for 193 species in the C-H-O-N system are presented in card image form and are of suitable format for use by common computer programs.

  8. Theoretical study of the C-H bond dissociation energy of acetylene

    NASA Technical Reports Server (NTRS)

    Taylor, Peter R.; Bauschlicher, Charles W., Jr.; Langhoff, Stephen R.

    1990-01-01

    The authors present a theoretical study of the convergence of the C-H bond dissociation energy (D sub o) of acetylene with respect to both the one- and n-particle spaces. Their best estimate for D sub o of 130.1 plus or minus 1.0 kcal/mole is slightly below previous theoretical estimates, but substantially above the value determined using Stark anticrossing spectroscopy that is asserted to be an upper bound.

  9. Unprotected Amino Acids as Stable Radical Precursors for Heterocycle C-H Functionalization.

    PubMed

    Mai, Duy N; Baxter, Ryan D

    2016-08-01

    An efficient and general method for the C-H alkylation of heteroarenes using unprotected amino acids as stable alkyl radical precursors is reported. This one-pot procedure is performed open to air under aqueous conditions and is effective for several natural and unnatural amino acids. Heterocycles of varying structure are suitably functionalized, and reactivity trends reflect the nucleophilic character of the radical species generated. PMID:27452036

  10. Electrophilic C-H Borylation and Related Reactions of B-H Boron Cations.

    PubMed

    Prokofjevs, Aleksandrs; Jermaks, Janis; Borovika, Alina; Kampf, Jeff W; Vedejs, Edwin

    2013-11-25

    Catalytic procedures are described for aminedirected borylation of aliphatic and aromatic tertiary amine boranes. Sequential double borylation is observed in cases where two or more C-H bonds are available that allow 5-center or 6-center intramolecular borylation. The HNTf2 catalyzed borylation of benzylamine boranes provides a practical means for the synthesis of ortho-substituted arylboronic acid derivatives, suitable for Suzuki-Miyaura cross-coupling applications. PMID:24347788

  11. Synthesis of carbazoles by copper-catalyzed intramolecular C-H/N-H coupling.

    PubMed

    Takamatsu, Kazutaka; Hirano, Koji; Satoh, Tetsuya; Miura, Masahiro

    2014-06-01

    A Cu-catalyzed intramolecular C-H amination for the synthesis of carbazoles has been developed. The key to success is the installation of the picolinamide-based directing group, which is spontaneously removed after the coupling event. The Cu catalysis proceeded smoothly under Pd- and I(III)-free conditions, and its mild oxidation aptitude enables the rapid and concise construction of heteroatom-incorporated carbazole core π-systems. PMID:24813821

  12. Asymmetric Intramolecular Alkylation of Chiral Aromatic Imines via Catalytic C-H Bond Activation

    SciTech Connect

    Watzke, Anja; Wilson, Rebecca; O'Malley, Steven; Bergman, Robert; Ellman, Jonathan

    2007-04-16

    The asymmetric intramolecular alkylation of chiral aromatic aldimines, in which differentially substituted alkenes are tethered meta to the imine, was investigated. High enantioselectivities were obtained for imines prepared from aminoindane derivatives, which function as directing groups for the rhodium-catalyzed C-H bond activation. Initial demonstration of catalytic asymmetric intramolecular alkylation also was achieved by employing a sterically hindered achiral imine substrate and catalytic amounts of a chiral amine.

  13. Photocatalytic Hydrogen-Evolution Cross-Couplings: Benzene C-H Amination and Hydroxylation.

    PubMed

    Zheng, Yi-Wen; Chen, Bin; Ye, Pan; Feng, Ke; Wang, Wenguang; Meng, Qing-Yuan; Wu, Li-Zhu; Tung, Chen-Ho

    2016-08-17

    We present a blueprint for aromatic C-H functionalization via a combination of photocatalysis and cobalt catalysis and describe the utility of this strategy for benzene amination and hydroxylation. Without any sacrificial oxidant, we could use the dual catalyst system to produce aniline directly from benzene and ammonia, and phenol from benzene and water, both with evolution of hydrogen gas under unusually mild conditions in excellent yields and selectivities. PMID:27467115

  14. Properties of photovoltaic characteristics of a-SiC:H film

    NASA Astrophysics Data System (ADS)

    Enomoto, K.; Nishiwaki, H.; Watanabe, K.; Nakashima, Y.; Tsuda, S.; Ohnishi, M.; Kuwano, Y.

    1982-01-01

    a-SiC:H films were prepared from a glow discharge in a mixture of SiH4 and CH4 in a capacitive coupled system with parallel plane electrodes. The fundamental properties of the a-SiC:H films were investigated. Using the a-SiC:H film for window material, Glass/SnO2/p(SiC)-i-n/Al cells were fabricated by the consecutive, separated reaction chamber method. The best conversion efficiency of the cell with a size of 4 sq mm was 8.15 percent, which is much larger than that prepared by the single reaction chamber method in the laboratory. It seems that one of the main reasons for the difference in the conversion efficiency is the undesirable mixing of carbon in the non-doped a-Si:H layer. An integrated type Glass/SnO2/p(SiC)-i-n/Al cell with a size of 10 cm x 10 cm was also fabricated. The best conversion efficiency was 6.35 percent.

  15. Ru-Catalyzed C-H Arylation of Fluoroarenes with Aryl Halides.

    PubMed

    Simonetti, Marco; Perry, Gregory J P; Cambeiro, Xacobe C; Juliá-Hernández, Francisco; Arokianathar, Jude N; Larrosa, Igor

    2016-03-16

    Although the ruthenium-catalyzed C-H arylation of arenes bearing directing groups with haloarenes is well-known, this process has never been achieved in the absence of directing groups. We report the first example of such a process and show that unexpectedly the reaction only takes place in the presence of catalytic amounts of a benzoic acid. Furthermore, contrary to other transition metals, the arylation site selectivity is governed by both electronic and steric factors. Stoichiometric and NMR mechanistic studies support a catalytic cycle that involves a well-defined η(6)-arene-ligand-free Ru(II) catalyst. Indeed, upon initial pivalate-assisted C-H activation, the aryl-Ru(II) intermediate generated is able to react with an aryl bromide coupling partner only in the presence of a benzoate additive. In contrast, directing-group-containing substrates (such as 2-phenylpyridine) do not require a benzoate additive. Deuterium labeling and kinetic isotope effect experiments indicate that C-H activation is both reversible and kinetically significant. Computational studies support a concerted metalation-deprotonation (CMD)-type ruthenation mode and shed light on the unusual arylation regioselectivity. PMID:26942551

  16. Palladium-catalysed norbornene-mediated C-H functionalization of arenes

    NASA Astrophysics Data System (ADS)

    Ye, Juntao; Lautens, Mark

    2015-11-01

    The Catellani reaction -- a palladium-catalysed C-H functionalization reaction mediated by norbornene -- was first reported in 1997. The capacity to functionalize both the ortho and ipso positions of aryl halides in a single transformation held great appeal. We reported an annulative Catellani reaction in 2000. Since then, our two groups have explored the synthetic utility of this reaction and dramatic progress has been made by a number of groups in the past five years. Whereas the original Catellani reaction uses Pd(0) catalysts, recent studies have shown that Pd(II) catalysts can be used in combination with norbornene to effect (1) direct 2-alkylation of indoles and pyrroles and (2) selective meta-C-H functionalization of arenes bearing commonly used ortho-directing groups, thereby opening new avenues for future research. We describe the most recent developments concerning the Pd-catalysed norbornene-mediated C-H functionalization of arenes, including applications in natural products synthesis. We outline challenges and future opportunities.

  17. Melting evaporation and recrystallization of a-SiC:H films by excimer laser

    SciTech Connect

    Wickramanayaka, S.; Kitamura, K.; Nakanishi, Y.; Hatanaka, Y.

    1996-12-31

    A study of laser annealing of a-SiC:H films was carried out in order to obtain poly-SiC films. First, a-SiC:H films were fabricated at temperatures ranging from 30 to 400 C. All these films show amorphous structure before the annealing process. After annealing by a single pulse of 248 nm laser, films show poly-SiC structure. The pulse energies used for these anneals varied from 30 to 300 mJ/pulse. After exposing to a laser pulse, the a-SiC:H films melt and recrystallize forming poly-SiC structure. In addition to this process, a fraction of the film is observed to be vaporized. This vaporized fraction depends on the original film composition, hardness and the laser pulse-energy. Electrical resistivity of the films before the annealing process lies in the region of 10{sup 15} {Omega}cm. This resistivity drops drastically after the annealing process.

  18. Palladium-catalysed norbornene-mediated C-H functionalization of arenes.

    PubMed

    Ye, Juntao; Lautens, Mark

    2015-11-01

    The Catellani reaction--a palladium-catalysed C-H functionalization reaction mediated by norbornene--was first reported in 1997. The capacity to functionalize both the ortho and ipso positions of aryl halides in a single transformation held great appeal. We reported an annulative Catellani reaction in 2000. Since then, our two groups have explored the synthetic utility of this reaction and dramatic progress has been made by a number of groups in the past five years. Whereas the original Catellani reaction uses Pd(0) catalysts, recent studies have shown that Pd(II) catalysts can be used in combination with norbornene to effect (1) direct 2-alkylation of indoles and pyrroles and (2) selective meta-C-H functionalization of arenes bearing commonly used ortho-directing groups, thereby opening new avenues for future research. We describe the most recent developments concerning the Pd-catalysed norbornene-mediated C-H functionalization of arenes, including applications in natural products synthesis. We outline challenges and future opportunities. PMID:26492005

  19. Enantioselective Functionalization of Allylic C-H Bonds Following a Strategy of Functionalization and Diversification

    PubMed Central

    Sharma, Ankit; Hartwig, John F.

    2013-01-01

    We report the enantioselective functionalization of allylic C-H bonds in terminal alkenes by a strategy involving the installation of a temporary functional group at the terminal carbon atom by C-H bond functionalization, followed by diversification of this intermediate with a broad scope of reagents. The method consists of a one-pot sequence of palladium-catalyzed allylic C-H bond oxidation under neutral conditions to form linear allyl benzoates, followed by iridium-catalyzed allylic substitution. This overall transformation forms a variety of chiral products containing a new C-N, C-O, C-S or C-C bond at the allylic position in good yield with high branched-to-linear selectivity and excellent enantioselectivity (ee ≤ 97%). The broad scope of the overall process results from separating the oxidation and functionalization steps; by doing so, the scope of nucleophile encompasses those sensitive to direct oxidative functionalization. The high enantioselectivity of the overall process is achieved by developing an allylic oxidation that occurs without acid to form the linear isomer with high selectivity. These allylic functionalization processes are amenable to an iterative sequence leading to (1,n)-functionalized products with catalyst-controlled diastereo- and enantioselectivity. The utility of the method in the synthesis of biologically active molecules has been demonstrated. PMID:24156776

  20. Density functional study of hydrazine adsorption and its Nsbnd N bond cleaving on Fe(110) surface

    NASA Astrophysics Data System (ADS)

    Fathurrahman, Fadjar; Kasai, Hideaki

    2015-09-01

    We report density-functional-theory-based calculations of hydrazine adsorption and its Nsbnd N bond cleaving on clean Fe(110) surface. It is found that hydrazine may adopt several adsorption configurations among which the most energetically stable is the bridging configuration. Adsorption on short bridge site generally has larger adsorption energies than those on long bridge site. Nsbnd N bond cleaving is an exothermic process with reaction energies of 1.90 and 1.67 eV on long and short bridge site, respectively. Nudged elastic band method is used to estimate the activation energies of Nsbnd N bond cleaving. Our results indicate that Nsbnd N bond cleaving on long bridge site has lower activation energy (0.27 eV) compared to that of short bridge site (0.36 eV). By examining the molecular orbitals of the initial state it is found that this difference stems from stronger bond between the two NH2 fragments adsorbed on short bridge site as compared to long bridge.

  1. Cleaving of TOPAS and PMMA microstructured polymer optical fibers: Core-shift and statistical quality optimization

    NASA Astrophysics Data System (ADS)

    Stefani, A.; Nielsen, K.; Rasmussen, H. K.; Bang, O.

    2012-04-01

    We fabricated an electronically controlled polymer optical fiber cleaver, which uses a razor-blade guillotine and provides independent control of fiber temperature, blade temperature, and cleaving speed. To determine the optimum cleaving conditions of microstructured polymer optical fibers (mPOFs) with hexagonal hole structures we developed a program for cleaving quality optimization, which reads in a microscope image of the fiber end-facet and determines the core-shift and the statistics of the hole diameter, hole-to-hole pitch, hole ellipticity, and direction of major ellipse axis. For 125 μm in diameter mPOFs of the standard polymer PMMA we found the optimum temperatures to be 77.5 °C for both blade and fiber. For 280 μm in diameter mPOFs of the humidity insensitive polymer TOPAS® (grade 8007) the optimum temperature was 40° for both blade and fiber. A 100 μm thick flat-edge blade was found to minimize the core-shift by the cleaving to only 298 nm or 5% of the pitch for the PMMA mPOF at the optimal temperature.

  2. In vitro selection of RNA-cleaving DNAzymes for bacterial detection.

    PubMed

    Zhang, Wenqing; Feng, Qian; Chang, Dingran; Tram, Kha; Li, Yingfu

    2016-08-15

    DNAzymes refer to single-stranded DNA molecules with catalytic activity and can be isolated from synthetic random-sequence DNA pools using the technique of in vitro selection. DNAzymes that cleave RNA, known as "RNA-cleaving DNAzymes", represent one of the best-studied classes of DNAzymes and have been widely used for the development of biosensors and bioassays for various analytes. We have been interested in developing RNA-cleaving DNAzymes as bacterial sensors and these DNAzymes are engineered to perform three linked functions: recognition of a bacterial biomarker, RNA cleavage, and fluorescence generation. These fluorogenic DNAzymes emit fluorescence automatically in the presence of a bacterium of interest and can be used to set up a simple "mix-and-read" assay to detect this bacterium. In this article, we will discuss this DNAzyme system and present a proven strategy for isolating highly specific bacteria-responding DNAzyme probes from random-sequence DNA pools. We will also provide an in vitro selection protocol successfully used to derive RNA-cleaving fluorogenic DNAzyme probes that are capable of recognizing a targeted strain of Clostridium difficile. PMID:27017912

  3. CleavPredict: A Platform for Reasoning about Matrix Metalloproteinases Proteolytic Events

    PubMed Central

    Kumar, Sonu; Ratnikov, Boris I.; Kazanov, Marat D.; Smith, Jeffrey W.; Cieplak, Piotr

    2015-01-01

    CleavPredict (http://cleavpredict.sanfordburnham.org) is a Web server for substrate cleavage prediction for matrix metalloproteinases (MMPs). It is intended as a computational platform aiding the scientific community in reasoning about proteolytic events. CleavPredict offers in silico prediction of cleavage sites specific for 11 human MMPs. The prediction method employs the MMP specific position weight matrices (PWMs) derived from statistical analysis of high-throughput phage display experimental results. To augment the substrate cleavage prediction process, CleavPredict provides information about the structural features of potential cleavage sites that influence proteolysis. These include: secondary structure, disordered regions, transmembrane domains, and solvent accessibility. The server also provides information about subcellular location, co-localization, and co-expression of proteinase and potential substrates, along with experimentally determined positions of single nucleotide polymorphism (SNP), and posttranslational modification (PTM) sites in substrates. All this information will provide the user with perspectives in reasoning about proteolytic events. CleavPredict is freely accessible, and there is no login required. PMID:25996941

  4. CleavPredict: A Platform for Reasoning about Matrix Metalloproteinases Proteolytic Events.

    PubMed

    Kumar, Sonu; Ratnikov, Boris I; Kazanov, Marat D; Smith, Jeffrey W; Cieplak, Piotr

    2015-01-01

    CleavPredict (http://cleavpredict.sanfordburnham.org) is a Web server for substrate cleavage prediction for matrix metalloproteinases (MMPs). It is intended as a computational platform aiding the scientific community in reasoning about proteolytic events. CleavPredict offers in silico prediction of cleavage sites specific for 11 human MMPs. The prediction method employs the MMP specific position weight matrices (PWMs) derived from statistical analysis of high-throughput phage display experimental results. To augment the substrate cleavage prediction process, CleavPredict provides information about the structural features of potential cleavage sites that influence proteolysis. These include: secondary structure, disordered regions, transmembrane domains, and solvent accessibility. The server also provides information about subcellular location, co-localization, and co-expression of proteinase and potential substrates, along with experimentally determined positions of single nucleotide polymorphism (SNP), and posttranslational modification (PTM) sites in substrates. All this information will provide the user with perspectives in reasoning about proteolytic events. CleavPredict is freely accessible, and there is no login required. PMID:25996941

  5. Cysteine digestive peptidases function as post-glutamine cleaving enzymes in tenebrionid stored product pests

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cereals have storage proteins with high amounts of the amino acids glutamine and proline. Therefore, storage pests need to have digestive enzymes that are efficient in hydrolyzing these types of proteins. Post-glutamine cleaving peptidases (PGP) were isolated from the midgut of the stored product pe...

  6. Localization of two post-proline cleaving peptidases in the midgut of Tenebrio molitor larvae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Two soluble post-proline cleaving peptidase activities, PPCP1 and PPCP2, were demonstrated in the midgut of Tenebrio molitor larvae with the substrate benzyloxycarbonyl-L-alanyl-L-proline p-nitroanilide. Both activities were serine peptidases. PPCP1 was active in acidic buffers, with maximum activit...

  7. The CRISPR-associated DNA-cleaving enzyme Cpf1 also processes precursor CRISPR RNA.

    PubMed

    Fonfara, Ines; Richter, Hagen; Bratovič, Majda; Le Rhun, Anaïs; Charpentier, Emmanuelle

    2016-04-28

    CRISPR-Cas systems that provide defence against mobile genetic elements in bacteria and archaea have evolved a variety of mechanisms to target and cleave RNA or DNA. The well-studied types I, II and III utilize a set of distinct CRISPR-associated (Cas) proteins for production of mature CRISPR RNAs (crRNAs) and interference with invading nucleic acids. In types I and III, Cas6 or Cas5d cleaves precursor crRNA (pre-crRNA) and the mature crRNAs then guide a complex of Cas proteins (Cascade-Cas3, type I; Csm or Cmr, type III) to target and cleave invading DNA or RNA. In type II systems, RNase III cleaves pre-crRNA base-paired with trans-activating crRNA (tracrRNA) in the presence of Cas9 (refs 13, 14). The mature tracrRNA-crRNA duplex then guides Cas9 to cleave target DNA. Here, we demonstrate a novel mechanism in CRISPR-Cas immunity. We show that type V-A Cpf1 from Francisella novicida is a dual-nuclease that is specific to crRNA biogenesis and target DNA interference. Cpf1 cleaves pre-crRNA upstream of a hairpin structure formed within the CRISPR repeats and thereby generates intermediate crRNAs that are processed further, leading to mature crRNAs. After recognition of a 5'-YTN-3' protospacer adjacent motif on the non-target DNA strand and subsequent probing for an eight-nucleotide seed sequence, Cpf1, guided by the single mature repeat-spacer crRNA, introduces double-stranded breaks in the target DNA to generate a 5' overhang. The RNase and DNase activities of Cpf1 require sequence- and structure-specific binding to the hairpin of crRNA repeats. Cpf1 uses distinct active domains for both nuclease reactions and cleaves nucleic acids in the presence of magnesium or calcium. This study uncovers a new family of enzymes with specific dual endoribonuclease and endonuclease activities, and demonstrates that type V-A constitutes the most minimalistic of the CRISPR-Cas systems so far described. PMID:27096362

  8. Comparison of flat cleaved and cylindrical diffusing fibers as treatment sources for interstitial photodynamic therapy

    SciTech Connect

    Baran, Timothy M. Foster, Thomas H.

    2014-02-15

    Purpose: For interstitial photodynamic therapy (iPDT) of bulky tumors, careful treatment planning is required in order to ensure that a therapeutic dose is delivered to the tumor, while minimizing damage to surrounding normal tissue. In clinical contexts, iPDT has typically been performed with either flat cleaved or cylindrical diffusing optical fibers as light sources. Here, the authors directly compare these two source geometries in terms of the number of fibers and duration of treatment required to deliver a prescribed light dose to a tumor volume. Methods: Treatment planning software for iPDT was developed based on graphics processing unit enhanced Monte Carlo simulations. This software was used to optimize the number of fibers, total energy delivered by each fiber, and the position of individual fibers in order to deliver a target light dose (D{sub 90}) to 90% of the tumor volume. Treatment plans were developed using both flat cleaved and cylindrical diffusing fibers, based on tissue volumes derived from CT data from a head and neck cancer patient. Plans were created for four cases: fixed energy per fiber, fixed number of fibers, and in cases where both or neither of these factors were fixed. Results: When the number of source fibers was fixed at eight, treatment plans based on flat cleaved fibers required each to deliver 7180–8080 J in order to deposit 90 J/cm{sup 2} in 90% of the tumor volume. For diffusers, each fiber was required to deliver 2270–2350 J (333–1178 J/cm) in order to achieve this same result. For the case of fibers delivering a fixed 900 J, 13 diffusers or 19 flat cleaved fibers at a spacing of 1 cm were required to deliver the desired dose. With energy per fiber fixed at 2400 J and the number of fibers fixed at eight, diffuser fibers delivered the desired dose to 93% of the tumor volume, while flat cleaved fibers delivered this dose to 79%. With both energy and number of fibers allowed to vary, six diffusers delivering 3485–3600 J

  9. Microstructure characterization of advanced protective Cr/CrN+a-C:H/a-C:H:Cr multilayer coatings on carbon fibre composite (CFC).

    PubMed

    Major, L; Janusz, M; Lackner, J M; Kot, M; Major, B

    2016-06-01

    Studies of advanced protective chromium-based coatings on the carbon fibre composite (CFC) were performed. Multidisciplinary examinations were carried out comprising: microstructure transmission electron microscopy (TEM, HREM) studies, micromechanical analysis and wear resistance. Coatings were prepared using a magnetron sputtering technique with application of high-purity chromium and carbon (graphite) targets deposited on the CFC substrate. Selection of the CFC for surface modification in respect to irregularities on the surface making the CFC surface more smooth was performed. Deposited coatings consisted of two parts. The inner part was responsible for the residual stress compensation and cracking initiation as well as resistance at elevated temperatures occurring namely during surgical tools sterilization process. The outer part was responsible for wear resistance properties and biocompatibility. Experimental studies revealed that irregularities on the substrate surface had a negative influence on the crystallites growth direction. Chromium implanted into the a-C:H structure reacted with carbon forming the cubic nanocrystal chromium carbides of the Cr23 C6 type. The cracking was initiated at the coating/substrate interface and the energy of brittle cracking was reduced because of the plastic deformation at each Cr interlayer interface. The wear mechanism and cracking process was described in micro- and nanoscale by means of transmission electron microscope studies. Examined materials of coated CFC type would find applications in advanced surgical tools. PMID:26788794

  10. Influenza A penetrates host mucus by cleaving sialic acids with neuraminidase

    PubMed Central

    2013-01-01

    Background Influenza A virus (IAV) neuraminidase (NA) cleaves sialic acids (Sias) from glycans. Inhibiting NA with oseltamivir suppresses both viral infection, and viral release from cultured human airway epithelial cells. The role of NA in viral exit is well established: it releases budding virions by cleaving Sias from glycoconjugates on infected cells and progeny virions. The role of NA in viral entry remains unclear. Host respiratory epithelia secrete a mucus layer rich in heavily sialylated glycoproteins; these could inhibit viral entry by mimicking sialylated receptors on the cell surface. It has been suggested that NA allows influenza to penetrate the mucus by cleaving these sialylated decoys, but the exact mechanism is not yet established. Methods We tested IAV interaction with secreted mucus using frozen human trachea/bronchus tissue sections, and bead-bound purified human salivary mucins (HSM) and purified porcine submaxillary mucins (PSM). The protective effect of mucus was analyzed using MDCK cells coated with purified HSM and PSM with known Sia content. Oseltamivir was used to inhibit NA activity, and the fluorescent reporter substrate, 4MU-Neu5Ac, was used to quantify NA activity. Results IAV binds to the secreted mucus layer of frozen human trachea/bronchus tissues in a Sia dependent manner. HSM inhibition of IAV infection is Sia dose-dependent, but PSM cannot inhibit infection of underlying cells. HSM competitively inhibits NA cleavage of 4MU-Neu5Ac, reporter substrate. Human IAV effectively cleaves Sias from HSM but not from PSM, and binds to HSM but not to PSM. Conclusion IAV interacts with human mucus on frozen tissue sections and mucus-coated beads. Inhibition of IAV infection by sialylated human mucus is dose-dependent, and enhanced when NA is inhibited with oseltamivir. Thus NA cleaves sialylated decoys during initial stages of infection. Understanding IAV interactions with host mucins is a promising new avenue for drug development. PMID

  11. Astacin Proteases Cleave Dentin Sialophosphoprotein (Dspp) to Generate Dentin Phosphoprotein (Dpp)

    PubMed Central

    Tsuchiya, Shuhei; Simmer, James P; Hu, Jan C-C; Richardson, Amelia S; Yamakoshi, Fumiko; Yamakoshi, Yasuo

    2011-01-01

    Dentin sialophosphoprotein (Dspp) is critical for proper dentin biomineralization because genetic defects in DSPP cause dentin dysplasia type II and dentinogenesis imperfecta types II and III. Dspp is processed by proteases into smaller subunits; the initial cleavage releases dentin phosphoprotein (Dpp). We incubated fluorescence resonance energy transfer (FRET) peptides containing the amino acid context of the Dpp cleavage site (YEFDGKSMQGDDPN, designated Dspp-FRET) or a mutant version of that context (YEFDGKSIEGDDPN, designated mutDspp-FRET) with BMP-1, MEP1A, MEP1B, MMP-2, MMP-8, MMP-9, MT1-MMP, MT3-MMP, Klk4, MMP-20, plasmin, or porcine Dpp and characterized the peptide cleavage products. Only BMP-1, MEP1A, and MEP1B cleaved Dspp-FRET at the G–D peptide bond that releases Dpp from Dspp in vivo. We isolated Dspp proteoglycan from dentin power and incubated it with the three enzymes that cleaved Dspp-FRET at the G–D bond. In each case, the released Dpp domain was isolated, and its N-terminus was characterized by Edman degradation. BMP-1 and MEP1A both cleaved native Dspp at the correct site to generate Dpp, making both these enzymes prime candidates for the protease that cleaves Dspp in vivo. MEP1B was able to degrade Dpp when the Dpp was at sufficiently high concentration to deplete free calcium ion concentration. Immunohistochemistry of developing porcine molars demonstrated that astacins are expressed by odontoblasts, a result that is consistent with RT-PCR analyses. We conclude that during odontogenesis, astacins in the predentin matrix cleave Dspp before the DDPN sequence at the N-terminus of Dpp to release Dpp from the parent Dspp protein. © 2011 American Society for Bone and Mineral Research. PMID:20687161

  12. Troponate/Aminotroponate Ruthenium-Arene Complexes: Synthesis, Structure, and Ligand-Tuned Mechanistic Pathway for Direct C-H Bond Arylation with Aryl Chlorides in Water.

    PubMed

    Dwivedi, Ambikesh D; Binnani, Chinky; Tyagi, Deepika; Rawat, Kuber S; Li, Pei-Zhou; Zhao, Yanli; Mobin, Shaikh M; Pathak, Biswarup; Singh, Sanjay K

    2016-07-01

    A series of water-soluble troponate/aminotroponate ruthenium(II)-arene complexes were synthesized, where O,O and N,O chelating troponate/aminotroponate ligands stabilized the piano-stool mononuclear ruthenium-arene complexes. Structural identities for two of the representating complexes were also established by single-crystal X-ray diffraction studies. These newly synthesized troponate/aminotroponate ruthenium-arene complexes enable efficient C-H bond arylation of arylpyridine in water. The unique structure-activity relationship in these complexes is the key to achieve efficient direct C-H bond arylation of arylpyridine. Moreover, the steric bulkiness of the carboxylate additives systematically directs the selectivity toward mono- versus diarylation of arylpyridines. Detailed mechanistic studies were performed using mass-spectral studies including identification of several key cyclometalated intermediates. These studies provided strong support for an initial cycloruthenation driven by carbonate-assisted deprotonation of 2-phenylpyridine, where the relative strength of η(6)-arene and the troponate/aminotroponate ligand drives the formation of cyclometalated 2-phenylpyridine Ru-arene species, [(η(6)-arene)Ru(κ(2)-C,N-phenylpyridine) (OH2)](+) by elimination of troponate/aminotroponate ligands and retaining η(6)-arene, while cyclometalated 2-phenylpyridine Ru-troponate/aminotroponate species [(κ (2)-troponate/aminotroponate)Ru(κ(2)-C,N-phenylpyridine)(OH2)2] was generated by decoordination of η(6)-arene ring during initial C-H bond activation of 2-phenylpyridine. Along with the experimental mass-spectral evidence, density functional theory calculation also supports the formation of such species for these complexes. Subsequently, these cycloruthenated products activate aryl chloride by facile oxidative addition to generate C-H arylated products. PMID:27305143

  13. Pd-Catalyzed C-H activation/oxidative cyclization of acetanilide with norbornene: concise access to functionalized indolines.

    PubMed

    Gao, Yang; Huang, Yubing; Wu, Wanqing; Huang, Kefan; Jiang, Huanfeng

    2014-08-01

    An efficient Pd-catalyzed oxidative cyclization reaction for the synthesis of functionalized indolines by direct C-H activation of acetanilide has been developed. The norbornylpalladium species formed via direct ortho C-H activation of acetanilides is supposed to be a key intermediate in this transformation. PMID:24942255

  14. Palladium-catalyzed oxidative arylalkylation of activated alkenes: dual C-H bond cleavage of an arene and acetonitrile.

    PubMed

    Wu, Tao; Mu, Xin; Liu, Guosheng

    2011-12-23

    Not one but two: The title reaction proceeds through the dual C-H bond cleavage of both aniline and acetonitrile. The reaction affords a variety of cyano-bearing indolinones in excellent yield. Mechanistic studies demonstrate that this reaction involves a fast arylation of the olefin and a rate-determining C-H activation of the acetonitrile. PMID:22076660

  15. Direct Oxidation of Aliphatic C-H Bonds in Amino-Containing Molecules under Transition-Metal-Free Conditions.

    PubMed

    Li, Xin; Che, Xing; Chen, Gui-Hua; Zhang, Jun; Yan, Jia-Lei; Zhang, Yun-Fei; Zhang, Li-Sheng; Hsu, Chao-Ping; Gao, Yi Qin; Shi, Zhang-Jie

    2016-03-18

    By employing a simple, inexpensive, and transition-metal-free oxidation system, secondary C-H bonds in a series of phthaloyl protected primary amines and amino acid derivatives were oxidized to carbonyls with good regioselectivities. This method could also be applied to oxidize tertiary C-H bonds and modify synthetic dipeptides. PMID:26949833

  16. Metal-Free sp(2)-C-H Borylation as a Common Reactivity Pattern of Frustrated 2-Aminophenylboranes.

    PubMed

    Chernichenko, Konstantin; Lindqvist, Markus; Kótai, Bianka; Nieger, Martin; Sorochkina, Kristina; Pápai, Imre; Repo, Timo

    2016-04-13

    C-H borylation is a powerful and atom-efficient method for converting affordable and abundant chemicals into versatile organic reagents used in the production of fine chemicals and functional materials. Herein we report a facile C-H borylation of aromatic and olefinic C-H bonds with 2-aminophenylboranes. Computational and experimental studies reveal that the metal-free C-H insertion proceeds via a frustrated Lewis pair mechanism involving heterolytic splitting of the C-H bond by cooperative action of the amine and boryl groups. The adapted geometry of the reactive B and N centers results in an unprecedentently low kinetic barrier for both insertion into the sp(2)-C-H bond and intramolecular protonation of the sp(2)-C-B bond in 2-ammoniophenyl(aryl)- or -(alkenyl)borates. This common reactivity pattern serves as a platform for various catalytic reactions such as C-H borylation and hydrogenation of alkynes. In particular, we demonstrate that simple 2-aminopyridinium salts efficiently catalyze the C-H borylation of hetarenes with catecholborane. This reaction is presumably mediated by a borenium species isoelectronic to 2-aminophenylboranes. PMID:27003334

  17. Rhodium-Catalyzed C6-Selective C-H Borylation of 2-Pyridones.

    PubMed

    Miura, Wataru; Hirano, Koji; Miura, Masahiro

    2016-08-01

    A pyridine-directed, rhodium-catalyzed C6-selective C-H borylation of 2-pyridones with bis(pinacolato)diboron (pinB-Bpin) has been developed. The reaction proceeds smoothly under relatively mild conditions, and the corresponding C6-borylated 2-pyridones are obtained with perfect site selectivity. Subsequent palladium-catalyzed Suzuki-Miyaura cross-coupling is followed by the removal of the pyridine directing group to form the C6-arylated NH-pyridone in an acceptable overall yield. PMID:27420925

  18. Annulation of Aromatic Imines via Directed C-H BondActivation

    SciTech Connect

    Thalji, Reema K.; Ahrendt, Kateri A.; Bergman, Robert G.; Ellman,Jonathan A.

    2005-04-14

    A directed C-H bond activation approach to the synthesis of indans, tetralins, dihydrofurans, dihydroindoles, and other polycyclic aromatic compounds is presented. Cyclization of aromatic ketimines and aldimines containing alkenyl groups tethered at the meta position relative to the imine directing group has been achieved using (PPh{sub 3}){sub 3}RhCl (Wilkinson's catalyst). The cyclization of a range of aromatic ketimines and aldimines provides bi- and tricyclic ring systems with good regioselectivity. Different ring sizes and substitution patterns can be accessed through the coupling of monosubstituted, 1,1- or 1,2-disubstituted, and trisubstituted alkenes bearing both electron-rich and electron-deficient functionality.

  19. A C-H functionalization protocol for the direct synthesis of benzobisthiazole derivatives.

    PubMed

    Bon, Jennifer L; Feng, Daijun; Marder, Seth R; Blakey, Simon B

    2014-08-15

    Benzobisthiazole and thiazolothiazole derivatives are useful components in a variety of organic electronics devices resulting from their absorption, electroluminescence, and charge-transport properties. A convenient synthesis of these molecules via palladium/copper cocatalyzed C-H bond functionalization is described. Reaction conditions were optimized in a bromobenzene/benzobisthiazole system that allowed for the one-pot functionalization of both thioimidate positions of benzobisthiazole. The extension of this methodology to the synthesis of cruciform architectures and the functionalization of thiazolothiazole is also described. PMID:25078255

  20. Annulation of aromatic imines via directed C-H bond activation.

    PubMed

    Thalji, Reema K; Ahrendt, Kateri A; Bergman, Robert G; Ellman, Jonathan A

    2005-08-19

    A directed C-H bond activation approach to the synthesis of indans, tetralins, dihydrofurans, dihydroindoles, and other polycyclic aromatic compounds is presented. Cyclization of aromatic ketimines and aldimines containing alkenyl groups tethered at the meta position relative to the imine directing group has been achieved using (PPh3)3RhCl (Wilkinson's catalyst). The cyclization of a range of aromatic ketimines and aldimines provides bi- and tricyclic ring systems with good regioselectivity. Different ring sizes and substitution patterns can be accessed through the coupling of monosubstituted, 1,1- or 1,2-disubstituted, and trisubstituted alkenes bearing both electron-rich and electron-deficient functionality. PMID:16095296

  1. Formal Gold- and Rhodium-Catalyzed Regiodivergent C-H Alkynylation of 2-Pyridones.

    PubMed

    Li, Yunyun; Xie, Fang; Li, Xingwei

    2016-01-15

    Formal regiodivergent C-H alkynylation of 2-pyridones bearing different N-substituents has been realized under Au(I) and Rh(III) catalysis using a hypervalent iodine alkyne reagent. When catalyzed by Au(I), the alkynylation occurred at the most electron-rich 5-position via an electrophilic alkynylation pathway. The selectivity was switched to the 6-position under assistance of an N-chelation group when a Rh(III) catalyst was employed. A rhodacylic complex has been isolated as a key intermediate. PMID:26709449

  2. Palladium-Catalyzed Deaminative Phenanthridinone Synthesis from Aniline via C-H Bond Activation.

    PubMed

    Yedage, Subhash L; Bhanage, Bhalchandra M

    2016-05-20

    This work reports palladium-catalyzed phenanthridinone synthesis using the coupling of aniline and amide by formation of C-C and C-N bonds in a one-pot fashion via dual C-H bond activation. It involves simultaneous cleavage of four bonds and the formation of two new bonds. The present protocol is ligand-free, takes place under mild reaction conditions, and is environmentally benign as nitrogen gas and water are the only side products. This transformation demonstrates a broad range of aniline and amide substrates with different functional groups and has been scaled up to gram level. PMID:27088815

  3. Titanium-Thiolate-Aluminum-Carbide Complexes by Multiple C-H Bond Activation.

    PubMed

    Guérin; Stephan

    1999-12-16

    All three C-H bonds of a methyl group are activated in the reaction of [Cp(iPr(3)PN)Ti(SR)(2)] with AlMe(3) [Eq. (1)]. The Ti-Al-carbide clusters formed contain a severely distorted tetrahedral carbide carbon atom with a relatively short bond to Ti, which is attributed to a relative increase in the Lewis acidity of the Ti center as a result of the interaction of the S and N donors with Al. PMID:10649329

  4. Selective molecular recognition, C-H bond activation, and catalysis in nanoscale reaction vessels

    SciTech Connect

    Fiedler, Dorothea; Leung, Dennis H.; Raymond, Kenneth N.; Bergman, Robert G.

    2004-11-27

    Supramolecular chemistry represents a way to mimic enzyme reactivity by using specially designed container molecules. We have shown that a chiral self-assembled M{sub 4}L{sub 6} supramolecular tetrahedron can encapsulate a variety of cationic guests, with varying degrees of stereoselectivity. Reactive iridium guests can be encapsulated and the C-H bond activation of aldehydes occurs, with the host cavity controlling the ability of substrates to interact with the metal center based upon size and shape. In addition, the host container can act as a catalyst by itself. By restricting reaction space and preorganizing the substrates into reactive conformations, it accelerates the sigmatropic rearrangement of enammonium cations.

  5. The C/H ratio in Jupiter from the Voyager infrared investigation

    NASA Technical Reports Server (NTRS)

    Gautier, D.; Bezard, B.; Marten, A.; Baluteau, J. P.; Scott, N.; Chedin, A.; Kunde, K.; Hanel, R.

    1982-01-01

    From a selection Voyager IRIS spectra corresponding to cloud-free areas of Jupiter, the CH4/H2 volume ratio in the atmosphere of this planet has been determined to be equal to 0.00195 + or - 0.00022, which corresponds to 2.07 + or - 0.24 times the solar value of Lambert (C/H = 0.00047). The estimate of errors includes both instrument noise and systematic uncertainties. Implications of this result for the formation and evolution of Jupiter are discussed.

  6. C/H ratio in Jupiter from the Voyager infrared investigation

    SciTech Connect

    Gautier, D.; Bezard, B.; Marten, A.; Baluteau, J.P.; Scott, N.; Chedin, A.; Kunde, V.; Hanel, R.

    1982-06-15

    From a selection of Voyager IRIS spectra corresponding to cloud-free areas of Jupiter, we have determined the CH/sub 4//H/sub 2/ volume ratio in the atmosphere of this planet as equal to (1.95 +- 0.22)10/sup -3/ which corresponds to 2.07 +- 0.24 times the solar value of Lambert (C/H = 4.7 x 10/sup -4/). Estimate of errors includes both instrument noise and systematic uncertainties. Implications of this result on the formation and evolution of Jupiter are discussed.

  7. Local network structure of a-SiC:H and its correlation with dielectric function

    NASA Astrophysics Data System (ADS)

    Kageyama, Shota; Matsuki, Nobuyuki; Fujiwara, Hiroyuki

    2013-12-01

    The microscopic disordered structures of hydrogenated amorphous silicon carbide (a-Si1-xCx:H) layers with different carbon contents have been determined based on the correlations between the dielectric function in the ultraviolet/visible region and the local bonding states studied by high-sensitivity infrared attenuated total reflection spectroscopy. We find that the microscopic structure of the a-Si1-xCx:H layers fabricated by plasma-enhanced chemical vapor deposition shows a sharp structural transition at a boundary of x = 6.3 at. %. In the regime of x ≤ 6.3 at. %, (i) the amplitude of the a-SiC:H dielectric function reduces and (ii) the SiH2 content increases drastically with x, even though most of the C atoms are introduced into the tetrahedral sites without bonding with H. In the regime of x > 6.3 at. %, on the other hand, (i) the amplitude of the dielectric function reduces further and (ii) the concentration of the sp3 CHn (n = 2,3) groups increases. Moreover, we obtained the direct evidence that the sp2 C bonding state in the a-SiC matrix exists in the configuration of C = CH2 and the generation of the graphite-like C = CH2 unit suppresses the band gap widening significantly. At high C contents of x > 6.3 at. %, the a-SiC:H layers show quite porous structures due to the formation of microvoids terminated with the SiH2/CHn groups. By taking the SiH2/CHn microvoid generation in the network and the high-energy shift of the dielectric function by the local bonding states into account, the a-SiC:H dielectric function model has been established. From the analysis using this model, we have confirmed that the a-SiC:H optical properties in the ultraviolet/visible region are determined almost completely by the local network structures.

