Reactions involving the heterolytic cleavage of carbon-element σ-bonds by Grignard reagents

NASA Astrophysics Data System (ADS)

Polivin, Yurii N.; Karakhanov, Robert A.; Postnov, Victor N.

1990-03-01

The reactions involving the heterolysis of the C-O, C-C, C-N, C-S, C-Cl, etc. bonds by organomagnesium compounds are examined and the nature of this interesting phenomenon is analysed. On the basis of the analysis of the characteristic features of the cleavage under discussion, it is shown that the heterolysis of the carbon-element bond is, firstly, a general reaction for all classes of organic compounds (provided that two conditions are observed: the substrate molecule must fragment into two stable species — a carbonium ion and an anion — and the strength of the Lewis acid properties should be adequate for the occurrence of the above reaction) and, secondly, the heterolysis of the carbon-element bond is one of the independent pathways in the reactions of the Grignard reagents. The bibliography includes 158 references.

Elucidating Direct Photolysis Mechanisms of Different Dissociation Species of Norfloxacin in Water and Mg2+ Effects by Quantum Chemical Calculations.

PubMed

Wang, Se; Wang, Zhuang

2017-11-11

The study of pollution due to combined antibiotics and metals is urgently needed. Photochemical processes are an important transformation pathway for antibiotics in the environment. The mechanisms underlying the effects of metal-ion complexation on the aquatic photochemical transformation of antibiotics in different dissociation forms are crucial problems in science, and beg solutions. Herein, we investigated the mechanisms of direct photolysis of norfloxacin (NOR) in different dissociation forms in water and metal ion Mg 2+ effects using quantum chemical calculations. Results show that different dissociation forms of NOR had different maximum electronic absorbance wavelengths (NOR 2+ < NOR⁰ < NOR⁺) and showed different photolysis reactivity. Analysis of transition states (TS) and reaction activation energies ( E a ) indicated NOR⁺ generally underwent loss of the piperazine ring (C10-N13 bond cleavage) and damage to piperazine ring (N13-C14 bond cleavage). For NOR 2+ , the main direct photolysis pathways were de-ethylation (N7-C8 bond cleavage) and decarboxylation (C2-C5 bond cleavage). Furthermore, the presence of Mg 2+ changed the order of the wavelength at maximum electronic absorbance (NOR⁺-Mg 2+ < NOR⁰-Mg 2+ < NOR 2+ -Mg 2+ ) and increased the intensities of absorbance peaks of all three dissociation species of NOR, implying that Mg 2+ played an important role in the direct photolysis of NOR⁰, NOR⁺, and NOR 2+ . The calculated TS results indicated that the presence of Mg 2+ increased E a for most direct photolysis pathways of NOR, while it decreased E a for some direct photolysis pathways such as the loss of the piperazine ring and the damage of the piperazine ring of NOR⁰ and the defluorination of NOR⁺.

Photoinduced reactions of both 2-formyl-2H-azirine and isoxazole: A theoretical study based on electronic structure calculations and nonadiabatic dynamics simulations.

PubMed

Cao, Jun

2015-06-28

In the present work, the combined electronic structure calculations and dynamics simulations have been performed to explore photocleavages of 2-formyl-2H-azirine and isoxazole in the gas phase and the subsequent rearrangement reactions. The carbonyl n → π(*) transition induces a cleavage of the C-N single bond of 2-formyl-2H-azirine to yield β-formylvinylnitrene in open-shell singlet state. However, the n → π(*) excitation of the imine chromophore results in a cleavage of the C-C single bond, producing a nitrile ylide intermediate through an internal conversion to the ground state. β-formylvinylnitrene and nitrile ylide with the carbonyl group are easily transformed into 2-formyl-2H-azirine and oxazole, respectively. The N-O bond cleavages on both S1((1)ππ(*)) and S2((1)nNπ(*)) of isoxazole are ultrafast processes, and they give products of 2-formyl-2H-azirine, 3-formylketenimine, HCN + CHCHO, and HCO + CHCHN. Both 2H-azirines and ketenimines were suggested to be formed from the triplet vinylnitrenes by intersystem crossing in the previous studies. However, our calculations show that the singlet β-formylvinylnitrene is responsible for the formation of 2-formyl-2H-azirine and 3-formylketenimine, and the singlet vinylnitrenes can play a key role in the photoinduced reactions of both 2H-azirines and isoxazoles.

Cleavage of Sn-C and S-C(alkyl) bonds on an organotin scaffold: synthesis and characterization of a novel organotin-sulfite cluster bearing methyltin- and dimethyltin fragments.

PubMed

Shankar, Ravi; Jain, Archana; Kociok-Köhn, Gabriele; Mahon, Mary F; Molloy, Kieran C

2010-05-17

Hydrolysis of the mixed-ligand dimethyltin(ethoxy)ethanesulfonate, [Me(2)Sn(OEt)(OSO(2)Et)](n) (1a) in moist hexane proceeds via disproportionation and partial cleavage of Sn-C and S-C bonds to afford a novel oxo-/hydroxo- organotin cluster of the composition [(Me(2)Sn)(MeSn)(4)(OSO(2)Et)(2)(OH)(4)(O)(2)(SO(3))(2)] (1) bearing both mono- and dimethyltin fragments and in situ generated sulfite (SO(3)(2-)) anion in the structural framework. On the other hand, similar reactions with analogous mixed ligand diorganotin precursors, [R(2)Sn(OR(1))(OSO(2)R(1))](n) (R = n-Bu, R(1) = Et (2a); R = Et, R(1) = Me (3a)), result in the formation of tetranuclear diorganotin clusters, [{(n-Bu(2)Sn)(2)(OH)(OSO(2)Et)}O](2) (2) and [(Et(2)Sn)(4)(OH)(O)(2)(OSO(2)Me)(3)] (3), respectively. The activation of the Sn-C or S-C bond is not observed in these cases. These findings provide a preliminary insight into the unusual reactivity of 1a under hydrolytic conditions.

Theoretical study of the alkaline hydrolysis of an aza-β-lactam derivative of clavulanic acid

NASA Astrophysics Data System (ADS)

Garcías, Rafael C.; Coll, Miguel; Donoso, Josefa; Muñoz, Francisco

2003-04-01

DFT calculations based on the hybrid functional B3LYP/6-31+G * were used to study the alkaline hydrolysis of an aza-clavulanic acid, which results from the substitution of the carbon atom at position 6 in clavulanic acid by a nitrogen atom. The presence of the nitrogen atom endows the compound with special properties; in fact, once formed, the tetrahedral intermediate can evolve with cleavage of the N 4-C 7 or N 6-C 7 bond, which obviously leads to different reaction products. These differential bond cleavages may play a central role in the inactivation of β-lactamases, so the compound may be a powerful inactivator of these enzymes.

METABOLIC ENGINEERING TO DEVELOP A PATHWAY FOR THE SELECTIVE CLEAVAGE OF CARBON-NITROGEN BONDS

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

John J. Kilbane III

The objective of the project is to develop biochemical pathways for the selective cleavage of C-N bonds in molecules found in petroleum. The initial phase of the project will focus on the isolation or development of an enzyme capable of cleaving the C-N bond in aromatic amides, specifically 2-aminobiphenyl. The objective of the second phase of the research will be to construct a biochemical pathway for the selective removal of nitrogen from carbazole by combining the carA genes from Sphingomonas sp. GTIN11 with the gene(s) encoding an appropriate amidase. The objective of the final phase of the project will bemore » to develop derivative CN bond cleaving enzymes that have broader substrate ranges and to demonstrate the use of such strains to selectively remove nitrogen from petroleum. The project is on schedule and no major difficulties have been encountered. During the first year of the project (October, 2002-September, 2003) enrichment culture experiments have resulted in the isolation of promising cultures that may be capable of cleaving C-N bonds in aromatic amides, several amidase genes have been cloned and are currently undergoing directed evolution to obtain derivatives that can cleave C-N bonds in aromatic amides, and the carA genes from Sphingomonas sp. GTIN11, and Pseudomonas resinovorans CA10 were cloned in vectors capable of replicating in Escherichia coli. Future research will address expression of these genes in Rhodococcus erythropolis. Enrichment culture experiments and directed evolution experiments continue to be a main focus of research activity and further work is required to obtain an appropriate amidase that will selectively cleave C-N bonds in aromatic substrates. Once an appropriate amidase gene is obtained it must be combined with genes encoding an enzyme capable of converting carbazole to 2'aminobiphenyl-2,3-diol: specifically carA genes. The carA genes from two sources have been cloned and are ready for construction of C-N bond cleavage pathway. The construction of a new metabolic pathway to selectively remove nitrogen from carbazole and other molecules typically found in petroleum should lead to the development of a process to improve oil refinery efficiency by reducing the poisoning, by nitrogen, of catalysts used in the hydrotreating and catalytic cracking of petroleum.« less

5-Nitrosalicylic Acid as a Novel Matrix for In-Source Decay in Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry

PubMed Central

Asakawa, Daiki

2013-01-01

The matrix-assisted laser desorption/ionization in-source decay (MALDI-ISD) of peptides and glycans was studied using an oxidizing chemical, 5-nitrosalicylic acid (5-NSA) as the matrix. The use of 5-NSA for the MALDI-ISD of peptides and glycans promoted fragmentation pathways involving “hydrogen-deficient” radical precursors. Hydrogen abstraction from peptides resulted in the production of a “hydrogen-deficient” peptide radical that contained a radical site on the amide nitrogen in the peptide backbone with subsequent radical-induced cleavage at the Cα–C bonds. Cleavage at the Cα–C bond leads to the production of an a•/x fragment pair and the radical a• ions then undergo further hydrogen abstraction to form a ions after Cα–C bond cleavage. Since the Pro residue does not contain a nitrogen-centered radical site, Cα–C bond cleavage does not occur at this site. Alternatively, the specific cleavage of CO−N bonds leads to a b•/y fragment pair at Xxx−Pro which occurs via hydrogen abstraction from the Cα−H in the Pro residue. In contrast, “hydrogen-deficient” glycan radicals were generated by hydrogen abstraction from hydroxyl groups in glycans. Both glycosidic and cross-ring cleavages occurred as the result of the degradation of “hydrogen-deficient” glycan radicals. Cross-ring cleavage ions are potentially useful in linkage analysis, one of the most critical steps in the characterization of glycans. Moreover, isobaric glycans could be distinguished by structure specific ISD ions, and the molar ratio of glycan isomers in a mixture can be estimated from their fragment ions abundance ratios. MALDI-ISD with 5-NSA could be a useful method for the sequencing of peptides including the location of post-translational modifications, identification and semi-quantitative analysis of mixtures of glycan isomers. PMID:24860709

Microbial cleavage of organic C-S bonds

DOEpatents

Kilbane, J.J. II.

1994-10-25

A microbial process is described for selective cleavage of organic C-S bonds which may be used for reducing the sulfur content of sulfur-containing organic carbonaceous materials. Microorganisms of Rhodococcus rhodochrous and Bacillus sphaericus have been found which have the ability of selective cleavage of organic C-S bonds. Particularly preferred microorganisms are Rhodococcus rhodochrous strain ATCC 53968 and Bacillus sphaericus strain ATCC 53969 and their derivatives.

Microbial cleavage of organic C-S bonds

DOEpatents

Kilbane, II, John J.

1994-01-01

A microbial process for selective cleavage of organic C--S bonds which may be used for reducing the sulfur content of sulfur-containing organic carbonaceous materials, Microorganisms of Rhodococcus rhodochrous and Bacillus sphaericus have been found which have the ability of selective cleavage of organic C--S bonds. Particularly preferred microorganisms are Rhodococcus rhodochrous strain ATCC 53968 and Bacillus sphaericus strain ATCC 53969 and their derivatives.

Degradation of Glyphosate by Mn-Oxide May Bypass Sarcosine and Form Glycine Directly after C-N Bond Cleavage.