  8. Tribological behaviour of nanostructured Ti-C:H coatings for biomedical applications

    NASA Astrophysics Data System (ADS)

    Polcar, Tomas; Vitu, Tomas; Cvrcek, Ladislav; Novak, Rudolf; Vyskocil, Jiri; Cavaleiro, Albano

    2009-10-01

    The development of a mechanically stable, functionally graded Ti-doped a-C:H interface layer in combination with a functional a-C:H coating requires a reduction of the brittle phases which induce generally problems in the transitions from Ti to TiC/a-C:H. The core objective of this study was to develop an optimum interlayer between the substrate and the functional top layer for biomedical applications, namely for tooth implants. Since the interlayer may be exposed to the sliding process, in the case of local failure of the top layer it has to fulfil the same criteria: biocompatibility, high wear resistance and low friction. The functional Ti-C:H layers with thickness in the range 2.5-3.5 μm were deposited by a magnetron sputtering/PECVD hybrid process by sputtering a Ti-target in a C 2H 2 + Ar atmosphere in dc discharge regime. The sets of coating samples were prepared by varying the C and H concentrations controlled by the C 2H 2 flow during the deposition process. The tribological properties were evaluated on a pin-on-disc tribometer at room temperature (RT) and at 100 °C using 440C balls with a diameter of 6 mm. The tests at 100 °C were performed to investigate the effect of the sterilization temperature on the tribological properties and the coating lifetime as well. The tribological performance was examined with respect to the friction coefficient, the wear rates of the coating and the counter-parts and the analysis of the wear debris. The Ti/C ratio decreased almost linearly from 4.5 to 0.1 with increasing C 2H 2 flow; the hydrogen content showed a minimum of 5 at.% at C 2H 2 flow of 30 sccm, while for lower flows it was about 10 at.%. The coatings could be divided into three groups based on the C 2H 2 flow: (i) 10-15 sccm, exhibiting severe abrasive damage during the sliding tests, (ii) 20-45 sccm, showing the highest hardness and friction values, and (iii) 52-60 sccm, with moderate hardness and minimal values of the friction coefficient and the wear rate.

  9. MMPs are less efficient than ADAMTS5 in cleaving aggrecan core protein.

    PubMed

    Durigova, Michaela; Nagase, Hideaki; Mort, John S; Roughley, Peter J

    2011-03-01

    Aggrecan degradation in articular cartilage occurs predominantly through proteolysis and has been attributed to the action of members of the matrix metalloproteinase (MMP) and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) families. Both families of enzymes cleave aggrecan at specific sites within the aggrecan core protein. One cleavage site within the interglobular domain (IGD), between Glu(373-374)Ala and five additional sites in the chondroitin sulfate-2 (CS-2) region of aggrecan were characterized as "aggrecanase" (ADAMTS) cleavage sites, while cleavage between Ser(341-342)Phe within the IGD of bovine aggrecan is attributed to MMP action. The objective of this study was to assess the cleavage efficiency of MMPs relative to ADAMTS and their contribution to aggrecan proteolysis in vitro. The analysis of aggrecan IGD degradation in bovine articular cartilage explants treated with catabolic cytokines over a 19-day period showed that MMP-mediated degradation of aggrecan within the IGD can only be observed following day 12 of culture. This delay is associated with the lack of activation of proMMPs during the first 12 days of culture. Analysis of MMP1, 2, 3, 7, 8, 9, 12, 13 and ADAMTS5 efficiencies at cleaving within the aggrecan IGD and CS-2 region in vitro was carried out by the digestion of bovine aggrecan with the various enzymes and Western blot analysis using aggrecan anti-G1 and anti-G3 antibodies. Of these MMPs, MMP12 was the most efficient at cleaving within the aggrecan IGD. In addition to cleavage in the IGD, MMP, 3, 7, 8 and 12 were also able to degrade the aggrecan CS-2 region. MMP3 and MMP12 were able to degrade aggrecan at the very C-terminus of the CS-2 region, cleaving the Glu(2047-2048)Ala bond which was previously shown to be cleaved by ADAMTS5. However, in comparison to ADAMTS5, MMP3 was about 100 times and 10 times less efficient at cleaving within the aggrecan IGD and CS-2 regions, respectively. Collectively, our results

  10. A novel β-glucosidase from Aspergillus fumigates releases diosgenin from spirostanosides of Dioscorea zingiberensis C. H. Wright (DZW).

    PubMed

    Lei, Jing; Niu, Hai; Li, Tianhong; Huang, Wen

    2012-03-01

    A β-glucosidase effectively releasing diosgenin from spirostanosides of Dioscorea zingiberensis C. H. Wright (DZW), named AfG, was purified from a strain of Aspergillus fumigates. The molecular weight of AfG was 113 kDa. Analysis of protein fragments by ESI-Q-TOF indicated that AfG was a β-glucosidase. The circular dichroism spectrum suggested that the main secondary structure of AfG in Milli-Q water was α-helixes. Atomic force microscopy revealed that it was a globular protein. AfG maintained high activity from pH 3.6 to 5.0 and from 50 to 90°C. With the strong heat stability, AfG retained 55% of its original activity at 65°C for 120 h. AfG utilized muti-3-O-glycosides of various steroidal saponins from DZW as substrate, such as trillin, diosgenin diglucoside, dioscin, deltonin and gracillin, to yield diosgenin, suggesting the possibility of producing diosgenin from total saponins of DZW using a single enzyme. PMID:22805852

  11. Chelation-assisted Pd-catalysed ortho-selective oxidative C-H/C-H cross-coupling of aromatic carboxylic acids with arenes and intramolecular Friedel-Crafts acylation: one-pot formation of fluorenones.

    PubMed

    Sun, Denan; Li, Bijin; Lan, Jingbo; Huang, Quan; You, Jingsong

    2016-03-01

    Pd-Catalysed ortho-selective oxidative C-H/C-H cross-coupling of aromatic carboxylic acids with arenes and subsequent intramolecular Friedel-Crafts acylation has been accomplished for the first time through a chelation-assisted C-H activation strategy. Starting from the readily available substrates, a variety of fluorenone derivatives are obtained in one pot. The direct use of naturally occurring carboxylic acid functionalities as directing groups avoids unnecessary steps for installation and removal of an extra directing group. PMID:26861768

  12. Enzymatic hydroxylation of an unactivated methylene C-H bond guided by molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Narayan, Alison R. H.; Jiménez-Osés, Gonzalo; Liu, Peng; Negretti, Solymar; Zhao, Wanxiang; Gilbert, Michael M.; Ramabhadran, Raghunath O.; Yang, Yun-Fang; Furan, Lawrence R.; Li, Zhe; Podust, Larissa M.; Montgomery, John; Houk, K. N.; Sherman, David H.

    2015-08-01

    The hallmark of enzymes from secondary metabolic pathways is the pairing of powerful reactivity with exquisite site selectivity. The application of these biocatalytic tools in organic synthesis, however, remains under-utilized due to limitations in substrate scope and scalability. Here, we report how the reactivity of a monooxygenase (PikC) from the pikromycin pathway is modified through computationally guided protein and substrate engineering, and applied to the oxidation of unactivated methylene C-H bonds. Molecular dynamics and quantum mechanical calculations were used to develop a predictive model for substrate scope, site selectivity and stereoselectivity of PikC-mediated C-H oxidation. A suite of menthol derivatives was screened computationally and evaluated through in vitro reactions, where each substrate adhered to the predicted models for selectivity and conversion to product. This platform was also expanded beyond menthol-based substrates to the selective hydroxylation of a variety of substrate cores ranging from cyclic to fused bicyclic and bridged bicyclic compounds.

  13. A theoretical view on CrO2+-mediated C-H bond activation in ethane

    NASA Astrophysics Data System (ADS)

    Tong, YongChun; Zhang, XiaoYong; Wang, QingYun; Xu, XinJian; Wang, YongCheng

    2015-06-01

    The gas-phase reaction of C-H bond activation in ethane by CrO2+ has been investigated using density functional theory (DFT) at the UB3LYP/6-311G(2d,p) level. Our results reveal that the activation process is actually a spin-forbidden reaction. The involved crossing point between the doublet and quartet potential energy surfaces (PES) has been discussed by two well-known methods, i.e., intrinsic reaction coordinate (IRC) approach for crossing point (CP) and Harvey's algorithm for minimum energy crossing point (MECP). The obtained single ( P1ISC = 2.48 × 10-3) and double ( P1ISC = 4.95 × 10-3) passes estimated at MECP show that the intersystem crossing (ISC) occurs with a little probability. The C-H bond activation processes should proceed to be endothermic by 73.16 kJ/mol on the doublet surface without any spin change.

  14. C-H Hot Bands in the Near-IR Emission Spectra of Leonids

    NASA Technical Reports Server (NTRS)

    Freund, F. T.; Scoville, J.; Holm, R.; Seelemann, R.; Freund, M. M.

    2002-01-01

    The reported infrared (IR) emission spectra from 1999 Leonid fireballs show a 3.4 micron C-H emission band and unidentified bands at longer wavelengths. Upon atmospheric entry, the Leonid meteorites were flash-heated to temperatures around 2400K, which would destroy any organics on the surface of the meteorite grains. We propose that the nu(sub )CH emission band in the Leonid emission spectra arises from matrix-embedded C(sub n)-H-O entities that are protected from instant pyrolysis. Our model is based on IR absorption nu(sub )CH bands, which we observed in laboratory-grown MgO and natural olivine single crystals, where they arise from C(sub n)-H-O units imbedded in the mineral matrix, indicative of aliphatic -CH2- and -CH3 organics. Instead of being pyrolyzed, the C(sub n)-H-O entities in the Leonid trails become vibrationally excited to higher levels n = 1, 2, 3 etc. During de-excitation they emit at 3.4 microns, due to the (0 => 1) transition, and at longer wavelengths, due to hot bands. As a first step toward verifying this hypothesis we measured the C-H vibrational manifold of hexane (C6H14). The calculated positions of the (2 => l ) , (3 => 2), and possibly (4 => 3) hot bands agree with the Leonid emission bands at 3.5, 3.8 and 4.l microns.

  15. Novel Stable Compounds in the C-H-O Ternary System at High Pressure

    PubMed Central

    Saleh, Gabriele; Oganov, Artem R.

    2016-01-01

    The chemistry of the elements is heavily altered by high pressure, with stabilization of many new and often unexpected compounds, the emergence of which can profoundly change models of planetary interiors, where high pressure reigns. The C-H-O system is one of the most important planet-forming systems, but its high-pressure chemistry is not well known. Here, using state-of-the-art variable-composition evolutionary searches combined with quantum-mechanical calculations, we explore the C-H-O system at pressures up to 400 GPa. Besides uncovering new stable polymorphs of high-pressure elements and known molecules, we predicted the formation of new compounds. A 2CH4:3H2 inclusion compound forms at low pressure and remains stable up to 215 GPa. Carbonic acid (H2CO3), highly unstable at ambient conditions, was predicted to form exothermically at mild pressure (about 1 GPa). As pressure rises, it polymerizes and, above 314 GPa, reacts with water to form orthocarbonic acid (H4CO4). This unexpected high-pressure chemistry is rationalized by analyzing charge density and electron localization function distributions, and implications for general chemistry and planetary science are also discussed. PMID:27580525

  16. Novel Stable Compounds in the C-H-O Ternary System at High Pressure.

    PubMed

    Saleh, Gabriele; Oganov, Artem R

    2016-01-01

    The chemistry of the elements is heavily altered by high pressure, with stabilization of many new and often unexpected compounds, the emergence of which can profoundly change models of planetary interiors, where high pressure reigns. The C-H-O system is one of the most important planet-forming systems, but its high-pressure chemistry is not well known. Here, using state-of-the-art variable-composition evolutionary searches combined with quantum-mechanical calculations, we explore the C-H-O system at pressures up to 400 GPa. Besides uncovering new stable polymorphs of high-pressure elements and known molecules, we predicted the formation of new compounds. A 2CH4:3H2 inclusion compound forms at low pressure and remains stable up to 215 GPa. Carbonic acid (H2CO3), highly unstable at ambient conditions, was predicted to form exothermically at mild pressure (about 1 GPa). As pressure rises, it polymerizes and, above 314 GPa, reacts with water to form orthocarbonic acid (H4CO4). This unexpected high-pressure chemistry is rationalized by analyzing charge density and electron localization function distributions, and implications for general chemistry and planetary science are also discussed. PMID:27580525

  17. High-Turnover Aromatic C-H Borylation Catalyzed by POCOP-Type Pincer Complexes of Iridium.

    PubMed

    Press, Loren P; Kosanovich, Alex J; McCulloch, Billy J; Ozerov, Oleg V

    2016-08-01

    The catalytic C-H borylation of arenes with HBpin (pin = pinacolate) using POCOP-type pincer complexes of Ir has been demonstrated, with turnover numbers exceeding 10 000 in some cases. The selectivity of C-H activation was based on steric preferences and largely mirrored that found in other Ir borylation catalysts. Catalysis in the (POCOP)Ir system depends on the presence of stoichiometric quantities of sacrificial olefin, which is hydrogenated to consume the H2 equivalents generated in the borylation of C-H bonds with HBpin. Smaller olefins such as ethylene or 1-hexene were more advantageous to catalysis than sterically encumbered tert-butylethylene (TBE). Olefin hydroboration is a competing side reaction. The synthesis and isolation of multiple complexes potentially relevant to catalysis permitted examination of several key elementary reactions. These experiments indicate that the C-H activation step in catalysis ostensibly involves oxidative addition of an aromatic C-H bond to the three-coordinate (POCOP)Ir species. The olefin is mechanistically critical to gain access to this 14-electron, monovalent Ir intermediate. C-H activation at Ir(I) here is in contrast to the olefin-free catalysis with state-of-the-art Ir complexes supported by neutral bidentate ligands, where the C-H activating step is understood to involve trivalent Ir-boryl intermediates. PMID:27327895

  18. A widespread self-cleaving ribozyme class is revealed by bioinformatics

    PubMed Central

    Roth, Adam; Weinberg, Zasha; Chen, Andy G. Y.; Kim, Peter B.; Ames, Tyler D.; Breaker, Ronald R.

    2013-01-01

    Ribozymes are noncoding RNAs that promote chemical transformations with rate enhancements approaching those of protein enzymes. Although ribozymes are likely to have been abundant during the RNA world era, only ten classes are known to exist among contemporary organisms. We report the discovery and analysis of an additional self-cleaving ribozyme class, called twister, which is present in many species of bacteria and eukarya. Nearly 2700 twister ribozymes were identified that conform to a secondary structure consensus that is small yet complex, with three stems conjoined by internal and terminal loops. Two pseudoknots provide tertiary structure contacts that are critical for catalytic activity. The twister ribozyme motif provides another example of a natural RNA catalyst and calls attention to the potentially varied biological roles of this and other classes of widely distributed self-cleaving RNAs. PMID:24240507

  19. Friction imprint effect in mechanically cleaved BaTiO3 (001)

    NASA Astrophysics Data System (ADS)

    Long, Christian J.; Ebeling, Daniel; Solares, Santiago D.; Cannara, Rachel J.

    2014-09-01

    Adsorption, chemisorption, and reconstruction at the surfaces of ferroelectric materials can all contribute toward the pinning of ferroelectric polarization, which is called the electrical imprint effect. Here, we show that the opposite is also true: freshly cleaved, atomically flat surfaces of (001) oriented BaTiO3 exhibit a persistent change in surface chemistry that is driven by ferroelectric polarization. This surface modification is explored using lateral force microscopy (LFM), while the ferroelectric polarization is probed using piezoresponse force microscopy. We find that immediately after cleaving BaTiO3, LFM reveals friction contrast between ferroelectric domains. We also find that this surface modification remains after the ferroelectric domain distribution is modified, resulting in an imprint of the original ferroelectric domain distribution on the sample surface. This friction imprint effect has implications for surface patterning as well as ferroelectric device operation and failure.

  20. Density functional study of hydrazine N-N bond cleaving on 3d metal surfaces

    NASA Astrophysics Data System (ADS)

    Fathurrahman, Fadjar; Kasai, Hideaki

    2015-11-01

    Theoretical calculations based on dispersion-corrected density functional theory (DFT-D2) has been performed to investigate hydrazine adsorption and N-N bond cleaving on closed packed surfaces of 3d metals: Fe(110), Co(0001), Ni(111), Cu(111), and Zn(0001). The activation energies of N-N bond cleaving of hydrazine on each surface are estimated using climbing-image nudged elastic band (CINEB) method. The results showed that the activation energies for this process have increasing trend from Fe(110) to Zn(0001). By examining the electronic structure of the adsorbed hydrazine, it is found that this trend is related to occupation of derived 6σ* orbitals. It is also found that approximate linear relationship between reaction energy and activation energy (the Brønsted-Evans-Polanyi (BEP) relationship) holds for those surfaces.

  1. Scribe-cleave-passivate (SCP) slim edge technology for silicon sensors

    NASA Astrophysics Data System (ADS)

    Fadeyev, V.; Sadrozinski, H. F.-W.; Ely, S.; Wright, J. G.; Christophersen, M.; Phlips, B. F.; Pellegrini, G.; Grinstein, S.; Dalla Betta, G.-F.; Boscardin, M.; Klingenberg, R.; Wittig, T.; Macchiolo, A.; Weigell, P.; Creanza, D.; Bates, R.; Blue, A.; Eklund, L.; Maneuski, D.; Stewart, G.; Casse, G.; Gorelov, I.; Hoeferkamp, M.; Metcalfe, J.; Seidel, S.; Kramberger, G.

    2013-12-01

    We are pursuing scribe-cleave-passivate (SCP) technology of making “slim edge” sensors. Such sensors have only a minimal amount of inactive peripheral region, which benefits construction of large-area tracker and imaging systems. Key application steps of this method are surface scribing, cleaving, and passivation of the resulting sidewall. We are working on developing both the technology and physical understanding of the processed devices performance. In this paper we begin by reviewing the manufacturing options of SCP technology. Then we show new results regarding the technology automation and device physics performance. The latter includes charge collection efficiency near the edge and radiation hardness study. We also report on the status of devices processed at the request of the RD50 collaborators.

  2. Cleaved thioredoxin fusion protein enables the crystallization of poorly soluble ERα in complex with synthetic ligands

    SciTech Connect

    Cura, Vincent; Gangloff, Monique; Eiler, Sylvia; Moras, Dino; Ruff, Marc

    2008-01-01

    A new crystallization strategy: the presence of cleaved thioredoxin fusion is critical for crystallization of the estrogen nuclear receptor ligand binding domain in complex with synthetic ligands. This novel technique should be regarded as an interesting alternative for crystallization of difficult proteins. The ligand-binding domain (LBD) of human oestrogen receptor α was produced in Escherichia coli as a cleavable thioredoxin (Trx) fusion in order to improve solubility. Crystallization trials with either cleaved and purified LBD or with the purified fusion protein both failed to produce crystals. In another attempt, Trx was not removed from the LBD after endoproteolytic cleavage and its presence promoted nucleation and subsequent crystal growth, which allowed the structure determination of two different LBD–ligand–coactivator peptide complexes at 2.3 Å resolution. This technique is likely to be applicable to other low-solubility proteins.

  3. Friction imprint effect in mechanically cleaved BaTiO{sub 3} (001)

    SciTech Connect

    Long, Christian J.; Ebeling, Daniel; Solares, Santiago D.; Cannara, Rachel J.

    2014-09-28

    Adsorption, chemisorption, and reconstruction at the surfaces of ferroelectric materials can all contribute toward the pinning of ferroelectric polarization, which is called the electrical imprint effect. Here, we show that the opposite is also true: freshly cleaved, atomically flat surfaces of (001) oriented BaTiO{sub 3} exhibit a persistent change in surface chemistry that is driven by ferroelectric polarization. This surface modification is explored using lateral force microscopy (LFM), while the ferroelectric polarization is probed using piezoresponse force microscopy. We find that immediately after cleaving BaTiO{sub 3}, LFM reveals friction contrast between ferroelectric domains. We also find that this surface modification remains after the ferroelectric domain distribution is modified, resulting in an imprint of the original ferroelectric domain distribution on the sample surface. This friction imprint effect has implications for surface patterning as well as ferroelectric device operation and failure.

  4. The Streptococcal Cysteine Protease SpeB Is Not a Natural Immunoglobulin-Cleaving Enzyme

    PubMed Central

    Persson, Helena; Vindebro, Reine

    2013-01-01

    The human bacterial pathogen Streptococcus pyogenes has developed a broad variety of virulence mechanisms to evade the actions of the host immune defense. One of the best-characterized factors is the streptococcal cysteine protease SpeB, an important multifunctional protease that contributes to group A streptococcal pathogenesis in vivo. Among many suggested activities, SpeB has been described to degrade various human plasma proteins, including immunoglobulins (Igs). In this study, we show that SpeB has no Ig-cleaving activity under physiological conditions and that only Igs in a reduced state, i.e., semimonomeric molecules, are cleaved and degraded by SpeB. Since reducing conditions outside eukaryotic cells have to be considered nonphysiological and IgG in a reduced state lacks biological effector functions, we conclude that SpeB does not contribute to S. pyogenes virulence through the proteolytic degradation of Igs. PMID:23569114

  5. Trichosanthin, a potent HIV-1 inhibitor, can cleave supercoiled DNA in vitro.

    PubMed Central

    Li, M X; Yeung, H W; Pan, L P; Chan, S I

    1991-01-01

    Trichosanthin, an abortifacient, immunosuppressive and anti-tumor protein purified from the traditional Chinese herb medicine Tian Hua Fen, is a potent inhibitor against HIV-1 replication. Under normal enzymatic digestion conditions, trichosanthin cleaves the supercoiled double-stranded DNA to produce nicked circular and linear DNA. Trichosanthin has no effect on linear double-stranded DNA. Neither does it convert relaxed circular duplex DNA into a supercoiled form in the presence of ATP. Thus trichosanthin is not a DNA gyrase. However, trichosanthin can cleave the relaxed circular DNA into a linear form, indicating that both the circular as well as the supercoiled forms are essential for trichosanthin recognition. In addition, trichosanthin contains one calcium metal ion per protein molecule, which presumably is related to its endonucleolytic activity. Images PMID:1659689

  6. The Host Targeting motif in exported Plasmodium proteins is cleaved in the parasite endoplasmic reticulum

    PubMed Central

    Osborne, Andrew R.; Speicher, Kaye D.; Tamez, Pamela A.; Bhattacharjee, Souvik; Speicher, David W.; Haldar, Kasturi

    2010-01-01

    During the blood stage of its lifecycle, the malaria parasite resides and replicates inside a membrane vacuole within its host cell, the human erythrocyte. The parasite exports many proteins across the vacuole membrane and into the host cell cytoplasm. Most exported proteins are characterized by the presence of a Host Targeting (HT) motif, also referred to as a Plasmodium Export Element (PEXEL), which corresponds to the consensus sequence RxLxE/D/Q. During export the HT motif is cleaved by an unknown protease. Here, we generate parasite lines expressing HT motif containing proteins that are localized to different compartments within the parasite or host cell. We find that the HT motif in a protein that is retained in the parasite endoplasmic reticulum, is cleaved and N-acetylated as efficiently as a protein that is exported. This shows that cleavage of the HT motif occurs early in the secretory pathway, in the parasite endoplasmic reticulum. PMID:20117149

  7. Silver(I) complexes in coordination supramolecular system with bulky acridine-based ligands: syntheses, crystal structures, and theoretical investigations on C-H...Ag close interaction.

    PubMed

    Liu, Chun-Sen; Chen, Pei-Quan; Yang, En-Cui; Tian, Jin-Lei; Bu, Xian-He; Li, Zheng-Ming; Sun, Hong-Wei; Lin, Zhenyang

    2006-07-24

    to Ag(I) ions. Also, these results strongly support the existence of C-H...Ag close interactions and allow us to have a better understanding of the nature of such interactions in the coordination supramolecular systems. PMID:16841986

  8. Unveiling Secrets of Overcoming the "Heteroatom Problem" in Palladium-Catalyzed Aerobic C-H Functionalization of Heterocycles: A DFT Mechanistic Study.

    PubMed

    Dang, Yanfeng; Deng, Xi; Guo, Jiandong; Song, Chunyu; Hu, Wenping; Wang, Zhi-Xiang

    2016-03-01

    Directed C-H functionalization of heterocycles through an exocyclic directing group (DG) is challenging due to the interference of the endocyclic heteroatom(s). Recently, the "heteroatom problem" was circumvented with the development of the protection-free Pd-catalyzed aerobic C-H functionalization of heterocycles guided by an exocyclic CONHOMe DG. We herein provide DFT mechanistic insights to facilitate the expansion of the strategy. The transformation proceeds as follows. First, the Pd2(dba)3 precursor interacts with t-BuNC (L, one of the substrates) and O2 to form the L2Pd(II)-η(2)-O2 peroxopalladium(II) species that can selectively oxidize N-methoxy amide (e.g., PyCONHOMe) substrate, giving an active L2Pd(II)X2 (X = PyCONOMe) species and releasing H2O2. After t-BuNC ligand migratory insertion followed by a 1,3-acyl migration and association with another t-BuNC, L2Pd(II)X2 converts to a more stable C-amidinyl L2Pd(II)XX' (X' = PyCON(t-Bu)C═NOMe) species. Finally, L2Pd(II)XX' undergoes C-H activation and C-C reductive elimination, affording the product. The C-H activation is the rate-determining step. The success of the strategy has three origins: (i) the N-methoxy amide DG can be easily oxidized in situ to generate the active L2Pd(II)X2 species via the oxidase pathway, thus preventing the destructive oxygenase pathway leading to stable t-BuNCO or the O-bridged dimeric Pd(II) species. The methoxy group in this amide DG greatly facilitates the oxidase pathway, and the tautomerization of N-methoxy amide to its imidic acid tautomer makes the oxidation of the substrate even easier. (ii) The X group in L2Pd(II)X2 can serve as an internal base to promote the C-H activation via CMD (concerted metalation-deprotonation) mechanism. (iii) The strong coordination ability of t-BuNC substrate/ligand suppresses the conventional cyclopalladation pathway enabled by the coordination of an endocyclic heteroatom to the Pd-center. PMID:26846963

  9. A level set simulation for ordering of quantum dots via cleaved-edge overgrowth

    NASA Astrophysics Data System (ADS)

    Niu, X. B.; Uccelli, E.; Fontcuberta i Morral, A.; Ratsch, C.

    2009-07-01

    Cleaved-edge overgrowth (CEO) is a promising technique to obtain ordered arrays of quantum dots, where the size and position of the dots can be controlled very well. We present level set simulations for CEO. Our simulations illustrate how the quality of the CEO technique depends on the potential energy surface (PES) for adatom diffusion, and thus suggest how variations of the PES can potentially improve the uniformity of quantum dot arrays.

  10. A direct experimental evidence for an aromatic C-H⋯O hydrogen bond by fluorescence-detected infrared spectroscopy

    NASA Astrophysics Data System (ADS)

    Venkatesan, V.; Fujii, A.; Ebata, T.; Mikami, N.

    2004-08-01

    Formation of a weak aromatic C-H⋯O hydrogen bond has been discerned both experimentally and computationally in the 1,2,4,5-tetrafluorobenzene (TFB)-water system. The intermolecular structure of the isolated TFB-water cluster in a supersonic jet was characterized using fluorescence-detected infrared spectroscopy. The formation of a weak hydrogen bond in the cluster was directly evidenced by a low-frequency shift and intensity enhancement of the hydrogen-bonded aromatic C-H stretch in the TFB moiety. This is the first direct observation of an aromatic C-H⋯O hydrogen bond in isolated gas phase clusters.

  11. Synthesis of Triarylpyridines in Thiopeptide Antibiotics by Using a C-H Arylation/Ring-Transformation Strategy.

    PubMed

    Amaike, Kazuma; Itami, Kenichiro; Yamaguchi, Junichiro

    2016-03-18

    We have described a C-H arylation/ring-transformation strategy for the synthesis of triarylpyridines, which form the core structure of thiopeptide antibiotics. This synthetic method readily gave 2,3,6-triarylpyridines in a regioselective manner by a two-phase approach: C-H arylation (a nickel-catalyzed decarbonylative Suzuki-Miyaura cross-coupling and decarbonylative C-H coupling for the synthesis of 2,4-diaryloxazoles) and ring transformation ([4+2] cycloaddition of 2,4-diaryloxazoles with (hetero)arylacrylic acids). To showcase these methods, we have accomplished the formal synthesis of thiopeptide antibiotics GE2270 s and amythiamicins. PMID:26833497

  12. The human brm protein is cleaved during apoptosis: the role of cathepsin G.

    PubMed

    Biggs, J R; Yang, J; Gullberg, U; Muchardt, C; Yaniv, M; Kraft, A S

    2001-03-27

    The human brm (hbrm) protein (homologue of the Drosophila melanogaster brahma and Saccharomyces cervisiae SNF-2 proteins) is part of a polypeptide complex believed to regulate chromatin conformation. We have shown that the hbrm protein is cleaved in NB4 leukemic cells after induction of apoptosis by UV-irradiation, DNA damaging agents, or staurosporine. Because hbrm is found only in the nucleus, we have investigated the nature of the proteases that may regulate the degradation of this protein during apoptosis. In an in vitro assay, the hbrm protein could not be cleaved by caspase-3, -7, or -6, the "effector" caspases generally believed to carry out the cleavage of nuclear protein substrates. In contrast, we find that cathepsin G, a granule enzyme found in NB4 cells, cleaves hbrm in a pattern similar to that observed in vivo during apoptosis. In addition, a peptide inhibitor of cathepsin G blocks hbrm cleavage during apoptosis but does not block activation of caspases or cleavage of the nuclear protein polyADP ribose polymerase (PARP). Although localized in granules and in the Golgi complex in untreated cells, cathepsin G becomes diffusely distributed during apoptosis. Cleavage by cathepsin G removes a 20-kDa fragment containing a bromodomain from the carboxyl terminus of hbrm. This cleavage disrupts the association between hbrm and the nuclear matrix; the 160-kDa hbrm cleavage fragment is less tightly associated with the nuclear matrix than full-length hbrm. PMID:11259672

  13. RecA-dependent programmable endonuclease Ref cleaves DNA in two distinct steps

    PubMed Central

    Ronayne, Erin A.; Cox, Michael M.

    2014-01-01

    The bacteriophage P1 recombination enhancement function (Ref) protein is a RecA-dependent programmable endonuclease. Ref targets displacement loops formed when an oligonucleotide is bound by a RecA filament and invades homologous double-stranded DNA sequences. Mechanistic details of this reaction have been explored, revealing that (i) Ref is nickase, cleaving the two target strands of a displacement loop sequentially, (ii) the two strands are cleaved in a prescribed order, with the paired strand cut first and (iii) the two cleavage events have different requirements. Cutting the paired strand is rapid, does not require RecA-mediated ATP hydrolysis and is promoted even by Ref active site variant H153A. The displaced strand is cleaved much more slowly, requires RecA-mediated ATP hydrolysis and does not occur with Ref H153A. The two cleavage events are also affected differently by solution conditions. We postulate that the second cleavage (displaced strand) is limited by some activity of RecA protein. PMID:24371286

  14. Meprin A impairs epithelial barrier function, enhances monocyte migration, and cleaves the tight junction protein occludin

    PubMed Central

    Bao, Jialing; Yura, Renee E.; Matters, Gail L.; Bradley, S. Gaylen; Shi, Pan; Tian, Fang

    2013-01-01

    Meprin metalloproteases are highly expressed at the luminal interface of the intestine and kidney and in certain leukocytes. Meprins cleave a variety of substrates in vitro, including extracellular matrix proteins, adherens junction proteins, and cytokines, and have been implicated in a number of inflammatory diseases. The linkage between results in vitro and pathogenesis, however, has not been elucidated. The present study aimed to determine whether meprins are determinative factors in disrupting the barrier function of the epithelium. Active meprin A or meprin B applied to Madin-Darby canine kidney (MDCK) cell monolayers increased permeability to fluorescein isothiocyanate-dextran and disrupted immunostaining of the tight junction protein occludin but not claudin-4. Meprin A, but not meprin B, cleaved occludin in MDCK monolayers. Experiments with recombinant occludin demonstrated that meprin A cleaves the protein between Gly100 and Ser101 on the first extracellular loop. In vivo experiments demonstrated that meprin A infused into the mouse bladder increased the epithelium permeability to sodium fluorescein. Furthermore, monocytes from meprin knockout mice on a C57BL/6 background were less able to migrate through an MDCK monolayer than monocytes from their wild-type counterparts. These results demonstrate the capability of meprin A to disrupt epithelial barriers and implicate occludin as one of the important targets of meprin A that may modulate inflammation. PMID:23804454

  15. Fibronectin fragments and the cleaving enzyme ADAM-8 in the degenerative human intervertebral disc

    PubMed Central

    Ruel, Nancy; Markova, Dessislava Z.; Adams, Sherrill L.; Scanzello, Carla; Cs-Szabo, Gabriella; Gerard, David; Shi, Peng; Anderson, D. Greg; Zack, Marc; An, Howard S.; Chen, Di; Zhang, Yejia

    2014-01-01

    Study Design The presence fibronectin fragments (FN-fs) and the cleaving enzyme, A disintegrin and metalloproteinase domain-containing protein (ADAM)-8 were examined in human intervertebral disc (IVD) tissue in vitro. Objective To investigate the presence and pathophysiological concentration of FN-fs and their cleaving enzyme, ADAM-8, in the human IVD tissue. Summary of Background Data The 29kDa FN-f has been shown to result in extracellular matrix loss in rabbit IVDs. However, the concentration of this biologically active fragment in the degenerative human IVD tissue has previously not been determined. Further, it is critical to identify the enzyme(s) responsible for FN cleavage in the IVD. Methods Human degenerative IVD tissues were removed during spinal surgery. A normal appearing young adult and an infant human cadaveric sample were obtained as controls. Soluble proteins were extracted, and analyzed by Western blotting utilizing antibodies specific for the human FN neoepitope VRAA271. A purified 29 kDa FN-f was used to allow estimation of the concentration of FN-fs in the tissues. ADAM-8, a FN-cleaving enzyme, was analyzed by Western blotting and immunostaining. Results All adult IVD tissues contain many FN-f species, but these species were absent from the infant disc tissue. Moderately degenerative discs contained the highest amount of FN-fs; the concentration was estimated to be in the nanomolar range per gram of tissue. ADAM-8, known to cleave FN resulting in the VRAA271 neoepitope, was present in the human disc. ADAM-8 primarily localized in the pericellular matrix of the nucleus pulposus (NP) tissue, as determined by immunostaining. Conclusion This is the first report that N-terminal FN-fs are consistently present in IVD tissues from adult subjects. The pathophysiological concentration of these fragments is estimated to be at nanomolar range per gram of IVD tissue. Further, ADAM-8, known to cleave FN, is present at the pericellular matrix of disc cells

  16. Porcine Epidemic Diarrhea Virus 3C-Like Protease Regulates Its Interferon Antagonism by Cleaving NEMO

    PubMed Central

    Wang, Dang; Fang, Liurong; Shi, Yanling; Zhang, Huan; Gao, Li; Peng, Guiqing; Chen, Huanchun; Li, Kui

    2015-01-01

    ABSTRACT Porcine epidemic diarrhea virus (PEDV) is an enteropathogenic coronavirus causing lethal watery diarrhea in piglets. Since 2010, a PEDV variant has spread rapidly in China, and it emerged in the United States in 2013, posing significant economic and public health concerns. The ability to circumvent the interferon (IFN) antiviral response, as suggested for PEDV, promotes viral survival and regulates pathogenesis of PEDV infections, but the underlying mechanisms remain obscure. Here, we show that PEDV-encoded 3C-like protease, nsp5, is an IFN antagonist that proteolytically cleaves the nuclear transcription factor kappa B (NF-κB) essential modulator (NEMO), an essential adaptor bridging interferon-regulatory factor and NF-κB activation. NEMO is cleaved at glutamine 231 (Q231) by PEDV, and this cleavage impaired the ability of NEMO to activate downstream IFN production and to act as a signaling adaptor of the RIG-I/MDA5 pathway. Mutations specifically disrupting the cysteine protease activity of PEDV nsp5 abrogated NEMO cleavage and the inhibition of IFN induction. Structural analysis suggests that several key residues outside the catalytic sites of PEDV nsp5 probably impact NEMO cleavage by modulating potential interactions of nsp5 with their substrates. These data show that PEDV nsp5 disrupts type I IFN signaling by cleaving NEMO. Previously, we and others demonstrated that NEMO is also cleaved by 3C or 3C-like proteinases of picornavirus and artertivirus. Thus, NEMO probably represents a prime target for 3C or 3C-like proteinases of different viruses. IMPORTANCE The continued emergence and reemergence of porcine epidemic diarrhea virus (PEDV) underscore the importance of studying how this virus manipulates the immune responses of its hosts. During coevolution with its hosts, PEDV has acquired mechanisms to subvert host innate immune responses for its survival advantage. At least two proteins encoded by PEDV have been identified as interferon (IFN

  17. 2008 C. H. McCloy lecture. Social psychology and physical activity: back to the future.

    PubMed

    Gill, Diane L

    2009-12-01

    In the early 1970s, both my academic career and the psychology subdiscipline within kinesiology began as "social psychology and physical activity. "Since then, sport and exercise psychology research has shifted away from the social to a narrower biopsycho-(no social) approach, and professional practice has focused on the elite rather than the larger public. Psychology can contribute to an integrative and relevant professional discipline by going back to the future as social psychology and physical activity and by incorporating three of C. H. McCloy's themes (a) evidence-based practice, (b) beyond dualisms, and (c) commitment to public service. Our scholarship must move beyond dualisms to recognize complexities and connections and be truly scholarship for practice. Social psychology and physical activity can serve the public by advocating for inclusive, empowering physical activity programs that promote health and well being for all. PMID:20025109

  18. Metal-ligand multiple bonds as frustrated Lewis pairs for C-H functionalization.

    PubMed

    Whited, Matthew T

    2012-01-01

    The concept of frustrated Lewis pairs (FLPs) has received considerable attention of late, and numerous reports have demonstrated the power of non- or weakly interacting Lewis acid-base pairs for the cooperative activation of small molecules. Although most studies have focused on the use of organic or main-group FLPs that utilize steric encumbrance to prevent adduct formation, a related strategy can be envisioned for both organic and inorganic complexes, in which "electronic frustration" engenders reactivity consistent with both nucleophilic (basic) and electrophilic (acidic) character. Here we propose that such a description is consistent with the behavior of many coordinatively unsaturated transition-metal species featuring metal-ligand multiple bonds, and we further demonstrate that the resultant reactivity may be a powerful tool for the functionalization of C-H and E-H bonds. PMID:23209486

  19. Rapid thermal annealing of Amorphous Hydrogenated Carbon (a-C:H) films

    NASA Technical Reports Server (NTRS)

    Alterovitz, Samuel A.; Pouch, John J.; Warner, Joseph D.

    1987-01-01

    Amorphous hydrogenated carbon (a-C:H) films were deposited on silicon and quartz substrates by a 30 kHz plasma discharge technique using methane. Rapid thermal processing of the films was accomplished in nitrogen gas using tungsten halogen light. The rapid thermal processing was done at several fixed temperatures (up to 600 C), as a function of time (up to 1800 sec). The films were characterized by optical absorption and by ellipsometry in the near UV and the visible. The bandgap, estimated from extrapolation of the linear part of a Tauc plot, decreases both with the annealing temperature and the annealing time, with the temperature dependence being the dominating factor. The density of states parameter increases up to 25 percent and the refractive index changes up to 20 percent with temperature increase. Possible explanations of the mechanisms involved in these processes are discussed.

  20. A reinvestigation of the rate of the C/+/ + H2 radiative association reaction. [interstellar chemistry

    NASA Technical Reports Server (NTRS)

    Herbst, E.

    1982-01-01

    It is noted that new experimental results and statistical theories have prompted a reinvestigation of the rate coefficient of the interstellar reaction in which C(+) + H2 yields CH2(+) + h(nu) in the 10-100 K temperature range. The results presented here indicate a rate coefficient between 10 to the -16 and 10 to the -15 cu cm/s at all temperatures studied. In applying the modified thermal and phase space theories, it is expected that they will be as accurate as for radiative association as for three-body association, provided the ab initio value for the radiative decay rate is correct. It is expected that the calculated values of the rate coefficient will be accurate to within an order of magnitude and will have the correct temperature dependence.

  1. Selective Heterogeneous C-H Activation/Halogenation Reactions Catalyzed by Pd@MOF Nanocomposites.

    PubMed

    Pascanu, Vlad; Carson, Fabian; Solano, Marta Vico; Su, Jie; Zou, Xiaodong; Johansson, Magnus J; Martín-Matute, Belén

    2016-03-01

    A directed heterogeneous C-H activation/halogenation reaction catalyzed by readily synthesized Pd@MOF nanocatalysts was developed. The heterogeneous Pd catalysts used were a novel and environmentally benign Fe-based metal-organic framework (MOF) (Pd@MIL-88B-NH2 (Fe)) and the previously developed Pd@MIL-101-NH2 (Cr). Very high conversions and selectivities were achieved under very mild reaction conditions and in short reaction times. A wide variety of directing groups, halogen sources, and substitution patterns were well tolerated, and valuable polyhalogenated compounds were synthesized in a controlled manner. The synthesis of the Pd-functionalized Fe-based MOF and the recyclability of the two catalysts are also presented. PMID:26481867

  2. Matching plasmon resonances to the C=C and C-H bonds in estradiol

    NASA Astrophysics Data System (ADS)

    Mbomson, Ifeoma G.; McMeekin, Scott; De La Rue, Richard; Johnson, Nigel P.

    2015-03-01

    We tune nanoantennas to resonate within mid-infrared wavelengths to match the vibrational resonances of C=C and C-H of the hormone estradiol. Modelling and fabrication of the nanoantennas produce plasmon resonances between 2 μm to 7 μm. The hormone estradiol was dissolved in ethanol and evaporated, leaving thickness of a few hundreds of nanometres on top of gold asymmetric split H-like shaped on a fused silica substrate. The reflectance was measured and a red-shift is recorded from the resonators plasmonic peaks. Fourier transform infrared spectroscopy is use to observe enhanced spectra of the stretching modes for the analyte which belongs to alkenyl biochemical group.

  3. Mechanistic Insights into the Palladium-Catalyzed Aziridination of Aliphatic Amines by C-H Activation.

    PubMed

    Smalley, Adam P; Gaunt, Matthew J

    2015-08-26

    Detailed kinetic studies and computational investigations have been performed to elucidate the mechanism of a palladium-catalyzed C-H activation aziridination. A theoretical rate law has been derived that matches with experimental observations and has led to an improvement in the reaction conditions. Acetic acid was found to be beneficial in controlling the formation of an off-cycle intermediate, allowing a decrease in catalyst loading and improved yields. Density functional theory (DFT) studies were performed to examine the selectivities observed in the reaction. Evidence for electronic-controlled regioselectivity for the cyclopalladation step was obtained by a distortion-interaction analysis, whereas the aziridination product was justified through dissociation of acetic acid from the palladium(IV) intermediate preceding the product-forming reductive elimination step. The understanding of this reaction mechanism under the synthesis conditions should provide valuable assistance in the comprehension and design of palladium-catalyzed reactions on similar systems. PMID:26247373

  4. Copper-catalyzed formal C - H carboxylation of aromatic compounds with carbon dioxide through arylaluminum intermediates.

    PubMed

    Ueno, Atsushi; Takimoto, Masanori; O, Wylie W N; Nishiura, Masayoshi; Ikariya, Takao; Hou, Zhaomin

    2015-04-01

    The C - H bond carboxylation of various aromatic compounds with CO2 was achieved by the deprotonative alumination with a mixed alkyl amido lithium aluminate compound iBu3 Al(TMP)Li followed by the NHC-copper-catalyzed carboxylation of the resulting arylaluminum species, which afforded the corresponding carboxylation products in high yield and high selectivity. In addition to benzene derivatives, heteroarenes such as benzofuran, benzothiophene, and indole derivatives are also suitable substrates. Functional groups such as Cl, Br, I, vinyl, amide, and CN could survive the reaction conditions. Some key reaction intermediates such as the copper aryl and isobutyl complexes and their carboxylation products were isolated and structurally characterized by X-ray crystallographic analyses, thus offering important information on the reaction mechanism. PMID:25491488

  5. Intramolecular cyclopropanation and C-H insertion reactions with metal carbenoids generated from cyclopropenes.

    PubMed

    Archambeau, Alexis; Miege, Frédéric; Meyer, Christophe; Cossy, Janine

    2015-04-21

    Activation of unsaturated carbon-carbon bonds by means of transition metal catalysts is an exceptionally active research field in organic synthesis. In this context, due to their high ring strain, cyclopropenes constitute an interesting class of substrates that displays a versatile reactivity in the presence of transition metal catalysts. Metal complexes of vinyl carbenes are involved as key intermediates in a wide variety of transition metal-catalyzed ring-opening reactions of cyclopropenes. Most of the reported transformations rely on intermolecular or intramolecular addition of nucleophiles to these latter reactive species. This Account focuses specifically on the reactivity of carbenoids resulting from the ring-opening of cyclopropenes in cyclopropanation and C-H insertion reactions, which are arguably two of the most representative transformations of metal complexes of carbenes. Compared with the more conventional α-diazo carbonyl compounds, the use of cyclopropenes as precursors of metal carbenoids in intramolecular cyclopropanation or C-H insertion reactions has been largely underexploited. One of the challenges is to devise appropriately substituted and readily available cyclopropenes that would not only undergo regioselective ring-opening under mild conditions but also trigger the subsequent desired transformations with a high level of chemoselectivity and stereoselectivity. These goals were met by considering several substrates derived from the readily available 3,3-dimethylcyclopropenylcarbinols or 3,3-dimethylcyclopropenylcarbinyl amines. In the case of 1,6-cyclopropene-enes, highly efficient and diastereoselective gold(I)-catalyzed ring-opening/intramolecular cyclopropanations were developed as a route to diversely substituted heterocycles and carbocycles possessing a bicyclo[4.1.0]heptane framework. The use of rhodium(II) catalysts enabled us to widen the scope of this transformation for the synthesis of medium-sized heterocyclic scaffolds

  6. Triiodide-Mediated δ-Amination of Secondary C-H Bonds.

    PubMed

    Wappes, Ethan A; Fosu, Stacy C; Chopko, Trevor C; Nagib, David A

    2016-08-16

    The Cδ -H amination of unactivated, secondary C-H bonds to form a broad range of functionalized pyrrolidines has been developed by a triiodide (I3 (-) )-mediated strategy. By in situ 1) oxidation of sodium iodide and 2) sequestration of the transiently generated iodine (I2 ) as I3 (-) , this approach precludes undesired I2 -mediated decomposition which can otherwise limit synthetic utility to only weak C(sp(3) )-H bonds. The mechanism of this triiodide-mediated cyclization of unbiased, secondary C(sp(3) )-H bonds, by either thermal or photolytic initiation, is supported by NMR and UV/Vis data, as well as intercepted intermediates. PMID:27384522

  7. Recommended Thermal Rate Coefficients for the C + H3+ Reaction and Some Astrochemical Implications

    NASA Astrophysics Data System (ADS)

    Vissapragada, Shreyas; Buzard, Cam; Miller, Kenneth A.; O'Connor, Aodh; De Ruette, Nathalie; Urbain, Xavier; Savin, Daniel Wolf

    2016-06-01

    We have incorporated our experimentally derived thermal rate coefficients for C + H3+ forming CH+ and CH2+ into a commonly used astrochemical model. We find that the Arrhenius-Kooij equation typically used in chemical models does not accurately fit our data and use instead a more versatile fitting formula. At a temperature of 10 K and a density of 104 cm-3, we find no significant differences in the predicted abundances, but at higher temperatures of 50, 100, and 300 K we find up to factor of 2 changes. Additionally, we find that the relatively small error on our measurements (~15%) significantly reduces the uncertainties on the predicted abundances compared to those obtained using the currently implemented Langevin rate coefficient with its estimated factor of 2 uncertainty.

  8. A Selective C-H Deprotonation Strategy to Access Functionalized Arynes by Using Hypervalent Iodine.

    PubMed

    Sundalam, Sunil K; Nilova, Aleksandra; Seidl, Thomas L; Stuart, David R

    2016-07-11

    Described here is an efficient method to access highly functionalized arynes from unsymmetrical aryl(mesityl)iodonium tosylate salts. The iodonium salts are prepared in a single pot from either commercially available aryl iodides or arylboronic acids. The aryne intermediates are generated by ortho-C-H deprotonation of aryl(mesityl)iodonium salt with a commercially available amide base and trapped in a cycloaddition reaction with furan in moderate to good yields. Coupling partners for the aryne intermediates beyond furan are also described, including benzyl azide and alicyclic amine nucleophiles. The regio- and chemoselectivity of this reaction is discussed and evidence for the spectator aryl ligand of the iodonium salt as a critical control element in selectivity is presented. PMID:27239971

  9. 5-Position-selective C-H trifluoromethylation of 8-aminoquinoline derivatives.

    PubMed

    Kuninobu, Yoichiro; Nishi, Mitsumi; Kanai, Motomu

    2016-09-14

    We developed a copper-catalyzed 5-position-selective C-H trifluoromethylation of 8-aminoquinoline derivatives. The reaction proceeded with high functional group tolerance under mild conditions. In the case of quinolines with an amide, carbamate, urea, or sulfonamide group at the 8-position of quinoline moieties, a radical scavenger experiment indicated that the reaction proceeded via a radical pathway. The protecting group of an 8-amidoquinoline derivative could be removed by hydrolysis. On the other hand, the trifluoromethylation of 8-aminoquinolines was also promoted by other Lewis acids as well as a copper catalyst and proceeded even in the presence of a radical scavenger. These results indicated that the trifluoromethylation of 8-aminoquinolines proceeded via a Friedel-Crafts-type reaction. Interestingly, the copper salt works as either a catalyst for the formation of a CF3 radical or a Lewis acid to promote a Friedel-Crafts-type reaction, depending on the substrate. PMID:27506919

  10. Erosion of a-C:H in the afterglow of ammonia plasma

    NASA Astrophysics Data System (ADS)

    Drenik, Aleksander; Mourkas, Angelos; Zaplotnik, Rok; Primc, Gregor; Mozetič, Miran; Panjan, Peter; Alegre, Daniel; Tabarés, Francisco L.

    2016-07-01

    Amorphous hydrogenated carbon (a-C:H) deposits were eroded in the afterglow of a NH3 plasma, created with an inductively coupled RF generator in pure NH3 at the gas pressure of 50 Pa. The plasma system was characterised by optical emission spectroscopy and mass spectrometry, and the erosion process was monitored in-situ with a laser interferometry system. Based on the mass spectrometry measurements, the degree of dissociation of the NH3 molecules was estimated at 90% at the highest generator forward power in the discharge region, however the densities of N and H atoms were significantly smaller at the location of the sample holder. The erosion rates were found to increase with surface temperature and forward generator power. In the high dissociation regime, the composition of the afterglow and the reaction products highlight the role of N atoms in the erosion process.

  11. Total Synthesis of Verruculogen and Fumitremorgin A Enabled by Ligand-Controlled C-H Borylation.

    PubMed

    Feng, Yu; Holte, Dane; Zoller, Jochen; Umemiya, Shigenobu; Simke, Leah R; Baran, Phil S

    2015-08-19

    Verruculogen and fumitremorgin A are bioactive alkaloids that contain a unique eight-membered endoperoxide. Although related natural products such as fumitremorgins B and C have been previously synthesized, we report the first synthesis of the more complex, endoperoxide-containing members of this family. A concise route to verruculogen and fumitremorgin A relied not only on a hydroperoxide/indole hemiaminal cyclization, but also on the ability to access the seemingly simple starting material, 6-methoxytryptophan. An iridium-catalyzed C-H borylation/Chan-Lam procedure guided by an N-TIPS group enabled the conversion of a tryptophan derivative into a 6-methoxytryptophan derivative, proving to be a general way to functionalize the C6 position of an N,C3-disubstituted indole for the synthesis of indole-containing natural products and pharmaceuticals. PMID:26256033

  12. R.E.A.C.H. to Teach: Making Patient and Family Education "Stick".

    PubMed

    Cutilli, Carolyn Crane

    2016-01-01

    Healthcare professionals teach patients and families about their health every day. Regulatory and accreditation organizations mandate patient and family education to promote better health outcomes. And recently, financial rewards for healthcare organizations are being tied to patient satisfaction (Hospital Consumer Assessment of Healthcare Providers and Systems-HCAHPS). A University of Pennsylvania Health System group of staff and patients, devoted to excellence in patient and family education, developed the graphic "R.E.A.C.H. to Teach." The purpose of the graphic is to make evidence-based practice (EBP) for patient and family education "stick" with staff. The group used concepts from the marketing book, Made to Stick, to demonstrate how to develop effective staff and patient and family education. Ideas (education) that survive ("stick") have the following attributes: simple, unexpected, concrete, credible, emotional, and narrative (story). This article demonstrates how to apply these principles and EBP to patient and family education. PMID:27441879

  13. Manganese-Mediated C-H Alkylation of Unbiased Arenes Using Alkylboronic Acids.

    PubMed

    Castro, Susana; Fernández, Juan J; Fañanás, Francisco J; Vicente, Rubén; Rodríguez, Félix

    2016-06-27

    The alkylation of arenes is an essential synthetic step of interest not only from the academic point of view but also in the bulk chemical industry. Despite its limitations, the Friedel-Crafts reaction is still the method of choice for most of the arene alkylation processes. Thus, the development of new strategies to synthesize alkyl arenes is a highly desirable goal, and herein, we present an alternative method to those conventional reactions. Particularly, a simple protocol for the direct C-H alkylation of unbiased arenes with alkylboronic acids in the presence of Mn(OAc)3 ⋅2H2 O is reported. Primary or secondary unactivated alkylboronic acids served as alkylating agents for the direct functionalization of representative polyaromatic hydrocarbons (PAHs) or benzene. The results are consistent with a free-radical mechanism. PMID:27124250

  14. C-H activation of ethers by pyridine tethered PCsp3P-type iridium complexes.

    PubMed

    Cui, Peng; Babbini, Dominic C; Iluc, Vlad M

    2016-06-14

    Iridium PCsp3P complexes featuring a novel bis(2-diphenylphosphinophenyl)-2-pyridylmethane ligand (PC(Py)HP) are reported. C-H activation reactions between the dihydride complex [(PC(Py)P)Ir(H)2] and tetrahydrofuran or methyl tert-butyl ether in the presence of a hydrogen acceptor, norbornene (NBE), at ambient temperature led exclusively to the hydrido oxyalkyl complexes, [(PC(Py)P)IrH(C4H7O)] and [(PC(Py)P)IrH(CH2O(t)Bu)], respectively. The internal pyridine donor is important and stabilizes these species by coordination to the iridium center. The coordination of pyridine to the iridium center is labile, however, and its dissociation occurs in the presence of a suitable substrate, as demonstrated by the intramolecular nucleophilic attack of pyridine on a vinylidene intermediate generated from PhC[triple bond, length as m-dash]CH. PMID:27052422

  15. Native functionality in triple catalytic cross-coupling: sp³ C-H bonds as latent nucleophiles.

    PubMed

    Shaw, Megan H; Shurtleff, Valerie W; Terrett, Jack A; Cuthbertson, James D; MacMillan, David W C

    2016-06-10

    The use of sp(3) C-H bonds--which are ubiquitous in organic molecules--as latent nucleophile equivalents for transition metal-catalyzed cross-coupling reactions has the potential to substantially streamline synthetic efforts in organic chemistry while bypassing substrate activation steps. Through the combination of photoredox-mediated hydrogen atom transfer (HAT) and nickel catalysis, we have developed a highly selective and general C-H arylation protocol that activates a wide array of C-H bonds as native functional handles for cross-coupling. This mild approach takes advantage of a tunable HAT catalyst that exhibits predictable reactivity patterns based on enthalpic and bond polarity considerations to selectively functionalize α-amino and α-oxy sp(3) C-H bonds in both cyclic and acyclic systems. PMID:27127237

  16. C-H arylation of benzoquinone in water through aniline activation: synergistic effect of graphite-supported copper oxide nanoparticles.

    PubMed

    Honraedt, Aurélien; Le Callonnec, François; Le Grognec, Erwan; Fernandez, Vincent; Felpin, François-Xavier

    2013-05-01

    A homemade CuONPs/Gr catalyst was found to be efficient for the C-H arylation of benzoquinone. This methodology represents the first example of a Meerwein arylation catalyzed by a heterogeneous catalyst. PMID:23551327

  17. C-H arylation of azaheterocycles: a direct ligand-free and Cu-catalyzed approach using diaryliodonium salts.

    PubMed

    Kumar, Dalip; Pilania, Meenakshi; Arun, V; Pooniya, Savita

    2014-09-01

    An efficient and high yielding Cu-catalyzed direct C-H arylation of azaheterocycles including oxadiazoles, thiadiazoles, benzoxazoles and benzothiazoles has been achieved by employing easily accessible diaryliodonium salts. PMID:25017573

  18. Silylation of C-H bonds in aromatic heterocycles by an Earth-abundant metal catalyst

    NASA Astrophysics Data System (ADS)

    Toutov, Anton A.; Liu, Wen-Bo; Betz, Kerry N.; Fedorov, Alexey; Stoltz, Brian M.; Grubbs, Robert H.

    2015-02-01

    Heteroaromatic compounds containing carbon-silicon (C-Si) bonds are of great interest in the fields of organic electronics and photonics, drug discovery, nuclear medicine and complex molecule synthesis, because these compounds have very useful physicochemical properties. Many of the methods now used to construct heteroaromatic C-Si bonds involve stoichiometric reactions between heteroaryl organometallic species and silicon electrophiles or direct, transition-metal-catalysed intermolecular carbon-hydrogen (C-H) silylation using rhodium or iridium complexes in the presence of excess hydrogen acceptors. Both approaches are useful, but their limitations include functional group incompatibility, narrow scope of application, high cost and low availability of the catalysts, and unproven scalability. For this reason, a new and general catalytic approach to heteroaromatic C-Si bond construction that avoids such limitations is highly desirable. Here we report an example of cross-dehydrogenative heteroaromatic C-H functionalization catalysed by an Earth-abundant alkali metal species. We found that readily available and inexpensive potassium tert-butoxide catalyses the direct silylation of aromatic heterocycles with hydrosilanes, furnishing heteroarylsilanes in a single step. The silylation proceeds under mild conditions, in the absence of hydrogen acceptors, ligands or additives, and is scalable to greater than 100 grams under optionally solvent-free conditions. Substrate classes that are difficult to activate with precious metal catalysts are silylated in good yield and with excellent regioselectivity. The derived heteroarylsilane products readily engage in versatile transformations enabling new synthetic strategies for heteroaromatic elaboration, and are useful in their own right in pharmaceutical and materials science applications.

  19. Iron Mineral Catalyzed C-H Activation As a Potential Pathway for Halogenation Processes

    NASA Astrophysics Data System (ADS)

    Tubbesing, C.; Schoeler, H. F.; Benzing, K.; Krause, T.; Lippe, S.; Rudloff, M.

    2014-12-01

    Due to increasing drinking water demand of mankind and an expected climate change the impact of salt lakes and salt deserts will increase within the next decades. Furthermore, a rising sea level influences coastal areas like salt marshes and abets processes which will lead to elevated organohalogen formation. An additional increase of the global warming potential, of particle formation and stratospheric ozone depletion is expected. Understanding these multifaceted processes is essential for mankind to be prepared for these alterations of the atmosphere. For example, Keppler et al. (2000) described the production of volatile halogenated organic compounds via oxidation of organic matter driven by ferric iron. However, the formation of long-chained alkyl halides in salt lakes is yet undisclosed. Despite the relative "inertness" of alkanes a direct halogenation of these compounds might be envisaged. In 2005 Vaillancourt et al. discovered a nonheme iron enzyme which is able to halogenate organic compounds via generating the high valent ferryl cation as reaction center. Based on various publications about C-H activation (Bergman, 2007) we postulate a halogenation process in which an iron containing minerals catalyse the C-H bond cleavage of organic compounds in soils. The generated organic radicals are highly reactive towards halides connected to the iron complex. We suggest that next to diagenetically altered iron containing enzymes, minerals such as oxides, hydroxides and sulfides are involved in abiotic halogenation processes. We applied the amino acid methionine as organic model compound and soluble iron species as reactants. All samples were incubated in aqueous phases containing various NaCl concentrations. As a result various halogenated ethanes and ethenes were identified as reaction products. References Bergman, R. G. (2007) Nature, 446(7134) 391-393 Keppler, F., et al. (2000) Nature, 403(6767) 298-301 Vaillancourt, F. H., et al. (2005) Nature, 436(7054) 1191-1194

  20. Deposition of a-C:H films on inner surface of high-aspect-ratio microchannel

    NASA Astrophysics Data System (ADS)

    Hirata, Yuki; Choi, Junho

    2016-08-01

    Hydrogenated amorphous carbon (a-C:H) films were prepared on inner surface of 100-μm-width microchannel by using a bipolar-type plasma based ion implantation and deposition. The microchannel was fabricated using a silicon plate, and two kinds of microchannels were prepared, namely, with a bottom layer (open at one end) and without a bottom layer (open at both ends). The distribution of thickness and hardness of films was evaluated by SEM and nanoindentation measurements, respectively, and the microstructures of films were evaluated by Raman spectroscopy. Furthermore, the behavior of ions and radicals was analyzed simultaneously by combining the calculation methods of Particle-In-Cell/Monte Carlo Collision and Direct Simulation Monte Carlo to investigate the coating mechanism for the microchannel. It was found that the film thickness decreased as the depth of the coating position increased in the microchannels where it is open at one end. The uniformity of the film thickness improved by increasing the negative pulse voltage because ions can arrive at the deeper part of the microchannel. In addition, the hardness increased as the depth of the coating position increased. This is because the radicals do not arrive at the deeper part of the microchannel, and the incident proportion of ions relative to that of radicals increases, resulting in a high hardness due to the amorphization of the film. The opening area of the microchannel where the aspect ratio is very small, radicals dominate the incident flux, whereas ions prevail over radicals above an aspect ratio of about 7.5. On the other hand, in the microchannels that are open at both ends, there were great improvements in uniformity of the film thickness, hardness, and the film structure. The a-C:H films were successfully deposited on the entire inner surface of a microchannel with an aspect ratio of 20.

  1. Accurate NMR determination of C-H or N-H distances for unlabeled molecules.

    PubMed

    Nishiyama, Y; Malon, M; Potrzebowski, M J; Paluch, P; Amoureux, J P

    2016-02-01

    Cross-Polarization with Variable Contact-time (CP-VC) is very efficient at ultra-fast MAS (νR ≥ 60 kHz) to measure accurately the dipolar interactions corresponding to C-H or N-H short distances, which are very useful for resonance assignment and for analysis of dynamics. Here, we demonstrate the CP-VC experiment with (1)H detection. In the case of C-H distances, we compare the CP-VC signals with direct ((13)C) and indirect ((1)H) detection and find that the latter allows a S/N gain of ca. 2.5, which means a gain of ca. 6 in experimental time. The main powerful characteristics of CP-VC methods are related to the ultra-fast spinning speed and to the fact that most of the time only the value of the dipolar peak separation has to be used to obtain the information. As a result, CP-VC methods are: (i) easy to set up and to use, and robust with respect to (ii) rf-inhomogeneity thus allowing the use of full rotor samples, (iii) rf mismatch, and (iv) offsets and chemical shift anisotropies. It must be noted that the CP-VC 2D method with indirect (1)H detection requires the proton resolution and is thus mainly applicable to small or perdeuterated molecules. We also show that an analysis of the dynamics can even be performed, with a reasonable experimental time, on unlabeled samples with (13)C or even (15)N natural abundance. PMID:26169913

  2. Contrasting electronic requirements for C-H binding and C-H activation in d(6) half-sandwich complexes of rhenium and tungsten.

    PubMed

    Thenraj, Murugesan; Samuelson, Ashoka G

    2015-09-15

    A computational study of the interaction half-sandwich metal fragments (metal = Re/W, electron count = d(6)), containing linear nitrosyl (NO(+) ), carbon monoxide (CO), trifluorophosphine (PF3 ), N-heterocyclic carbene (NHC) ligands with alkanes are conducted using density functional theory employing the hybrid meta-GGA functional (M06). Electron deficiency on the metal increases with the ligand in the order NHC < CO < PF3 < NO(+). Electron-withdrawing ligands like NO(+) lead to more stable alkane complexes than NHC, a strong electron donor. Energy decomposition analysis shows that stabilization is due to orbital interaction involving charge transfer from the alkane to the metal. Reactivity and dynamics of the alkane fragment are facilitated by electron donors on the metal. These results match most of the experimental results known for CO and PF3 complexes. The study suggests activation of alkane in metal complexes to be facile with strong donor ligands like NHC. PMID:26174521

  3. Coal structural inferences derived from the alkylation of acidic C--H bonds with pK sub a > 33

    SciTech Connect

    Chambers, R.R. Jr. )

    1989-01-01

    Our approach for analyzing the acidic C--H bonds in coal is to treat O-methyl coal with a series of indicator bases, BLi, followed by methylation with C-14 methyl iodide. By varying the identity of BLi, and thus the pK{sub a} of the conjugate acid BH, it is possible to evaluate the number of C--H bonds as a function of pK{sub a}. 13 refs.

  4. Toluene derivatives as simple coupling precursors for cascade palladium-catalyzed oxidative C-H bond acylation of acetanilides.

    PubMed

    Wu, Yinuo; Choy, Pui Ying; Mao, Fei; Kwong, Fuk Yee

    2013-01-25

    A palladium-catalyzed cascade cross-coupling of acetanilide and toluene for the synthesis of ortho-acylacetanilide is described. Toluene derivatives can act as effective acyl precursors (upon sp(3)-C-H bond oxidation by a Pd/TBHP system) in the oxidative coupling between two C-H bonds. This dehydrogenative Pd-catalyzed ortho-acylation proceeds under mild reaction conditions. PMID:23230572

  5. Aminoquinoline-assisted vinylic C-H arylation of unsubstituted acrylamide for the selective synthesis of Z olefins.

    PubMed

    Cheng, Xiuzhi; Chen, Zhen; Gao, Yadong; Xue, Fengtian; Jiang, Chao

    2016-03-15

    A method for Pd-catalyzed, aminoquinoline-directed arylation of vinylic C-H bonds with aryl iodides has been developed. This reaction represents a rare example of Pd-catalyzed vinylic C-H functionalization of unsubstituted acrylamide, allowing for the highly regio- and stereoselective preparation of Z-olefins. High tolerance to functional groups is observed with good yields and excellent selectivity. It offers a complementary synthetic method to traditional pathways for Z-olefins. PMID:26932744

  6. Enantioselective Allylic C-H Oxidation of Terminal Olefins to Isochromans by Palladium(II)/Chiral Sulfoxide Catalysis.

    PubMed

    Ammann, Stephen E; Liu, Wei; White, M Christina

    2016-08-01

    The enantioselective synthesis of isochroman motifs has been accomplished by palladium(II)-catalyzed allylic C-H oxidation from terminal olefin precursors. Critical to the success of this goal was the development and utilization of a novel chiral aryl sulfoxide-oxazoline (ArSOX) ligand. The allylic C-H oxidation reaction proceeds with the broadest scope and highest levels of asymmetric induction reported to date (avg. 92 % ee, 13 examples with greater than 90 % ee). PMID:27376625

  7. Cobalt-Catalyzed Oxidase C-H/N-H Alkyne Annulation: Mechanistic Insights and Access to Anticancer Agents.

    PubMed

    Mei, Ruhuai; Wang, Hui; Warratz, Svenja; Macgregor, Stuart A; Ackermann, Lutz

    2016-05-10

    Cp*-free cobalt-catalyzed alkyne annulations by C-H/N-H functionalizations were accomplished with molecular O2 as the sole oxidant. The user-friendly oxidase strategy proved viable with various internal and terminal alkynes through kinetically relevant C-H cobaltation, providing among others step-economical access to the anticancer topoisomerase-I inhibitor 21,22-dimethoxyrosettacin. DFT calculations suggest that electronic effects control the regioselectivity of the alkyne insertion step. PMID:26992149

  8. Convergent Synthesis of Diverse Nitrogen Heterocycles via Rh(III)-Catalyzed C-H Conjugate Addition/Cyclization Reactions.

    PubMed

    Weinstein, Adam B; Ellman, Jonathan A

    2016-07-01

    The development of Rh(III)-catalyzed C-H conjugate addition/cyclization reactions that provide access to synthetically useful fused bi- and tricyclic nitrogen heterocycles is reported. A broad scope of C-H functionalization substrates and electrophilic olefin coupling partners is effective, and depending on the nature of the directing group, cyclic imide, amide, or heteroaromatic products are obtained. An efficient synthesis of a pyrrolophenanthridine alkaloid natural product, oxoassoanine, highlights the utility of this method. PMID:27337641

  9. Synthesis of Antiviral Tetrahydrocarbazole Derivatives by Photochemical and Acid-catalyzed C-H Functionalization via Intermediate Peroxides (CHIPS)

    PubMed Central

    Gulzar, Naeem; Klussmann, Martin

    2014-01-01

    The direct functionalization of C-H bonds is an important and long standing goal in organic chemistry. Such transformations can be very powerful in order to streamline synthesis by saving steps, time and material compared to conventional methods that require the introduction and removal of activating or directing groups. Therefore, the functionalization of C-H bonds is also attractive for green chemistry. Under oxidative conditions, two C-H bonds or one C-H and one heteroatom-H bond can be transformed to C-C and C-heteroatom bonds, respectively. Often these oxidative coupling reactions require synthetic oxidants, expensive catalysts or high temperatures. Here, we describe a two-step procedure to functionalize indole derivatives, more specifically tetrahydrocarbazoles, by C-H amination using only elemental oxygen as oxidant. The reaction uses the principle of C-H functionalization via Intermediate PeroxideS (CHIPS). In the first step, a hydroperoxide is generated oxidatively using visible light, a photosensitizer and elemental oxygen. In the second step, the N-nucleophile, an aniline, is introduced by Brønsted-acid catalyzed activation of the hydroperoxide leaving group. The products of the first and second step often precipitate and can be conveniently filtered off. The synthesis of a biologically active compound is shown. PMID:24998636

  10. Monolithic integration of InGaAsP/InP semiconductor lasers using the stop-cleaving technique

    SciTech Connect

    Antreasyan, A.; Napholtz, S.G.; Wilt, D.P.; Garbinski, P.A.

    1986-07-01

    In this paper the authors describe the stop-cleaving technique for locally cleaving the mirrors of semiconductor lasers without cleaving the entire substrate, and its applications. The technique is suitable for batch processing with a good yield and, therefore, can be applied to preparing optoelectronic integrated circuits (OEIC's). InGaAsP/InP double-channel-planar-buried-heterostructure lasers emitting at 1.3 ..mu..m are fabricated utilizing this technique with threshold currents as low as 20 mA and differential quantum efficiencies as high as 60 percent (two facets). The implementation of this technique for preparing a monolithically integrated pair of lasers is also demonstrated. The integrated dual-laser configuration is utilized to obtain a monolithically integrated laser-detector pair by operating one of the lasers under reserve bias, and to enhance longitudinal mode discrimination by utilizing the optical feedback from the self-aligned stop-cleaved facet of the second cavity.

  11. Direct Functionalization of Nitrogen Heterocycles via Rh-Catalyzed C-H Bond Activation

    PubMed Central

    Lewis, Jared C.; Bergman, Robert G.; Ellman, Jonathan A.

    2008-01-01

    Conspectus Nitrogen heterocycles are present in many compounds of enormous practical importance, ranging from pharmaceutical agents and biological probes to electroactive materials. Direct functionalization of nitrogen heterocycles through C-H bond activation constitutes a powerful means of regioselectively introducing a variety of substituents with diverse functional groups onto the heterocycle scaffold. Working together, our two groups have developed a family of Rh-catalyzed heterocycle alkylation and arylation reactions that are notable for their high level of functional-group compatibility. This Account describes our work in this area, emphasizing the relevant mechanistic insights that enabled synthetic advances and distinguished the resulting transformations from other methods. We initially discovered an intramolecular Rh-catalyzed C-2-alkylation of azoles by alkenyl groups. That reaction provided access to a number of di-, tri-, and tetracyclic azole derivatives. We then developed conditions that exploited microwave heating to expedite these reactions. While investigating the mechanism of this transformation, we discovered that a novel substrate-derived Rh-N-heterocyclic carbene (NHC) complex was involved as an intermediate. We then synthesized analogous Rh–NHC complexes directly by treating precursors to the intermediate [RhCl(PCy3)2] with N-methylbenzimidazole, 3-methyl-3,4-dihydroquinazoline, and 1-methyl-1,4-benzodiazepine-2-one. Extensive kinetic analysis and DFT calculations supported a mechanism for carbene formation in which the catalytically active RhCl(PCy3)2 fragment coordinates to the heterocycle before intramolecular activation of the C-H bond occurs. The resulting Rh-H intermediate ultimately tautomerizes to the observed carbene complex. With this mechanistic information and the discovery that acid co-catalysts accelerate the alkylation, we developed conditions that efficiently and intermolecularly alkylate a variety of heterocycles, including

  12. Direct Functionalization of Nitrogen Heterocycles via Rh-Catalyzed C-H Bond Activation

    SciTech Connect

    Lewis, Jared; Bergman, Robert; Ellman, Jonathan

    2008-02-04

    Nitrogen heterocycles are present in many compounds of enormous practical importance, ranging from pharmaceutical agents and biological probes to electroactive materials. Direct funtionalization of nitrogen heterocycles through C-H bond activation constitutes a powerful means of regioselectively introducing a variety of substituents with diverse functional groups onto the heterocycle scaffold. Working together, our two groups have developed a family of Rh-catalyzed heterocycle alkylation and arylation reactions that are notable for their high level of functional-group compatibility. This Account describes their work in this area, emphasizing the relevant mechanistic insights that enabled synthetic advances and distinguished the resulting transformations from other methods. They initially discovered an intramolecular Rh-catalyzed C-2-alkylation of azoles by alkenyl groups. That reaction provided access to a number of di-, tri-, and tetracyclic azole derivatives. They then developed conditions that exploited microwave heating to expedite these reactions. While investigating the mechanism of this transformation, they discovered that a novel substrate-derived Rh-N-heterocyclic carbene (NHC) complex was involved as an intermediate. They then synthesized analogous Rh-NHC complexes directly by treating precursors to the intermediate [RhCl(PCy{sub 3}){sub 2}] with N-methylbenzimidazole, 3-methyl-3,4-dihydroquinazolein, and 1-methyl-1,4-benzodiazepine-2-one. Extensive kinetic analysis and DFT calculations supported a mechanism for carbene formation in which the catalytically active RhCl(PCy{sub 3}){sub 2} fragment coordinates to the heterocycle before intramolecular activation of the C-H bond occurs. The resulting Rh-H intermediate ultimately tautomerizes to the observed carbene complex. With this mechanistic information and the discovery that acid co-catalysts accelerate the alkylation, they developed conditions that efficiently and intermolecularly alkylate a variety of

  13. Synthesis, Spectroscopy and Electrochemistry of Fe(II) and Fe(III) Quinonemonooxime Complexes and Their DNA Cleaving Activities

    PubMed Central

    Murugkar, Anupa; Deobagkar, Deepti

    1999-01-01

    Iron(II) and iron(III) complexes of 3,5-di-tert-butyl-o-benzoquinonemonooxime were synthesized and characterized by spectroscopic and electrochemical studies. Their ability to cleave DNA has been investigated under aerobic conditions at room temperature and in the presence and absence of H2 O2. The plasmid DNA pBR322 was effectively cleaved by these complexes in a concentration dependant manner. PMID:18475885

  14. C-H and C-C clumping in ethane by high-resolution mass spectrometry

    NASA Astrophysics Data System (ADS)

    Clog, M. D.; Eiler, J. M.

    2014-12-01

    Ethane (C2H6) is an important natural compound, and its geochemistry can be studied through 13C-13C, 13C-D and/or D-D clumping. Such measurements are potentially important both as a stepping stone towards the study of more complex organic molecules and, in its own regard, to understand processes controlling the generation, migration and destruction of natural gas. Isotopic clumping on C-C and C-H bonds could be influenced by thermodynamics, chemical kinetics, diffusion or gas mixing. Previous work showed that 13C-D clumping in methane generally reflects equilibrium and provides a measure of formation temperature (Stolper et al 2014a), whereas 13C-13C clumping in ethane is likely most controlled by chemical-kinetic processes and/or inheritance from the isotopic structure of source organic compounds (Clog et al 2014). 13C-D clumping in ethane has the potential to provide a thermometer for its synthesis, as it does for methane. However, the difference in C-H bond dissociation energy for these two compounds may suggest a lower 'blocking temperature' for this phenomenon in ethane (the blocking temperature for methane is ≥~250 C in geological conditions). We present analytical techniques to measure both 13C-13C and 13C-D clumping in ethane, using a novel two-instrument technique, including both the Thermo 253-Ultra and the Thermo DFS. In this method, the Ultra is used to measure the relative abundances of combinations nearly isobaric isotopologues: (13C12CH6 + 12C2DH5)/12C2H6 and (13C2H6 + 12C13CDH5)/12C2H6, free of other isobaric interferences like O2. The DFS, a very high resolution single-collector instrument, is then used to measure the ratios of isotopologues of ethane at a single cardinal mass: 12C2DH5/13C12CH6, and 12C13CDH5/13C2H6, with precisions of ~1 permil. Those 4 measurements allow us to calculate the bulk isotopic composition (D and 13C) as well as the abundance of 13C2H6 and 13C12CDH5. We also present progress on the development of software tools

  15. Mathematical modeling of bacterial track-altering motors: Track cleaving through burnt-bridge ratchets

    NASA Astrophysics Data System (ADS)

    Shtylla, Blerta; Keener, James P.

    2015-04-01

    The generation of directed movement of cellular components frequently requires the rectification of Brownian motion. Molecular motor enzymes that use ATP to walk on filamentous tracks are typically involved in cell transport, however, a track-altering motor can arise when an enzyme interacts with and alters its track. In Caulobacter crescentus and other bacteria, an active DNA partitioning (Par) apparatus is employed to segregate replicated chromosome regions to specific locations in dividing cells. The Par apparatus is composed of two proteins: ParA, an ATPase that can form polymeric structures on the nucleoid, and ParB, a protein that can bind and destabilize ParA structures. It has been proposed that the ParB-mediated alteration of ParA structures could be responsible for generating the directed movement of DNA during bacterial division. How precisely these actions are coordinated and translated into directed movement is not clear. In this paper we consider the C. crescentus segregation apparatus as an example of a track altering motor that operates using a so-called burnt-bridge mechanism. We develop and analyze mathematical models that examine how diffusion and ATP-hydrolysis-mediated monomer removal (or cleaving) can be combined to generate directed movement. Using a mean first passage approach, we analytically calculate the effective ParA track-cleaving velocities, effective diffusion coefficient, and other higher moments for the movement a ParB protein cluster that breaks monomers away at random locations on a single ParA track. Our model results indicate that cleaving velocities and effective diffusion constants are sensitive to ParB-induced ATP hydrolysis rates. Our analytical results are in excellent agreement with stochastic simulation results.