PubMed

Li, Hui; Wallace, Adam F; Sun, Mingjing; Reardon, Patrick; Jaisi, Deb P

2018-02-06

Glyphosate is the active ingredient of the common herbicide Roundup. The increasing presence of glyphosate and its byproducts has raised concerns about its potential impact on the environment and human health. In this research, we investigated abiotic pathways of glyphosate degradation as catalyzed by birnessite under aerobic and neutral pH conditions to determine whether certain pathways have the potential to generate less harmful intermediate products. Nuclear magnetic resonance (NMR) spectroscopy and high-performance liquid chromatography (HPLC) were utilized to identify and quantify reaction products, and density functional theory (DFT) calculations were used to investigate the bond critical point (BCP) properties of the C-N bond in glyphosate and Mn(IV)-complexed glyphosate. We found that sarcosine, the commonly recognized precursor to glycine, was not present at detectable levels in any of our experiments despite the fact that its half-life (∼13.6 h) was greater than our sampling intervals. Abiotic degradation of glyphosate largely followed the glycine pathway rather than the AMPA (aminomethylphosphonic acid) pathway. Preferential cleavage of the phosphonate adjacent C-N bond to form glycine directly was also supported by our BCP analysis, which revealed that this C-N bond was disproportionately affected by the interaction of glyphosate with Mn(IV). Overall, these results provide useful insights into the potential pathways through which glyphosate may degrade via relatively benign intermediates.

Catalytic Arylation and Vinylation Reactions Directed by Anionic Oxygen Functions via Cleavage of C - H and C - C Bonds

NASA Astrophysics Data System (ADS)

Satoh, Tetsuya; Miura, Masahiro

Aromatic compounds having oxygen-containing substituents such as phenols, phenyl ketones, benzyl alcohols, and benzoic acids undergo regioselective arylation and vinylation via C-H bond cleavage in the presence of transition-metal catalysts. The latter two substrates are also arylated and vinylated via C-C bond cleavage accompanied by liberation of ketones and CO2, respectively. Coordination of their anionic oxygen to the metal center is the key to activate the inert bonds effectively and regioselectively. The recent progress of these oxygen-directed reactions is summarized herein.

Theoretical Study on the Catalytic Reduction Mechanism of NO by CO on Tetrahedral Rh4 Subnanocluster.

PubMed

Yang, Hua-Qing; Fu, Hong-Quan; Su, Ben-Fang; Xiang, Bo; Xu, Qian-Qian; Hu, Chang-Wei

2015-11-25

The catalytic mechanism of 2NO + 2CO → N2 + 2CO2 on Rh4 cluster has been systematically investigated on the ground and first excited states at the B3LYP/6-311+G(2d),SDD level. For the overall reaction of 2NO + 2CO → N2 + 2CO2, the main reaction pathways take place on the facet site rather than the edge site of the Rh4 cluster. The turnover frequency (TOF) determining transition states are characteristic of the second N-O bond cleavage with rate constant k4 = 1.403 × 10(11) exp (-181 203/RT) and the N-N bond formation for the intermediate N2O formation with rate constant k2 = 3.762 × 10(12) exp (-207 817/RT). The TOF-determining intermediates of (3)N(b)Rh4NO and (3)N(b)Rh4O(b)(NO) are associated with the nitrogen-atom molecular complex, which is in agreement with the experimental observation of surface nitrogen. On the facet site of Rh4 cluster, the formation of CO2 stems solely from the recombination of CO and O atom, while N2 originates partly from the recombination of two N atoms and partly from the decomposition of N2O. For the N-O bond cleavage or the synchronous N-O bond cleavage and C-O bond formation, the neutral Rh4 cluster exhibits better catalytic performance than the cationic Rh4(+) cluster. Alternatively, for N-N bond formation, the cationic Rh4(+) cluster possesses better catalytic performance than the neutral Rh4 cluster.

Copper-Catalyzed Oxidative Reaction of β-Keto Sulfones with Alcohols via C-S Bond Cleavage: Reaction Development and Mechanism Study.

PubMed

Du, Bingnan; Wang, Wenmin; Wang, Yang; Qi, Zhenghang; Tian, Jiaqi; Zhou, Jie; Wang, Xiaochen; Han, Jianlin; Ma, Jing; Pan, Yi

2018-02-16

A Cu-catalyzed cascade oxidative radical process of β-keto sulfones with alcohols has been achieved by using oxygen as an oxidant. In this reaction, β-keto sulfones were converted into sulfinate esters under the oxidative conditions via cleavage of C-S bond. Experimental and computational studies demonstrate that a new pathway is involved in this reaction, which proceeds through the formation of the key four-coordinated Cu II intermediate, O-O bond homolysis induced C-S bond cleavage and Cu-catalyzed esterification to form the final products. This reaction provides a new strategy to sulfonate esters and enriches the research content of C-S bond cleavage and transformations. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structures of Highly Twisted Amides Relevant to Amide N-C Cross-Coupling: Evidence for Ground-State Amide Destabilization.

PubMed

Pace, Vittorio; Holzer, Wolfgang; Meng, Guangrong; Shi, Shicheng; Lalancette, Roger; Szostak, Roman; Szostak, Michal

2016-10-04

Herein, we show that acyclic amides that have recently enabled a series of elusive transition-metal-catalyzed N-C activation/cross-coupling reactions are highly twisted around the N-C(O) axis by a new destabilization mechanism of the amide bond. A unique effect of the N-glutarimide substituent, leading to uniformly high twist (ca. 90°) irrespective of the steric effect at the carbon side of the amide bond has been found. This represents the first example of a twisted amide that does not bear significant steric hindrance at the α-carbon atom. The (15) N NMR data show linear correlations between electron density at nitrogen and amide bond twist. This study strongly supports the concept of amide bond ground-state twist as a blueprint for activation of amides toward N-C bond cleavage. The new mechanism offers considerable opportunities for organic synthesis and biological processes involving non-planar amide bonds. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Aliphatic C-C Bond Cleavage in α-Hydroxy Ketones by a Dioxygen-Derived Nucleophilic Iron-Oxygen Oxidant.