  16. Mathematical modeling of bacterial track-altering motors: Track cleaving through burnt-bridge ratchets.

    PubMed

    Shtylla, Blerta; Keener, James P

    2015-04-01

    The generation of directed movement of cellular components frequently requires the rectification of Brownian motion. Molecular motor enzymes that use ATP to walk on filamentous tracks are typically involved in cell transport, however, a track-altering motor can arise when an enzyme interacts with and alters its track. In Caulobacter crescentus and other bacteria, an active DNA partitioning (Par) apparatus is employed to segregate replicated chromosome regions to specific locations in dividing cells. The Par apparatus is composed of two proteins: ParA, an ATPase that can form polymeric structures on the nucleoid, and ParB, a protein that can bind and destabilize ParA structures. It has been proposed that the ParB-mediated alteration of ParA structures could be responsible for generating the directed movement of DNA during bacterial division. How precisely these actions are coordinated and translated into directed movement is not clear. In this paper we consider the C. crescentus segregation apparatus as an example of a track altering motor that operates using a so-called burnt-bridge mechanism. We develop and analyze mathematical models that examine how diffusion and ATP-hydrolysis-mediated monomer removal (or cleaving) can be combined to generate directed movement. Using a mean first passage approach, we analytically calculate the effective ParA track-cleaving velocities, effective diffusion coefficient, and other higher moments for the movement a ParB protein cluster that breaks monomers away at random locations on a single ParA track. Our model results indicate that cleaving velocities and effective diffusion constants are sensitive to ParB-induced ATP hydrolysis rates. Our analytical results are in excellent agreement with stochastic simulation results. PMID:25974531

  17. Activation of the Kexin from Schizosaccharomyces pombe Requires Internal Cleavage of Its Initially Cleaved Prosequence

    PubMed Central

    Powner, Dale; Davey, John

    1998-01-01

    Members of the kexin family of processing enzymes are responsible for the cleavage of many proproteins during their transport through the secretory pathway. The enzymes themselves are made as inactive precursors, and we investigated the activation process by studying the maturation of Krp1, a kexin from the fission yeast Schizosaccharomyces pombe. Using a cell-free translation-translocation system prepared from Xenopus eggs, we found that Krp1 is made as a preproprotein that loses the presequence during translocation into the endoplasmic reticulum. The prosequence is also rapidly cleaved in a reaction that is autocatalytic and probably intramolecular and is inhibited by disruption of the P domain. Prosequence cleavage normally occurs at Arg-Tyr-Lys-Arg102↓ (primary cleavage site) but can occur at Lys-Arg82 (internal cleavage site) and/or Trp-Arg99 when the basic residues are removed from the primary site. Cleavage of the prosequence is necessary but not sufficient for activation, and Krp1 is initially unable to process substrates presented in trans. Full activation is achieved after further incubation in the extract and is coincident with the addition of O-linked sugars. O glycosylation is not, however, essential for activity, and the crucial event appears to be cleavage of the initially cleaved prosequence at the internal site. Our results are consistent with a model in which the cleaved prosequence remains noncovalently associated with the catalytic domain and acts as an autoinhibitor of the enzyme. Inhibition is then relieved by a second (internal) cleavage of the inhibitory prosequence. Further support for this model is provided by our finding that overexpression of a Krp1 prosequence lacking a cleavable internal site dramatically reduced the growth rate of otherwise wild-type S. pombe cells, an effect that was not seen after overexpression of the normal, internally cleavable, prosequence or prosequences that lack the Lys-Arg102 residues. PMID:9418887

  18. Cleaved iron oxide nanoparticles as T2 contrast agents for magnetic resonance imaging.

    PubMed

    Jeon, Sung Lan; Chae, Min Kyung; Jang, Eun Ju; Lee, Chulhyun

    2013-03-25

    Iron oxide nanoparticles as contrast agents are reported to effectively improve magnetic resonance imaging of tissues and cells. In this work, cleaved iron oxide nanoparticles (CIONPs) were generated from hydrophobic FeO nanoparticles (HIONPs) by coating their surfaces with PEG-phospholipids, oxidizing them under water, and slowly removing the residual FeO phase in phthalate buffer. The synthesized CIONPs showed good r2 values of up to 258 s(-1)  mM(-1). Thus, the CIONPs can be employed as vectors for drug delivery due to their unique structure with an empty inner space, which enables their use in a wide range of applications. PMID:23345158

  19. Proteolytic Processing of Neuregulin 1 Type III by Three Intramembrane-cleaving Proteases.

    PubMed

    Fleck, Daniel; Voss, Matthias; Brankatschk, Ben; Giudici, Camilla; Hampel, Heike; Schwenk, Benjamin; Edbauer, Dieter; Fukumori, Akio; Steiner, Harald; Kremmer, Elisabeth; Haug-Kröper, Martina; Rossner, Moritz J; Fluhrer, Regina; Willem, Michael; Haass, Christian

    2016-01-01

    Numerous membrane-bound proteins undergo regulated intramembrane proteolysis. Regulated intramembrane proteolysis is initiated by shedding, and the remaining stubs are further processed by intramembrane-cleaving proteases (I-CLiPs). Neuregulin 1 type III (NRG1 type III) is a major physiological substrate of β-secretase (β-site amyloid precursor protein-cleaving enzyme 1 (BACE1)). BACE1-mediated cleavage is required to allow signaling of NRG1 type III. Because of the hairpin nature of NRG1 type III, two membrane-bound stubs with a type 1 and a type 2 orientation are generated by proteolytic processing. We demonstrate that these stubs are substrates for three I-CLiPs. The type 1-oriented stub is further cleaved by γ-secretase at an ϵ-like site five amino acids N-terminal to the C-terminal membrane anchor and at a γ-like site in the middle of the transmembrane domain. The ϵ-cleavage site is only one amino acid N-terminal to a Val/Leu substitution associated with schizophrenia. The mutation reduces generation of the NRG1 type III β-peptide as well as reverses signaling. Moreover, it affects the cleavage precision of γ-secretase at the γ-site similar to certain Alzheimer disease-associated mutations within the amyloid precursor protein. The type 2-oriented membrane-retained stub of NRG1 type III is further processed by signal peptide peptidase-like proteases SPPL2a and SPPL2b. Expression of catalytically inactive aspartate mutations as well as treatment with 2,2'-(2-oxo-1,3-propanediyl)bis[(phenylmethoxy)carbonyl]-l-leucyl-l-leucinamide ketone inhibits formation of N-terminal intracellular domains and the corresponding secreted C-peptide. Thus, NRG1 type III is the first protein substrate that is not only cleaved by multiple sheddases but is also processed by three different I-CLiPs. PMID:26574544

  20. Nuclei growth kinetics during the nucleation of gold on UHV-cleaved mica substrates

    NASA Technical Reports Server (NTRS)

    Elliot, A. G.

    1974-01-01

    Measurements of crystalline sizes during nucleation of gold on mica surfaces cleaved in ultra-high vacuum (UHV) reveal the presence of symmetric, sharply peaked distributions which flatten and broaden with increasing nucleation time. When the number density of nuclei increases, the growth rate is suppressed. The time taken to reach a given size increases with increasing temperature when the nuclei are growing as isolated particles. When the nuclei are spaced so far that their diffusion fields overlap, then the time taken to reach a given size decreases with increasing temperature.

  1. Cleaved thioredoxin fusion protein enables the crystallization of poorly soluble ERα in complex with synthetic ligands

    PubMed Central

    Cura, Vincent; Gangloff, Monique; Eiler, Sylvia; Moras, Dino; Ruff, Marc

    2008-01-01

    The ligand-binding domain (LBD) of human oestrogen receptor α was produced in Escherichia coli as a cleavable thioredoxin (Trx) fusion in order to improve solubility. Crystallization trials with either cleaved and purified LBD or with the purified fusion protein both failed to produce crystals. In another attempt, Trx was not removed from the LBD after endoproteolytic cleavage and its presence promoted nucleation and subsequent crystal growth, which allowed the structure determination of two different LBD–ligand–coactivator peptide complexes at 2.3 Å resolution. This technique is likely to be applicable to other low-solubility proteins. PMID:18097104

  2. Laser-damage processes in cleaved and polished CaF{sub 2} at 248nm

    SciTech Connect

    Reichling, M.; Gogoll, S.; Stenzel, S.

    1996-12-31

    Single-shot irradiation of single crystal CaF{sub 2} with 248nm/14ns laser light results in various degrees of degradation and damage depending on the applied laser fluence. Phenomena range from subtle, non-topographic surface modification only detectable by secondary electrons of scanning electron microscopy (SE-SEM) over cracking along crystallographic directions to the ablation of crystalline material. Significant differences are found for cleaved and polished surfaces. Findings from SEM investigations, in-situ photoacoustic mirage measurements and visual inspection of irradiated samples form a comprehensive picture of the stages of laser-induced damage.

  3. In situ investigation of the mobility of small gold clusters on cleaved MgO surfaces

    NASA Technical Reports Server (NTRS)

    Metois, J. J.; Heinemann, K.; Poppa, H.

    1976-01-01

    The mobility of small clusters of gold (about 10 A in diameter) on electron-beam-cleaved MgO surfaces was studied by in situ transmission electron microscopy under controlled vacuum and temperature conditions. During the first 10 min following a deposition at room temperature, over 10 per cent of the crystallites moved over short distances (about 20 A) discontinuously, with a velocity greater than 150 A/sec. Eighty per cent of the mobility events were characterized by the avoidance of proximity of other crystallites, and this was tentatively explained as the result of repulsive elastic forces between the interacting crystallites.

  4. Hepatitis A Virus 3C Protease Cleaves NEMO To Impair Induction of Beta Interferon

    PubMed Central

    Wang, Dang; Fang, Liurong; Wei, Dahai; Zhang, Huan; Luo, Rui; Chen, Huanchun

    2014-01-01

    NEMO (NF-κB essential modulator) is a bridging adaptor indispensable for viral activation of interferon (IFN) antiviral response. Herein, we show that hepatitis A virus (HAV) 3C protease (3Cpro) cleaves NEMO at the Q304 residue, negating its signaling adaptor function and abrogating viral induction of IFN-β synthesis via the retinoic acid-inducible gene I/melanoma differentiation-associated protein 5 (RIG-I/MDA5) and Toll-like receptor 3 (TLR3) pathways. NEMO cleavage and IFN antagonism, however, were lost upon ablation of the catalytic activity of 3Cpro. These data describe a novel immune evasion mechanism of HAV. PMID:24920812

  5. 1Surface structure of cleaved (001) USB2 single crystal surface

    SciTech Connect

    Chen, Shao-ping

    2009-01-01

    We have achieved what we believe to be the first atomic resolution STM images for a uranium compound USb2 taken at room temperature. The a, b, and c lattice parameters in the images confirm that the tetragonal USb2crystals cleave on the (00 I) basal plane as expected. Our calculations indicate a symmetric cut between Sb planes to be the most favorable cleavage plane and U atoms to be responsible for most ofthe density of states measured by STM. Since the spacing between Sb atoms and between U atoms is the same, STM topography only cannot unambiguously identify the surface atom species.

  6. Study of the effects of polishing, etching, cleaving, and water leaching on the UV laser damage of fused silica

    SciTech Connect

    Yoshiyama, J.; Genin, F.Y.; Salleo, A.; Thomas, I.; Kozlowski, M.R.; Sheehan, L.M.; Hutcheon, I.D.; Camp, D.W.

    1997-12-23

    A damage morphology study was performed with a 355 nm Nd:YAG laser on synthetic UV-grade fused silica to determine the effects of post- polish chemical etching on laser-induced damage, compare damage morphologies of cleaved and polished surfaces, and understand the effects of the hydrolyzed surface layer and waste-crack interactions. The samples were polished , then chemically etched in buffered HF solution to remove 45,90,135, and 180 nm of surface material. Another set of samples was cleaved and soaked in boiling distilled water for 1 second and 1 hour. All the samples were irradiated at damaging fluencies and characterized by Normarski optical microscopy and scanning electron microscopy. Damage was initiated as micro-pits on both input and output surfaces of the polished fused silica sample. At higher fluencies, the micro-pits generated cracks on the surface. Laser damage of the polished surface showed significant trace contamination levels within a 50 nm surface layer. Micro-pit formation also appeared after irradiating cleaved fused silica surfaces at damaging fluences. Linear damage tracks corresponding cleaving tracks were often observed on cleaved surfaces. Soaking cleaved samples in water produced wide laser damage tracks.

  7. Overcoming the "oxidant problem": strategies to use O2 as the oxidant in organometallic C-H oxidation reactions catalyzed by Pd (and Cu).

    PubMed

    Campbell, Alison N; Stahl, Shannon S

    2012-06-19

    Oxidation reactions are key transformations in organic chemistry because they can increase chemical complexity and incorporate heteroatom substituents into carbon-based molecules. This principle is manifested in the conversion of petrochemical feedstocks into commodity chemicals and in the synthesis of fine chemicals, pharmaceuticals, and other complex organic molecules. The utility and function of these molecules correlate directly with the presence and specific placement of oxygen and nitrogen heteroatoms and other functional groups within the molecules. Methods for selective oxidation of C-H bonds have expanded significantly over the past decade, and their role in the synthesis of organic chemicals will continue to increase. Our group's contributions to this field are linked to our broader interest in the development and mechanistic understanding of aerobic oxidation reactions. Molecular oxygen (O(2)) is the ideal oxidant. Its low cost and lack of toxic byproducts make it a highly appealing reagent that can address key "green chemistry" priorities in industry. With strong economic and environmental incentives to use O(2), the commmodity chemicals industry often uses aerobic oxidation reactions. In contrast, O(2) is seldom used to prepare more-complex smaller-volume chemicals, a limitation that reflects, in part, the limited synthetic scope and utility of existing aerobic reactions. Pd-catalyzed reactions represent some of the most versatile methods for selective C-H oxidation, but they often require stoichiometric transition-metal or organic oxidants, such as Cu(II), Ag(I), or benzoquinone. This Account describes recent strategies that we have identified to use O(2) as the oxidant in these reactions. In Pd-catalyzed C-H oxidation reactions that form carbon-heteroatom bonds, the stoichiometric oxidant is often needed to promote difficult reductive elimination steps in the catalytic mechanism. To address this challenge, we have identified new ancillary ligands for

  8. Iridium-bipyridine periodic mesoporous organosilica catalyzed direct C-H borylation using a pinacolborane.

    PubMed

    Maegawa, Yoshifumi; Inagaki, Shinji

    2015-08-01

    Heterogeneous catalysis for direct C-H borylation of arenes and heteroarenes in the combination of iridium (Ir) complex fixed on periodic mesoporous organosilica containing bipyridine ligands within the framework (Ir-BPy-PMO) and pinacolborane (HBpin) is reported. Ir-BPy-PMO showed higher catalytic activity toward the borylation of benzene with inexpensive HBpin compared to expensive bis(pinacolato)diboron (B2pin2). The precatalyst could be handled without the use of a glove box. The catalyst was easily recovered from reaction mixtures by simple filtration under air. The recovered catalyst still showed good catalytic activity for at least three more times for the borylation of benzene. A variety of arenes and heteroarenes were successfully borylated with high boron efficiency by Ir-BPy-PMO using HBpin, whereas almost no activity was observed for borylation of some heteroarenes with B2pin2. The system using Ir-BPy-PMO and HBpin was also utilized in syntheses of multi-boronated thiophene-based building blocks containing ladder-, acenefused-, and fused-thiophene skeletons. The combination of a stable and reusable solid catalyst and inexpensive HBpin is expected to be superior to conventional approaches for the development of industrial applications. PMID:25748945

  9. Properties of a-C:H:Si thin films deposited by middle-frequency magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Jiang, Jinlong; Wang, Yubao; Du, Jinfang; Yang, Hua; Hao, Junying

    2016-08-01

    The silicon doped hydrogenated amorphous carbon (a-C:H:Si) films were prepared on silicon substrates by middle-frequency magnetron sputtering silicon target in an argon and methane gas mixture atmosphere. The deposition rate, chemical composition, structure, surface properties, stress, hardness and tribological properties in the ambient air of the films were systemically investigated using X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), atomic force microscopy (AFM), nanoindentation and tribological tester. The results show that doped silicon content in the films is controlled in the wide range from 39.7 at.% to 0.2 at.% by various methane gas flow rate, and methane flow rate affects not only the silicon content but also its chemical bonding structure in the films due to the transformation of sputtering modes. Meanwhile, the sp3 carbon component in the films linearly increases with increasing of methane flow rate. The film deposited at moderate methane flow rate of 40-60 sccm exhibits the very smooth surface (RMS roughness 0.4 nm), low stress (0.42 GPa), high hardness (21.1 GPa), as well as low friction coefficient (0.038) and wear rate (1.6 × 10-7 mm3/Nm). The superior tribological performance of the films could be attributed to the formation and integral covering of the transfer materials on the sliding surface and their high hardness.

  10. Thermal effects on the Ga+ ion beam induced structural modification of a-SiC:H

    NASA Astrophysics Data System (ADS)

    Tsvetkova, T.; Wright, C. D.; Craciun, M. F.; Bischoff, L.; Angelov, O.; Dimova-Malinovska, D.

    2012-12-01

    The effects of implantation temperature and post-implantation thermal annealing on the Ga+ ion beam induced optical contrast formation in hydrogenated silicon-carbon alloy (a-SiC:H) films and underlying structural modifications have been studied. The optical contrast formed (between implanted and unimplanted regions of the film material) has been made use of in the form of optical pattern formation by computer-operated Ga+-focused ion beam. Possible applications of this effect in the area of submicron lithography and high-density optical data storage have been suggested with regard to the most widely spread focused micro-beam systems based on Ga+ liquid metal ion sources. The implanted samples were structurally analysed using vibrational spectroscopies, like Raman and infra-red (IR) spectroscopy, to define optimum implantation conditions. The precise role of implantation temperature effects, i.e. the target temperature during Ga+ ion irradiation, on the structural modification obtainable has been therefore a key part of this study. Appropriate post-implantation annealing treatments were also studied, since these are expected to offer further benefits in reducing the required ion dose and enhancing the optical contrast, thus increasing the cost-effectiveness of the method.

  11. Studies of beauty baryon decays to D0ph- and Λc+h- final states

    NASA Astrophysics Data System (ADS)

    Aaij, R.; Adeva, B.; Adinolfi, M.; Adrover, C.; Affolder, A.; Ajaltouni, Z.; Albrecht, J.; Alessio, F.; Alexander, M.; Ali, S.; Alkhazov, G.; Alvarez Cartelle, P.; Alves, A. A.; Amato, S.; Amerio, S.; Amhis, Y.; Anderlini, L.; Anderson, J.; Andreassen, R.; Andreotti, M.; Andrews, J. E.; Appleby, R. B.; Aquines Gutierrez, O.; Archilli, F.; Artamonov, A.; Artuso, M.; Aslanides, E.; Auriemma, G.; Baalouch, M.; Bachmann, S.; Back, J. J.; Badalov, A.; Balagura, V.; Baldini, W.; Barlow, R. J.; Barschel, C.; Barsuk, S.; Barter, W.; Batozskaya, V.; Bauer, Th.; Bay, A.; Beddow, J.; Bedeschi, F.; Bediaga, I.; Belogurov, S.; Belous, K.; Belyaev, I.; Ben-Haim, E.; Bencivenni, G.; Benson, S.; Benton, J.; Berezhnoy, A.; Bernet, R.; Bettler, M.-O.; van Beuzekom, M.; Bien, A.; Bifani, S.; Bird, T.; Bizzeti, A.; Bjørnstad, P. M.; Blake, T.; Blanc, F.; Blouw, J.; Blusk, S.; Bocci, V.; Bondar, A.; Bondar, N.; Bonivento, W.; Borghi, S.; Borgia, A.; Bowcock, T. J. V.; Bowen, E.; Bozzi, C.; Brambach, T.; van den Brand, J.; Bressieux, J.; Brett, D.; Britsch, M.; Britton, T.; Brook, N. H.; Brown, H.; Bursche, A.; Busetto, G.; Buytaert, J.; Cadeddu, S.; Calabrese, R.; Callot, O.; Calvi, M.; Calvo Gomez, M.; Camboni, A.; Campana, P.; Campora Perez, D.; Carbone, A.; Carboni, G.; Cardinale, R.; Cardini, A.; Carranza-Mejia, H.; Carson, L.; Carvalho Akiba, K.; Casse, G.; Castillo Garcia, L.; Cattaneo, M.; Cauet, Ch.; Cenci, R.; Charles, M.; Charpentier, Ph.; Cheung, S.-F.; Chiapolini, N.; Chrzaszcz, M.; Ciba, K.; Cid Vidal, X.; Ciezarek, G.; Clarke, P. E. L.; Clemencic, M.; Cliff, H. V.; Closier, J.; Coca, C.; Coco, V.; Cogan, J.; Cogneras, E.; Collins, P.; Comerma-Montells, A.; Contu, A.; Cook, A.; Coombes, M.; Coquereau, S.; Corti, G.; Couturier, B.; Cowan, G. A.; Craik, D. C.; Cruz Torres, M.; Cunliffe, S.; Currie, R.; D'Ambrosio, C.; Dalseno, J.; David, P.; David, P. N. Y.; Davis, A.; De Bonis, I.; De Bruyn, K.; De Capua, S.; De Cian, M.; De Miranda, J. M.; De Paula, L.; De Silva, W.; De Simone, P.; Decamp, D.; Deckenhoff, M.; Del Buono, L.; Déléage, N.; Derkach, D.; Deschamps, O.; Dettori, F.; Di Canto, A.; Dijkstra, H.; Dogaru, M.; Donleavy, S.; Dordei, F.; Dorosz, P.; Dosil Suárez, A.; Dossett, D.; Dovbnya, A.; Dupertuis, F.; Durante, P.; Dzhelyadin, R.; Dziurda, A.; Dzyuba, A.; Easo, S.; Egede, U.; Egorychev, V.; Eidelman, S.; van Eijk, D.; Eisenhardt, S.; Eitschberger, U.; Ekelhof, R.; Eklund, L.; El Rifai, I.; Elsasser, Ch.; Falabella, A.; Färber, C.; Farinelli, C.; Farry, S.; Ferguson, D.; Fernandez Albor, V.; Ferreira Rodrigues, F.; Ferro-Luzzi, M.; Filippov, S.; Fiore, M.; Fiorini, M.; Fitzpatrick, C.; Fontana, M.; Fontanelli, F.; Forty, R.; Francisco, O.; Frank, M.; Frei, C.; Frosini, M.; Furfaro, E.; Gallas Torreira, A.; Galli, D.; Gandelman, M.; Gandini, P.; Gao, Y.; Garofoli, J.; Garosi, P.; Garra Tico, J.; Garrido, L.; Gaspar, C.; Gauld, R.; Gersabeck, E.; Gersabeck, M.; Gershon, T.; Ghez, Ph.; Gibson, V.; Giubega, L.; Gligorov, V. V.; Göbel, C.; Golubkov, D.; Golutvin, A.; Gomes, A.; Gordon, H.; Grabalosa Gándara, M.; Graciani Diaz, R.; Granado Cardoso, L. A.; Graugés, E.; Graziani, G.; Grecu, A.; Greening, E.; Gregson, S.; Griffith, P.; Grillo, L.; Grünberg, O.; Gui, B.; Gushchin, E.; Guz, Yu.; Gys, T.; Hadjivasiliou, C.; Haefeli, G.; Haen, C.; Hafkenscheid, T. W.; Haines, S. C.; Hall, S.; Hamilton, B.; Hampson, T.; Hansmann-Menzemer, S.; Harnew, N.; Harnew, S. T.; Harrison, J.; Hartmann, T.; He, J.; Head, T.; Heijne, V.; Hennessy, K.; Henrard, P.; Hernando Morata, J. A.; van Herwijnen, E.; Heß, M.; Hicheur, A.; Hicks, E.; Hill, D.; Hoballah, M.; Hombach, C.; Hulsbergen, W.; Hunt, P.; Huse, T.; Hussain, N.; Hutchcroft, D.; Hynds, D.; Iakovenko, V.; Idzik, M.; Ilten, P.; Jacobsson, R.; Jaeger, A.; Jans, E.; Jaton, P.; Jawahery, A.; Jing, F.; John, M.; Johnson, D.; Jones, C. R.; Joram, C.; Jost, B.; Jurik, N.; Kaballo, M.; Kandybei, S.; Kanso, W.; Karacson, M.; Karbach, T. M.; Kenyon, I. R.; Ketel, T.; Khanji, B.; Klaver, S.; Kochebina, O.; Komarov, I.; Koopman, R. F.; Koppenburg, P.; Korolev, M.; Kozlinskiy, A.; Kravchuk, L.; Kreplin, K.; Kreps, M.; Krocker, G.; Krokovny, P.; Kruse, F.; Kucharczyk, M.; Kudryavtsev, V.; Kurek, K.; Kvaratskheliya, T.; La Thi, V. N.; Lacarrere, D.; Lafferty, G.; Lai, A.; Lambert, D.; Lambert, R. W.; Lanciotti, E.; Lanfranchi, G.; Langenbruch, C.; Latham, T.; Lazzeroni, C.; Le Gac, R.; van Leerdam, J.; Lees, J.-P.; Lefèvre, R.; Leflat, A.; Lefrançois, J.; Leo, S.; Leroy, O.; Lesiak, T.; Leverington, B.; Li, Y.; Li Gioi, L.; Liles, M.; Lindner, R.; Linn, C.; Lionetto, F.; Liu, B.; Liu, G.; Lohn, S.; Longstaff, I.; Lopes, J. H.; Lopez-March, N.; Lu, H.; Lucchesi, D.; Luisier, J.; Luo, H.; Luppi, E.; Lupton, O.; Machefert, F.; Machikhiliyan, I. V.; Maciuc, F.; Maev, O.; Malde, S.

    2014-02-01

    Decays of beauty baryons to the D0ph- and Λc+h- final states (where h indicates a pion or a kaon) are studied using a data sample of pp collisions, corresponding to an integrated luminosity of 1.0 fb-1, collected by the LHCb detector. The Cabibbo-suppressed decays Λb0→D0pK- and Λb0→Λc+K- are observed, and their branching fractions are measured with respect to the decays Λb0→D0pπ- and Λb0→Λc+π-. In addition, the first observation is reported of the decay of the neutral beauty-strange baryon Ξb0 to the D0pK- final state, and a measurement of the Ξb0 mass is performed. Evidence of the Ξb0→Λc+K- decay is also reported.

  12. Improved ReaxFF force field parameters for Au-S-C-H systems.

    PubMed

    Bae, Gyun-Tack; Aikens, Christine M

    2013-10-10

    Evaluation and reparameterization of previously reported ReaxFF parameters (Järvi, T. T.; et al. J. Phys. Chem. A 2011, 115, 10315-10322) is carried out for Au-S-C-H systems. Changes in Au-S and Au-Au bond parameters and S-Au-S angle bending parameters yield improvements for bond bending potential energy surfaces. The new ReaxFF parameters lead to good agreement with density functional theory geometries of small clusters and gold-thiolate nanoparticles. The energies of Au38(SCH3)24 clusters are compared, and the new ReaxFF calculations are also in good agreement with PBE calculations for the isomer orderings. In addition, the relative energies of Au40(SCH3)24 nanoparticles and Au-thiolate SAMs are calculated using the updated parameters. These new ReaxFF parameters will enable the study of the geometries and reactivity of larger gold-thiolate nanoparticles. PMID:24041237

  13. Copper-catalyzed direct C-H oxidative trifluoromethylation of heteroarenes.

    PubMed

    Chu, Lingling; Qing, Feng-Ling

    2012-01-18

    This article describes the copper-catalyzed oxidative trifluoromethylation of heteroarenes and highly electron-deficient arenes with CF(3)SiMe(3) through direct C-H activation. In the presence of catalyst Cu(OAc)(2), ligand 1,10-phenanthroline and cobases tert-BuONa/NaOAc, oxidative trifluoromethylation of 1,3,4-oxadiazoles with CF(3)SiMe(3) proceeded smoothly using either air or di-tert-butyl peroxide as an oxidant to give the corresponding trifluoromethylated 1,3,4-oxadiazoles in high yields. Di-tert-butyl peroxide was chosen as the suitable oxidant for oxidative trifluoromethylation of 1,3-azoles and perfluoroarenes. Cu(OH)(2) and Ag(2)CO(3) were the best catalyst and oxidant for direct oxidative trifluoromethyaltion of indoles. The optimum reaction conditions enable oxidative trifluoromethylation of a range of heteroarenes that bear numerous functional groups. The prepared trifluoromethylated heteroarenes are of importance in the areas of pharmaceuticals and agrochemicals. The preliminary mechanistic studies of these oxidative trifluoromethylations are also reported. PMID:22145831

  14. Palladium-catalysed directed C-H activation by anilides and ureas; water participation in a general base mechanism.

    PubMed

    Rauf, Waqar; Brown, John M

    2016-06-21

    C-H activation plays a central role in organometallic catalysis. Concerted metallation-deprotonation (CMD) has been dominant as the pathway for C-H bond cleavage. In the course of studying the mechanism of C-H activation of arylamides and arylureas with Pd complexes as part of catalytic oxidative Heck reactions, DFT calculations were carried out. The turnover-limiting C-H activation is acid-catalysed and can occur readily in the absence of acetate or other coordinating bases. The calculations simulated experiment, so that ligated sulfonate and water, both previously observed by X-ray characterization, were incorporated in the model. A Wheland-type complex between acetanilide and Pd was readily located, but the reactive C-H and the coordinated sulfonate were poorly placed for intramolecular proton transfer. Involvement of a water molecule coordinated to sulfonate provides a low-energy pathway to the palladacycle. The relative reactivity of substituted acetanilides and arylureas according to this model fits well with existing literature. General-base catalysis as described here has broader potential. PMID:27184358

  15. Rhodium(III)-Catalyzed Tandem [2+2+2] Annulation-Lactamization of Anilides with Two Alkynoates via Cleavage of Two Adjacent C-H or C-H/C-O bonds.

    PubMed

    Fukui, Miho; Shibata, Yu; Hoshino, Yuki; Sugiyama, Haruki; Teraoka, Kota; Uekusa, Hidehiro; Noguchi, Keiichi; Tanaka, Ken

    2016-08-19

    An electron-deficient Cp(E) rhodium(III) complex bearing a cyclopentadienyl ligand with two ethyl ester substituents catalyzes the tandem [2+2+2] annulation-lactamization of acetanilides with two alkynoates via cleavage of adjacent two C-H bonds to give densely substituted benzo[cd]indolones. The reactions of meta-methoxy-substituted acetanilides with two alkynoates also provided benzo[cd]indolones via cleavage of adjacent C-H/C-O bonds. Furthermore, 3,5-dimethoxyacetanilides reacted with two alkynoates to give dearomatized spiro compounds. PMID:27412046

  16. Specialization of the DNA-Cleaving Activity of a Group I Ribozyme Through In Vitro Evolution

    NASA Technical Reports Server (NTRS)

    Tsang, Joyce; Joyce, Gerald F.

    1996-01-01

    In an earlier study, an in vitro evolution procedure was applied to a large population of variants of the Tetrahymena group 1 ribozyme to obtain individuals with a 10(exp 5)-fold improved ability to cleave a target single-stranded DNA substrate under simulated physiological conditions. The evolved ribozymes also showed a twofold improvement, compared to the wild-type, in their ability to cleave a single-stranded RNA substrate. Here, we report continuation of the in vitro evolution process using a new selection strategy to achieve both enhanced DNA and diminished RNA-cleavage activity. Our strategy combines a positive selection for DNA cleavage with a negative selection against RNA binding. After 36 "generations" of in vitro evolution, the evolved population showed an approx. 100-fold increase in the ratio of DNA to RNA-cleavage activity. Site-directed mutagenesis experiment confirmed the selective advantage of two covarying mutations within the catalytic core of ribozyme that are largely responsible for this modified behavior. The population of ribozymes has now undergone a total of 63 successive generations of evolution, resulting in an average 28 mutations relative to the wild-type that are responsible for the altered phenotype.

  17. The first non Clostridial botulinum-like toxin cleaves VAMP within the juxtamembrane domain.

    PubMed

    Zornetta, Irene; Azarnia Tehran, Domenico; Arrigoni, Giorgio; Anniballi, Fabrizio; Bano, Luca; Leka, Oneda; Zanotti, Giuseppe; Binz, Thomas; Montecucco, Cesare

    2016-01-01

    The genome of Weissella oryzae SG25T was recently sequenced and a botulinum neurotoxin (BoNT) like gene was identified by bioinformatics methods. The typical three-domains organization of BoNTs with a N-terminal metalloprotease domain, a translocation and a cell binding domains could be identified. The BoNT family of neurotoxins is rapidly growing, but this was the first indication of the possible expression of a BoNT toxin outside the Clostridium genus. We performed molecular modeling and dynamics simulations showing that the 50 kDa N-terminal domain folds very similarly to the metalloprotease domain of BoNT/B, whilst the binding part is different. However, neither the recombinant metalloprotease nor the binding domains showed cross-reactivity with the standard antisera that define the seven serotypes of BoNTs. We found that the purified Weissella metalloprotease cleaves VAMP at a single site untouched by the other VAMP-specific BoNTs. This site is a unique Trp-Trp peptide bond located within the juxtamembrane segment of VAMP which is essential for neurotransmitter release. Therefore, the present study identifies the first non-Clostridial BoNT-like metalloprotease that cleaves VAMP at a novel and relevant site and we propose to label it BoNT/Wo. PMID:27443638

  18. Cathepsin X Cleaves Profilin 1 C-Terminal Tyr139 and Influences Clathrin-Mediated Endocytosis

    PubMed Central

    Pečar Fonović, Urša; Kos, Janko

    2015-01-01

    Cathepsin X, a cysteine carboxypeptidase, is upregulated in several types of cancer. Its molecular target in tumor cells is profilin 1, a known tumor suppressor and regulator of actin cytoskeleton dynamics. Cathepsin X cleaves off the C-terminal Tyr139 of profilin 1, affecting binding of poly-L-proline ligands and, consequently, tumor cell migration and invasion. Profilin 1 with mutations at the C-terminus, transiently expressed in prostate cancer cells PC-3, showed that Tyr139 is important for proper function of profilin 1 as a tumor suppressor. Cleaving off Tyr139 prevents the binding of clathrin, a poly-L-proline ligand involved in endocytosis. More profilin 1—clathrin complexes were present in PC-3 cells when cathepsin X was inhibited by its specific inhibitor AMS36 or silenced by siRNA. As a consequence, the endocytosis of FITC-labeled dextran and transferrin conjugate was significantly increased. These results constitute the first report of the regulation of clathrin-mediated endocytosis in tumor cells through proteolytic processing of profilin 1. PMID:26325675

  19. Sam68 is cleaved by caspases under apoptotic cell death induced by ionizing radiation.

    PubMed

    Cho, Seong-Jun; Choi, Moo Hyun; Nam, Seon Young; Kim, Ji Young; Kim, Cha Soon; Pyo, Suhkneung; Yang, Kwang Hee

    2015-03-01

    The RNA-binding protein Sam68, a mitotic substrate of tyrosine kinases, has been reported to participate in the cell cycle, apoptosis, and signaling. In particular, overexpression of Sam68 protein is known to suppress cell growth and cell cycle progression in NIH3T3 cells. Although Sam68 is involved in many cellular activities, the function of Sam68, especially in response to apoptotic stimulation, is not well understood. In this study, we found that Sam68 protein is cleaved in immune cells undergoing apoptosis induced by γ-radiation. Moreover, we found that Sam68 cleavage was induced by apoptotic stimuli containing γ-radiation in a caspase-dependent manner. In particular, we showed that activated casepase-3, 7, 8 and 9 can directly cleave Sam68 protein through in vitro protease cleavage assay. Finally, we found that the knockdown of Sam68 attenuated γ-radiation-induced cell death and growth suppression. Conclusively, the cleavage of Sam68 is a new indicator for the cell damaging effects of ionizing radiation. PMID:25666188

  20. Quantum Hall effect at a tunably sharp cleaved-edge potential

    NASA Astrophysics Data System (ADS)

    Zhou, Chuanle; Grayson, M.; Steinke, L.; Uccelli, E.; Koblmueller, G.; Bichler, M.; Abstreiter, G.; Schmult, S.; Dietsche, W.

    2010-03-01

    We study magnetotransport in the quantum Hall (QH) regime of a two-dimensional electron system with an epitaxially overgrown sharp cleaved-edge. A thick insulating barrier is overgrown at the cleaved-edge followed by a doped layer, serving as a side gate which can control depletion or accumulation at the sharp edge, hence can convert a sharp edge into a soft edge by changing the gate bias. This geometry leads to a tunable edge potential with either the standard incompressible strips in the ``soft edge'' limit, or thin or vanishing incompressible strips in the ``sharp edge'' limit. DC magnetotransport measurements show evidence of a longitudinal resistance minimum whose width depends on the current direction. This experimental result is consistent with recent theory on the role of edge potentials in defining the QH in small samples [1]. Size effect and gate bias dependence are studied. We also report an unexplained magnetic field hysteresis at the high field side of filling factors ν=1, 2, 3, 4 in the limit of negative side-gate bias.[4pt] [1] A. Siddiki, Euro. Phys. Lett. 87, 17008(2009)

  1. Precision UV laser scribing for cleaving mirror facets of GaN-based laser diodes

    NASA Astrophysics Data System (ADS)

    Krüger, O.; Kang, J.-H.; Spevak, M.; Zeimer, U.; Einfeldt, S.

    2016-04-01

    Laser scribing with a nanosecond-pulsed UV laser operating at 355 nm was used to create precise perforation for die separation of GaN-based laser diodes. Machining depth of single- and multiple-pass scribing was investigated. For pulse energies between 1 and 45 µJ at a pulse repetition frequency of 20 kHz and single scan at 100 mm/min, scribe depths from 15 to 180 µm were obtained. Processing parameters were adjusted to minimize the formation of microcracks due to laser-induced local heating. By using the laser skip-and-scribe technique, the propagation of the cleavage plane could be controlled, irregular breaking could be minimized, and die yield could be improved. Smooth mirror facets with low density of terraces were formed by cleaving. In the vicinity of the laser-treated zone, no detrimental effects on the crystal quality of the multi-quantum wells could be detected by cathodoluminescence. The electro-optical characteristics of broad-area laser diodes fabricated by the laser-assisted process were similar to the ones fabricated using the conventional diamond-tip edge-scribing technique that suffers from low die yield. Our results demonstrate that nanosecond-pulsed UV laser scribing followed by cleaving is a powerful technique for the formation of mirror facets of GaN-based laser diodes.

  2. The paracaspase MALT1 cleaves the LUBAC subunit HOIL1 during antigen receptor signaling.

    PubMed

    Douanne, Tiphaine; Gavard, Julie; Bidère, Nicolas

    2016-05-01

    Antigen-receptor-mediated activation of lymphocytes relies on a signalosome comprising CARMA1 (also known as CARD11), BCL10 and MALT1 (the CBM complex). The CBM activates nuclear factor κB (NF-κB) transcription factors by recruiting the 'linear ubiquitin assembly complex' (LUBAC), and unleashes MALT1 paracaspase activity. Although MALT1 enzyme shapes NF-κB signaling, lymphocyte activation and contributes to lymphoma growth, the identity of its substrates continues to be elucidated. Here, we report that the LUBAC subunit HOIL1 (also known as RBCK1) is cleaved by MALT1 following antigen receptor engagement. HOIL1 is also constitutively processed in the 'activated B-cell-like' (ABC) subtype of diffuse large B-cell lymphoma (DLBCL), which exhibits aberrant MALT1 activity. We further show that the overexpression of MALT1-insensitive HOIL1 mitigates T-cell-receptor-mediated NF-κB activation and subsequent cytokine production in lymphocytes. Thus, our results unveil HOIL1 as a negative regulator of lymphocyte activation cleaved by MALT1. This cleavage could therefore constitute an appealing therapeutic target for modulating immune responses. PMID:27006117

  3. Cleaving for growth: threonine aspartase 1-a protease relevant for development and disease.

    PubMed

    Stauber, Roland H; Hahlbrock, Angelina; Knauer, Shirley K; Wünsch, Désirée

    2016-03-01

    From the beginning of life, proteases are key to organismal development comprising morphogenesis, cellular differentiation, and cell growth. Regulated proteolytic activity is essential for the orchestration of multiple developmental pathways, and defects in protease activity can account for multiple disease patterns. The highly conserved protease threonine aspartase 1 is a member of such developmental proteases and critically involved in the regulation of complex processes, including segmental identity, head morphogenesis, spermatogenesis, and proliferation. Additionally, threonine aspartase 1 is overexpressed in numerous liquid as well as in solid malignancies. Although threonine aspartase 1 is able to cleave the master regulator mixed lineage leukemia protein as well as other regulatory proteins in humans, our knowledge of its detailed pathobiological function and the underlying molecular mechanisms contributing to development and disease is still incomplete. Moreover, neither effective genetic nor chemical inhibitors for this enzyme are available so far precluding the detailed dissection of the pathobiological functions of threonine aspartase 1. Here, we review the current knowledge of the structure-function relationship of threonine aspartase 1 and its mechanistic impact on substrate-mediated coordination of the cell cycle and development. We discuss threonine aspartase 1-mediated effects on cellular transformation and conclude by presenting a short overview of recent interference strategies.-Stauber, R. H., Hahlbrock, A., Knauer, S. K., Wünsch, D. Cleaving for growth: threonine aspartase 1-a protease relevant for development and disease. PMID:26578689

  4. Study of surface recombination on cleaved and passivated edges of Si detectors

    NASA Astrophysics Data System (ADS)

    Gaubas, E.; Ceponis, T.; Vaitkus, J. V.; Fadeyev, V.; Ely, S.; Galloway, Z.; F-W Sadrozinski, H.; Christophersen, M.; Phlips, B. F.; Gorelov, I.; Hoeferkamp, M.; Metcalfe, J.; Seidel, S.

    2016-03-01

    The effectiveness of the passivation of a cleaved boundary of large area strip detectors has been studied by using Al2O3 formed by atomic layer deposition technology for p-Si structures and Si x N y grown on n-Si by plasma enhanced chemical vapour deposition. The parameters of bulk and surface recombinations have been examined in a contactless mode implemented through analysis of the microwave-probed photoconductivity transients. Rather efficient and reproducible passivation, revealed through the reduction of surface recombination velocities from ˜2 × 104 to 5 × 103 cm s-1 for n-Si and from ˜2 × 104 to 3 × 102 cm s-1 for p-Si samples, has been obtained. The existence of trapping centres together with recombination defects has been revealed at the cleaved interface within the passivating layer. It has been revealed that the impact of surface recombination is negligible when bulk radiation defects are dominant in samples irradiated with fluences >1014 neq cm-2.

  5. The first non Clostridial botulinum-like toxin cleaves VAMP within the juxtamembrane domain

    PubMed Central

    Zornetta, Irene; Azarnia Tehran, Domenico; Arrigoni, Giorgio; Anniballi, Fabrizio; Bano, Luca; Leka, Oneda; Zanotti, Giuseppe; Binz, Thomas; Montecucco, Cesare

    2016-01-01

    The genome of Weissella oryzae SG25T was recently sequenced and a botulinum neurotoxin (BoNT) like gene was identified by bioinformatics methods. The typical three-domains organization of BoNTs with a N-terminal metalloprotease domain, a translocation and a cell binding domains could be identified. The BoNT family of neurotoxins is rapidly growing, but this was the first indication of the possible expression of a BoNT toxin outside the Clostridium genus. We performed molecular modeling and dynamics simulations showing that the 50 kDa N-terminal domain folds very similarly to the metalloprotease domain of BoNT/B, whilst the binding part is different. However, neither the recombinant metalloprotease nor the binding domains showed cross-reactivity with the standard antisera that define the seven serotypes of BoNTs. We found that the purified Weissella metalloprotease cleaves VAMP at a single site untouched by the other VAMP-specific BoNTs. This site is a unique Trp-Trp peptide bond located within the juxtamembrane segment of VAMP which is essential for neurotransmitter release. Therefore, the present study identifies the first non-Clostridial BoNT-like metalloprotease that cleaves VAMP at a novel and relevant site and we propose to label it BoNT/Wo. PMID:27443638

  6. Non-coordinating-Anion-Directed Reversal of Activation Site: Selective C-H Bond Activation of N-Aryl Rings.

    PubMed

    Wang, Dawei; Yu, Xiaoli; Xu, Xiang; Ge, Bingyang; Wang, Xiaoli; Zhang, Yaxuan

    2016-06-13

    An Rh-catalyzed selective C-H bond activation of diaryl-substituted anilides is described. In an attempt to achieve C-H activation of C-aryl rings, we unexpectedly obtained an N-aryl ring product under non-coordinating anion conditions, whereas the C-aryl ring product was obtained in the absence of a non-coordinating anion. This methodology has proved to be an excellent means of tuning and adjusting selective C-H bond activation of C-aryl and N-aryl rings. The approach has been rationalized by mechanistic studies and theoretical calculations. In addition, it has been found and verified that the catalytic activity of the rhodium catalyst is obviously improved by non-coordinating anions, which provides an efficient strategy for obtaining a highly chemoselective catalyst. Mechanistic experiments also unequivocally ruled out the possibility of a so-called "silver effect" in this transformation involving silver. PMID:27159169

  7. Ruthenium-Catalyzed Direct and Selective C-H Cyanation of N-(Hetero)aryl-7-azaindoles.

    PubMed

    Mishra, Aniket; Vats, Tripta Kumari; Deb, Indubhusan

    2016-08-01

    An efficient, highly regioselective, and scalable ruthenium-catalyzed o-aryl C-H mono-cyanation of N-aryl-7-azaindoles to form N-(2-cyanoaryl)-7-azaindoles has been developed through N-directed ortho C-H activation using N-cyano-N-phenyl-p-toluenesulfonamide as cyanating reagent in the presence of AgOTf and NaOAc in DCE. A range of substrates has furnished cyanated azaindoles in good to excellent yields under the simple reaction conditions. Involvement of C-H metalation has been supported by a kinetic study. This methodology provides easy access to a class of pharmaceutically significant molecules and their precursors. PMID:27408980

  8. Aromatic C-H Activation in the Triplet Excited State of Cyclometalated Platinum(II) Complexes Using Visible Light.

    PubMed

    Juliá, Fabio; González-Herrero, Pablo

    2016-04-27

    The visible-light driven cyclometalation of arene substrates containing an N-donor heteroaromatic moiety as directing group by monocyclometalated Pt(II) complexes is reported. Precursors of the type [PtMe(C^N)(N^CH)], where N^CH is 2-phenylpyridine (ppyH) or related compunds with diverse electronic properties and C^N is the corresponding cyclometalated ligand, afford homoleptic cis-[Pt(C^N)2] complexes upon irradiation with blue LEDs at room temperature with evolution of methane. Heteroleptic derivatives cis-[Pt(ppy)(C'^N')] are obtained analogously from [PtMe(ppy)(N'^C'H)], where N'^C'H represents an extended set of heteroaromatic compounds. Experimental and computational studies demonstrate an unprecedented C-H oxidative addition, which is initiated by a triplet excited state of metal-to-ligand charge-transfer (MLCT) character and leads to a detectable Pt(IV) methyl hydride intermediate. PMID:27058394

  9. Auger electron spectroscopy, secondary ion mass spectroscopy and optical characterization of a-C-H and BN films

    NASA Technical Reports Server (NTRS)

    Pouch, J. J.; Alterovitz, S. A.; Warner, J. D.

    1986-01-01

    The amorphous dielectrics a-C:H and BN were deposited on III-V semiconductors. Optical band gaps as high as 3 eV were measured for a-C:H generated by C4H10 plasmas; a comparison was made with bad gaps obtained from films prepared by CH4 glow discharges. The ion beam deposited BN films exhibited amorphous behavior with band gaps on the order of 5 eV. Film compositions were studied by Auger electron spectroscopy (AES), x-ray photoelectron spectroscopy (XPS) and secondary ion mass spectrometry (SIMS). The optical properties were characterized by ellipsometry, UV/VIS absorption, and IR reflection and transmission. Etching rates of a-C:H subjected to O2 dicharges were determined.

  10. Characterization of the visible photoluminescence from porous a-Si:H and porous a-Si:C:H thin films

    SciTech Connect

    Estes, M.J.; Hirsch, L.R.; Wichart, S.; Moddel, G.

    1996-12-31

    The authors report on the influence of doping, temperature, porosity, and bandgap on the visible photoluminescence properties of anodically-etched porous a-Si:H and a-Si:C:H thin films. Only boron-doped, p-type a-Si:H or a-Si:C:H samples exhibited any visible photoluminescence. The authors see evidence of discrete defect or impurity levels in temperature-dependent luminescence measurements. Unlike in porous crystalline silicon, they see no correlation of luminescence energy with porosity. The authors do, though, observe a correlation of luminescence energy with bandgap of the starting a-Si:C:H films. They discuss the implication of these observations on the nature of the luminescence mechanism.

  11. The Effect of Nano Confinement on the C-H Activation and its Corresponding Structure-Activity Relationship

    NASA Astrophysics Data System (ADS)

    Shao, Jing; Yuan, Linghua; Hu, Xingbang; Wu, Youting; Zhang, Zhibing

    2014-11-01

    The C-H activation of methane, ethane, and t-butane on inner and outer surfaces of nitrogen-doped carbon nanotube (NCNTs) are investigated using density functional theory. It includes NCNTs with different diameters, different N and O concentrations, and different types (armchair and zigzag). A universal structure-reactivity relationship is proposed to characterize the C-H activation occurring both on the inner and outer surfaces of the nano channel. The C-O bond distance, spin density and charge carried by active oxygen are found to be highly related to the C-H activation barriers. Based on these theoretical results, some useful strategies are suggested to guide the rational design of more effective catalysts by nano channel confinement.

  12. Thrombin-cleaved Fragments of Osteopontin Are Overexpressed in Malignant Glial Tumors and Provide a Molecular Niche with Survival Advantage*

    PubMed Central

    Yamaguchi, Yasuto; Shao, Zhifei; Sharif, Shadi; Du, Xiao-Yan; Myles, Timothy; Merchant, Milton; Harsh, Griffith; Glantz, Michael; Recht, Lawrence; Morser, John; Leung, Lawrence L. K.

    2013-01-01

    Osteopontin (OPN), which is highly expressed in malignant glioblastoma (GBM), possesses inflammatory activity modulated by proteolytic cleavage by thrombin and plasma carboxypeptidase B2 (CPB2) at a highly conserved cleavage site. Full-length OPN (OPN-FL) was elevated in cerebrospinal fluid (CSF) samples from all cancer patients compared with noncancer patients. However, thrombin-cleaved OPN (OPN-R) and thrombin/CPB2-double-cleaved OPN (OPN-L) levels were markedly increased in GBM and non-GBM gliomas compared with systemic cancer and noncancer patients. Cleaved OPN constituted ∼23 and ∼31% of the total OPN in the GBM and non-GBM CSF samples, respectively. OPN-R was also elevated in GBM tissues. Thrombin-antithrombin levels were highly correlated with cleaved OPN, but not OPN-FL, suggesting that the cleaved OPN fragments resulted from increased thrombin and CPB2 in this extracellular compartment. Levels of VEGF and CCL4 were increased in CSF of GBM and correlated with the levels of cleaved OPN. GBM cell lines were more adherent to OPN-R and OPN-L than OPN-FL. Adhesion to OPN altered gene expression, in particular genes involved with cellular processes, cell cycle regulation, death, and inflammation. OPN and its cleaved forms promoted motility of U-87 MG cells and conferred resistance to apoptosis. Although functional mutation of the RGD motif in OPN largely abolished these functions, OPNRAA-R regained significant cell binding and signaling function, suggesting that the SVVYGLR motif in OPN-R may substitute for the RGD motif if the latter becomes inaccessible. OPN cleavage contributes to GBM development by allowing more cells to bind in niches where they acquire anti-apoptotic properties. PMID:23204518

  13. Synthesis of Indole-2-carboxylate Derivatives via Palladium-Catalyzed Aerobic Amination of Aryl C-H Bonds.

    PubMed

    Clagg, Kyle; Hou, Haiyun; Weinstein, Adam B; Russell, David; Stahl, Shannon S; Koenig, Stefan G

    2016-08-01

    A direct oxidative C-H amination affording 1-acetyl indolecarboxylates starting from 2-acetamido-3-arylacrylates has been achieved. Indole-2-carboxylates can be targeted with a straightforward deacetylation of the initial reaction products. The C-H amination reaction is carried out using a catalytic Pd(II) source with oxygen as the terminal oxidant. The scope and application of this chemistry is demonstrated with good to high yields for numerous electron-rich and electron-poor substrates. Further reaction of selected products via Suzuki arylation and deacetylation provides access to highly functionalized indole structures. PMID:27404018

  14. Chemically Non-Innocent Cyclic (Alkyl)(Amino)Carbenes: Ligand Rearrangement, C-H and C-F Bond Activation.

    PubMed

    Turner, Zoë R

    2016-08-01

    A cyclic (alkyl)(amino)carbene (CAAC) was found to undergo unprecedented rearrangements and transformations of its core structure in the presence of Group 1 and 2 metals. Although the carbene was also found to be prone to intramolecular C-H activation, it was competent for intermolecular activation of a variety of sp-, sp(2) -, and sp(3) -hybridized C-H bonds. Double C-F activation of hexafluorobenzene was also observed in this work. These processes all hold relevance to the role of these carbenes in catalysis, as well as to their use in the synthesis of new and unusual main group or transition metal complexes. PMID:27363588

  15. Gold-catalysed facile access to indene scaffolds via sequential C-H functionalization and 5-endo-dig carbocyclization.

    PubMed

    Ma, Ben; Wu, Ziang; Huang, Ben; Liu, Lu; Zhang, Junliang

    2016-08-01

    A concise synthesis of functionalized indene derivatives via the gold(i)-catalysed cascade C-H functionalization/conia-ene type reaction of electron-rich aromatics with o-alkynylaryl α-diazoesters has been developed. In this transformation, the gold catalyst not only catalysed the formation of the zwitterionic intermediate via intermolecular C-H functionalization but promoted the subsequent intramolecular 5-endo-dig cyclization via activation of alkynes. The reaction is characterized by high chemo- and site-selectivity, readily available starting materials, nice functional-group tolerance and mild reaction conditions. PMID:27373228

  16. Cesium Carboxylate-Promoted Iridium Catalyzed C-H Amidation/Cyclization with 2,2,2-Trichloroethoxycarbonyl Azide.

    PubMed

    Zhang, Tao; Wang, Zhen; Hu, Xuejiao; Yu, Meng; Deng, Tianning; Li, Guigen; Lu, Hongjian

    2016-06-01

    An Ir(III)-catalyzed direct C-H amidation/cyclization of benzamides using 2,2,2-trichloroethoxycarbonyl azide (TrocN3) as the aminocarbonyl source is reported. With the aid of cesium carboxylate, the reactions proceed efficiently and with high regioselectivity, producing various functionalized quinazoline-2,4(1H,3H)-diones, which are important building blocks and key synthetic intermediates for biologically and medicinally important compounds. During the reactions, two new C-N bonds were formed by breaking C-H and N-H bonds sequence. PMID:27164005

  17. Indirect C-H azidation of heterocycles via copper-catalyzed regioselective fragmentation of unsymmetrical λ3-iodanes.

    PubMed

    Lubriks, Dmitrijs; Sokolovs, Igors; Suna, Edgars

    2012-09-19

    A C-H bond of electron-rich heterocycles is transformed into a C-N bond in a reaction sequence comprising the formation of heteroaryl(phenyl)iodonium azides and their in situ regioselective fragmentation to heteroaryl azides. A Cu(I) catalyst ensures complete regiocontrol in the fragmentation step and catalyzes the subsequent 1,3-dipolar cycloaddition of the formed azido heterocycles with acetylenes. The heteroaryl azides can also be conveniently reduced to heteroarylamines by aqueous ammonium sulfide. The overall C-H to C-N transformation is a mild and operationally simple one-pot sequential multistep process. PMID:22913396

  18. C-O/C-H Coupling of Polyfluoroarenes with Aryl Carbamates by Cooperative Ni/Cu Catalysis.

    PubMed

    Wang, Yang; Wu, Song-Bai; Shi, Wen-Juan; Shi, Zhang-Jie

    2016-06-01

    Cross-coupling of polyfluoroarenes with aryl carbamates through the cleavage of both sp(2) C-O and C-H bonds is reported. The reaction conditions are simple, and only transition-metal catalysts and ligands are essential. Mechanistic studies indicated that Ni catalyst played an important role in activating C-O bond, while the Cu one in activating C-H Bond. The developed system proved to be effective for cross-coupling of terminal alkynes with aryl carbamates. PMID:27205866

  19. Predicting the stability of aprotic solvents in Li-air batteries: pKa calculations of aliphatic C-H acids in dimethyl sulfoxide

    NASA Astrophysics Data System (ADS)

    Bryantsev, Vyacheslav S.

    2013-02-01

    Superoxide is a strong base that can induce base-catalyzed autoxidation of weakly acidic solvents. We report on the performance of several computational protocols for predicting pKa values for a wide range of aliphatic C-H acids in DMSO. Calculations at the MP2/CBS level with CCSD(T)/aug-cc-pVDZ corrections and solvent effects calculated using the SVPE model provide the best overall performance (rms deviation is 0.65 pKa). The B3LYP, M06, and M06-2X functionals can also achieve high accuracy (<1 pKa) by employing empirical corrections to fit the experimental data. Computational results provide a convenient means of screening for suitable solvents in Li-air batteries.

  20. Effect of Si and C concentration on the microstructure, and the mechanical, tribological and electrochemical properties of nanocomposite TiC/a-SiC:H/a-C:H coatings prepared by plasma enhanced chemical vapor deposition

    NASA Astrophysics Data System (ADS)

    Li, Duanjie; Hassani, Salim; Poulin, Suzie; Szpunar, Jerzy A.; Martinu, Ludvik; Klemberg-Sapieha, Jolanta E.

    2012-02-01

    The nanocomposite TiC/a-SiC:H/a-C:H (presented as Ti-Si-C) coatings attract considerable interest due to their possible applications such as wear protective coatings, diffusion barriers, and materials for solar cells and electrical contacts. In order to explore new film properties and open new opportunities, in the present work, we prepare a series of C-rich Ti-Si-C coatings with different Si and C concentrations using plasma enhanced chemical vapor deposition, and we systematically investigate the effect of elemental composition on the microstructure, and on the mechanical, tribological and electrochemical properties. XRD and XPS analyses demonstrate that the Ti-Si-C coatings mainly consist of nanocrystalline (nc-) TiC embedded in amorphous (a-) SiC:H and a-C:H matrices. Ti-Si-C coatings with a high Si concentration possess enhanced mechanical properties (high hardness), while those with additional C exhibit superior tribological behaviors. The increase of Si and/or C concentrations leads to a grain size refinement of the TiC nanocrystals and to an expansion of the amorphous phase. This in turn substantially enhances their corrosion resistance. Ti-Si-C coatings with the highest Si or C contents exhibit the best corrosion performance among the tested samples by improving the corrosion resistance of the SS410 substrate by a factor of ˜400.

  1. Rhodium-Catalyzed C-C Bond Formation via Heteroatom-Directed C-H Bond Activation

    SciTech Connect

    Colby, Denise; Bergman, Robert; Ellman, Jonathan

    2010-05-13

    Once considered the 'holy grail' of organometallic chemistry, synthetically useful reactions employing C-H bond activation have increasingly been developed and applied to natural product and drug synthesis over the past decade. The ubiquity and relative low cost of hydrocarbons makes C-H bond functionalization an attractive alternative to classical C-C bond forming reactions such as cross-coupling, which require organohalides and organometallic reagents. In addition to providing an atom economical alternative to standard cross - coupling strategies, C-H bond functionalization also reduces the production of toxic by-products, thereby contributing to the growing field of reactions with decreased environmental impact. In the area of C-C bond forming reactions that proceed via a C-H activation mechanism, rhodium catalysts stand out for their functional group tolerance and wide range of synthetic utility. Over the course of the last decade, many Rh-catalyzed methods for heteroatom-directed C-H bond functionalization have been reported and will be the focus of this review. Material appearing in the literature prior to 2001 has been reviewed previously and will only be introduced as background when necessary. The synthesis of complex molecules from relatively simple precursors has long been a goal for many organic chemists. The ability to selectively functionalize a molecule with minimal pre-activation can streamline syntheses and expand the opportunities to explore the utility of complex molecules in areas ranging from the pharmaceutical industry to materials science. Indeed, the issue of selectivity is paramount in the development of all C-H bond functionalization methods. Several groups have developed elegant approaches towards achieving selectivity in molecules that possess many sterically and electronically similar C-H bonds. Many of these approaches are discussed in detail in the accompanying articles in this special issue of Chemical Reviews. One approach that has

  2. The Ether-Cleaving Methyltransferase System of the Strict Anaerobe Acetobacterium dehalogenans: Analysis and Expression of the Encoding Genes▿

    PubMed Central

    Schilhabel, Anke; Studenik, Sandra; Vödisch, Martin; Kreher, Sandra; Schlott, Bernhard; Pierik, Antonio Y.; Diekert, Gabriele

    2009-01-01

    Anaerobic O-demethylases are inducible multicomponent enzymes which mediate the cleavage of the ether bond of phenyl methyl ethers and the transfer of the methyl group to tetrahydrofolate. The genes of all components (methyltransferases I and II, CP, and activating enzyme [AE]) of the vanillate- and veratrol-O-demethylases of Acetobacterium dehalogenans were sequenced and analyzed. In A. dehalogenans, the genes for methyltransferase I, CP, and methyltransferase II of both O-demethylases are clustered. The single-copy gene for AE is not included in the O-demethylase gene clusters. It was found that AE grouped with COG3894 proteins, the function of which was unknown so far. Genes encoding COG3894 proteins with 20 to 41% amino acid sequence identity with AE are present in numerous genomes of anaerobic microorganisms. Inspection of the domain structure and genetic context of these orthologs predicts that these are also reductive activases for corrinoid enzymes (RACEs), such as carbon monoxide dehydrogenase/acetyl coenzyme A synthases or anaerobic methyltransferases. The genes encoding the O-demethylase components were heterologously expressed with a C-terminal Strep-tag in Escherichia coli, and the recombinant proteins methyltransferase I, CP, and AE were characterized. Gel shift experiments showed that the AE comigrated with the CP. The formation of other protein complexes with the O-demethylase components was not observed under the conditions used. The results point to a strong interaction of the AE with the CP. This is the first report on the functional heterologous expression of acetogenic phenyl methyl ether-cleaving O-demethylases. PMID:19011025

  3. Plasmodium falciparum cysteine protease falcipain-2 cleaves erythrocyte membrane skeletal proteins at late stages of parasite development.

    PubMed

    Hanspal, Manjit; Dua, Meenakshi; Takakuwa, Yuichi; Chishti, Athar H; Mizuno, Akiko

    2002-08-01

    Plasmodium falciparum-derived cysteine protease falcipain-2 cleaves host erythrocyte hemoglobin at acidic pH and specific components of the membrane skeleton at neutral pH. Analysis of stage-specific expression of these 2 proteolytic activities of falcipain-2 shows that hemoglobin-hydrolyzing activity is maximum in early trophozoites and declines rapidly at late stages, whereas the membrane skeletal protein hydrolyzing activity is markedly increased at the late trophozoite and schizont stages. Among the erythrocyte membrane skeletal proteins, ankyrin and protein 4.1 are cleaved by native and recombinant falcipain-2 near their C-termini. To identify the precise peptide sequence at the hydrolysis site of protein 4.1, we used a recombinant construct of protein 4.1 as substrate followed by MALDI-MS analysis of the cleaved product. We show that falcipain-2-mediated cleavage of protein 4.1 occurs immediately after lysine 437, which lies within a region of the spectrin-actin-binding domain critical for erythrocyte membrane stability. A 16-mer peptide containing the cleavage site completely inhibited the enzyme activity and blocked falcipain-2-induced fragmentation of erythrocyte ghosts. Based on these results, we propose that falcipain-2 cleaves hemoglobin in the acidic food vacuole at the early trophozoite stage, whereas it cleaves specific components of the red cell skeleton at the late trophozoite and schizont stages. It is the proteolysis of skeletal proteins that causes membrane instability, which, in turn, facilitates parasite release in vivo. PMID:12130521

  4. Immunoexpression of cleaved caspase-3 shows lower apoptotic area indices in lip carcinomas than in intraoral cancer

    PubMed Central

    LEITE, Ana Flávia Schueler de Assumpção; BERNARDO, Vagner Gonçalves; BUEXM, Luisa Aguirre; da FONSECA, Eliene Carvalho; da SILVA, Licínio Esmeraldo; BARROSO, Danielle Resende Camisasca; LOURENÇO, Simone de Queiroz Chaves

    2016-01-01

    ABSTRACT Objective This study aimed to evaluate apoptosis by assessing cleaved caspase-3 immunoexpression in hyperplastic, potentially malignant disorder (PMD), and malignant tumors in intraoral and lower lip sites. Material and Methods A retrospective study using paraffin blocks with tissues from patients with inflammatory fibrous hyperplasia (IFH), actinic cheilitis, oral leukoplakia, lower lip and intraoral squamous cell carcinoma (SCC) was performed. The tissues were evaluated by immunohistochemical analysis with anti-cleaved caspase-3 antibody. Apoptotic area index was then correlated with lesion type. Results From 120 lesions assessed, 55 (46%) were cleaved caspase-3-positive. The SCC samples (n=40) had the highest apoptotic area indices (n=35; 87.5%). Significant differences were detected between SCCs and PMDs (p=0.0003), as well as SCCs and IFHs (p=0.001), regarding caspase-3 immunopositivity. Carcinomas of the lower lip had lower apoptotic area indices than intraoral cancer (p=0.0015). Conclusions Cleaved caspase-3 immunoexpression showed differences in oral SCCs and PMDs and demonstrated a distinct role of apoptosis in carcinogenesis of intraoral and lower lip cancer. In future, the expression of cleaved caspase-3 with other target molecules in oral cancer may be helpful in delineating the prognosis and treatment of these tumors. PMID:27556207

  5. Copper-catalyzed radical methylation/C-H amination/oxidation cascade for the synthesis of quinazolinones.

    PubMed

    Bao, Yajie; Yan, Yizhe; Xu, Kun; Su, Jihu; Zha, Zhenggen; Wang, Zhiyong

    2015-05-01

    A copper-catalyzed radical methylation/sp(3) C-H amination/oxidation reaction for the facile synthesis of quinazolinone was developed. In this cascade reaction, dicumyl peroxide acts not only as a useful oxidant but also as an efficient methyl source. Notably, a methyl radical, generated from peroxide, was confirmed by electron paramagnetic resonance for the first time. PMID:25849218

  6. Metal-free oxidative synthesis of quinazolinones via dual amination of sp3 C-H bonds.

    PubMed

    Zhao, Dan; Wang, Teng; Li, Jian-Xin

    2014-06-21

    A novel metal-free synthesis of quinazolinones via dual amination of sp(3) C-H bonds was developed. The sp(3) carbon in methylarenes or adjacent to a heteroatom in DMSO, DMF or DMA was used as the one carbon synthon. PMID:24816567

  7. Palladium-Catalyzed Synthesis of Phenanthridine/Benzoxazine-Fused Quinazolinones by Intramolecular C-H Bond Activation.

    PubMed

    Gupta, Puneet K; Yadav, Nisha; Jaiswal, Subodh; Asad, Mohd; Kant, Ruchir; Hajela, Kanchan

    2015-09-14

    A highly efficient synthesis of phenanthridine/benzoxazine-fused quinazolinones by ligand-free palladium-catalyzed intramolecular C-H bond activation under mild conditions has been developed. The C-C coupling provides the corresponding N-fused polycyclic heterocycles in good to excellent yields and with wide functional group tolerance. PMID:26230355

  8. Chelation-Assisted Copper-Mediated Direct Acetylamination of 2-Arylpyridine C-H Bonds with Cyanate Salts.

    PubMed

    Kianmehr, Ebrahim; Amiri Lomedasht, Yousef; Faghih, Nasser; Khan, Khalid Mohammed

    2016-07-15

    In this study, the coupling of 2-phenylpyridine derivatives and potassium cyanate through C-H bond functionalization in the presence of a copper salt is developed for the first time. By this protocol, various heteroarylated acetanilide derivatives are synthesized in good yields. 2-Phenylpyridines containing electron-donating and -withdrawing groups appear to be well-tolerated by this transformation. PMID:27295365

  9. Efficient photocatalytic selective nitro-reduction and C-H bond oxidation over ultrathin sheet mediated CdS flowers.

    PubMed

    Pahari, Sandip Kumar; Pal, Provas; Srivastava, Divesh N; Ghosh, Subhash Ch; Panda, Asit Baran

    2015-06-28

    We report here a visible light driven selective nitro-reduction and oxidation of saturated sp(3) C-H bonds using ultrathin (0.8 nm) sheet mediated uniform CdS flowers as catalyst under a household 40 W CFL lamp and molecular oxygen as oxidant. The CdS flowers were synthesized using a simple surfactant assisted hydrothermal method. PMID:26024214

  10. Transition-metal-free C-H oxidative activation: persulfate-promoted selective benzylic mono- and difluorination.

    PubMed

    Ma, Jing-jing; Yi, Wen-bin; Lu, Guo-ping; Cai, Chun

    2015-03-14

    An operationally simple and selective method for the direct conversion of benzylic C-H to C-F to obtain mono- and difluoromethylated arenes using Selectfluor™ as a fluorine source is developed. Persulfate can be used to selectively activate benzylic hydrogen atoms toward C-F bond formation without the aid of transition metal catalysts. PMID:25645405

  11. Asymmetric Synthesis of (-)-Incarvillateine Employing an Intramolecular Alkylation via Rh-Catalyzed Olefinic C-H Bond Activation

    SciTech Connect

    Tsai, Andy; Bergman, Robert; Ellman, Jonathan

    2008-02-18

    An asymmetric total synthesis of (-)-incarvillateine, a natural product having potent analgesic properties, has been achieved in 11 steps and 15.4% overall yield. The key step is a rhodium-catalyzed intramolecular alkylation of an olefinic C-H bond to set two stereocenters. Additionally, this transformation produces an exocyclic, tetrasubstituted alkene through which the bicyclic piperidine moiety can readily be accessed.

  12. Utilization of amorphous silicon carbide (a-Si:C:H) as a resistive layer in gas microstrip detectors

    SciTech Connect

    Hong, W.S.; Cho, H.S.; Perez-Mendez, V.; Gong, W.G.

    1995-04-01

    Thin semiconducting films of hydrogenated amorphous silicon (a-Si:H) and its carbon alloy (a-Si:C:H) were applied to gas microstrip detectors in order to control gain instabilities due to charges on the substrate. Thin ({approximately}100nm) layers of a-Si:H or p-doped a-Si:C:H were placed either over or under the electrodes using the plasma enhanced chemical vapor deposition (PECVD) technique to provide the substrate with a suitable surface conductivity. By changing the carbon content and boron doping density, the sheet resistance of the a-Si:C:H coating could be successfully controlled in the range of 10{sup 12} {approximately} 10{sup 17} {Omega}/{four_gradient}, and the light sensitivity, which causes the resistivity to vary with ambient light conditions, was minimized. An avalanche gain of 5000 and energy resolution of 20% FWHM were achieved and the gain remained constant over a week of operation. A-Si:C:H film is an attractive alternative to ion-implanted or semiconducting glass due to the wide range of resistivities possible and the feasibility of making deposits over a large area at low cost.

  13. Utilization of amorphous silicon carbide (a-Si:C:H) as a resistive layer in gas microstrip detectors

    NASA Astrophysics Data System (ADS)

    Hong, W. S.; Cho, H. S.; Perez-Mendez, V.; Gong, W. G.

    1995-04-01

    Thin semiconducting films of hydrogenated amorphous silicon (a-Si:H) and its carbon alloy (a-Si:C:H) were applied to gas microstrip detectors in order to control gain instabilities due to charges on the substrate. Thin (approximately 100nm) layers of a-Si:H or p-doped a-Si:C:H were placed either over or under the electrodes using the plasma enhanced chemical vapor deposition (PECVD) technique to provide the substrate with a suitable surface conductivity. By changing the carbon content and boron doping density, the sheet resistance of the a-Si:C:H coating could be successfully controlled in the range of 10(exp 12) to approximately 10(exp 17) Omega/(four gradient), and the light sensitivity, which causes the resistivity to vary with ambient light conditions, was minimized. An avalanche gain of 5000 and energy resolution of 20% FWHM were achieved and the gain remained constant over a week of operation. A-Si:C:H film is an attractive alternative to ion-implanted or semiconducting glass due to the wide range of resistivities possible and the feasibility of making deposits over a large area at low cost.

  14. Rh(iii)-catalyzed C-H activation/cyclization of oximes with alkenes for regioselective synthesis of isoquinolines.

    PubMed

    Chen, Renjie; Qi, Jifeng; Mao, Zhenjun; Cui, Sunliang

    2016-07-14

    A Rh(iii)-catalyzed C-H activation/cyclization of oximes and alkenes for facile and regioselective access to isoquinolines has been developed. This protocol features mild reaction conditions and easily accessible starting materials, and has been applied to the concise synthesis of moxaverine. A kinetic isotope effect study was conducted and a plausible mechanism was proposed. PMID:27273816

  15. Amidines for Versatile Cobalt(III)-Catalyzed Synthesis of Isoquinolines through C-H Functionalization with Diazo Compounds.

    PubMed

    Li, Jie; Tang, Mengyao; Zang, Lei; Zhang, Xiaolei; Zhang, Zhao; Ackermann, Lutz

    2016-06-01

    A cobalt(III)-catalyzed C-H/N-H bond functionalization for the synthesis of 1-aminoisoquinolines from aryl amidines and diazo compounds has been developed. The reaction proceeds under mild reaction conditions, obviates the need for oxidants, produces only N2 and H2O as the byproducts, and features a broad substrate scope. PMID:27219713

  16. Selective Synthesis of Isoquinolines by Rhodium(III)-Catalyzed C-H/N-H Functionalization with α-Substituted Ketones.

    PubMed

    Li, Jie; Zhang, Zhao; Tang, Mengyao; Zhang, Xiaolei; Jin, Jian

    2016-08-01

    A rhodium(III)-catalyzed C-H/N-H bond functionalization for the synthesis of 1-aminoisoquinolines from aryl amidines and α-MsO/TsO/Cl ketones was achieved under mild reaction conditions. Thus, this approach provides a practical method for the site-selective synthesis of various synthetically valuable isoquinolines with wide functional group tolerance. PMID:27441726

  17. Investigation of the structure and properties of a-C:H coatings with metal and silicon containing interlayers

    NASA Astrophysics Data System (ADS)

    Nöthe, M.; Breuer, U.; Koch, F.; Penkalla, H. J.; Rehbach, W. P.; Bolt, H.

    2001-07-01

    The structure of the interface of a-C:H coatings deposited with metal and Si-containing interlayers has been studied. Carbide forming metals (Al, Ti, Cr) can improve the chemical bonding compared with a substrate material which does not form carbides extensively by itself. In addition, a graded transition zone enlarges the interface between the carbon layer and the interlayer metal. In the present work the metal atoms were evaporated and ionized into a dense Ar plasma and deposited onto Si (100) substrates. A graded interface between the metal interlayer and the a-C:H coating was produced by introducing C 2H 2 with increasing amount into the Ar/He plasma during the PAPVD metal deposition process. The PACVD a-C:H deposition process was continued after the termination of metal evaporation to produce the pure a-C:H top layer. Further to Al-, Cr-, Ti- and Cu-interlayers, Si-containing interlayers were investigated. The Si-containing interlayers were deposited by a PACVD process using tetraethoxysilane Si(OC 2H 5) 4 (TEOS) and tetramethylsilane Si(CH 3) 4 (TMS). The characterization of the deposited layer systems was performed by SIMS, SNMS and XPS analyses as well as SEM and analytical TEM methods.

  18. Electron microscopy studies of undoped and phosphorus doped Si:H and Si,C:H films

    SciTech Connect

    Chen, Y.L.; Wang, C.; Lucovsky, G.; Maher, D.M.; Bentley, J.

    1993-12-31

    Microstructure of undoped and phosphorus doped Si:H and Si,C:H films was analyzed by selected-area diffraction, conical dark-field imaging, energy-dispersive x-ray spectroscopy, and electron energy-loss spectroscopy in transmission electron microscopes. Thin films were synthesized by remote plasma-enhanced chemical vapor deposition and characterized in terms of degree of crystallinity. Distribution of phosphorus in Si:H and Si,C:H films, and of carbon in Si,C:H films was evaluated. Results indicate that (i) the microstructure of a film may be two phase, consisting of silicon microcrystallites in an amorphous matrix, (ii) phosphorus doping as well as the presence of carbon influences the degree of crystallinity by reducing the average size and volume fraction of microcrystallites, (iii) the presence of carbon and phosphorus doping completely suppresses the crystalline phase, (iv) phosphorus is distributed at approximately the same concentration in both the crystalline and amorphous phases of diphasic films, and (v) carbon is detected in the amorphous phase of the Si,C:H films.

  19. Rhodium(III)-catalyzed C-H activation/annulation with vinyl esters as an acetylene equivalent.

    PubMed

    Webb, Nicola J; Marsden, Stephen P; Raw, Steven A

    2014-09-19

    The behavior of electron-rich alkenes in rhodium-catalyzed C-H activation/annulation reactions is investigated. Vinyl acetate emerges as a convenient acetylene equivalent, facilitating the synthesis of sixteen 3,4-unsubstituted isoquinolones, as well as select heteroaryl-fused pyridones. The complementary regiochemical preferences of enol ethers versus enol esters/enamides is discussed. PMID:25165993

  20. Mechanistic elucidation of C-H oxidation by electron rich non-heme iron(IV)-oxo at room temperature.

    PubMed

    Rana, Sujoy; Dey, Aniruddha; Maiti, Debabrata

    2015-10-01

    Non-heme iron(IV)-oxo species form iron(III) intermediates during hydrogen atom abstraction (HAA) from the C-H bond. While synthesizing a room temperature stable, electron rich, non-heme iron(IV)-oxo compound, we obtained iron(III)-hydroxide, iron(III)-alkoxide and hydroxylated-substrate-bound iron(II) as the detectable intermediates. The present study revealed that a radical rebound pathway was operative for benzylic C-H oxidation of ethylbenzene and cumene. A dissociative pathway for cyclohexane oxidation was established based on UV-vis and radical trap experiments. Interestingly, experimental evidence including O-18 labeling and mechanistic study suggested an electron transfer mechanism to be operative during C-H oxidation of alcohols (e.g. benzyl alcohol and cyclobutanol). The present report, therefore, unveils non-heme iron(IV)-oxo promoted substrate-dependent C-H oxidation pathways which are of synthetic as well as biological significance. PMID:26277913

  1. Rationale of the effects from dopants on C-H bond activation for sp2 hybridized nanostructured carbon catalysts

    NASA Astrophysics Data System (ADS)

    Mao, Shanjun; Sun, Xiaoying; Li, Bo; Su, Dang Sheng

    2015-10-01

    Doping has become an effective way to tune the catalytic properties of nanostructured carbon catalysts. Taking C-H activation as an example, first-principles calculations propose that the relative energy level and the BEP rule might be applicable to explain the observed doping effects. Moreover, boron doping is proposed as an effective way to enhance the catalytic performance.Doping has become an effective way to tune the catalytic properties of nanostructured carbon catalysts. Taking C-H activation as an example, first-principles calculations propose that the relative energy level and the BEP rule might be applicable to explain the observed doping effects. Moreover, boron doping is proposed as an effective way to enhance the catalytic performance. Electronic supplementary information (ESI) available: The computational setup, the doping positions for B, N and S doping, the definition of the binding energy and dissociation energy for C2H5 and C2H6 respectively, the transition state and dissociation state structures for the C-H bond activation of C2H6 in the undoped case, and the lengths of the C-H bond of C2H6 at the transition states for both the undoped and doped cases. See DOI: 10.1039/c5nr05759k

  2. Enantioselective Intramolecular C-H Insertion of Donor and Donor/Donor Carbenes by a Nondiazo Approach.

    PubMed

    Zhu, Dong; Ma, Jun; Luo, Kui; Fu, Hongguang; Zhang, Li; Zhu, Shifa

    2016-07-11

    The first enantioselective intramolecular C-H insertion and cyclopropanation reactions of donor- and donor/donor-carbenes by a nondiazo approach are reported. The reactions were conducted in a one-pot manner without slow addition and provided the desired dihydroindole, dihydrobenzofuran, tetrahydrofuran, and tetrahydropyrrole derivatives with up to 99 % ee and 100 % atom efficiency. PMID:27265896

  3. Mechanism and Site Selectivity in Visible-Light Photocatalyzed C-H Functionalization: Insights from DFT Calculations.

    PubMed

    Demissie, Taye B; Hansen, Jørn H

    2016-08-19

    Visible-light photocatalyzed (VLPC) late-stage C-H functionalization is a powerful addition to the chemical synthesis toolkit. VLPC has a demonstrated potential for discovery of elusive and valuable transformations, particularly in functionalization of bioactive heterocycles. In order to fully harvest the potential of VLPC in the context of complex molecule synthesis, a thorough understanding of the elementary processes involved is crucial. This would enable more rational design of suitable reagents and catalysts, as well as prediction of activated C-H sites for functionalization. Such knowledge is essential when VLPC is to be employed in retrosynthetic analysis of complex molecules. Herein, we present a density functional theory (DFT) study of mechanistic details in the C-H functionalization of bioactive heterocycles exemplified by the methylation of the antifungal agent voriconazole. Moreover, we show that readily computed atomic charges can predict major site-selectivity in good agreement with experimental studies and thus be informative tools for the identification of active C-H functionalization sites in synthetic planning. PMID:27347684

  4. C-H bond activation enables the rapid construction and late-stage diversification of functional molecules

    NASA Astrophysics Data System (ADS)

    Wencel-Delord, Joanna; Glorius, Frank

    2013-05-01

    The beginning of the twenty-first century has witnessed significant advances in the field of C-H bond activation, and this transformation is now an established piece in the synthetic chemists' toolbox. This methodology has the potential to be used in many different areas of chemistry, for example it provides a perfect opportunity for the late-stage diversification of various kinds of organic scaffolds, ranging from relatively small molecules like drug candidates, to complex polydisperse organic compounds such as polymers. In this way, C-H activation approaches enable relatively straightforward access to a plethora of analogues or can help to streamline the lead-optimization phase. Furthermore, synthetic pathways for the construction of complex organic materials can now be designed that are more atom- and step-economical than previous methods and, in some cases, can be based on synthetic disconnections that are just not possible without C-H activation. This Perspective highlights the potential of metal-catalysed C-H bond activation reactions, which now extend beyond the field of traditional synthetic organic chemistry.

  5. Iridium- and rhodium-catalyzed C-H activation and formyl arylation of benzaldehydes under chelation-assistance.

    PubMed

    Yang, Xifa; Wang, He; Zhou, Xukai; Li, Xingwei

    2016-06-21

    Mild and efficient synthesis of benzophenones via Ir(iii)- and Rh(iii)-catalyzed, directing group-assisted formyl C-H arylation of benzaldehydes has been achieved using diaryliodonium salts, in which Rh(iii) and Ir(iii) catalysts exhibited a complementary substrate scope. PMID:27222168

  6. A two-electron shell game: Intermediates of the extradiol-cleaving catechol dioxygenases

    PubMed Central

    Fielding, Andrew J.

    2014-01-01

    Extradiol catechol ring-cleaving dioxygenases function by binding both the organic substrate and O2 at a divalent metal center in the active site. They have proven to be a particularly versatile group of enzymes with which to study the O2 activation process. Here, recent studies of homoprotocatechuate 2,3-dioxygenase (HPCD) are summarized with the objective of showing how Nature can utilize the enzyme structure and the properties of the metal and the substrate to select among many possible chemical paths to achieve both specificity and efficiency. Possible intermediates in the mechanism have been trapped by swapping active site metals, introducing active site amino acid substituted variants, and using substrates with different electron donating capacities. While each of these intermediates could form part of a viable reaction pathway, kinetic measurements significantly limit the likely candidates. Structural, kinetic, spectroscopic and computational analysis of the various intermediates shed light on how catalytic efficiency can be achieved. PMID:24615282

  7. Hole Transport and Spin Effects in Cleaved-Edge-Overgrowth Quantum Wires

    NASA Astrophysics Data System (ADS)

    Sulpizio, Joseph; Quay, Charis; de Picciotto, Rafi; West, K. W.; Pfeiffer, L. N.; Goldhaber-Gordon, David

    2009-03-01

    Transport measurements on ballistic GaAs electron wires have revealed a rich set of phenomena associated with one-dimensional (1D) quantum systems. Studies of transport in hole systems are a natural extension of these experiments due to the enhanced effective mass, g-factor, and spin-orbit coupling of holes over their electron counterparts. However, only recently has the creation of ballistic hole wire devices been possible due to breakthroughs in molecular beam epitaxy using the cleaved-edge-overgrowth (CEO) technique. We present measurements of hole transport in CEO GaAs quantum wires in magnetic field in a dilution refrigerator. Based on a simple model, we extract the g-factor for different field orientations, and also discuss evidence for observing spin-orbit coupling in a 1D system.