PubMed

Bhattacharya, Shrabanti; Rahaman, Rubina; Chatterjee, Sayanti; Paine, Tapan K

2017-03-17

A nucleophilic iron-oxygen oxidant, formed in situ in the reaction between an iron(II)-benzilate complex and O 2 , oxidatively cleaves the aliphatic C-C bonds of α-hydroxy ketones. In the cleavage reaction, α-hydroxy ketones without any α-C-H bond afford a 1:1 mixture of carboxylic acid and ketone. Isotope labeling studies established that one of the oxygen atoms from dioxygen is incorporated into the carboxylic acid product. Furthermore, the iron(II) complex cleaves an aliphatic C-C bond of 17-α-hydroxyprogesterone affording androstenedione and acetic acid. The O 2 -dependent aliphatic C-C bond cleavage of α-hydroxy ketones containing no α-C-H bond bears similarity to the lyase activity of the heme enzyme, cytochrome P450 17A1 (CYP17A1). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Decomposition of amino diazeniumdiolates (NONOates): Molecular mechanisms

DOE PAGES

Shaikh, Nizamuddin; Valiev, Marat; Lymar, Sergei V.

2014-08-23

Although diazeniumdiolates (X[N(O)NO] -) are extensively used in biochemical, physiological, and pharmacological studies due to their ability to release NO and/or its congeneric nitroxyl, the mechanisms of these processes remain obscure. In this work, we used a combination of spectroscopic, kinetic, and computational techniques to arrive at a quantitatively consistent molecular mechanism for decomposition of amino diazeniumdiolates (amino NONOates: R 2N[N(O)NO] -, where R = —N(C 2H 5) 2(1), —N(C 3H 4NH 2) 2(2), or —N(C 2H 4NH 2) 2(3)). Decomposition of these NONOates is triggered by protonation of their [NN(O)NO] - group with the apparent pKa and decomposition ratemore » constants of 4.6 and 1 s -1 for 1; 3.5 and 0.083 s -1 for 2; and 3.8 and 0.0033 s -1 for 3. Although protonation occurs mainly on the O atoms of the functional group, only the minor R 2N(H)N(O)NO tautomer (population ~ 10 -7, for 1) undergoes the N—N heterolytic bond cleavage (k d ~ 107 s -1 for 1) leading to amine and NO. Decompositions of protonated amino NONOates are strongly temperature-dependent; activation enthalpies are 20.4 and 19.4 kcal/mol for 1 and 2, respectively, which includes contributions from both the tautomerization and bond cleavage. Thus, the bond cleavage rates exhibit exceptional sensitivity to the nature of R substituents which strongly modulate activation entropy. At pH < 2, decompositions of all three NONOates that have been investigated are subject to additional acid catalysis that occurs through di-protonation of the [NN(O)NO] - group.« less

Aqueous phase hydrodeoxygenation of polyols over Pd/WO3-ZrO2: Role of Pd-WO3 interaction and hydrodeoxygenation pathway

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

Liu, Changjun; Sun, Junming; Brown, Heather M.

Aqueous-phase hydrodeoxygenation of sugar and sugar-derived molecules can be used to produce a range of alkanes and oxygenates. In this paper, we have identified the reaction intermediates and reaction chemistry for the aqueous-phase hydrodeoxygenation of sorbitol over a bifunctional catalyst (Pt/SiO2–Al2O3) that contains both metal (Pt) and acid (SiO2–Al2O3) sites. A wide variety of reactions occur in this process including Csingle bondC bond cleavage, Csingle bondO bond cleavage, and hydrogenation reactions. The key Csingle bondC bond cleavage reactions include: retro-aldol condensation and decarbonylation, which both occur on metal catalytic sites. Dehydration is the key Csingle bondO bond cleavage reaction andmore » occurs on acid catalytic sites. Sorbitol initially undergoes dehydration and ring closure to produce cyclic C6 molecules or retro-aldol condensation reactions to produce primarily C3 polyols. Isosorbide is the major final product from sorbitol dehydration. Isosorbide then undergoes ring opening hydrogenation reactions and a dehydration/hydrogenation step to form 1,2,6-hexanetriol. The hexanetriol is then converted into hexanol and hexane by dehydration/hydrogenation. Smaller oxygenates are produced by Csingle bondC bond cleavage. These smaller oxygenates undergo dehydration/hydrogenation reactions to produce alkanes from C1–C5. The results from this paper suggest that hydrodeoxygenation chemistry can be tuned to make a wide variety of products from biomass-derived oxygenates.« less

N-Methylamino Pyrimidyl Amides (MAPA): Highly Reactive, Electronically-Activated Amides in Catalytic N-C(O) Cleavage.

PubMed

Meng, Guangrong; Lalancette, Roger; Szostak, Roman; Szostak, Michal

2017-09-01

Despite recent progress in catalytic cross-coupling technologies, the direct activation of N-alkyl-N-aryl amides has been a challenging transformation. Here, we report the first Suzuki cross-coupling of N-methylamino pyrimidyl amides (MAPA) enabled by the controlled n N → π Ar conjugation and the resulting remodeling of the partial double bond character of the amide bond. The new mode of amide activation is suitable for generating acyl-metal intermediates from unactivated primary and secondary amides.