  8. Crystal growth of Bi2Te3 and noble cleaved (0001) surface properties

    NASA Astrophysics Data System (ADS)

    Atuchin, V. V.; Golyashov, V. A.; Kokh, K. A.; Korolkov, I. V.; Kozhukhov, A. S.; Kruchinin, V. N.; Loshkarev, I. D.; Pokrovsky, L. D.; Prosvirin, I. P.; Romanyuk, K. N.; Tereshchenko, O. E.

    2016-04-01

    A high quality Bi2Te3 crystal has been grown by Bridgman method with the use of rotating heat field. The phase purity and bulk structural quality of the crystal have been verified by XRD analysis and rocking curve observation. The atomically smooth Bi2Te3(0001) surface with an excellent crystallographic quality is formed by cleavage in the air. The chemical and microstructural properties of the surface have been evaluated with RHEED, AFM, STM, SE and XPS. The Bi2Te3(0001) cleaved surface is formed by atomically smooth terraces with the height of the elemental step of ~1.04±0.1 nm, as estimated by AFM. There is no surface oxidation process detected over a month keeping in the air at normal conditions, as shown by comparative core level photoelectron spectroscopy.

  9. A two-electron-shell game: intermediates of the extradiol-cleaving catechol dioxygenases.

    PubMed

    Fielding, Andrew J; Lipscomb, John D; Que, Lawrence

    2014-06-01

    Extradiol-cleaving catechol dioxygenases function by binding both the organic substrate and O2 at a divalent metal center in the active site. They have proven to be a particularly versatile group of enzymes with which to study the O2 activation process. Here, recent studies of homoprotocatechuate 2,3-dioxygenase are summarized, showing how nature can utilize the enzyme structure and the properties of the metal and the substrate to select among many possible chemical paths to achieve both specificity and efficiency. Possible intermediates in the mechanism have been trapped by swapping active-site metals, introducing active-site amino acid substituted variants, and using substrates with different electron-donating capacities. Although each of these intermediates could form part of a viable reaction pathway, kinetic measurements significantly limit the likely candidates. Structural, kinetic, spectroscopic, and computational analyses of the various intermediates shed light on how catalytic efficiency can be achieved. PMID:24615282

  10. Ethenolysis: A Green Catalytic Tool to Cleave Carbon-Carbon Double Bonds.

    PubMed

    Bidange, Johan; Fischmeister, Cédric; Bruneau, Christian

    2016-08-22

    Remarkable innovations have been made in the field of olefin metathesis due to the design and preparation of new catalysts. Ethenolysis, which is cross-metathesis with ethylene, represents one catalytic transformation that has been used with the purpose of cleaving internal carbon-carbon double bonds. The objectives were either the ring opening of cyclic olefins to produce dienes or the shortening of unsaturated hydrocarbon chains to degrade polymers or generate valuable shorter terminal olefins in a controlled manner. This Review summarizes several aspects of this reaction: the catalysts, their degradation in the presence of ethylene, some parameters driving their productivity, the side reactions, and the applications of ethenolysis in organic synthesis and in potential industrial applications. PMID:27359344

  11. Chromogranin A Is Preferentially Cleaved into Proangiogenic Peptides in the Bone Marrow of Multiple Myeloma Patients.

    PubMed

    Bianco, Mimma; Gasparri, Anna Maria; Colombo, Barbara; Curnis, Flavio; Girlanda, Stefania; Ponzoni, Maurilio; Bertilaccio, Maria Teresa Sabrina; Calcinotto, Arianna; Sacchi, Angelina; Ferrero, Elisabetta; Ferrarini, Marina; Chesi, Marta; Bergsagel, P Leif; Bellone, Matteo; Tonon, Giovanni; Ciceri, Fabio; Marcatti, Magda; Caligaris-Cappio, Federico; Corti, Angelo

    2016-04-01

    Angiogenesis has been postulated to be critical for the pathogenesis of multiple myeloma, a neoplastic disease characterized by abnormal proliferation of malignant plasma cells in the bone marrow (BM). Cleavage of the N- and C-terminal regions of circulating chromogranin A (CgA, CHGA), classically an antiangiogenic protein, can activate latent antiangiogenic and proangiogenic sites, respectively. In this study, we investigated the distribution of CgA-derived polypeptides in multiple myeloma patients and the subsequent implications for disease progression. We show that the ratio of pro/antiangiogenic forms of CgA is altered in multiple myeloma patients compared with healthy subjects and that this ratio is higher in BM plasma compared with peripheral plasma, suggesting enhanced local cleavage of the CgA C-terminal region. Enhanced cleavage correlated with increased VEGF and FGF2 BM plasma levels and BM microvascular density. Using the Vk*MYC mouse model of multiple myeloma, we further demonstrate that exogenously administered CgA was cleaved in favor of the proangiogenic form and was associated with increased microvessel density. Mechanistic studies revealed that multiple myeloma and proliferating endothelial cells can promote CgA C-terminal cleavage by activating the plasminogen activator/plasmin system. Moreover, cleaved and full-length forms could also counter balance the pro/antiangiogenic activity of each other in in vitro angiogenesis assays. These findings suggest that the CgA-angiogenic switch is activated in the BM of multiple myeloma patients and prompt further investigation of this CgA imbalance as a prognostic or therapeutic target. Cancer Res; 76(7); 1781-91. ©2016 AACR. PMID:26869462

  12. Cleaving the n,n triple bond: the transformation of dinitrogen to ammonia by nitrogenases.

    PubMed

    Lee, Chi Chung; Ribbe, Markus W; Hu, Yilin

    2014-01-01

    Biological nitrogen fixation is a natural process that converts atmospheric nitrogen (N2) to bioavailable ammonia (NH3). This reaction not only plays a key role in supplying bio-accessible nitrogen to all life forms on Earth, but also embodies the powerful chemistry of cleaving the inert N,N triple bond under ambient conditions. The group of enzymes that carry out this reaction are called nitrogenases and typically consist of two redox active protein components, each containing metal cluster(s) that are crucial for catalysis. In the past decade, a number of crystal structures, including several at high resolutions, have been solved. However, the catalytic mechanism of nitrogenase, namely, how the N,N triple bond is cleaved by this enzyme under ambient conditions, has remained elusive. Nevertheless, recent biochemical and spectroscopic studies have led to a better understanding of the potential intermediates of N2 reduction by the molybdenum (Mo)-nitrogenase. In addition, it has been demonstrated that carbon monoxide (CO), which was thought to be an inhibitor of N2 reduction, could also be reduced by the vanadium (V)-nitrogenase to small alkanes and alkenes. This chapter will begin with an introduction to biological nitrogen fixation and Mo-nitrogenase, continue with a discussion of the catalytic mechanism of N2 reduction by Mo-nitrogenase, and conclude with a survey of the current knowledge of N2- and CO-reduction by V-nitrogenase and how V-nitrogenase compares to its Mo-counterpart in these catalytic activities. PMID:25416394

  13. Electrophilic, Ambiphilic, and Nucleophilic C-H bond Activation. Understanding the electronic continuum of C-H bond activation through transition-state and reaction pathway interaction energy decompositions

    SciTech Connect

    Ess, Daniel H.; Goddard, William A.; Periana, Roy A.

    2010-10-29

    The potential energy and interaction energy profiles for metal- and metal-ligand-mediated alkane C-H bond activation were explored using B3LYP density functional theory (DFT) and the absolutely localized molecular orbital energy decomposition analysis (ALMO-EDA). The set of complexes explored range from late transition metal group 10 (Pt and Pd) and group 11 (Au) metal centers to group 7-9 (Ir, Rh, Ru, and W) metal centers as well as a group 3 Sc complex. The coordination geometries, electron metal count (d8, d6, d4, and d0), and ligands (N-heterocycles, O-donor, phosphine, and Cp*) are also diverse. Quantitative analysis using ALMO-EDA of both directions of charge-transfer stabilization (occupied to unoccupied orbital stabilization) energies between the metal-ligand fragment and the coordinated C-H bond in the transition state for cleavage of the C-H bond allows classification of C-H activation reactions as electrophilic, ambiphilic, or nucleophilic on the basis of the net direction of charge-transfer energy stabilization. This bonding pattern transcends any specific mechanistic or bonding paradigm, such as oxidative addition, σ-bond metathesis, or substitution. Late transition metals such as Au(III), Pt(II), Pd(II), and Rh(III) metal centers with N-heterocycle, halide, or O-donor ligands show electrophilically dominated reaction profiles with forward charge-transfer from the C-H bond to the metal, leading to more stabilization than reverse charge transfer from the metal to the C-H bond. Transition states and reaction profiles for d6 Ru(II) and Ir(III) metals with Tp and acac ligands were found to have nearly equal forward and reverse charge-transfer energy stabilization. This ambiphilic region also includes the classically labeled electrophilic cationic species Cp*(PMe3)Ir(Me). Nucleophilic character, where the metal to C-H bond charge-transfer interaction is most stabilizing, was found in

  14. Origin of superlubricity in a-C:H:Si films: a relation to film bonding structure and environmental molecular characteristic.

    PubMed

    Chen, Xinchun; Kato, Takahisa; Nosaka, Masataka

    2014-08-27

    Superlubricity of Si-containing hydrogenated amorphous carbon (a-C:H:Si) films has been systematically investigated in relation to the film bonding structure and the environmental atmosphere. Structural diversity induced by hydrogen incorporation (i.e., 17.3-36.7 at. % H), namely sp(2)-bonded a-C, diamond-like or polymer-like, and tribointeractions activated by the participation of environmental gaseous molecules mainly determine the frictional behaviors of a-C:H:Si films. A suitable control of hydrogen content in the film (i.e., the inherent hydrogen coverage) is obligate to obtain durable superlubricity in a distinct gaseous atmosphere such as dry N2, reactive H2 or humid air. Rapid buildup of running-in-induced antifriction tribolayers at the contact interface, which is more feasible in self-mated sliding, is crucial for achieving a superlubric state. Superior tribological performances have been observed for the polymer-like a-C:H:Si (31.9 at. % H) film, as this hydrogen-rich sample can exhibit superlow friction in various atmospheres including dry inert N2 (μ ∼ 0.001), Ar (μ ∼ 0.012), reactive H2 (μ ∼ 0.003) and humid air (μ ∼ 0.004), and can maintain ultralow friction in corrosive O2 (μ ∼ 0.084). Hydrogen is highlighted for its decisive role in obtaining superlow friction. The occurrence of superlubricity in a-C:H:Si films is generally attributed to a synergistic effect of phase transformation, surface passivation and shear localization, for instance, the near-frictionless state occurred in dry N2. The contribution of each mechanism to the friction reduction depends on the specific intrafilm and interfilm interactions along with the atmospheric effects. These antifriction a-C:H:Si films are promising for industrial applications as lubricants. PMID:25100259

  15. Pathways and kinetics of methane and ethane C-H bond cleavage on PdO(101).

    PubMed

    Antony, Abbin; Asthagiri, Aravind; Weaver, Jason F

    2013-09-14

    We used conventional density functional theory (DFT) and dispersion-corrected DFT (DFT-D3) calculations to investigate C-H bond activation pathways for methane and ethane σ-complexes adsorbed on the PdO(101) surface. The DFT-D3 calculations predict lower and more physically realistic values of the apparent C-H bond cleavage barriers, which are defined relative to the gas-phase energy level, while giving nearly the same energy differences between stationary states as predicted by conventional DFT for a given reaction pathway. For the stable CH4 η(2) complex on PdO(101), DFT-D3 predicts that the C-H bond cleavage barriers are 55.2 and 16.1 kJ∕mol relative to the initial molecularly adsorbed and gaseous states, respectively. We also predict that dehydrogenation of the resulting CH3 groups and conversion to CH3O species are significantly more energetically demanding than the initial C-H bond activation of CH4 on PdO(101). Using DFT-D3, we find that an η(2) and an η(1) ethane complex can undergo C-H bond cleavage on PdO(101) with intrinsic energy barriers that are similar to that of the methane complex, but with apparent barriers that are close to zero. We also investigated the dissociation kinetics of methane and ethane on PdO(101) using microkinetic models, with parameters derived from the DFT-D3 relaxed structures. We find that a so-called 3N - 2 model, in which two frustrated adsorbate motions are treated as free motions, predicts desorption pre-factors and alkane dissociation probabilities that agree well with estimates obtained from the literature. The microkinetic simulations demonstrate the importance of accurately describing entropic contributions in kinetic simulations of alkane dissociative chemisorption. PMID:24050357

  16. Pathways and kinetics of methane and ethane C-H bond cleavage on PdO(101)

    NASA Astrophysics Data System (ADS)

    Antony, Abbin; Asthagiri, Aravind; Weaver, Jason F.

    2013-09-01

    We used conventional density functional theory (DFT) and dispersion-corrected DFT (DFT-D3) calculations to investigate C-H bond activation pathways for methane and ethane σ-complexes adsorbed on the PdO(101) surface. The DFT-D3 calculations predict lower and more physically realistic values of the apparent C-H bond cleavage barriers, which are defined relative to the gas-phase energy level, while giving nearly the same energy differences between stationary states as predicted by conventional DFT for a given reaction pathway. For the stable CH4 η2 complex on PdO(101), DFT-D3 predicts that the C-H bond cleavage barriers are 55.2 and 16.1 kJ/mol relative to the initial molecularly adsorbed and gaseous states, respectively. We also predict that dehydrogenation of the resulting CH3 groups and conversion to CH3O species are significantly more energetically demanding than the initial C-H bond activation of CH4 on PdO(101). Using DFT-D3, we find that an η2 and an η1 ethane complex can undergo C-H bond cleavage on PdO(101) with intrinsic energy barriers that are similar to that of the methane complex, but with apparent barriers that are close to zero. We also investigated the dissociation kinetics of methane and ethane on PdO(101) using microkinetic models, with parameters derived from the DFT-D3 relaxed structures. We find that a so-called 3N - 2 model, in which two frustrated adsorbate motions are treated as free motions, predicts desorption pre-factors and alkane dissociation probabilities that agree well with estimates obtained from the literature. The microkinetic simulations demonstrate the importance of accurately describing entropic contributions in kinetic simulations of alkane dissociative chemisorption.

  17. Update on scribe-cleave-passivate (SCP) slim edge technology for silicon sensors: Automated processing and radiation resistance

    NASA Astrophysics Data System (ADS)

    Fadeyev, V.; Ely, S.; Galloway, Z.; Ngo, J.; Parker, C.; Sadrozinski, H. F.-W.; Christophersen, M.; Phlips, B. F.; Pellegrini, G.; Rafi, J. M.; Quirion, D.; Dalla Betta, G.-F.; Boscardin, M.; Casse, G.; Gorelov, I.; Hoeferkamp, M.; Metcalfe, J.; Seidel, S.; Gaubas, E.; Ceponis, T.; Vaitkus, J. V.

    2014-11-01

    We pursue scribe-cleave-passivate (SCP) technology for making "slim edge" sensors. The goal is to reduce the inactive region at the periphery of the devices while maintaining their performance. In this paper we report on two aspects of the current efforts. The first one involves fabrication options for mass production. We describe the automated cleaving tests and a simplified version of SCP post-processing of n-type devices. Another aspect is the radiation resistance of the passivation. We report on the radiation tests of n- and p-type devices with protons and neutrons.

  18. Observation of a Metastable Periodic Structure for the (001) Surface of KTaO{sub 3} after Cleaving In Situ

    SciTech Connect

    Li, Jaime A.; Akhadov, E. A.; Baker, Jeff; Boatner, L. A.; Bonart, D.; Flaherty, F. A.; Fritsch, J.; Safron, S. A.; Schro''der, U.; Skofronick, J. G.

    2001-05-21

    Helium atom diffraction experiments carried out under ultrahigh vacuum conditions on a freshly cleaved (001) surface of KTaO{sub 3} reveal metastable features which decay over a period of several hours. The initial He diffraction pattern contains large scattering intensity satellite peaks very close to the specular reflection beam. As time from cleaving elapses, the satellite intensities diminish virtually to zero while the specular intensity increases, and the diffraction pattern evolves into one consistent with the (1x1) bulk termination surface. The data are compared with model calculations for scattering from a series of terraces at two heights with a distribution of terrace lengths [Surf.Sci. 384, 15 (1997)].

  19. Caught in the act: the crystal structure of cleaved cathepsin L bound to the active site of Cathepsin L.

    PubMed

    Sosnowski, Piotr; Turk, Dušan

    2016-04-01

    Cathepsin L is a ubiquitously expressed papain-like cysteine protease involved in the endosomal degradation of proteins and has numerous roles in physiological and pathological processes, such as arthritis, osteoporosis, and cancer. Insight into the specificity of cathepsin L is important for elucidating its physiological roles and drug discovery. To study interactions with synthetic ligands, we prepared a presumably inactive mutant and crystallized it. Unexpectedly, the crystal structure determined at 1.4 Å revealed that the cathepsin L molecule is cleaved, with the cleaved region trapped in the active site cleft of the neighboring molecule. Hence, the catalytic mutant demonstrated low levels of catalytic activity. PMID:26992470

  20. Microstructure of a-C:H films prepared on a microtrench and analysis of ions and radicals behavior

    NASA Astrophysics Data System (ADS)

    Hirata, Yuki; Choi, Junho

    2015-08-01

    Amorphous carbon films (a-C:H) were prepared on a microtrench (4-μm pitch and 4-μm depth), and the uniformity of film thickness and microstructure of the films on the top, sidewall, and bottom surfaces of the microtrench were evaluated by scanning electron microscopy and Raman spectroscopy. The a-C:H films were prepared by bipolar-type plasma based ion implantation and deposition (bipolar PBII&D), and the negative pulse voltage, which is the main parameter dominating the film structure, was changed from -1.0 to -15 kV. Moreover, the behavior of ions and radicals was analyzed simultaneously by combining the calculation methods of Particle-In-Cell/Monte Carlo Collision (PIC-MCC) and Direct Simulation Monte Carlo (DSMC) to investigate the coating mechanism for the microtrench. The results reveal that the thickness uniformity of a-C:H films improves with decreasing negative pulse voltage due to the decreasing inertia of incoming ions from the trench mouth, although the film thickness on the sidewall tends to be much smaller than that on the top and bottom surfaces of the trench. The normalized flux and the film thickness show similar behavior, i.e., the normalized flux or thickness at the bottom surface increases at low negative pulse voltages and then saturates at a certain value, whereas at the sidewall it monotonically decreases with increasing negative voltage. The microstructure of a-C:H films on the sidewall surface is very different from that on the top and bottom surfaces. The film structure at a low negative pulse voltage shifts to more of a polymer-like carbon (PLC) structure due to the lower incident energy of ions. Although the radical flux on the sidewall increases slightly, the overall film structure is not significantly changed because this film formation at a low negative voltage is originally dominated by radicals. On the other hand, the flux of radicals is dominant on the sidewall in the case of high negative pulse voltage, resulting in a deviation

  1. Microstructure of a-C:H films prepared on a microtrench and analysis of ions and radicals behavior

    SciTech Connect

    Hirata, Yuki; Choi, Junho

    2015-08-28

    Amorphous carbon films (a-C:H) were prepared on a microtrench (4-μm pitch and 4-μm depth), and the uniformity of film thickness and microstructure of the films on the top, sidewall, and bottom surfaces of the microtrench were evaluated by scanning electron microscopy and Raman spectroscopy. The a-C:H films were prepared by bipolar-type plasma based ion implantation and deposition (bipolar PBII&D), and the negative pulse voltage, which is the main parameter dominating the film structure, was changed from −1.0 to −15 kV. Moreover, the behavior of ions and radicals was analyzed simultaneously by combining the calculation methods of Particle-In-Cell/Monte Carlo Collision (PIC-MCC) and Direct Simulation Monte Carlo (DSMC) to investigate the coating mechanism for the microtrench. The results reveal that the thickness uniformity of a-C:H films improves with decreasing negative pulse voltage due to the decreasing inertia of incoming ions from the trench mouth, although the film thickness on the sidewall tends to be much smaller than that on the top and bottom surfaces of the trench. The normalized flux and the film thickness show similar behavior, i.e., the normalized flux or thickness at the bottom surface increases at low negative pulse voltages and then saturates at a certain value, whereas at the sidewall it monotonically decreases with increasing negative voltage. The microstructure of a-C:H films on the sidewall surface is very different from that on the top and bottom surfaces. The film structure at a low negative pulse voltage shifts to more of a polymer-like carbon (PLC) structure due to the lower incident energy of ions. Although the radical flux on the sidewall increases slightly, the overall film structure is not significantly changed because this film formation at a low negative voltage is originally dominated by radicals. On the other hand, the flux of radicals is dominant on the sidewall in the case of high negative pulse voltage, resulting in a

  2. Bipyridine- and phenanthroline-based metal-organic frameworks for highly efficient and tandem catalytic organic transformations via directed C-H activation.

    PubMed

    Manna, Kuntal; Zhang, Teng; Greene, Francis X; Lin, Wenbin

    2015-02-25

    We report here the synthesis of a series of robust and porous bipyridyl- and phenanthryl-based metal-organic frameworks (MOFs) of UiO topology (BPV-MOF, mBPV-MOF, and mPT-MOF) and their postsynthetic metalation to afford highly active single-site solid catalysts. While BPV-MOF was constructed from only bipyridyl-functionalized dicarboxylate linker, both mBPV- and mPT-MOF were built with a mixture of bipyridyl- or phenanthryl-functionalized and unfunctionalized dicarboxylate linkers. The postsynthetic metalation of these MOFs with [Ir(COD)(OMe)]2 provided Ir-functionalized MOFs (BPV-MOF-Ir, mBPV-MOF-Ir, and mPT-MOF-Ir), which are highly active catalysts for tandem hydrosilylation of aryl ketones and aldehydes followed by dehydrogenative ortho-silylation of benzylicsilyl ethers as well as C-H borylation of arenes using B2pin2. Both mBPV-MOF-Ir and mPT-MOF-Ir catalysts displayed superior activities compared to BPV-MOF-Ir due to the presence of larger open channels in the mixed-linker MOFs. Impressively, mBPV-MOF-Ir exhibited high TONs of up to 17,000 for C-H borylation reactions and was recycled more than 15 times. The mPT-MOF-Ir system is also active in catalyzing tandem dehydrosilylation/dehydrogenative cyclization of N-methylbenzyl amines to azasilolanes in the absence of a hydrogen acceptor. Importantly, MOF-Ir catalysts are significantly more active (up to 95 times) and stable than their homogeneous counterparts for all three reactions, strongly supporting the beneficial effects of active site isolation within MOFs. This work illustrates the ability to increase MOF open channel sizes by using the mixed linker approach and shows the enormous potential of developing highly active and robust single-site solid catalysts based on MOFs containing nitrogen-donor ligands for important organic transformations. PMID:25640998

  3. C-H arylations of 1,2,3-triazoles by reusable heterogeneous palladium catalysts in biomass-derived γ-valerolactone.

    PubMed

    Tian, Xu; Yang, Fanzhi; Rasina, Dace; Bauer, Michaela; Warratz, Svenja; Ferlin, Francesco; Vaccaro, Luigi; Ackermann, Lutz

    2016-07-28

    C-H arylations were accomplished with a user-friendly heterogeneous palladium catalyst in the biomass-derived γ-valerolactone (GVL) as an environmentally-benign reaction medium. The user-friendly protocol was characterized by ample substrate scope and high functional group tolerance in the C-H arylation of 1,2,3-triazoles, and the palladium catalyst could be recycled and reused in the C-H activation process. PMID:27419251

  4. Haemocompatibility of hydrogenated amorphous carbon (a-C:H) films synthesized by plasma immersion ion implantation-deposition

    NASA Astrophysics Data System (ADS)

    Yang, P.; Kwok, S. C. H.; Chu, P. K.; Leng, Y. X.; Chen, J. Y.; Wang, J.; Huang, N.

    2003-05-01

    Diamond-like-carbon has attracted much attention recently as a potential biomaterial in blood contacting biomedical devices. However, previous reports in this area have not adequately addressed the biocompatibility and acceptability of the materials in blood contacting applications. In this study, hydrogenated amorphous carbon (a-C:H) films were fabricated on silicon wafers (1 0 0) using plasma immersion ion implantation-deposition. A series of a-C:H films with different structures and chemical bonds were fabricated under different substrate voltages. The results indicate that film graphitization is promoted at higher substrate bias. The film deposited at a lower substrate bias of -75 V possesses better blood compatibility than the films at higher bias and stainless steel. Our results suggest two possible paths to improve the blood compatibility, suppression of the endogenic clotting system and reduction of platelet activation.

  5. Palladium-Catalyzed Carbonylative Cyclization of Arenes by C-H Bond Activation with DMF as the Carbonyl Source.

    PubMed

    Chen, Jianbin; Feng, Jian-Bo; Natte, Kishore; Wu, Xiao-Feng

    2015-11-01

    A novel palladium-catalyzed CO-gas- and autoclave-free protocol for the synthesis of 11H-pyrido[2,1-b]quinazolin-11-ones has been developed. Quinazolinones, which are omnipresent motif in many pharmaceuticals and agrochemicals, were prepared in good yields by C-H bond activation and annulation using DMF as the CO surrogate. A (13) CO-labelled DMF control experiment demonstrated that CO gas was released from the carbonyl of DMF with acid as the promotor. The kinetic isotope effect (KIE) value indicated that the C-H activation step may not be involved in the rate-determining step. This methodology is operationally simple and showed a broad substrate scope with good to excellent yields. PMID:26406903

  6. Erosion of a-C:H films deposited on W, Mo, and stainless steel under interaction with air glow discharge

    NASA Astrophysics Data System (ADS)

    Zalavutdinov, R. Kh.; Gorodetsky, A. E.; Bukhovets, V. L.; Zakharov, A. P.; Mazul, I. V.

    2011-08-01

    An air direct current glow discharge with a hollow cathode was used as source of chemically active oxygen for selective removal of amorphous hydrogenated (a-C:H) films deposited on W, Mo, and stainless steel. The films were removed both directly in the discharge and afterglow region. The film erosion rates depend on the sample position relatively to plasma and decrease in the order: hollow cathode, positive column, afterglow region. It was shown that primary (1-3 nm) continuous amorphous and secondary (1-30 nm) island-like oxide films were formed on the metal surfaces after removal of the a-C:H films. Polycrystalline island-like oxide films were generated due to recrystallization of the primary films. Material oxidation suppression was caused by reactions of oxygen ion neutralization and atomic oxygen recombination on metals.

  7. C-H bond activation with actinides: The first example of intramolecular ring bite of a pentamethylcyclopentadienyl methyl group

    SciTech Connect

    Peters, R.G.; Warner, B.P.; Scott, B.L.; Burns, C.J.

    1999-07-05

    Thermolysis of (C{sub 5}Me{sub 5}){sub 2}U({double_bond}NAd){sub 2}, 1 (Ad = 1-adamantyl), in benzene or hexane results in the intramolecular C-H bond activation of a methyl group on a pentamethylcyclopentadienyl ligand across the two imido functional groups. The product of this reaction has been spectroscopically and structurally characterized. The activation product is a reduced U(IV) metallocene bis(amide) complex with an N-bound methylene unit derived from the methyl group attached to one amide group. The activation parameters for this process have been determined; the results are consistent with a simple unimolecular process. This is the first example of intramolecular activation of a (C{sub 5}Me{sub 5}) methyl C-H bond in an actinide complex.

  8. Hydrostatic Pressure Studies Distinguish Global from Local Protein Motions in C-H Activation by Soybean Lipoxygenase-1.

    PubMed

    Hu, Shenshen; Cattin-Ortolá, Jérôme; Munos, Jeffrey W; Klinman, Judith P

    2016-08-01

    The proposed contributions of distinct classes of local versus global protein motions during enzymatic bond making/breaking processes has been difficult to verify. We employed soybean lipoxygenase-1 as a model system to investigate the impact of high pressure at variable temperatures on the hydrogen-tunneling properties of the wild-type protein and three single-site mutants. For all variants, pressure dramatically elevates the enthalpies of activation for the C-H activation. In contrast, the primary kinetic isotope effects (KIEs) for C-H activation and their corresponding temperature dependencies remain unchanged up to ca. 700 bar. The differential impact of elevated hydrostatic pressure on the temperature dependencies of rate constants versus substrate KIEs provides direct evidence for two distinct classes of protein motions: local, isotope-dependent donor-acceptor distance-sampling modes, and a more global, isotope-independent search for productive protein conformational sub-states. PMID:27348724

  9. The Breathing Orbital Valence Bond Method in Diffusion Monte Carlo: C-H Bond Dissociation ofAcetylene

    SciTech Connect

    Domin, D.; Braida, Benoit; Lester Jr., William A.

    2008-05-30

    This study explores the use of breathing orbital valence bond (BOVB) trial wave functions for diffusion Monte Carlo (DMC). The approach is applied to the computation of the carbon-hydrogen (C-H) bond dissociation energy (BDE) of acetylene. DMC with BOVB trial wave functions yields a C-H BDE of 132.4 {+-} 0.9 kcal/mol, which is in excellent accord with the recommended experimental value of 132.8 {+-} 0.7 kcal/mol. These values are to be compared with DMC results obtained with single determinant trial wave functions, using Hartree-Fock orbitals (137.5 {+-} 0.5 kcal/mol) and local spin density (LDA) Kohn-Sham orbitals (135.6 {+-} 0.5 kcal/mol).

  10. Ortho-Functionalized Aryltetrazines by Direct Palladium-Catalyzed C-H Halogenation: Application to Fast Electrophilic Fluorination Reactions.

    PubMed

    Testa, Christelle; Gigot, Élodie; Genc, Semra; Decréau, Richard; Roger, Julien; Hierso, Jean-Cyrille

    2016-04-25

    A general catalyzed direct C-H functionalization of s-tetrazines is reported. Under mild reaction conditions, N-directed ortho-C-H activation of tetrazines allows the introduction of various functional groups, thus forming carbon-heteroatom bonds: C-X (X=I, Br, Cl) and C-O. Based on this methodology, we developed electrophilic mono- and poly-ortho-fluorination of tetrazines. Microwave irradiation was optimized to afford fluorinated s-aryltetrazines, with satisfactory selectivity, within only ten minutes. This work provides an efficient and practical entry for further accessing highly substituted tetrazine derivatives (iodo, bromo, chloro, fluoro, and acetate precursors). It gives access to ortho-functionalized aryltetrazines which are difficult to obtain by classical Pinner-like syntheses. PMID:27010438

  11. Material properties and device evaluations of ECR-deposited a-Si:H and a-SiC:H films

    NASA Technical Reports Server (NTRS)

    Shing, Y. H.; Pool, F. S.; Essick, J. M.

    1991-01-01

    Device-quality a-Si:H and a-SiC:H films have been deposited using electron cyclotron resonance (ECR) microwave plasmas of SiH4, CH4, and H2 mixtures. Typical material properties of ECR-deposited, photosensitive a-Si:H films are: (1) high photosensitivity up to 2 x 106 with a photoconductivity of 10 exp -5 to 10 exp -4/(Ohm-cm), (2) a Tauc gap of 1.75 to 1.85 eV, (3) an Urbach slope of 50-60 meV determined by the constant photocurrent method, and (4) an integrated defect density of 1-2 x 10 exp 16/cu cm determined by junction capacitance measurements. Highly conductive, p-type a-SiC:H films have been produced by ECR plasmas with a conductivity of 0.2/(Ohm-cm).

  12. Conserved cryptic recombination signals in Vκ gene segments are cleaved in small pre-B cells

    PubMed Central

    Lieberman, Anne E; Kuraoka, Masayuki; Davila, Marco; Kelsoe, Garnett; Cowell, Lindsay G

    2009-01-01

    Background The cleavage of recombination signals (RS) at the boundaries of immunoglobulin V, D, and J gene segments initiates the somatic generation of the antigen receptor genes expressed by B lymphocytes. RS contain a conserved heptamer and nonamer motif separated by non-conserved spacers of 12 or 23 nucleotides. Under physiologic conditions, V(D)J recombination follows the "12/23 rule" to assemble functional antigen-receptor genes, i.e., cleavage and recombination occur only between RS with dissimilar spacer types. Functional, cryptic RS (cRS) have been identified in VH gene segments; these VH cRS were hypothesized to facilitate self-tolerance by mediating VH → VHDJH replacements. At the Igκ locus, however, secondary, de novo rearrangements can delete autoreactive VκJκ joins. Thus, under the hypothesis that V-embedded cRS are conserved to facilitate self-tolerance by mediating V-replacement rearrangements, there would be little selection for Vκ cRS. Recent studies have demonstrated that VH cRS cleavage is only modestly more efficient than V(D)J recombination in violation of the 12/23 rule and first occurs in pro-B cells unable to interact with exogenous antigens. These results are inconsistent with a model of cRS cleavage during autoreactivity-induced VH gene replacement. Results To test the hypothesis that cRS are absent from Vκ gene segments, a corollary of the hypothesis that the need for tolerizing VH replacements is responsible for the selection pressure to maintain VH cRS, we searched for cRS in mouse Vκ gene segments using a statistical model of RS. Scans of 135 mouse Vκ gene segments revealed highly conserved cRS that were shown to be cleaved in the 103/BCL2 cell line and mouse bone marrow B cells. Analogous to results for VH cRS, we find that Vκ cRS are conserved at multiple locations in Vκ gene segments and are cleaved in pre-B cells. Conclusion Our results, together with those for VH cRS, support a model of cRS cleavage in which cleavage is

  13. Cleaving the Halqeh-ye-nur diamonds: a dynamic fracture analysis

    PubMed Central

    Atkinson, Colin; Martineau, Philip M.; Khan, Rizwan U. A.; Field, John E.; Fisher, David; Davies, Nick M.; Samartseva, Julia V.; Putterman, Seth J.; Hird, Jonathan R.

    2015-01-01

    The degree of surface roughness and clarity with which a surface in a brittle material can be formed via fracture is known to be related to the speed of the propagating crack. Cracks traversing a brittle material at low speed produce very smooth surfaces, while those propagating faster create less reflective and rough surfaces (Buehler MJ, Gao H. 2006 Nature 439, 307–310 (doi:10.1038/nature04408)). The elastic wave speeds (cl≈18 000 m s−1, cs≈11 750 m s−1) in diamond are fast (Willmott GR, Field JE. 2006 Phil. Mag. 86, 4305–4318 (doi:10.1080/14786430500482336)) and present a particular problem in creating smooth surfaces during the cleaving of diamond—a routine operation in the fashioning of diamonds for gemstone purposes—as the waves are reflected from the boundaries of the material and can add a tensile component to the propagating crack tip causing the well-known cleavage steps observed on diamond surfaces (Field JE. 1971 Contemp. Phys. 12, 1–31 (doi:10.1080/00107517108205103); Field JE. 1979 Properties of diamond, 1st edn, Academic Press; Wilks EM. 1958 Phil. Mag. 3, 1074–1080 (doi:10.1080/14786435808237036)). Here we report an analysis of two diamonds, having large dimensions and high aspect ratio, which from a gemological analysis are shown to have been cleaved from the same 200 carat specimen. A methodology for their manufacture is calculated by an analysis of a model problem. This takes into account the effect of multiple reflections from the sample boundaries. It is suggested that the lapidary had an intuitive guide to how to apply the cleavage force in order to control the crack speed. In particular, it is shown that it is likely that this technique caused the fracture to propagate at a lower speed. The sacrifice of a large diamond with the intention of creating thin plates, rather than a faceted gemstone, demonstrates how symbolism and beliefs associated with gemstones have changed over the centuries (Harlow GE. 1998 The

  14. Porphyromonas gingivalis Type IX Secretion Substrates Are Cleaved and Modified by a Sortase-Like Mechanism

    PubMed Central

    Chen, Dina; Seers, Christine A.; Mitchell, Helen A.; Chen, Yu-Yen; Glew, Michelle D.; Dashper, Stuart G.; Reynolds, Eric C.

    2015-01-01

    The type IX secretion system (T9SS) of Porphyromonas gingivalis secretes proteins possessing a conserved C-terminal domain (CTD) to the cell surface. The C-terminal signal is essential for these proteins to translocate across the outer membrane via the T9SS. On the surface the CTD of these proteins is cleaved prior to extensive glycosylation. It is believed that the modification on these CTD proteins is anionic lipopolysaccharide (A-LPS), which enables the attachment of CTD proteins to the cell surface. However, the exact site of modification and the mechanism of attachment of CTD proteins to the cell surface are unknown. In this study we characterized two wbaP (PG1964) mutants that did not synthesise A-LPS and accumulated CTD proteins in the clarified culture fluid (CCF). The CTDs of the CTD proteins in the CCF were cleaved suggesting normal secretion, however, the CTD proteins were not glycosylated. Mass spectrometric analysis of CTD proteins purified from the CCF of the wbaP mutants revealed the presence of various peptide/amino acid modifications from the growth medium at the C-terminus of the mature CTD proteins. This suggested that modification occurs at the C-terminus of T9SS substrates in the wild type P. gingivalis. This was confirmed by analysis of CTD proteins from wild type, where a 648 Da linker was identified to be attached at the C-terminus of mature CTD proteins. Importantly, treatment with proteinase K released the 648 Da linker from the CTD proteins demonstrating a peptide bond between the C-terminus and the modification. Together, this is suggestive of a mechanism similar to sortase A for the cleavage and modification/attachment of CTD proteins in P. gingivalis. PG0026 has been recognized as the CTD signal peptidase and is now proposed to be the sortase-like protein in P. gingivalis. To our knowledge, this is the first biochemical evidence suggesting a sortase-like mechanism in Gram-negative bacteria. PMID:26340749

  15. Determination of surface structure of cleaved (001) USb2 single crystal

    SciTech Connect

    Chen, Shao-ping; Hawley, Marilyn; Bauer, Eric D; Stockum, Phil B; Manoharan, Hari C

    2009-01-01

    We have achieved what we believe to be the first atomic resolution STM images for a uranium compound taken at room temperature. The a, b, and c lattice parameters in the images confirm that the USb{sub 2} crystals cleave on the (001) basal plane as expected. The a and b dimensions were equal, with the atoms arranged in a cubic pattern. Our calculations indicate a symmetric cut between Sb planes to be the most favorable cleavage plane and U atoms to be responsible for most of the DOS measured by STM. Some strange features associated with vacancies were observed in the STM win be discussed in conjunction with ab initio calculations. The purpose of this work is to demonstrate the power of scanning tunneling microscopy (STM) techniques combined with a theoretical underpinning to determine the surface atomic structure and properties of actinide materials, such as the quasi 2-dimensional uranium dipnictide USb{sub 2} single crystal, thereby contributing to the understanding of their surface structural and electronic properties. The members of this interesting UX{sub 2} (X=P, As, Sb, Bi) series of compounds display dual localized and itinerant 5f electron behavior within the same compound due to the hybridization of the 5f orbitals with the conduction band. With the exception of UO{sub 2}, which has to be studied at elevated temperature to generate enough carriers for STM imaging, STM techniques have not been applied successfully to the characterization of the surface atomic structure of any other single crystal actinide compound, to the best of our knowledge. However, STM has been used to a limited extent for the study of some cerium compounds. STM probes electronic properties at the atomic level and can directly provide information about the local density of filled and empty states (LDOS) states simultaneously. A STM topograph provides the local atomic arrangement and spacing of the atoms on the surface, local defect structures (e.g. steps, vacancies, and kink sites

  16. Cleaving the Halqeh-ye-nur diamonds: a dynamic fracture analysis.

    PubMed

    Atkinson, Colin; Martineau, Philip M; Khan, Rizwan U A; Field, John E; Fisher, David; Davies, Nick M; Samartseva, Julia V; Putterman, Seth J; Hird, Jonathan R

    2015-03-28

    The degree of surface roughness and clarity with which a surface in a brittle material can be formed via fracture is known to be related to the speed of the propagating crack. Cracks traversing a brittle material at low speed produce very smooth surfaces, while those propagating faster create less reflective and rough surfaces (Buehler MJ, Gao H. 2006 Nature 439, 307-310 (doi:10.1038/nature04408)). The elastic wave speeds (c(l)≈18 000 m s(-1), c(s)≈11 750 m s(-1)) in diamond are fast (Willmott GR, Field JE. 2006 Phil. Mag. 86, 4305-4318 (doi:10.1080/14786430500482336)) and present a particular problem in creating smooth surfaces during the cleaving of diamond-a routine operation in the fashioning of diamonds for gemstone purposes--as the waves are reflected from the boundaries of the material and can add a tensile component to the propagating crack tip causing the well-known cleavage steps observed on diamond surfaces (Field JE. 1971 Contemp. Phys. 12, 1-31 (doi:10.1080/00107517108205103); Field JE. 1979 Properties of diamond, 1st edn, Academic Press; Wilks EM. 1958 Phil. Mag. 3, 1074-1080 (doi:10.1080/14786435808237036)). Here we report an analysis of two diamonds, having large dimensions and high aspect ratio, which from a gemological analysis are shown to have been cleaved from the same 200 carat specimen. A methodology for their manufacture is calculated by an analysis of a model problem. This takes into account the effect of multiple reflections from the sample boundaries. It is suggested that the lapidary had an intuitive guide to how to apply the cleavage force in order to control the crack speed. In particular, it is shown that it is likely that this technique caused the fracture to propagate at a lower speed. The sacrifice of a large diamond with the intention of creating thin plates, rather than a faceted gemstone, demonstrates how symbolism and beliefs associated with gemstones have changed over the centuries (Harlow GE. 1998 The nature

  17. Aspects of C-H Activation in Metal Complexes Containing Sulfur Ligands

    SciTech Connect

    Rakowski-DuBois, Mary C.

    2004-10-08

    those of related Cp-molybdenum complexes with sulfide ligands, which also activate hydrogen, but generally form hydrosulfido products without H2S elimination. C-H and C-S Cleavage Reactions. New mononuclear Cp{prime}Re(dithiolate) complexes such as Cp{prime}ReCl2(SC2H4S), 1, have been prepared and characterized and have been found to display a very interesting range of reactions. The thermal reaction of 1 involves the dehydrogenation of the alkanedithiolate ligand to form Cp{prime}ReCl2(SCH=CHS), 2 as well as a competing elimination of olefin from the dithiolate ligand in 1. On the basic of kinetic and related studies, the mechanism is proposed to involve a sequential series of reactions. In the first reaction, the olefin extrusion is proposed to produce a reactive Re-disulfide or Re-bis(sulfido) intermediate, CpReCl2S2 which serves as an oxidant for the dithiolate complex 1. The ability of the bis sulfido complex to dehydrogenate hydrocarbons is a unique feature and several additional dehydrogenation reactions with this system have been characterized, including the oxidation of other dithiolate complexes, of tetrahydro-naphthalene and of cyclohexadiene. Precedents for the role of metal sulfides in dehydrogenation reactions have been reported for heterogeneous metal sulfide surfaces. This work has begun to provide information about the electronic and structural features necessary for such reactivity. Carbon Sulfur Bond Formation. When the thermal reaction of 1 was carried out in the presence of excess dry ethene a new reaction was observed in which the dithiolate ligand is displaced by incoming olefin to form the cyclic organic product, 1,4-dithiane. The Re product is identified as Cp{prime}Re(alkene)Cl2 on the basis of NMR and mass spectroscopic data. Similar reactions with alkynes have been found to form unsaturated 6-membered rings and reactions with 1,3 dithiolate complexes form the organic 7-membered rings. To our knowledge the formation of cyclic bis-thioethers by

  18. Copper-catalyzed domino synthesis of quinazolinones via Ullmann-type coupling and aerobic oxidative C-H amidation.

    PubMed

    Xu, Wei; Jin, Yibao; Liu, Hongxia; Jiang, Yuyang; Fu, Hua

    2011-03-18

    An efficient copper-catalyzed approach to quinazolinone derivatives has been developed, and the protocol uses cheap and readily available substituted 2-halobenzamides and (aryl)methanamines as the starting materials as well as economical and environmentally friendly air as the oxidant. This can be the first example of constructing N-heterocycles via sequential Ullmann-type coupling under air and aerobic oxidative C-H amidation. PMID:21344914

  19. A photosensitizing decatungstate-based MOF as heterogeneous photocatalyst for the selective C-H alkylation of aliphatic nitriles.

    PubMed

    Shi, Dongying; He, Cheng; Sun, Wenlong; Ming, Zheng; Meng, Changgong; Duan, Chunying

    2016-03-17

    The efficient photosensitizing of decatungstate-based MOF with 1D channels was achieved via in situ synthesis under solvothermal conditions for light driven acceleration of β- or γ-site C-H alkylation of aliphatic nitriles. The high catalytic efficiency, excellent size selectivity, high stability and good recyclability of the photocatalyst offer an environmentally-friendly route for widening the scope of accessible nitriles in both laboratory and industry. PMID:26954389

  20. Catalytic Reductive ortho-C-H Silylation of Phenols with Traceless, Versatile Acetal Directing Groups and Synthetic Applications of Dioxasilines.

    PubMed

    Hua, Yuanda; Asgari, Parham; Avullala, Thirupataiah; Jeon, Junha

    2016-06-29

    A new, highly selective, bond functionalization strategy, achieved via relay of two transition metal catalysts and the use of traceless acetal directing groups, has been employed to provide facile formation of C-Si bonds and concomitant functionalization of a silicon group in a single vessel. Specifically, this approach involves the relay of Ir-catalyzed hydrosilylation of inexpensive and readily available phenyl acetates, exploiting disubstituted silyl synthons to afford silyl acetals and Rh-catalyzed ortho-C-H silylation to provide dioxasilines. A subsequent nucleophilic addition to silicon removes the acetal directing groups and directly provides unmasked phenol products and, thus, useful functional groups at silicon achieved in a single vessel. This traceless acetal directing group strategy for catalytic ortho-C-H silylation of phenols was also successfully applied to preparation of multisubstituted arenes. Remarkably, a new formal α-chloroacetyl directing group has been developed that allows catalytic reductive C-H silylation of sterically hindered phenols. In particular, this new method permits access to highly versatile and nicely differentiated 1,2,3-trisubstituted arenes that are difficult to access by other catalytic routes. In addition, the resulting dioxasilines can serve as chromatographically stable halosilane equivalents, which allow not only removal of acetal directing groups but also introduce useful functional groups leading to silicon-bridged biaryls. We demonstrated that this catalytic C-H bond silylation strategy has powerful synthetic potential by creating direct applications of dioxasilines to other important transformations, examples of which include aryne chemistry, Au-catalyzed direct arylation, sequential orthogonal cross-couplings, and late-stage silylation of phenolic bioactive molecules and BINOL scaffolds. PMID:27265033

  1. Rhodium- and iridium-catalyzed dehydrogenative cyclization through double C-H bond cleavages to produce fluorene derivatives.

    PubMed

    Itoh, Masaki; Hirano, Koji; Satoh, Tetsuya; Shibata, Yu; Tanaka, Ken; Miura, Masahiro

    2013-02-15

    The rhodium-catalyzed cyclization of a series of 2,2-diarylalkanoic acids in the presence of copper acetate as an oxidant smoothly proceeded through double C-H bond cleavages and subsequent decarboxylation to produce the corresponding fluorene derivatives. The direct cyclization of triarylmethanols also took place efficiently by using an iridium catalyst in place of the rhodium, while the hydroxy function was still intact. PMID:23360206

  2. Palladium-Catalyzed Highly Chemoselective Intramolecular C-H Aminocarbonylation of Phenethylamines to Six-Membered Benzolactams.

    PubMed

    Taneda, Hiroshi; Inamoto, Kiyofumi; Kondo, Yoshinori

    2016-06-01

    A palladium-catalyzed highly selective intramolecular C-H aminocarbonylation of Br-functionalized phenethylamines in the presence of CO was achieved while leaving the C-Br bond unreacted to afford six-membered benzolactams with good to high yields. The remaining C-Br group in the cyclized product was successfully used as a reactive center for further functionalization through various palladium-catalyzed coupling reactions. PMID:27214155

  3. Rhodium(III)-Catalyzed Mild Alkylation of (Hetero)Arenes with Cyclopropanols via C-H Activation and Ring Opening.

    PubMed

    Zhou, Xukai; Yu, Songjie; Qi, Zisong; Kong, Lingheng; Li, Xingwei

    2016-06-01

    The rhodium(III)-catalyzed regioselective alkylation of (hetero)arenes using cyclopropanols as a reactive and efficient coupling partner under oxidative conditions has been developed. This coupling occurred at room temperature via C-H activation of arenes and C-C cleavage of cyclopropanols. Various types of (hetero)arenes (indolines, carbazole, tetrahydrocarbazole, pyrrole, thiophene, etc.) were all successfully reacted under the present conditions. This protocol provides the facile and efficient construction of C7-alkylated indoline scaffolds. PMID:27166521

  4. Rh- and Cu-Cocatalyzed Aerobic Oxidative Approach to Quinazolines via [4 + 2] C-H Annulation with Alkyl Azides.

    PubMed

    Wang, Xiaoyang; Jiao, Ning

    2016-05-01

    A novel and efficient rhodium- and copper-co-catalyzed C-H bond activation and annulation for the construction of bioactively important quinazolines has been developed. This [4 + 2] annulation strategy utilizing alkyl azides as the carbon-heteroatom synthons shows high efficiency in the synthesis of six-membered benzoheterocycles containing two heteroatoms. This aerobic oxidative protocol provides a useful application of simple alkyl azides in N-heterocycle synthesis with N2 and H2O as byproducts. PMID:27081916

  5. Decoding of B.C.H. and R.S. codes with errors and erasures using continued fractions

    NASA Technical Reports Server (NTRS)

    Reed, I. S.; Truong, T. K.; Miller, R. L.

    1979-01-01

    Through the use of continuing fractions, a simplified algorithm for decoding B.C.H. and R.S. codes is developed that corrects both erasures and errors on a finite field GF(q to the m). It is noted that the decoding method is a modification of the Forney-Belekamp technique. Finally, it is believed that the present scheme is both simpler to understand and to implement than more conventional algorithms.

  6. Tandem Rh(III)-Catalyzed C-H Amination/Annulation Reactions: Synthesis of Indoloquinoline Derivatives in Water.

    PubMed

    Shi, Liangliang; Wang, Baiquan

    2016-06-17

    An efficient Rh(III)-catalyzed synthetic method for indoloquinoline derivatives from readily available indoles and isoxazoles was developed. This annulation procedure undergoes tandem C-H activation, cyclization, and condensation steps. In this domino cyclization reaction, water is an efficient solvent. A catalytically competent five-membered rhodacycle has been isolated and characterized, thus revealing a key intermediate in the catalytic cycle. PMID:27266834

  7. Palladium-Catalyzed Site-Selective C-H Functionalization of Weakly Coordinating Sulfonamides: Synthesis of Biaryl Sulfonamides.

    PubMed

    Vanjari, Rajeshwer; Guntreddi, Tirumaleswararao; Singh, Krishna Nand

    2016-03-01

    A novel and site selective C-H functionalization of unsubstituted sulfonamides has been developed for the synthesis of ortho aryl sulfonamides. The reaction involves highly regioselective ortho mono arylation of weakly coordinating SO2 NH2 directing group by means of aryl iodides. Palladium acetate in the presence of silver(I) oxide is found to be the most effective catalytic system. PMID:26763530

  8. The Z' = 12 superstructure of Λ-cobalt(III) sepulchrate trinitrate governed by C-H...O hydrogen bonds.

    PubMed

    Dey, Somnath; Schönleber, Andreas; Mondal, Swastik; Prathapa, Siriyara Jagannatha; van Smaalen, Sander; Larsen, Finn Krebs

    2016-06-01

    Λ-Cobalt(III) sepulchrate trinitrate crystallizes in P6322 with Z = 2 (Z' = 1/6) at room temperature. Slabs perpendicular to the hexagonal axis comprise molecules Co(sepulchrate) alternating with nitrate groups A and B. Coordinated by six sepulchrate molecules, highly disordered nitrate groups C are accommodated between the slabs. Here we report the fully ordered, low-temperature crystal structure of Co(sep)(NO3)3. It is found to be a high-Z' structure with Z' = 12 of the 12-fold 6a_{h}\\times\\sqrt{3}b_{h}\\times c_{h} superstructure with monoclinic symmetry P21 (c unique). Correlations between structural parameters are effectively removed by refinements within the superspace approach. Superstructure formation is governed by a densification of the packing in conjunction with ordering of nitrate group C, the latter assuming different orientations for each of the Z' = 12 independent copies in the superstructure. The Co(sep) moiety exhibits small structural variations over its 12 independent copies, while orientations of nitrate groups A and B vary less than the orientations of the nitrate group C do. Molecular packing in the superstructure is found to be determined by short C-H...H-C contacts, with H...H distances of 2.2-2.3 Å, and by short C-H...O contacts, with H...O distances down to 2.2 Å. These contacts presumably represent weak C-H...O hydrogen bonds, but in any case they prevent further densification of the structure and strengthening of weak N-H...O hydrogen bonds with observed H...O distances of 2.4-2.6 Å. PMID:27240768

  9. Iron-mediated oxidative C-H coupling of arenes and alkenes directed by sulfur: an expedient route to dihydrobenzofurans.

    PubMed

    Cavanagh, Craig W; Aukland, Miles H; Laurent, Quentin; Hennessy, Alan; Procter, David J

    2016-06-21

    A novel route to medicinally-relevant dihydrobenzofurans utilises a sulfur-directed C-H ortho-coupling of arenes and unactivated terminal alkenes mediated by iron, and a palladium-catalysed deallylation/heterocyclisation sequence. The iron-mediated coupling affords linear products of alkene chloroarylation in good yield and with complete regioselectivity. The coupling likely proceeds by redox-activation of the arene partner by iron(iii) and alkene addition to the resultant radical cation. PMID:27198174

  10. More insights into the ZnO/a-SiC:H(B) interface -- an improved TCO/p contact

    SciTech Connect

    Boehmer, E.; Siebke, F.; Rech, B.; Beneking, C.; Wagner, H.

    1996-12-31

    Solar cells based on amorphous silicon (a-Si:H) exhibit a decreased fill factor if ZnO is used as front electrode instead of SnO{sub 2} This is due to a poor electric contact between the ZnO and the p-type a-SiC:H(B) layer. To gain a deeper understanding of the chemical and electronic properties of the ZnO/p interface, in-situ XPS measurements were applied to thin a-SiC:H(B) films deposited on ZnO. The effects of CO{sub 2} and H{sub 2} plasma pretreatments on clean ZnO surfaces and the influence of deposition conditions on the ZnO/a-SiC:H interface were investigated. Upon H{sub 2} plasma treatment the formation of SiO{sub x} by chemical transport of Si from the reactor walls is observed. Furthermore, a shift of all core levels towards higher binding energies indicates the formation of an accumulation layer. CO{sub 2} plasma treatments show no effects on ZnO. Depth profiling across the ZnO/a-SiC:H interface indicates SiO{sub 2} formation on ZnO. The depth profile of ZnO related core levels exhibits two features: a reduction of the ZnO at the interface, and, after longer sputter times, a core level shift towards higher binding energy due to an hydrogen induced accumulation layer in the n-type ZnO. The latter causes a depletion of the p-layer resulting in an enhanced series resistance and diminished fill factor. To reduce the depletion layer thin highly conductive microcrystalline layers were introduced, increasing the fill factor up to 74%.

  11. Effect of CO on the oxidative addition of arene C-H bonds by cationic rhodium complexes.

    PubMed

    Montag, Michael; Efremenko, Irena; Cohen, Revital; Shimon, Linda J W; Leitus, Gregory; Diskin-Posner, Yael; Ben-David, Yehoshoa; Salem, Hiyam; Martin, Jan M L; Milstein, David

    2010-01-01

    Sequential addition of CO molecules to cationic aryl-hydrido Rh(III) complexes of phosphine-based (PCP) pincer ligands was found to lead first to C-H reductive elimination and then to C-H oxidative addition, thereby demonstrating a dual role of CO. DFT calculations indicate that the oxidative addition reaction is directly promoted by CO, in contrast to the commonly accepted view that CO hinders such reactions. This intriguing effect was traced to repulsive pi interactions along the aryl-Rh-CO axis, which are augmented by the initially added CO ligand (due to antibonding interactions between occupied Rh d(pi) orbitals and occupied pi orbitals of both CO and the arene moiety), but counteracted by the second CO ligand (due to significant pi back-donation). These repulsive interactions were themselves linked to significant weakening of the pi-acceptor character of CO in the positively charged rhodium complexes, which is concurrent with an enhanced sigma-donating capability. Replacement of the phosphine ligands by an analogous phosphinite-based (POCOP) pincer ligand led to significant changes in reactivity, whereby addition of CO did not result in C-H reductive elimination, but yielded relatively stable mono- and dicarbonyl aryl-hydrido POCOP-Rh(III) complexes. DFT calculations showed that the stability of these complexes arises from the higher electrophilicity of the POCOP ligand, relative to PCP, which leads to partial reduction of the excessive pi-electron density along the aryl-Rh-CO axis. Finally, comparison between the effects of CO and acetonitrile on C-H oxidative addition revealed that they exhibit similar reactivity, despite their markedly different electronic properties. However, DFT calculations indicate that the two ligands operate by different mechanisms. PMID:19918810

  12. Carboxylate-Assisted Iridium-Catalyzed C-H Amination of Arenes with Biologically Relevant Alkyl Azides.

    PubMed

    Zhang, Tao; Hu, Xuejiao; Wang, Zhen; Yang, Tiantian; Sun, Hao; Li, Guigen; Lu, Hongjian

    2016-02-24

    An iridium-catalyzed C-H amination of arenes with a wide substrate scope is reported. Benzamides with electron-donating and -withdrawing groups and linear, branched, and cyclic alkyl azides are all applicable. Cesium carboxylate is crucial for both reactivity and regioselectivity of the reactions. Many biologically relevant molecules, such as amino acid, peptide, steroid, sugar, and thymidine derivatives can be introduced to arenes with high yields and 100 % chiral retention. PMID:26712274

  13. Up-scaling the production of modified a-C:H coatings in the framework of plasma polymerization processes

    NASA Astrophysics Data System (ADS)

    Corbella, C.; Bialuch, I.; Kleinschmidt, M.; Bewilogua, K.

    2009-10-01

    Hydrogenated amorphous carbon (a-C:H) films with silicon and oxygen additions, which exhibit mechanical, tribological and wetting properties adequate for protective coating performance, have been synthesized at room temperature in a small- (0.1 m 3) and a large-scale (1 m 3) coaters by low-pressure Plasma-Activated Chemical Vapour Deposition (PACVD). Hence, a-C:H:Si and a-C:H:Si:O coatings were produced in atmospheres of tetramethylsilane (TMS) and hexamethyldisiloxane (HMDSO), respectively, excited either by radiofrequency (RF - small scale) or by pulsed-DC power (large scale). Argon was employed as a carrier gas to stabilize the glow discharge. Several series of 2-5 μm thick coatings have been prepared at different mass deposition rates, Rm, by varying total gas flow, F, and input power, W. Arrhenius-type plots of Rm/ F vs. ( W/ F) -1 show linear behaviours for both plasma reactors, as expected for plasma polymerization processes at moderated energies. The calculation of apparent activation energy, Ea, in each series permitted us to define the regimes of energy-deficient and monomer-deficient PACVD processes as a function of the key parameter W/ F. Moreover, surface properties of the modified a-C:H coatings, such as contact angle, abrasive wear rate and hardness, appear also correlated to this parameter. This work shows an efficient methodology to scale up PACVD processes from small, lab-scale plasma machines to industrial plants by the unique evaluation of macroscopic parameters of deposition.

  14. Pd-catalyzed benzylic C-H amidation with benzyl alcohols in water: a strategy to construct quinazolinones.

    PubMed

    Hikawa, Hidemasa; Ino, Yukari; Suzuki, Hideharu; Yokoyama, Yuusaku

    2012-08-17

    A novel method for the synthesis of 4-phenylquinazolinones via a palladium-catalyzed domino reaction of o-aminobenzamides with benzyl alcohols is developed. This protocol involves N-benzylation, benzylic C-H amidation, and dehydrogenation in water, which may play an important role in the smooth generation of the (η(3)-benzyl)palladium species by activation of the hydroxyl group of the benzyl alcohol. PMID:22852777

  15. Iron(0) mediated C-H activation of 1-hexyne: a mechanistic study using time-resolved infrared spectroscopy.

    PubMed

    Blank, Jan H; Raju, Rajesh K; Yan, Tao; Brothers, Edward N; Darensbourg, Marcetta Y; Bengali, Ashfaq A

    2016-08-01

    Photolysis of an iron tricarbonyl complex in the presence of 1-hexyne results in the activation of the terminal C-H bond to yield an iron-alkynyl species. The reaction proceeds through a single transition state with an activation enthalpy of 13.5 kcal mol(-1). The resulting molecule may have potential as a C-C bond formation reagent. PMID:27436484

  16. Two-step C-H, C-P bond activation at an α-diimine iron dinitrogen complex.

    PubMed

    Ghosh, Chandrani; Groy, Thomas L; Bowman, Amanda C; Trovitch, Ryan J

    2016-03-15

    Reduction of 6-coordinate under N2 results in formation of the terminal dinitrogen complex, ((Ph2PPr)DI)FeN2. Heating this product to 75 °C allows for C-H and C-P activation of the chelate to generate the cisoid and transoid isomers of [(μ-PrPPh-κ(5)-P,N,N,Cγ,P-(Ph2PPr)DI(PrPPh))Fe]2. Mechanistic possibilities for this transformation are discussed. PMID:26939725

  17. Design and kinetic analysis of hammerhead ribozyme and DNAzyme that specifically cleave TEL-AML1 chimeric mRNA

    SciTech Connect

    Choi, Woo-Hyung; Choi, Bo-Ra; Kim, Jae Hyun; Yeo, Woon-Seok; Oh, Sangtaek; Kim, Dong-Eun

    2008-09-12

    In order to develop the oligonucleotides to abolish an expression of TEL-AML1 chimeric RNA, which is a genetic aberration that causes the acute lymphoblastic leukemia (ALL), hammerhead ribozymes and deoxyoligoribozymes that can specifically cleave TEL-AML1 fusion RNA were designed. Constructs of the deoxyribozyme with an asymmetric substrate binding arm (Dz26) and the hammerhead ribozyme with a 4 nt-bulged substrate binding arm in the stem III (buRz28) were able to cleave TEL-AML1 chimeric RNA specifically at sites close to the junction in vitro, without cleaving the normal TEL and AML1 RNA. Single-turnover kinetic analysis under enzyme-excess condition revealed that the buRz28 is superior to the Dz26 in terms of substrate binding and RNA-cleavage. In conjunction with current progress in a gene-delivery technology, the designed oligonucleotides that specifically cleave the TEL-AML1 chimeric mRNA are hoped to be applicable for the treatment of ALL in vivo.

  18. "Self-cleaving" 2A peptide from porcine teschovirus-1 mediates cleavage of dual fluorescent proteins in transgenic Eimeria tenella.

    PubMed

    Tang, Xinming; Liu, Xianyong; Tao, Geru; Qin, Mei; Yin, Guangwen; Suo, Jingxia; Suo, Xun

    2016-01-01

    The "self-cleaving" 2A sequence of picornavirus, which mediates ribosome-skipping events, enables the generation of two or more separate peptide products from one mRNA containing one or more "self-cleaving" 2A sequences. In this study, we introduced a single 2A sequence of porcine teschovirus-1 (P2A) linked to two fluorescent protein genes, the enhanced yellow fluorescent protein (EYFP) gene and the red fluorescent protein (RFP) gene, in a single cassette into transgenic Eimeria tenella (EtER). As expected, we obtained two separated protein molecules rather than a fused protein, although the two molecules were translated from the same mRNA carrying a single "self-cleaving" 2A sequence. Importantly, RFP led by a secretion signal was secreted into parasitophorous vacuoles, while EYFP localized mainly to the nucleus of EtER. Our results demonstrate that the "self-cleaving" 2A sequence actively mediated cleavage of polyproteins in the apicomplexan parasite E. tenella. PMID:27352927

  19. Polyglycine hydrolases: fungal b-lactamase-like endoproteases that cleave polyglycine regions within plant class IV chitinases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Polyglycine hydrolases are secreted fungal proteases that cleave glycine-glycine peptide bonds in the inter-domain linker region of specific plant defense chitinases. Previously, we reported the catalytic activity of polyglycine hydrolases from the phytopathogens Epicoccum sorghi (Es-cmp) and Cochli...

  20. Raman Spectroscopy of a-C:H Films Deposited Using Ar + H2 + C7H8 Plasma CVD

    NASA Astrophysics Data System (ADS)

    Dong, Xiao; Koga, Kazunori; Yamashita, Daisuke; Seo, Hyunwoong; Itagaki, Naho; Shiratani, Masaharu; Setsuhara, Yuichi; Sekine, Makoto; Hori, Masaru

    2015-09-01

    We investigated the effects of ion energy on Raman spectra of a-C:H films prepared by Ar + H2 + C7H8 plasma CVD. Raman spectra were measured with a laser Raman spectrometer (JASCO NRS-3100). Both the D-peak position and G-peak position shift toward higher wavenumbers as ion energy increases. The intensity ratio of the D-peak and G-peak, ID/IG increases with increasing the ion energy, indicating that the amount of ring-like sp2 clusters increases. The H content in a-C:H derived from photoluminescence (PL) background decreases with increasing the ion energy. The full width at half maximum of the G-peak, FWHMG related to the C-C sp3 content and H content increases with increasing the ion energy to 100 eV, whereas it decreases with increasing further the ion energy to 105 eV. The variation of FWHMG is consistent with that of mass density. There results indicate that the structure of a-C:H films transforms from polymer-like carbon to diamond-like one with increasing the ion energy above the threshold value of ~ 100 eV.

  1. Nuclear magnetic resonance studies of the interaction of FN-C/H II, a pentadecapeptide from fibronectin, with heparin

    SciTech Connect

    Hari, S.P.; Rabenstein, D.L.

    1995-12-01

    Arrest of circulating tumor cells by adhesion to components of the extracellular matrix (ECM) is a critical step in metastasis. Tumor cell adhesion involves the binding of cell surface receptors, including heparan sulfate proteoglycan (HSPG) receptors, to fibronectin and other proteins of the ECM. Interruption of tumor cell adhesion has therapeutic potential in metastasis prevention. The peptide FN-C/H II, a pentadecapeptide (KNNQKSEPLIGRKKT) from module III{sub 14} of fibronectin binds to the heparan sulfate part of HSPG on the surface of highly metastatic mouse melanoma cells, and inhibits experimental metastasis of the melanoma cells, presumably by inhibition of their arrest by competitive binding to cell surface receptor sites. In this poster, results of one and two dimensional NMR studies to characterize FN-C/H II and related peptides and their binding by heparin will be reported. Structural information obtained from NOESY spectra for FN-C/H II indicates that the peptide free in solution has little structure, but that the heparin-complexed peptide is highly structured. NOESY data for the bound peptide are consistent with a helical structure. In the helical structure, 3 of the 5 arginine and lysine residues are located together on one side, thus presenting a region of high positive charge density for binding to the highly negatively charged heparin.

  2. Structure and spectroscopic properties of neutral and cationic tetratomic [C,H,N,Zn] isomers: A theoretical study

    SciTech Connect

    Redondo, Pilar; Largo, Antonio; Vega-Vega, Álvaro; Barrientos, Carmen

    2015-05-14

    The structure and spectroscopic parameters of the most relevant [C,H,N,Zn] isomers have been studied employing high-level quantum chemical methods. For each isomer, we provide predictions for their molecular structure, thermodynamic stabilities as well as vibrational and rotational spectroscopic parameters which could eventually help in their experimental detection. In addition, we have carried out a detailed study of the bonding situations by means of a topological analysis of the electron density in the framework of the Bader’s quantum theory of atoms in molecules. The analysis of the relative stabilities and spectroscopic parameters suggests two linear isomers of the neutral [C,H,N,Zn] composition, namely, cyanidehydridezinc HZnCN ({sup 1}Σ) and hydrideisocyanidezinc HZnNC ({sup 1}Σ), as possible candidates for experimental detections. For the cationic [C,H,N,Zn]{sup +} composition, the most stable isomers are the ion-molecule complexes arising from the direct interaction of the zinc cation with either the nitrogen or carbon atom of either hydrogen cyanide or hydrogen isocyanide, namely, HCNZn{sup +} ({sup 2}Σ) and HCNZn{sup +} ({sup 2}Σ)

  3. Human Immunodeficiency Virus Integration Protein Expressed in Escherichia Coli Possesses Selective DNA Cleaving Activity

    NASA Astrophysics Data System (ADS)

    Sherman, Paula A.; Fyfe, James A.

    1990-07-01

    The human immunodeficiency virus (HIV) integration protein, a potential target for selective antiviral therapy, was expressed in Escherichia coli. The purified protein, free of detectable contaminating endonucleases, selectively cleaved double-stranded DNA oligonucleotides that mimic the U3 and the U5 termini of linear HIV DNA. Two nucleotides were removed from the 3' ends of both the U5 plus strand and the U3 minus strand; in both cases, cleavage was adjacent to a conserved CA dinucleotide. The reaction was metal-ion dependent, with a preference for Mn2+ over Mg2+. Reaction selectivity was further demonstrated by the lack of cleavage of an HIV U5 substrate on the complementary (minus) strand, an analogous substrate that mimics the U3 terminus of an avian retrovirus, and an HIV U5 substrate in which the conserved CA dinucleotide was replaced with a TA dinucleotide. Such an integration protein-mediated cleavage reaction is expected to occur as part of the integration event in the retroviral life cycle, in which a double-stranded DNA copy of the viral RNA genome is inserted into the host cell DNA.

  4. Development of an efficiently cleaved, bioactive, highly pure FLAG-tagged recombinant human Mullerian Inhibiting Substance

    PubMed Central

    Papakostas, Thanos D.; Pieretti-Vanmarcke, Rafael; Nicolaou, Fotini; Thanos, Aristomenis; Trichonas, George; Koufomichali, Xanthi; Anago, Kosisochukwu; Donahoe, Patricia K.; Teixeira, Jose; MacLaughlin, David T.; Vavvas, Demetrios

    2013-01-01

    Mullerian Inhibiting Substance (MIS), a member of the TGF-β family, causes regression of the Mullerian duct in male embryos, after binding to Mullerian Inhibiting Substance Receptor II (MISRII). It has also been extensively demonstrated that it can inhibit proliferation of various cancer cell lines such as ovarian, prostate, and breast cancer in vitro and in vivo. Hence, the availability of a recombinant, epitope tagged, bioactive MIS is important for the selection of patients for treatment and for probing novel molecular targets for MIS in various tissues. To this end, we have expressed a recombinant, internally FLAG-tagged form of hMIS with the tag (DYKDDDDK) immediately after the cleavage site (427–428) of MIS at the C-terminus with a modified dibasic cleavage motif sequence. We show that this construct results in a highly pure, endogenously processed (cleaved) FLAG MIS, that causes complete regression of the Mullerian Duct in an organ culture assay. In addition, purified FLAG MIS was able to bind and affinity purify both transfected and endogenous MIS type II receptor. The availability of this fully functional, epitope tagged form of MIS should facilitate scale-up for preclinical and clinical use and should also be used for the study of MIS binding proteins and for tracking in pharmacokinetic studies. PMID:19755162

  5. Myelin Basic Protein Cleaves Cell Adhesion Molecule L1 and Improves Regeneration After Injury.

    PubMed

    Lutz, David; Kataria, Hardeep; Kleene, Ralf; Loers, Gabriele; Chaudhary, Harshita; Guseva, Daria; Wu, Bin; Jakovcevski, Igor; Schachner, Melitta

    2016-07-01

    Myelin basic protein (MBP) is a serine protease that cleaves neural cell adhesion molecule L1 and generates a transmembrane L1 fragment which facilitates L1-dependent functions in vitro, such as neurite outgrowth, neuronal cell migration and survival, myelination by Schwann cells as well as Schwann cell proliferation, migration, and process formation. Ablation and blocking of MBP or disruption of its proteolytic activity by mutation of a proteolytically active serine residue abolish L1-dependent cellular responses. In utero injection of adeno-associated virus encoding proteolytically active MBP into MBP-deficient shiverer mice normalizes differentiation, myelination, and synaptogenesis in the developing postnatal spinal cord, in contrast to proteolytically inactive MBP. Application of active MBP to the injured wild-type spinal cord and femoral nerve augments levels of a transmembrane L1 fragment, promotes remyelination, and improves functional recovery after injury. Application of MBP antibody impairs recovery. Virus-mediated expression of active MBP in the lesion site after spinal cord injury results in improved functional recovery, whereas injection of virus encoding proteolytically inactive MBP fails to do so. The present study provides evidence for a novel L1-mediated function of MBP in the developing spinal cord and in the injured adult mammalian nervous system that leads to enhanced recovery after acute trauma. PMID:26081148

  6. Drosophila insulin degrading enzyme and rat skeletal muscle insulin protease cleave insulin at similar sites

    SciTech Connect

    Duckworth, W.C.; Garcia, J.V.; Liepnieks, J.J.; Hamel, F.G.; Hermodson, M.A.; Frank, B.H.; Rosner, M.R. )

    1989-03-21

    Insulin degradation is an integral part of the cellular action of insulin. Recent evidence suggests that the enzyme insulin protease is involved in the degradation of insulin in mammalian tissues. Drosophila, which has insulin-like hormones and insulin receptor homologues, also expresses an insulin degrading enzyme with properties that are very similar to those of mammalian insulin protease. In the present study, the insulin cleavage products generated by the Drosophila insulin degrading enzyme were identified and compared with the products generated by the mammalian insulin protease. Both purified enzymes were incubated with porcine insulin specifically labeled with {sup 125}I on either the A19 or B26 position, and the degradation products were analyzed by HPLC before and after sulfitolysis. Isolation and sequencing of the cleavage products indicated that both enzymes cleave the A chain of intact insulin at identical sites between residues A13 and A14 and A14 and A15. These results demonstrate that all the insulin cleavage sites generated by the Drosopohila insulin degrading enzyme are shared in common with the mammalian insulin protease. These data support the hypothesis that there is evolutionary conservation of the insulin degrading enzyme and further suggest that this enzyme plays an important role in cellular function.

  7. Substrate-Induced Conformational Changes Occur in All Cleaved Forms of Caspase-6

    SciTech Connect

    S Vaidya; E Velazquez-Delgado; G Abbruzzese; J Hardy

    2011-12-31

    Caspase-6 is an apoptotic cysteine protease that also governs disease progression in Huntington's and Alzheimer's diseases. Caspase-6 is of great interest as a target for treatment of these neurodegenerative diseases; however, the molecular basis of caspase-6 function and regulation remains poorly understood. In the recently reported structure of caspase-6, the 60's and 130's helices at the base of the substrate-binding groove extend upward, in a conformation entirely different from that of any other caspase. Presently, the central question about caspase-6 structure and function is whether the extended conformation is the catalytically competent conformation or whether the extended helices must undergo a large conformational rearrangement in order to bind substrate. We have generated a series of caspase-6 cleavage variants, including a novel constitutively two-chain form, and determined crystal structures of caspase-6 with and without the intersubunit linker. This series allows evaluation of the role of the prodomain and intersubunit linker on caspase-6 structure and function before and after substrate binding. Caspase-6 is inherently more stable than closely related caspases. Cleaved caspase-6 with both the prodomain and the linker present is the most stable, indicating that these two regions act in concert to increase stability, but maintain the extended conformation in the unliganded state. Moreover, these data suggest that caspase-6 undergoes a significant conformational change upon substrate binding, adopting a structure that is more like canonical caspases.

  8. Nuclear localization of the caspase-3-cleaved form of p73 in anoikis

    PubMed Central

    Alsafadi, Samar; Tourpin, Sophie; Bessoltane, Nadia; Salomé-Desnoulez, Sophie; Vassal, Gilles; André, Fabrice; Ahomadegbe, Jean-Charles

    2016-01-01

    The transcription factor p73 is a homologue of p53 that can be expressed as pro- or anti-apoptotic isoforms. Unlike p53, p73 is rarely mutated or lost in cancers and it is found to replace defective p53 inducing apoptosis. Here, we investigated the p73 involvement in anoikis, a type of apoptosis caused by inadequate cell-matrix interactions. Breast cancer cell lines with different p53 status were treated with doxorubicin (DOX) or docetaxel (DOC) and cells detached from the extracellular matrix were analyzed. We demonstrate for the first time that DOX-induced cell detachment is associated with p73 cleavage and caspase activation, independently of the p53 status. However, we did not detect p73 cleavage or caspase activation in detached cells under DOC treatment. Overexpressing the apoptotic isoform of p73 led to cell detachment associated with p73 cleavage and caspase activation. Interestingly, p73 cleaved forms localize to the nucleus during the late phase of cell death indicating an increase in the transcriptional activity. Our study suggests that the cleavage of p73 on specific sites may release its pro-apoptotic function and contribute to cell death. PMID:26575022

  9. Subcutaneously Administered Self-Cleaving Hydrogel-Octreotide Conjugates Provide Very Long-Acting Octreotide.

    PubMed

    Schneider, Eric L; Henise, Jeff; Reid, Ralph; Ashley, Gary W; Santi, Daniel V

    2016-07-20

    We developed a long-acting drug-delivery system that supports subcutaneous administration of the peptidic somatostatin agonist octreotide-a blockbuster drug used to treat acromegaly and neuroendocrine tumors. The current once-a-month polymer-encapsulated octreotide, Sandostatin LAR, requires a painful intragluteal injection through a large needle by a health-care professional. To overcome such shortcomings, Tetra-PEG hydrogel microspheres were covalently attached to the α-amine of d-Phe(1) or the ε-amine of Lys(5) of octreotide by a self-cleaving β-eliminative linker; upon subcutaneous injection in the rat using a small-bore needle, octreotide was slowly released. The released drug from the ε-octreotide conjugate showed a remarkably long serum half-life that exceeded two months. The α-octreotide conjugate had a half-life of ∼2 weeks, and showed an excellent correlation of in vitro and in vivo drug release. Pharmacokinetic models indicate these microspheres should support once-weekly to once-monthly self-administered subcutaneous dosing in humans. The hydrogel-octreotide conjugate shows the favorable pharmacokinetics of Sandostatin LAR without its drawbacks. PMID:27253622

  10. The mitochondrial intramembrane protease PARL cleaves human Pink1 to regulate Pink1 trafficking.

    PubMed

    Meissner, Cathrin; Lorenz, Holger; Weihofen, Andreas; Selkoe, Dennis J; Lemberg, Marius K

    2011-06-01

    Intramembrane proteolysis is a conserved mechanism that regulates a variety of cellular processes ranging from transcription control to signaling. In mitochondria, the inner membrane rhomboid protease PARL has been implicated in the control of life span and apoptosis by a so far uncharacterized mechanism. Here, we show that PARL cleaves human Pink1, which is implicated in Parkinson's disease, within its conserved membrane anchor. Mature Pink1 is then free to be released into the cytosol or the mitochondrial intermembrane space. Upon depolarization of the mitochondrial membrane potential, the canonical import of Pink1 and PARL-catalyzed processing is blocked, leading to accumulation of the Pink1 precursor. As targeting of this precursor to the outer mitochondrial membrane has been shown to trigger mitophagy, we suggest that the PARL-catalyzed removal of the Pink1 signal sequence in the canonical import pathway acts as a cellular checkpoint for mitochondrial integrity. Furthermore, we show that two Parkinson's disease-causing mutations decrease the processing of Pink1 by PARL, with attendant implications for pathogenesis. PMID:21426348

  11. Signal peptide peptidase functions in ERAD to cleave the unfolded protein response regulator XBP1u.

    PubMed

    Chen, Chia-yi; Malchus, Nicole S; Hehn, Beate; Stelzer, Walter; Avci, Dönem; Langosch, Dieter; Lemberg, Marius K

    2014-11-01

    Signal peptide peptidase (SPP) catalyzes intramembrane proteolysis of signal peptides at the endoplasmic reticulum (ER), but has also been suggested to play a role in ER-associated degradation (ERAD). Here, we show that SPP forms a complex with the ERAD factor Derlin1 and the E3 ubiquitin ligase TRC8 to cleave the unfolded protein response (UPR) regulator XBP1u. Cleavage occurs within a so far unrecognized type II transmembrane domain, which renders XBP1u as an SPP substrate through specific sequence features. Additionally, Derlin1 acts in the complex as a substrate receptor by recognizing the luminal tail of XBP1u. Remarkably, this interaction of Derlin1 with XBP1u obviates the need for ectodomain shedding prior to SPP cleavage, commonly required for intramembrane cuts. Furthermore, we show that XBP1u inhibits the UPR transcription factor XBP1s by targeting it toward proteasomal degradation. Thus, we identify an ERAD complex that controls the abundance of XBP1u and thereby tunes signaling through the UPR. PMID:25239945

  12. Signal peptide peptidase functions in ERAD to cleave the unfolded protein response regulator XBP1u

    PubMed Central

    Chen, Chia-yi; Malchus, Nicole S; Hehn, Beate; Stelzer, Walter; Avci, Dönem; Langosch, Dieter; Lemberg, Marius K

    2014-01-01

    Signal peptide peptidase (SPP) catalyzes intramembrane proteolysis of signal peptides at the endoplasmic reticulum (ER), but has also been suggested to play a role in ER-associated degradation (ERAD). Here, we show that SPP forms a complex with the ERAD factor Derlin1 and the E3 ubiquitin ligase TRC8 to cleave the unfolded protein response (UPR) regulator XBP1u. Cleavage occurs within a so far unrecognized type II transmembrane domain, which renders XBP1u as an SPP substrate through specific sequence features. Additionally, Derlin1 acts in the complex as a substrate receptor by recognizing the luminal tail of XBP1u. Remarkably, this interaction of Derlin1 with XBP1u obviates the need for ectodomain shedding prior to SPP cleavage, commonly required for intramembrane cuts. Furthermore, we show that XBP1u inhibits the UPR transcription factor XBP1s by targeting it toward proteasomal degradation. Thus, we identify an ERAD complex that controls the abundance of XBP1u and thereby tunes signaling through the UPR. PMID:25239945

  13. Emerging role of the interleukin-8 cleaving enzyme SpyCEP in clinical Streptococcus pyogenes infection.

    PubMed

    Turner, Claire E; Kurupati, Prathiba; Jones, Michael D; Edwards, Robert J; Sriskandan, Shiranee

    2009-08-15

    Neutrophil chemoattractant interleukin (IL)-8 is cleaved and inactivated by the Streptococcus pyogenes cell envelope protease SpyCEP. A range of clinical S. pyogenes strains of differing emm type demonstrated SpyCEP activity, although transcription of the SpyCEP gene cepA differed 1000-fold between isolates. Disruption of the 2-component regulatory system covR/S in pharyngeal isolates increased cepA transcription 100-fold; this finding is consistent with endogenous CovR/S-mediated repression of cepA being responsible for low SpyCEP expression in some S. pyogenes strains associated with pharyngitis. Among patients with invasive S. pyogenes infection, disease severity and outcome were associated with the SpyCEP activity of the isolate. Lethal invasive isolate H292 (emm81) expressed more cepA than did other tested isolates. This strain carried a unique covR mutation that impaired binding to the cepA promoter. CovR/S sequence comparison in other clinical isolates revealed community-wide dissemination of covS mutations but not covR mutations. The results highlight a potential hazard and underline the importance of continuing molecular epidemiological surveillance for community-wide dissemination of CovR/S mutant hyperinvasive strains. PMID:19591574

  14. Substrate-induced conformational changes occur in all cleaved forms of caspase-6

    PubMed Central

    Vaidya, Sravanti; Velázquez-Delgado, Elih M.; Abbruzzese, Genevieve; Hardy, Jeanne A.