Structural and Biochemical Characterization of Organotin and Organolead Compounds Binding to the Organomercurial Lyase MerB Provide New Insights into Its Mechanism of Carbon–Metal Bond Cleavage

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

Wahba, Haytham M.; Stevenson, Michael J.; Mansour, Ahmed

2017-01-03

The organomercurial lyase MerB has the unique ability to cleave carbon–Hg bonds, and structural studies indicate that three residues in the active site (C96, D99, and C159 in E. coli MerB) play important roles in the carbon–Hg bond cleavage. However, the role of each residue in carbon–metal bond cleavage has not been well-defined. To do so, we have structurally and biophysically characterized the interaction of MerB with a series of organotin and organolead compounds. Studies with two known inhibitors of MerB, dimethyltin (DMT) and triethyltin (TET), reveal that they inhibit by different mechanisms. In both cases the initial binding ismore » to D99, but DMT subsequently binds to C96, which induces a conformation change in the active site. In contrast, diethyltin (DET) is a substrate for MerB and the SnIV product remains bound in the active site in a coordination similar to that of HgII following cleavage of organomercurial compounds. The results with analogous organolead compounds are similar in that trimethyllead (TML) is not cleaved and binds only to D99, whereas diethyllead (DEL) is a substrate and the PbIV product remains bound in the active site. Binding and cleavage is an exothermic reaction, while binding to D99 has negligible net heat flow. These results show that initial binding of organometallic compounds to MerB occurs at D99 followed, in some cases, by cleavage and loss of the organic moieties and binding of the metal ion product to C96, D99, and C159. The N-terminus of MerA is able to extract the bound PbVI but not the bound SnIV. These results suggest that MerB could be utilized for bioremediation applications, but certain organolead and organotin compounds may present an obstacle by inhibiting the enzyme.« less

Decomposition of amino diazeniumdiolates (NONOates): molecular mechanisms.

PubMed

Shaikh, Nizamuddin; Valiev, Marat; Lymar, Sergei V

2014-12-01

Although diazeniumdiolates (X[N(O)NO](-)) are extensively used in biochemical, physiological, and pharmacological studies due to their ability to release NO and/or its congeneric nitroxyl, the mechanisms of these processes remain obscure. In this work, we used a combination of spectroscopic, kinetic, and computational techniques to arrive at a quantitatively consistent molecular mechanism for decomposition of amino diazeniumdiolates (amino NONOates: R2N[N(O)NO](-), where R=N(C2H5)2 (1), N(C3H4NH2)2 (2), or N(C2H4NH2)2 (3)). Decomposition of these NONOates is triggered by protonation of their [NN(O)NO](-) group with the apparent pKa and decomposition rate constants of 4.6 and 1 s(-1) for 1; 3.5 and 0.083 s(-1) for 2; and 3.8 and 0.0033 s(-1) for 3. Although protonation occurs mainly on the O atoms of the functional group, only the minor R2N(H)N(O)NO tautomer (population ~10(-7), for 1) undergoes the NN heterolytic bond cleavage (kd~10(7) s(-1) for 1) leading to amine and NO. Decompositions of protonated amino NONOates are strongly temperature-dependent; activation enthalpies are 20.4 and 19.4 kcal/mol for 1 and 2, respectively, which includes contributions from both the tautomerization and bond cleavage. The bond cleavage rates exhibit exceptional sensitivity to the nature of R substituents which strongly modulate activation entropy. At pH<2, decompositions of all three NONOates that have been investigated are subject to additional acid catalysis that occurs through di-protonation of the [NN(O)NO](-) group. Copyright © 2014 Elsevier Inc. All rights reserved.

Iron-Catalyzed Intramolecular C(sp(2))-N Cyclization of 1-(N-Arylpyrrol-2-yl)ethanone O-Acetyl Oximes toward Pyrrolo[1,2-a]quinoxaline Derivatives.

PubMed

Zhang, Zhiguo; Li, Junlong; Zhang, Guisheng; Ma, Nana; Liu, Qingfeng; Liu, Tongxin

2015-07-02

An efficient and convenient iron-catalyzed protocol has been developed for the synthesis of substituted pyrrolo[1,2-a]quinoxalines from 1-(N-arylpyrrol-2-yl)ethanone O-acetyl oximes through N-O bond cleavage and intramolecular directed C-H arylation reactions in acetic acid.

Degradation of neurotensin by rat brain synaptic membranes: involvement of a thermolysin-like metalloendopeptidase (enkephalinase), angiotensin-converting enzyme, and other unidentified peptidases.

PubMed

Checler, F; Vincent, J P; Kitabgi, P

1983-08-01

Neurotensin was inactivated by membrane-bound and soluble degrading activities present in purified preparations of rat brain synaptic membranes. Degradation products were identified by HPLC and amino acid analysis. The major points of cleavage of neurotensin were the Arg8-Arg9, Pro10-Tyr11, and Tyr11-Ile12 peptide bonds with the membrane-bound activity and the Arg8-Arg9 and Pro10-Tyr11 bonds with the soluble activity. Several lines of evidence indicated that the cleavage of the Arg8-Arg9 bond by the membrane-bound activity resulted mainly from the conversion of neurotensin1-10 to neurotensin1-8 by a dipeptidyl carboxypeptidase. In particular, captopril inhibited this cleavage with an IC50 (5.7 nM) close to its K1 (7 nM) for angiotensin-converting enzyme. Thiorphan inhibited the cleavage at the Tyr11-Ile12 bond by the membrane-bound activity with an IC50 (17 nM) similar to its K1 (4.7 nM) for enkephalinase. Both cleavages were inhibited by 1,10-phenanthroline. These and other data suggested that angiotensin-converting enzyme and a thermolysin-like metalloendopeptidase (enkephalinase) were the membrane-bound peptidases responsible for cleavages at the Arg8-Arg9 and Tyr11-Ile12 bonds, respectively. In contrast, captopril had no effect on the cleavage at the Arg8-Arg9 bond by the soluble activity, indicating that the enzyme responsible for this cleavage was different from angiotensin-converting enzyme. The cleavage at the Pro10-Tyr11 bond by both the membrane-bound and the soluble activities appeared to be catalyzed by an endopeptidase different from known brain proline endopeptidases. The possibility is discussed that the enzymes described here participate in physiological mechanisms of neurotensin inactivation at the synaptic level.

Copper-catalyzed aerobic oxidative N-S bond functionalization for C-S bond formation: regio- and stereoselective synthesis of sulfones and thioethers.