    2010-01-01

    Caspase-6 is an apoptotic cysteine protease that also governs disease progression in Huntington’s and Alzheimer’s Diseases. Caspase-6 is of great interest as a target for treatment of these neurodegenerative diseases, however the molecular basis of caspase-6 function and regulation remains poorly understood. In the recently reported structure of caspase-6, the 60’s and 130’s helices at the base of the substrate-binding groove extend upward, in a conformation entirely different from that of any other caspase. Presently, the central question about caspase-6 structure and function is whether the extended conformation is the catalytically competent conformation or whether the extended helices must undergo a large conformational rearrangement in order to bind substrate. We have generated a series of caspase-6 cleavage variants including a novel constitutively two-chain form and determined crystal structures of caspase-6 with and without the intersubunit linker. This series allows evaluation of the role of the prodomain and intersubunit linker on caspase-6 structure and function before and after substrate binding. Caspase-6 is inherently more stable than closely related caspases. Cleaved caspase-6 with both the prodomain and linker present is the most stable indicating that these two regions act in concert to increase stability, but maintain the extended conformation in the unliganded state. Most importantly, these data suggest that caspase-6 undergoes a significant conformational change upon substrate binding, adopting a structure that is more like canonical caspases. PMID:21111746

  15. In vitro evolution of distinct self-cleaving ribozymes in diverse environments

    PubMed Central

    Popović, Milena; Fliss, Palmer S.; Ditzler, Mark A.

    2015-01-01

    In vitro evolution experiments have long been used to evaluate the roles of RNA in both modern and ancient biology, and as a tool for biotechnology applications. The conditions under which these experiments have been conducted, however, do not reflect the range of cellular environments in modern biology or our understanding of chemical environments on the early earth, when the atmosphere and oceans were largely anoxic and soluble Fe2+ was abundant. To test the impact of environmental factors relevant to RNA's potential role in the earliest forms of life, we evolved populations of self-cleaving ribozymes in an anoxic atmosphere with varying pH in the presence of either Fe2+ or Mg2+. Populations evolved under these different conditions are dominated by different sequences and secondary structures, demonstrating global differences in the underlying fitness landscapes. Comparisons between evolutionary outcomes and catalytic activities also indicate that Mg2+ can readily take the place of Fe2+ in supporting the catalysis of RNA cleavage at neutral pH, but not at lower pH. These results highlight the importance of considering the specific environments in which functional biopolymers evolve when evaluating their potential roles in the origin of life, extant biology, or biotechnology. PMID:26130717

  16. In vitro evolution of distinct self-cleaving ribozymes in diverse environments.

    PubMed

    Popović, Milena; Fliss, Palmer S; Ditzler, Mark A

    2015-08-18

    In vitro evolution experiments have long been used to evaluate the roles of RNA in both modern and ancient biology, and as a tool for biotechnology applications. The conditions under which these experiments have been conducted, however, do not reflect the range of cellular environments in modern biology or our understanding of chemical environments on the early earth, when the atmosphere and oceans were largely anoxic and soluble Fe(2+) was abundant. To test the impact of environmental factors relevant to RNA's potential role in the earliest forms of life, we evolved populations of self-cleaving ribozymes in an anoxic atmosphere with varying pH in the presence of either Fe(2+) or Mg(2+). Populations evolved under these different conditions are dominated by different sequences and secondary structures, demonstrating global differences in the underlying fitness landscapes. Comparisons between evolutionary outcomes and catalytic activities also indicate that Mg(2+) can readily take the place of Fe(2+) in supporting the catalysis of RNA cleavage at neutral pH, but not at lower pH. These results highlight the importance of considering the specific environments in which functional biopolymers evolve when evaluating their potential roles in the origin of life, extant biology, or biotechnology. PMID:26130717

  17. A C4-oxidizing Lytic Polysaccharide Monooxygenase Cleaving Both Cellulose and Cello-oligosaccharides*

    PubMed Central

    Isaksen, Trine; Westereng, Bjørge; Aachmann, Finn L.; Agger, Jane W.; Kracher, Daniel; Kittl, Roman; Ludwig, Roland; Haltrich, Dietmar; Eijsink, Vincent G. H.; Horn, Svein J.

    2014-01-01

    Lignocellulosic biomass is a renewable resource that significantly can substitute fossil resources for the production of fuels, chemicals, and materials. Efficient saccharification of this biomass to fermentable sugars will be a key technology in future biorefineries. Traditionally, saccharification was thought to be accomplished by mixtures of hydrolytic enzymes. However, recently it has been shown that lytic polysaccharide monooxygenases (LPMOs) contribute to this process by catalyzing oxidative cleavage of insoluble polysaccharides utilizing a mechanism involving molecular oxygen and an electron donor. These enzymes thus represent novel tools for the saccharification of plant biomass. Most characterized LPMOs, including all reported bacterial LPMOs, form aldonic acids, i.e., products oxidized in the C1 position of the terminal sugar. Oxidation at other positions has been observed, and there has been some debate concerning the nature of this position (C4 or C6). In this study, we have characterized an LPMO from Neurospora crassa (NcLPMO9C; also known as NCU02916 and NcGH61–3). Remarkably, and in contrast to all previously characterized LPMOs, which are active only on polysaccharides, NcLPMO9C is able to cleave soluble cello-oligosaccharides as short as a tetramer, a property that allowed detailed product analysis. Using mass spectrometry and NMR, we show that the cello-oligosaccharide products released by this enzyme contain a C4 gemdiol/keto group at the nonreducing end. PMID:24324265

  18. A C4-oxidizing lytic polysaccharide monooxygenase cleaving both cellulose and cello-oligosaccharides.

    PubMed

    Isaksen, Trine; Westereng, Bjørge; Aachmann, Finn L; Agger, Jane W; Kracher, Daniel; Kittl, Roman; Ludwig, Roland; Haltrich, Dietmar; Eijsink, Vincent G H; Horn, Svein J

    2014-01-31

    Lignocellulosic biomass is a renewable resource that significantly can substitute fossil resources for the production of fuels, chemicals, and materials. Efficient saccharification of this biomass to fermentable sugars will be a key technology in future biorefineries. Traditionally, saccharification was thought to be accomplished by mixtures of hydrolytic enzymes. However, recently it has been shown that lytic polysaccharide monooxygenases (LPMOs) contribute to this process by catalyzing oxidative cleavage of insoluble polysaccharides utilizing a mechanism involving molecular oxygen and an electron donor. These enzymes thus represent novel tools for the saccharification of plant biomass. Most characterized LPMOs, including all reported bacterial LPMOs, form aldonic acids, i.e., products oxidized in the C1 position of the terminal sugar. Oxidation at other positions has been observed, and there has been some debate concerning the nature of this position (C4 or C6). In this study, we have characterized an LPMO from Neurospora crassa (NcLPMO9C; also known as NCU02916 and NcGH61-3). Remarkably, and in contrast to all previously characterized LPMOs, which are active only on polysaccharides, NcLPMO9C is able to cleave soluble cello-oligosaccharides as short as a tetramer, a property that allowed detailed product analysis. Using mass spectrometry and NMR, we show that the cello-oligosaccharide products released by this enzyme contain a C4 gemdiol/keto group at the nonreducing end. PMID:24324265

  19. RNase MRP Cleaves Pre-tRNASer-Met in the tRNA Maturation Pathway

    PubMed Central

    Adachi, Kousuke; Nobe, Yuko; Kobayashi, Junya; Hirota, Kouji; Oliveira, Douglas V.; Taoka, Masato; Isobe, Toshiaki

    2014-01-01

    Ribonuclease mitochondrial RNA processing (RNase MRP) is a multifunctional ribonucleoprotein (RNP) complex that is involved in the maturation of various types of RNA including ribosomal RNA. RNase MRP consists of a potential catalytic RNA and several protein components, all of which are required for cell viability. We show here that the temperature-sensitive mutant of rmp1, the gene for a unique protein component of RNase MRP, accumulates the dimeric tRNA precursor, pre-tRNASer-Met. To examine whether RNase MRP mediates tRNA maturation, we purified the RNase MRP holoenzyme from the fission yeast Schizosaccharomyces pombe and found that the enzyme directly and selectively cleaves pre-tRNASer-Met, suggesting that RNase MRP participates in the maturation of specific tRNA in vivo. In addition, mass spectrometry–based ribonucleoproteomic analysis demonstrated that this RNase MRP consists of one RNA molecule and 11 protein components, including a previously unknown component Rpl701. Notably, limited nucleolysis of RNase MRP generated an active catalytic core consisting of partial mrp1 RNA fragments, which constitute “Domain 1” in the secondary structure of RNase MRP, and 8 proteins. Thus, the present study provides new insight into the structure and function of RNase MRP. PMID:25401760

  20. Cleaved high-molecular-weight kininogen inhibits neointima formation following vascular injury.

    PubMed

    Daniel, Jan-Marcus; Reich, Fabian; Dutzmann, Jochen; Weisheit, Simona; Teske, Rebecca; Gündüz, Dursun; Bauersachs, Johann; Preissner, Klaus T; Sedding, Daniel G

    2015-08-31

    Cleaved high-molecular-weight kininogen (HKa) or its peptide domain 5 (D5) alone exert anti-adhesive properties in vitro related to impeding integrin-mediated cellular interactions. However, the anti-adhesive effects of HKa in vivo remain elusive. In this study, we investigated the effects of HKa on leukocyte recruitment and neointima formation following wire-induced injury of the femoral artery in C57BL/6 mice. Local application of HKa significantly reduced the accumulation of monocytes and also reduced neointimal lesion size 14 days after injury. Moreover, C57BL/6 mice transplanted with bone marrow from transgenic mice expressing enhanced green fluorescence protein (eGFP) showed a significantly reduced accumulation of eGFP+-cells at the arterial injury site and decreased neointimal lesion size after local application of HKa or the polypeptide D5 alone. A differentiation of accumulating eGFP+-cells into highly specific smooth muscle cells (SMC) was not detected in any group. In contrast, application of HKa significantly reduced the proliferation of locally derived neointimal cells. In vitro, HKa and D5 potently inhibited the adhesion of SMC to vitronectin, thus impairing their proliferation, migration, and survival rates. In conclusion, application of HKa or D5 decreases the inflammatory response to vascular injury and exerts direct effects on SMC by impeding the binding of integrins to extracellular matrix components. Therefore, HKa and D5 may hold promise as novel therapeutic substances to prevent neointima formation. PMID:26063414

  1. [Stable expression and characterization of the von Willebrand factor cleaving protease].

    PubMed

    Ma, Zhenni; Dong, Ningzheng; Zhang, Jingyu; Su, Jian; Wang, Anyou; Ruan, Changgeng

    2010-02-01

    This study was to acquire recombinant protein of von Willebrand factor cleaving protease (ADAMTS13, a disintegrin and metalloprotease with a thromboSpondin type 1 motifs 13), for further studies on its biological function in thrombosis and hemostasis. We transfected the Hela cells with the plasmid pSecTag-ADAMTS13 by lipofectamine. A positive cell cloning was selected by hygromycin-B. The recombinant protein was purified with Ni-NTA agarose column by gradient imidazole. The purity and immune activity of purified products were identified with SDS-PAGE and Western blotting respectively. We also measured the enzymatic activity of recombinant protein (rADAMTS13) by GST-His two-site ELISA assay. The results showed that we successfully constructed Hela cells ADAMTS2-4 which expressed high level of rADAMTS13. We received about 5.8 mg recombinant protein in culture supernantants per liter purified with Ni-NTA column. The protein formed a main lane at the position of 190 kDa with SDS-PAGE and reacted with polyclonal antibody against ADAMTS13 by Western blotting. The amount of rADAMTS13 activity was 6.4 U/mL, according to the normal plasma defined as 1 U/mL. In conclusion, rADAMTS13 protein had high purity, immune activity and good enzymatic activity, which could establish the experimental foundation for further research on biological function and mechanism of this unique metalloprotease. PMID:20432945

  2. In Silico Prediction of Mutant HIV-1 Proteases Cleaving a Target Sequence

    PubMed Central

    Jensen, Jan H.; Willemoës, Martin; Winther, Jakob R.; De Vico, Luca

    2014-01-01

    HIV-1 protease represents an appealing system for directed enzyme re-design, since it has various different endogenous targets, a relatively simple structure and it is well studied. Recently Chaudhury and Gray (Structure (2009) 17: 1636–1648) published a computational algorithm to discern the specificity determining residues of HIV-1 protease. In this paper we present two computational tools aimed at re-designing HIV-1 protease, derived from the algorithm of Chaudhuri and Gray. First, we present an energy-only based methodology to discriminate cleavable and non cleavable peptides for HIV-1 proteases, both wild type and mutant. Secondly, we show an algorithm we developed to predict mutant HIV-1 proteases capable of cleaving a new target substrate peptide, different from the natural targets of HIV-1 protease. The obtained in silico mutant enzymes were analyzed in terms of cleavability and specificity towards the target peptide using the energy-only methodology. We found two mutant proteases as best candidates for specificity and cleavability towards the target sequence. PMID:24796579

  3. Ribozyme cleaves rex/tax mRNA and inhibits bovine leukemia virus expression.

    PubMed Central

    Cantor, G H; McElwain, T F; Birkebak, T A; Palmer, G H

    1993-01-01

    Bovine leukemia virus (BLV) encodes at least two regulatory proteins, Rex and Tax. Tax, the transactivating protein, stimulates the long terminal repeat to promote viral transcription and may be involved in tumorigenesis. Rex is involved in the transition from early expression of regulatory proteins to later expression of viral structural proteins. We have targeted ribozymes against the mRNA encoding Rex and Tax. The ribozymes consist of the hammer-head catalytic motif flanked by antisense sequences that hybridize with the complementary rex/tax mRNA. To evaluate cleavage in a cell-free system, we transcribed portions of rex/tax mRNA and incubated them with synthetic RNA ribozymes. A ribozyme was identified that cleaves > 80% of the target RNA. Synthetic DNA encoding this ribozyme was cloned into the expression vector pRc/RSV and transfected into BLV-infected bat lung cells. Intracellular cleavage of rex/tax mRNA was confirmed by reverse transcriptase PCR. In cells expressing the ribozyme, viral expression was markedly inhibited. Expression of the BLV core protein p24 was inhibited by 61%, and reverse transcriptase activity in supernatant was inhibited by 92%. Ribozyme inhibition of BLV expression suggests that cattle expressing these sequences may be able to control BLV replication. Images Fig. 2 Fig. 4 Fig. 5 Fig. 6 PMID:7504287

  4. Synthesis, photochemical properties and DNA binding studies of dna cleaving agents based on chiral dipyridine dihydrodioxins salts

    NASA Astrophysics Data System (ADS)

    Shamaev, Alexei

    activated by UV-light. The mechanism of o-quinone release and intramolecular ET was studied in detail by methods of Ultrafast Transient Absortion Spectroscopy and supported by high-level quantum mechanical calculations. The binding properties of chiral intercalators based on PDHD to various DNA oligonucleotides were studied by various methods and DNA cleavage properties indicating strong binding and cleaving ability of the synthesized PDHDs. Also, a new method for synthesis of cyclohexa[e]pyrenes which possibly capable of intramolecular ET and electron transfer-oxidative stress (ET-OS) DNA cleavage was developed and partially accomplished.

  5. Mechanical and tribological properties of gradient a-C:H/Ti coatings

    NASA Astrophysics Data System (ADS)

    Batory, D.; Szymański, W.; Cłapa, M.

    2013-08-01

    The unusual combination of high hardness and very low friction coefficient are the most attractive tribological parameters of DLC (diamond-like carbon) layers. However, their usability is strongly restricted by the limited thickness due to high residual stress. The main goal of the presented work was to obtain thick, wear resistant and well adherent DLC layers while keeping their perfect friction parameters. As a proposed solution a Ti-Ti x C y gradient layer was manufactured as the adhesion improving interlayer followed by a thick diamond-like carbon film. This kind of combination seems to be very promising for many applications, where dry friction conditions for highly loaded elements can be observed. Both layers were obtained in one process using a hybrid deposition system combining PVD and CVD techniques in one reaction chamber. The investigation was performed on nitrided samples made from X53CrMnNiN21-9 valve steel. Structural features, surface topography, tribological and mechanical properties of manufactured layers were evaluated. The results of the investigation confirmed that the presented deposition technique makes it possible to manufacture thick and well adherent carbon layers with high hardness and very good tribological parameters. Preliminary investigation results prove the possibility of application of presented technology in automotive industry.

  6. Titanium containing amorphous hydrogenated carbon films (a-C: H/Ti): surface analysis and evaluation of cellular reactions using bone marrow cell cultures in vitro.

    PubMed

    Schroeder, A; Francz, G; Bruinink, A; Hauert, R; Mayer, J; Wintermantel, E

    2000-03-01

    Amorphous hydrogenated carbon (a-C : H) coatings, also called diamond-like carbon (DLC), have many properties required for a protective coating material in biomedical applications. The purpose of this study is to evaluate a new surface coating for bone-related implants by combining the hardness and inertness of a-C : H films with the biological acceptance of titanium. For this purpose, different amounts of titanium were incorporated into a-C : H films by a combined radio frequency (rf) and magnetron sputtering set-up. The X-ray photoelectron spectroscopy (XPS) of air-exposed a-C : H/titanium (a-C : H/Ti) films revealed that the films were composed of TiO2 and TiC embedded in and connected to an a-C : H matrix. Cell culture tests using primary adult rat bone marrow cell cultures (BMC) were performed to determine effects on cell number and on osteoblast and osteoclast differentiation. By adding titanium to the carbon matrix, cellular reactions such as increased proliferation and reduced osteoclast-like cell activity could be obtained, while these reactions were not seen on pure a-C : H films and on glass control samples. In summary, a-C : H/Ti could be a valuable coating for bone implants, by supporting bone cell proliferation while reducing osteoclast-like cell activation. PMID:10674809

  7. Copper-catalyzed intramolecular direct amination of sp2 C-H bonds for the synthesis of N-aryl acridones.

    PubMed

    Zhou, Wang; Liu, Yong; Yang, Youqing; Deng, Guo-Jun

    2012-11-01

    A copper-catalyzed approach for the synthesis of N-aryl acridones via sp(2) C-H bond amination using air as oxidant under neutral conditions is disclosed. This reaction not only provides a complementary method for synthesizing medicinally important acridones, but also offers a new strategy for sp(2) C-H bond amination. PMID:23010788

  8. Rhodium(III)-catalyzed cyanation of vinylic C-H bonds: N-cyano-N-phenyl-p-toluenesulfonamide as a cyanation reagent.

    PubMed

    Su, Wei; Gong, Tian-Jun; Xiao, Bin; Fu, Yao

    2015-07-28

    Rh(III)-catalyzed direct vinylic C-H cyanation reaction has been developed as a practical method for the synthesis of alkenyl nitriles. N-Cyano-N-phenyl-p-methylbenzenesulfonamide (NCTS), a user-friendly cyanation reagent, was used in the transformation. Both acrylamides and ketoximes can be employed in the new C-H cyanation process. PMID:26108194

  9. Quality Improvements in the Early Care and Education Workforce: Outcomes and Impact of the T.E.A.C.H. Early Childhood[R] Project

    ERIC Educational Resources Information Center

    Miller, Joyce Ann; Bogatova, Tania

    2009-01-01

    To date there has not been a systematic, longitudinal research to assess the efficacy of public investments in the professional development of early childhood educators that are funded through the T.E.A.C.H. Early Childhood[R] Project. This study of the T.E.A.C.H. Early Childhood[R] Project Pennsylvania provides a longitudinal analysis of the data…

  10. Assessment of the Electronic Factors Determining the Thermodynamics of "Oxidative Addition" of C-H and N-H Bonds to Ir(I) Complexes.

    PubMed

    Wang, David Y; Choliy, Yuriy; Haibach, Michael C; Hartwig, John F; Krogh-Jespersen, Karsten; Goldman, Alan S

    2016-01-13

    A study of electronic factors governing the thermodynamics of C-H and N-H bond addition to Ir(I) complexes was conducted. DFT calculations were performed on an extensive series of trans-(PH3)2IrXL complexes (L = NH3 and CO; X = various monodentate ligands) to parametrize the relative σ- and π-donating/withdrawing properties of the various ligands, X. Computed energies of oxidative addition of methane to a series of three- and four-coordinate Ir(I) complexes bearing an ancillary ligand, X, were correlated with the resulting (σ(X), π(X)) parameter set. Regression analysis indicates that the thermodynamics of addition of methane to trans-(PH3)2IrX are generally strongly disfavored by increased σ-donation from the ligand X, in contradiction to widely held views on oxidative addition. The trend for oxidative addition of methane to four-coordinate Ir(I) was closely related to that observed for the three-coordinate complexes, albeit slightly more complicated. The computational analysis was found to be consistent with the rates of reductive elimination of benzene from a series of isoelectronic Ir(III) phenyl hydride complexes, measured experimentally in this work and previously reported. Extending the analysis of ancillary ligand energetic effects to the oxidative addition of ammonia to three-coordinate Ir(I) complexes leads to the conclusion that increasing σ-donation by X also disfavors oxidative addition of N-H bonds to trans-(PH3)2IrX. However, coordination of NH3 to the Ir(I) center is disfavored even more strongly by increasing σ-donation by X, which explains why the few documented examples of H-NH2 oxidative addition to transition metals involve complexes with strongly σ-donating ligands situated trans to the site of addition. An orbital-based rationale for the observed results is presented. PMID:26652221

  11. Anaerobic biodegradation of ether compounds by ether bond-cleaving bacteria and methanogenic consortia

    SciTech Connect

    Dwyer, D.F.

    1989-01-01

    Ether compounds are manufactured for use in nonionic detergents, plastics, pesticides and other products and occur as toxic organic compounds, the most famous being tetrachlorodibenzo-p-dioxin. Ether compounds were considered recalcitrant to anaerobic biodegradation due to the lack of an appropriate oxidant for ether bond-cleavage in reducing environments. Many of these compounds reside in anaerobic environments or are exposed to anaerobic waste treatment processes. Thus, it is of interest to identify: (i) whether ether compounds are anaerobically biodegradable, (ii) the anaerobic microorganisms able to degrade these compounds, and (iii) the mechanism(s) of anaerobic ether bond-cleavage. The ether bonds of polyethylene glycol (PEG; HO-(CH{sub 2}CH{sub 2}-O-){sub n}H), phenyl ether ((C{sub 6}H{sub 5}){sub 2}O), and dibenzo-p-dioxin ((C{sub 6}H{sub 4}){sub 2}O{sub 2}) were shown to be degraded in methanogenic consortia enriched with these compounds and polyethoxylate (nonionic) surfactants as substrates. Two anaerobic microorganisms which used PEGs as sole substrates were isolated and characterized. Desulfovibrio desulfuricans strain DG2 degraded the monomer ethylene glycol and oligomers up to tetraethylene glycol (HO-(CH{sub 2}CH{sub 2}-O-){sub 4}H) in length. Bacteroides sp. strain PG1 degraded diethylene glycol and all other polymer lengths of PEG. PEGs were degraded by Bacteroides sp. strain PG1 via an external depolymerization which was either a hydrolytic or a reductive cleavage of the ether bond. The ether bond of diaryl ethers was apparently cleaved by a reductive mechanism which produced benzene and phenol as products from phenyl ether degradation and benzene and, by indirect analysis, catechol from dibenzo-dioxin.

  12. MIB–MIP is a mycoplasma system that captures and cleaves immunoglobulin G

    PubMed Central

    Arfi, Yonathan; Minder, Laetitia; Di Primo, Carmelo; Le Roy, Aline; Ebel, Christine; Coquet, Laurent; Claverol, Stephane; Vashee, Sanjay; Jores, Joerg; Blanchard, Alain; Sirand-Pugnet, Pascal

    2016-01-01

    Mycoplasmas are “minimal” bacteria able to infect humans, wildlife, and a large number of economically important livestock species. Mycoplasma infections include a spectrum of clinical manifestations ranging from simple fever to fulminant inflammatory diseases with high mortality rates. These infections are mostly chronic, suggesting that mycoplasmas have developed means to evade the host immune response. Here we present and functionally characterize a two-protein system from Mycoplasma mycoides subspecies capri that is involved in the capture and cleavage of IgG. The first component, Mycoplasma Ig binding protein (MIB), is an 83-kDa protein that is able to tightly bind to the Fv region of a wide range of IgG. The second component, Mycoplasma Ig protease (MIP), is a 97-kDa serine protease that is able to cleave off the VH domain of IgG. We demonstrate that MIB is necessary for the proteolytic activity of MIP. Cleavage of IgG requires a sequential interaction of the different partners of the system: first MIB captures the IgG, and then MIP is recruited to the MIB–IgG complex, enabling protease activity. MIB and MIP are encoded by two genes organized in tandem, with homologs found in the majority of pathogenic mycoplasmas and often in multiple copies. Phylogenetic studies suggest that genes encoding the MIB–MIP system are specific to mycoplasmas and have been disseminated by horizontal gene transfer. These results highlight an original and complex system targeting the host immunoglobulins, playing a potentially key role in the immunity evasion by mycoplasmas. PMID:27114507

  13. Plasmodium falciparum signal peptide peptidase cleaves malaria heat shock protein 101 (HSP101). Implications for gametocytogenesis

    SciTech Connect

    Baldwin, Michael; Russo, Crystal; Li, Xuerong; Chishti, Athar H.

    2014-08-08

    Highlights: • PfSPP is an ER resident protease. • PfSPP is expressed both as a monomer and dimer. • The signal peptide of HSP101 is the first known substrate of PfSPP. • Reduced PfSPP activity may significantly affect ER homeostasis. - Abstract: Previously we described the identification of a Plasmodium falciparum signal peptide peptidase (PfSPP) functioning at the blood stage of malaria infection. Our studies also demonstrated that mammalian SPP inhibitors prevent malaria parasite growth at the late-ring/early trophozoite stage of intra-erythrocytic development. Consistent with its role in development, we tested the hypothesis that PfSPP functions at the endoplasmic reticulum of P.falciparum where it cleaves membrane-bound signal peptides generated following the enzyme activity of signal peptidase. The localization of PfSPP to the endoplasmic reticulum was confirmed by immunofluorescence microscopy and immunogold electron microscopy. Biochemical analysis indicated the existence of monomer and dimer forms of PfSPP in the parasite lysate. A comprehensive bioinformatics screen identified several candidate PfSPP substrates in the parasite genome. Using an established transfection based in vivo luminescence assay, malaria heat shock protein 101 (HSP101) was identified as a substrate of PfSPP, and partial inhibition of PfSPP correlated with the emergence of gametocytes. This finding unveils the first known substrate of PfSPP, and provides new perspectives for the function of intra-membrane proteolysis at the erythrocyte stage of malaria parasite life cycle.

  14. Cell-specific and developmental expression of lectican-cleaving proteases in mouse hippocampus and neocortex.

    PubMed

    Levy, C; Brooks, J M; Chen, J; Su, J; Fox, M A

    2015-03-01

    Mounting evidence has demonstrated that a specialized extracellular matrix exists in the mammalian brain and that this glycoprotein-rich matrix contributes to many aspects of brain development and function. The most prominent supramolecular assemblies of these extracellular matrix glycoproteins are perineuronal nets, specialized lattice-like structures that surround the cell bodies and proximal neurites of select classes of interneurons. Perineuronal nets are composed of lecticans, a family of chondroitin sulfate proteoglycans that includes aggrecan, brevican, neurocan, and versican. These lattice-like structures emerge late in postnatal brain development, coinciding with the ending of critical periods of brain development. Despite our knowledge of the presence of lecticans in perineuronal nets and their importance in regulating synaptic plasticity, we know little about the development or distribution of the extracellular proteases that are responsible for their cleavage and turnover. A subset of a large family of extracellular proteases (called a disintegrin and metalloproteinase with thrombospondin motifs [ADAMTS]) is responsible for endogenously cleaving lecticans. We therefore explored the expression pattern of two aggrecan-degrading ADAMTS family members, ADAMTS15 and ADAMTS4, in the hippocampus and neocortex. Here, we show that both lectican-degrading metalloproteases are present in these brain regions and that each exhibits a distinct temporal and spatial expression pattern. Adamts15 mRNA is expressed exclusively by parvalbumin-expressing interneurons during synaptogenesis, whereas Adamts4 mRNA is exclusively generated by telencephalic oligodendrocytes during myelination. Thus, ADAMTS15 and ADAMTS4 not only exhibit unique cellular expression patterns but their developmental upregulation by these cell types coincides with critical aspects of neural development. PMID:25349050

  15. MIB-MIP is a mycoplasma system that captures and cleaves immunoglobulin G.

    PubMed

    Arfi, Yonathan; Minder, Laetitia; Di Primo, Carmelo; Le Roy, Aline; Ebel, Christine; Coquet, Laurent; Claverol, Stephane; Vashee, Sanjay; Jores, Joerg; Blanchard, Alain; Sirand-Pugnet, Pascal

    2016-05-10

    Mycoplasmas are "minimal" bacteria able to infect humans, wildlife, and a large number of economically important livestock species. Mycoplasma infections include a spectrum of clinical manifestations ranging from simple fever to fulminant inflammatory diseases with high mortality rates. These infections are mostly chronic, suggesting that mycoplasmas have developed means to evade the host immune response. Here we present and functionally characterize a two-protein system from Mycoplasma mycoides subspecies capri that is involved in the capture and cleavage of IgG. The first component, Mycoplasma Ig binding protein (MIB), is an 83-kDa protein that is able to tightly bind to the Fv region of a wide range of IgG. The second component, Mycoplasma Ig protease (MIP), is a 97-kDa serine protease that is able to cleave off the VH domain of IgG. We demonstrate that MIB is necessary for the proteolytic activity of MIP. Cleavage of IgG requires a sequential interaction of the different partners of the system: first MIB captures the IgG, and then MIP is recruited to the MIB-IgG complex, enabling protease activity. MIB and MIP are encoded by two genes organized in tandem, with homologs found in the majority of pathogenic mycoplasmas and often in multiple copies. Phylogenetic studies suggest that genes encoding the MIB-MIP system are specific to mycoplasmas and have been disseminated by horizontal gene transfer. These results highlight an original and complex system targeting the host immunoglobulins, playing a potentially key role in the immunity evasion by mycoplasmas. PMID:27114507

  16. Granzyme B Cleaves Decorin, Biglycan and Soluble Betaglycan, Releasing Active Transforming Growth Factor-β1

    PubMed Central

    Boivin, Wendy A.; Shackleford, Marlo; Vanden Hoek, Amanda; Zhao, Hongyan; Hackett, Tillie L.; Knight, Darryl A.; Granville, David J.

    2012-01-01

    Objective Granzyme B (GrB) is a pro-apoptotic serine protease that contributes to immune-mediated target cell apoptosis. However, during inflammation, GrB accumulates in the extracellular space, retains its activity, and is capable of cleaving extracellular matrix (ECM) proteins. Recent studies have implicated a pathogenic extracellular role for GrB in cardiovascular disease, yet the pathophysiological consequences of extracellular GrB activity remain largely unknown. The objective of this study was to identify proteoglycan (PG) substrates of GrB and examine the ability of GrB to release PG-sequestered TGF-β1 into the extracellular milieu. Methods/Results Three extracellular GrB PG substrates were identified; decorin, biglycan and betaglycan. As all of these PGs sequester active TGF-β1, cytokine release assays were conducted to establish if GrB-mediated PG cleavage induced TGF-β1 release. Our data confirmed that GrB liberated TGF-β1 from all three substrates as well as from endogenous ECM and this process was inhibited by the GrB inhibitor 3,4-dichloroisocoumarin. The released TGF-β1 retained its activity as indicated by the induction of SMAD-3 phosphorylation in human coronary artery smooth muscle cells. Conclusion In addition to contributing to ECM degradation and the loss of tissue structural integrity in vivo, increased extracellular GrB activity is also capable of inducing the release of active TGF-β1 from PGs. PMID:22479366

  17. Rational design of self-cleaving pre-tRNA-ribonuclease P RNA conjugates.

    PubMed

    Frank, D N; Harris, M E; Pace, N R

    1994-09-01

    Ribonuclease P (RNaseP) generates the mature 5' end of tRNAs by removing 5'leader sequences from pre-tRNAs. In vitro, the RNA subunit is sufficient to catalyze this reaction and is therefore a ribozyme. The kinetic analysis of RNase P-mediated catalysis is complicated because product release is normally rate-limiting. Furthermore, the intermolecular nature of the cleavage reaction precludes many applications of in vitro selection schemes to the analysis of RNaseP. To examine and manipulate the RNase P function more effectively, we designed a pair of ribozymes in which the RNase P RNA is covalently linked to a pre-tRNA substrate. To facilitate intramolecular cleavage, pre-tRNA molecules were tethered to circulatory permuted RNaseP RNA molecules at nucleotides implicated in substrate binding. These "active-site-tethered" pre-tRNA-RNaseP RNA conjugates undergo accurate and efficient self-cleavage in vitro, with first-order reaction rates equivalent to the rate of the chemical step of the native RNase P reaction. Unlike most ribozymes, RNase P recognizes its substrate through tertiary RNA-RNA interactions, rather than through extensive Watson-Crick base-pairing. However, the development of the active-site-tethered conjugates has led us to create a sequence-specific endonuclease, termed Endo.P. In the Endo.P configuration, the 3'half of the pre-tRNA acceptor stem binds exogenous RNA substrates via Watson-Crick base-pairing; the bound substrate is subsequently cleaved at the predicted site. The demonstration of sequence-specific cleavage by Endo.P expands the potential of RNase P and its derivatives as reagents in gene therapy. PMID:8075082

  18. Fine mapping of 28S rRNA sites specifically cleaved in cells undergoing apoptosis.

    PubMed Central

    Houge, G; Robaye, B; Eikhom, T S; Golstein, J; Mellgren, G; Gjertsen, B T; Lanotte, M; Døskeland, S O

    1995-01-01

    Bona fide apoptosis in rat and human leukemia cells, rat thymocytes, and bovine endothelial cells was accompanied by limited and specific cleavage of polysome-associated and monosome-associated 28S rRNA, with 18S rRNA being spared. Specific 28S rRNA cleavage was observed in all instances of apoptotic death accompanied by internucleosomal DNA fragmentation, with cleavage of 28S rRNA and of DNA being linked temporally. This indicates that 28S rRNA fragmentation may be as general a feature of apoptosis as internucleosomal DNA fragmentation and that concerted specific cleavage of intra- and extranuclear polynucleotides occurs in apoptosis. Apoptosis-associated cleavage sites were mapped to the 28S rRNA divergent domains D2, D6 (endothelial cells), and D8. The D2 cuts occurred in hairpin loop junctions considered to be buried in the intact ribosome, suggesting that this rRNA region becomes a target for RNase attack in apoptotic cells. D8 was cleaved in two exposed UU(U) sequences in bulge loops. Treatment with agents causing necrotic cell death or aging of cell lysates failed to produce any detectable limited D2 cleavage but did produce a more generalized cleavage in the D8 region. Of potential functional interest was the finding that the primary cuts in D2 exactly flanked a 0.3-kb hypervariable subdomain (D2c), allowing excision of the latter. The implication of hypervariable rRNA domains in apoptosis represents the first association of any functional process with these enigmatic parts of the ribosomes. PMID:7891700

  19. Cell-specific and developmental expression of lectican-cleaving proteases in mouse hippocampus and neocortex

    PubMed Central

    Levy, C.; Brooks, J.M.; Chen, J.; Su, J.; Fox, M.A.

    2014-01-01

    Mounting evidence has demonstrated that a specialized extracellular matrix exists in the mammalian brain, and this glycoprotein-rich matrix contributes to many aspects of brain development and function. The most prominent supramolecular assembly of these ECM glycoproteins are perineuronal nets, specialized lattice-like structures that surround the cell bodies and proximal neurites of select classes of interneurons. Perineuronal nets are composed of lecticans – a family of chondroitin sulfate proteoglycans [CSPGs] that includes aggrecan, brevican, neurocan, and versican. The presence of these lattice-like structures emerge late in postnatal brain development and coincides with the ending of critical periods of brain development. Despite our knowledge of the presence of lecticans in perineuronal nets and their importance in regulating synaptic plasticity, we know little about the development or distribution of extracellular proteases that are responsible for their cleavage and turnover. A subset of the large “A Disintegrin and Metalloproteinase with Thrombospondin Motifs” (ADAMTS) family of extracellular proteases is responsible for endogenously cleaving lecticans. We therefore explored the expression pattern of 2 aggrecan-degrading ADAMTS family members, ADAMTS15 and ADAMTS4, in hippocampus and neocortex. Here, we show that both lectican-degrading metalloproteases are present in these brain regions and each exhibits a distinct temporal and spatial expression pattern. Adamts15 mRNA is expressed exclusively by Parvalbumin-expressing interneurons during synaptogenesis, whereas, Adamts4 mRNA is exclusively generated by telencephalic oligodendrocytes during myelination. Thus, ADAMTS15 and ADAMTS4 not only exhibit unique cellular expression patterns but their developmental upregulation by these cell types coincides with critical aspects of neural development. PMID:25349050

  20. Characterization of the Self-Cleaving Effector Protein NopE1 of Bradyrhizobium japonicum ▿

    PubMed Central

    Schirrmeister, Jana; Friedrich, Lars; Wenzel, Mandy; Hoppe, Markus; Wolf, Christine; Göttfert, Michael; Zehner, Susanne

    2011-01-01

    NopE1 is a type III-secreted protein of the symbiont Bradyrhizobium japonicum which is expressed in nodules. In vitro it exhibits self-cleavage in a duplicated domain of unknown function (DUF1521) but only in the presence of calcium. Here we show that either domain is self-sufficient for cleavage. An exchange of the aspartic acid residue at the cleavage site with asparagine prevented cleavage; however, cleavage was still observed with glutamic acid at the same position, indicating that a negative charge at the cleavage site is sufficient. Close to each cleavage site, an EF-hand-like motif is present. A replacement of one of the conserved aspartic acid residues with alanine prevented cleavage at the neighboring site. Except for EDTA, none of several protease inhibitors blocked cleavage, suggesting that a known protease-like mechanism is not involved in the reaction. In line with this, the reaction takes place within a broad pH and temperature range. Interestingly, magnesium, manganese, and several other divalent cations did not induce cleavage, indicating a highly specific calcium-binding site. Based on results obtained by blue-native gel electrophoresis, it is likely that the uncleaved protein forms a dimer and that the fragments of the cleaved protein oligomerize. A database search reveals that the DUF1521 domain is present in proteins encoded by Burkholderia phytofirmans PsNJ (a plant growth-promoting betaproteobacterium) and Vibrio coralliilyticus ATCC BAA450 (a pathogenic gammaproteobacterium). Obviously, this domain is more widespread in proteobacteria, and it might contribute to the interaction with hosts. PMID:21642459