PubMed

Li, Xianwei; Xu, Yanli; Wu, Wanqing; Jiang, Chang; Qi, Chaorong; Jiang, Huanfeng

2014-06-23

A regio- and stereoselective synthesis of sulfones and thioethers by means of Cu(I)-catalyzed aerobic oxidative N-S bond cleavage of sulfonyl hydrazides, followed by cross-coupling reactions with alkenes and aromatic compounds to form the C sp 2-S bond, is described herein. N2 and H2O are the byproducts of this transformation, thus offering an environmentally benign process with a wide range of potential applications in organic synthesis and medicinal chemistry. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Energetics and dynamics of the fragmentation reactions of protonated peptides containing methionine sulfoxide or aspartic acid via energy- and time-resolved surface induced dissociation.

PubMed

Lioe, Hadi; Laskin, Julia; Reid, Gavin E; O'Hair, Richard A J

2007-10-25

The surface-induced dissociation (SID) of six model peptides containing either methionine sulfoxide or aspartic acid (GAILM(O)GAILR, GAILM(O)GAILK, GAILM(O)GAILA, GAILDGAILR, GAILDGAILK, and GAILDGAILA) have been studied using a specially configured Fourier transform ion-cyclotron resonance mass spectrometer (FT-ICR MS). In particular, we have investigated the energetics and dynamics associated with (i) preferential cleavage of the methionine sulfoxide side chain via the loss of CH3SOH (64 Da), and (ii) preferential cleavage of the amide bond C-terminal to aspartic acid. The role of proton mobility in these selective bond cleavage reactions was examined by changing the C-terminal residue of the peptide from arginine (nonmobile proton conditions) to lysine (partially mobile proton conditions) to alanine (mobile proton conditions). Time- and energy-resolved fragmentation efficiency curves (TFECs) reveal that selective cleavages due to the methionine sulfoxide and aspartic acid residues are characterized by slow fragmentation kinetics. RRKM modeling of the experimental data suggests that the slow kinetics is associated with large negative entropy effects and these may be due to the presence of rearrangements prior to fragmentation. It was found that the Arrhenius pre-exponential factor (A) for peptide fragmentations occurring via selective bond cleavages are 1-2 orders of magnitude lower than nonselective peptide fragmentation reactions, while the dissociation threshold (E0) is relatively invariant. This means that selective bond cleavage is kinetically disfavored compared to nonselective amide bond cleavage. It was also found that the energetics and dynamics for the preferential loss of CH3SOH from peptide ions containing methionine sulfoxide are very similar to selective C-terminal amide bond cleavage at the aspartic acid residue. These results suggest that while preferential cleavage can compete with amide bond cleavage energetically, dynamically, these processes are much slower compared to amide bond cleavage, explaining why these selective bond cleavages are not observed if fragmentation is performed under mobile proton conditions. This study further affirms that fragmentation of peptide ions in the gas phase are predominantly governed by entropic effects.

Condensed tannins: A novel rearrangement of procyanidins and prodelphinidins in thiolytic cleavage

Treesearch

G. Wayne McGraw; Jan P. Steynberg; Richard W. Hemingway

1993-01-01

Conditions commonly used for the thiolytic cleavage of interflavanoid bonds of condensed tannins also result in cleavage of the C4 to C10 bond of flavan units. Subsequenet lectrophilic attack of the C4 carbocation on the C2' or C6' of the B-ring, and loss of phloroglucinol (the A-ring), result in the formation of a mixture of 1,3-dithiobenzyl-2,4,s,6-...

Radical Cation Salt-initiated Aerobic C-H Phosphorylation of N-Benzylanilines: Synthesis of a-Aminophosphonates.

PubMed

Jia, Xiao Dong; Liu, Xiaofei; Yuan, Yu; Li, Pengfei; Hou, Wentao; He, Kaixuan

2018-06-03

A radical cation salt-initiated phosphorylation of N-benzylanilines was realized through the aerobic oxidation of sp3 C-H bond, providing a series of α-aminophosphonates in high yields. The investigation of the reaction scope revealed that this mild catalyst system is superior in good functional group tolerance and high reaction efficiency. The mechanistic study implied that the cleavage of the sp3 C-H bond was involved in the rate-determining step. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A Novel Mechanism for Resistance to the Antimetabolite N-Phosphonoacetyl-l-Aspartate by Helicobacter pylori

PubMed Central

Burns, Brendan P.; Mendz, George L.; Hazell, Stuart L.

1998-01-01

The mechanism of resistance to N-phosphonoacetyl-l-aspartate (PALA), a potent inhibitor of aspartate carbamoyltransferase (which catalyzes the first committed step of de novo pyrimidine biosynthesis), in Helicobacter pylori was investigated. At a 1 mM concentration, PALA had no effects on the growth and viability of H. pylori. The inhibitor was taken up by H. pylori cells and the transport was saturable, with a Km of 14.8 mM and a Vmax of 19.1 nmol min−1 μl of cell water−1. By 31P nuclear magnetic resonance (NMR) spectroscopy, both PALA and phosphonoacetate were shown to have been metabolized in all isolates of H. pylori studied. A main metabolic end product was identified as inorganic phosphate, suggesting the presence of an enzyme activity which cleaved the carbon-phosphorus (C-P) bonds. The kinetics of phosphonate group cleavage was saturable, and there was no evidence for substrate inhibition at higher concentrations of either compound. C-P bond cleavage activity was temperature dependent, and the activity was lost in the presence of the metal chelator EDTA. Other cleavages of PALA were observed by 1H NMR spectroscopy, with succinate and malate released as main products. These metabolic products were also formed when N-acetyl-l-aspartate was incubated with H. pylori lysates, suggesting the action of an aspartase. Studies of the cellular location of these enzymes revealed that the C-P bond cleavage activity was localized in the soluble fraction and that the aspartase activity appeared in the membrane-associated fraction. The results suggested that the two H. pylori enzymes transformed the inhibitor into noncytotoxic products, thus providing the bacterium with a mechanism of resistance to PALA toxicity which appears to be unique. PMID:9791105

Silylene-Nickel Promoted Cleavage of B-O Bonds: From Catechol Borane to the Hydroborylene Ligand.

PubMed

Hadlington, Terrance J; Szilvási, Tibor; Driess, Matthias

2017-06-19

The first 16 valence electron [bis(NHC)](silylene)Ni 0 complex 1, [( TMS L)ClSi:→Ni(NHC) 2 ], bearing the acyclic amido-chlorosilylene ( TMS L)ClSi: ( TMS L=N(SiMe 3 )Dipp; Dipp=2,6-Pr i 2 C 6 H 4 ) and two NHC ligands (N-heterocyclic carbene=:C[(Pr i )NC(Me)] 2 ) was synthesized in high yield and structurally characterized. Compound 1 is capable of facile dihydrogen activation under ambient conditions to give the corresponding HSi-NiH complex 2. Most notably, 1 reacts with catechol borane to afford the unprecedented hydroborylene-coordinated (chloro)(silyl)nickel(II) complex 3, {[cat( TMS L)Si](Cl)Ni←:BH(NHC) 2 }, via the cleavage of two B-O bonds and simultaneous formation of two Si-O bonds. The mechanism for the formation of 3 was rationalized by means of DFT calculations, which highlight the powerful synergistic effects of the Si:→Ni moiety in the breaking of incredibly strong B-O bonds. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Carboxylate-assisted ruthenium-catalyzed alkyne annulations by C-H/Het-H bond functionalizations.

PubMed

Ackermann, Lutz

2014-02-18

To improve the atom- and step-economy of organic syntheses, researchers would like to capitalize upon the chemistry of otherwise inert carbon-hydrogen (C-H) bonds. During the past decade, remarkable progress in organometallic chemistry has set the stage for the development of increasingly viable metal catalysts for C-H bond activation reactions. Among these methods, oxidative C-H bond functionalizations are particularly attractive because they avoid the use of prefunctionalized starting materials. For example, oxidative annulations that involve sequential C-H and heteroatom-H bond cleavages allow for the modular assembly of regioselectively decorated heterocycles. These structures serve as key scaffolds for natural products, functional materials, crop protecting agents, and drugs. While other researchers have devised rhodium or palladium complexes for oxidative alkyne annulations, my laboratory has focused on the application of significantly less expensive, yet highly selective ruthenium complexes. This Account summarizes the evolution of versatile ruthenium(II) complexes for annulations of alkynes via C-H/N-H, C-H/O-H, or C-H/N-O bond cleavages. To achieve selective C-H bond functionalizations, we needed to understand the detailed mechanism of the crucial C-H bond metalation with ruthenium(II) complexes and particularly the importance of carboxylate assistance in this process. As a consequence, our recent efforts have resulted in widely applicable methods for the versatile preparation of differently decorated arenes and heteroarenes, providing access to among others isoquinolones, 2-pyridones, isoquinolines, indoles, pyrroles, or α-pyrones. Most of these reactions used Cu(OAc)2·H2O, which not only acted as the oxidant but also served as the essential source of acetate for the carboxylate-assisted ruthenation manifold. Notably, the ruthenium(II)-catalyzed oxidative annulations also occurred under an ambient atmosphere of air with cocatalytic amounts of Cu(OAc)2·H2O. Moreover, substrates displaying N-O bonds served as "internal oxidants" for the syntheses of isoquinolones and isoquinolines. Detailed experimental mechanistic studies have provided strong support for a catalytic cycle that relies on initial carboxylate-assisted C-H bond ruthenation, followed by coordinative insertion of the alkyne, reductive elimination, and reoxidation of the thus formed ruthenium(0) complex.

Identification of succinimide sites in proteins by N-terminal sequence analysis after alkaline hydroxylamine cleavage.

PubMed Central

Kwong, M. Y.; Harris, R. J.

1994-01-01

Under favorable conditions, Asp or Asn residues can undergo rearrangement to a succinimide (cyclic imide), which may also serve as an intermediate for deamidation and/or isoaspartate formation. Direct identification of such succinimides by peptide mapping is hampered by their lability at neutral and alkaline pH. We determined that incubation in 2 M hydroxylamine, 0.2 M Tris buffer, pH 9, for 2 h at 45 degrees C will specifically cleave on the C-terminal side of succinimides without cleavage at Asn-Gly bonds; yields are typically approximately 50%. N-terminal sequence analysis can then be used to identify an internal sequence generated by cleavage of the succinimide, hence identifying the succinimide site. PMID:8142891

Bond Dissociation Free Energies (BDFEs) of the Acidic H-A Bonds in HA(*)(-) Radical Anions by Three Different Pathways.

PubMed

Zhao, Yongyu; Bordwell, Frederick G.

1996-09-20

Cleavage of radical anions, HA(*)(-), have been considered to give either H(*) + A(-) (path a) or H(-) + A(*) (path b), and factors determining the preferred mode of cleavage have been discussed. It is conceivable that cleavage to give a proton and a radical dianion, HA(*)(-) right harpoon over left harpoon H(+) + A(*)(2)(-) (path c), might also be feasible. A method, based on a thermodynamic cycle, to estimate the bond dissociation free energy (BDFE) by path c has been devised. Comparison of the BDFEs for cleavage of the radical anions derived from 24 nitroaromatic OH, SH, NH, and CH acids by paths a, b, c has shown that path c is favored thermodynamically.

Aging pathways for organophosphate-inhibited human butyrylcholinesterase, including novel pathways for isomalathion, resolved by mass spectrometry.

PubMed

Li, He; Schopfer, Lawrence M; Nachon, Florian; Froment, Marie-Thérèse; Masson, Patrick; Lockridge, Oksana

2007-11-01

Some organophosphorus compounds are toxic because they inhibit acetylcholinesterase (AChE) by phosphylation of the active site serine, forming a stable conjugate: Ser-O-P(O)-(Y)-(XR) (where X can be O, N, or S and Y can be methyl, OR, or SR). The inhibited enzyme can undergo an aging process, during which the X-R moiety is dealkylated by breaking either the P-X or the X-R bond depending on the specific compound, leading to a nonreactivatable enzyme. Aging mechanisms have been studied primarily using AChE. However, some recent studies have indicated that organophosphate-inhibited butyrylcholinesterase (BChE) may age through an alternative pathway. Our work utilized matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry to study the aging mechanism of human BChE inhibited by dichlorvos, echothiophate, diisopropylfluorophosphate (DFP), isomalathion, soman, sarin, cyclohexyl sarin, VX, and VR. Inhibited BChE was aged in the presence of H2O18 to allow incorporation of (18)O, if cleavage was at the P-X bond. Tryptic-peptide organophosphate conjugates were identified through peptide mass mapping. Our results showed no aging of VX- and VR-treated BChE at 25 degrees C, pH 7.0. However, BChE inhibited by dichlorvos, echothiophate, DFP, soman, sarin, and cyclohexyl sarin aged exclusively through O-C bond cleavage, i.e., the classical X-R scission pathway. In contrast, isomalathion aged through both X-R and P-X pathways; the main aged product resulted from P-S bond cleavage and a minor product resulted from O-C and/or S-C bond cleavage.

Iodide-catalyzed synthesis of N-nitrosamines via C-N cleavage of nitromethane.

PubMed

Zhang, Jie; Jiang, Jiewen; Li, Yuling; Wan, Xiaobing

2013-11-15

An iodide-catalyzed process to synthesize N-nitrosamines has been developed using TBHP as the oxidant. The mild catalytic system succeeded in cleaving the carbon-nitrogen bond in nitromethane. This methodology uses commercially available, inexpensive catalysts and oxidants and has a wide substrate scope and operational simplicity.

Structure and photochemistry of a saccharyl thiotetrazole.

PubMed

Ismael, A; Borba, A; Henriques, M S C; Paixão, J A; Fausto, R; Cristiano, M L S

2015-01-02

The molecular structure and photochemistry of 5-thiosaccharyl-1-methyltetrazole (TSMT) were studied by means of matrix-isolation FTIR spectroscopy, X-ray crystallography, and theoretical calculations. The calculations predicted two conformers of TSMT that differ in energy by more than 15 kJ mol(-1). The infrared spectrum of TSMT isolated in solid argon was fully assigned on the basis of the spectrum calculated (O3LYP/6-311++G(3df,3pd)) for the most stable conformer. In the crystal, TSMT molecules were found to assume the same conformation as for the isolated molecule, with each molecule forming four hydrogen bonds with three neighboring molecules, leading to a network of TSMT oligomers. Upon UV (λ = 265 nm) irradiation of the matrix-isolated TSMT, two photodegradation pathways were observed, both arising from cleavage of the tetrazolyl ring. Pathway a involves cleavage of the N1-N2 and N3-N4 bonds with extrusion of N2, leading to photostable diazirine and thiocarbodiimide derivatives. The photostability of the photoproduced diazirine under the conditions used precluded its rearrangement to the nitrile imine, as reported for 5-phenyltetrazole by Bégué et al. ( J. Am. Chem. Soc. 2012 , 134 , 5339 ). Pathway b involves cleavage of the C5-N1 and N4-N3 bonds, leading to a thiocyanate and methyl azide, the latter undergoing subsequent fragmentation to give CNH.

Electron transfer dissociation of synthetic and natural peptides containing lanthionine/methyllanthionine bridges.

PubMed

Dolle, Ashwini B; Jagadeesh, Narasimhappagari; Bhaumik, Suman; Prakash, Sunita; Biswal, Himansu S; Gowd, Konkallu Hanumae

2018-06-15

The modes of cleavage of lanthionine/methyllanthionine bridges under electron transfer dissociation (ETD) were investigated using synthetic and natural lantipeptides. Knowledge of the mass spectrometric fragmentation of lanthionine/methyllanthionine bridges may assist in the development of analytical methods for the rapid discovery of new lantibiotics. The present study strengthens the advantage of ETD in the characterization of posttranslational modifications of peptides and proteins. Synthetic and natural lantipeptides were obtained by desulfurization of peptide disulfides and cyanogen bromide digestion of the lantibiotic nisin, respectively. These peptides were subjected to electrospray ionization collision-induced dissociation tandem mass spectrometry (CID-MS/MS) and ETD-MS/MS using an HCT ultra ETDII ion trap mass spectrometer. MS 3 CID was performed on the desired product ions to prove cleavage of the lanthionine/methyllanthionine bridge during ETD-MS/MS. ETD has advantages over CID in the cleavage of the side chain of lanthionine/methyllanthionine bridges. The cleavage of the N-Cα backbone peptide bond followed by C-terminal side chain of the lanthionine bridge results in formation of c •+ and z + ions. Cleavage at the preceding peptide bond to the C-terminal side chain of lanthionine/methyllanthionine bridges yields specific fragments with the cysteine/methylcysteine thiyl radical and dehydroalanine. ETD successfully cleaves the lanthionine/methyllanthionine bridges of synthetic and natural lantipeptides. Diagnostic fragment ions of ETD cleavage of lanthionine/methyllanthionine bridges are the N-terminal cysteine/methylcysteine thiyl radical and C-terminal dehydroalanine. Detection of the cysteine/methylcysteine thiyl radical and dehydroalanine in combined ETD-CID-MS may be used for the rapid identification of lantipeptide natural products. Copyright © 2018 John Wiley & Sons, Ltd.

Photo-induced oxidant-free oxidative C-H/N-H cross-coupling between arenes and azoles

NASA Astrophysics Data System (ADS)

Niu, Linbin; Yi, Hong; Wang, Shengchun; Liu, Tianyi; Liu, Jiamei; Lei, Aiwen

2017-02-01

Direct cross-coupling between simple arenes and heterocyclic amines under mild conditions is undoubtedly important for C-N bonds construction. Selective C(sp2)-H amination is more valuable. Herein we show a selective C(sp2)-H amination of arenes (alkyl-substituted benzenes, biphenyl and anisole derivatives) accompanied by hydrogen evolution by using heterocyclic azoles as nitrogen sources. The reaction is selective for C(sp2)-H bonds, providing a mild route to N-arylazoles. The KIE (kinetic isotope effect) experiment reveals the cleavage of C-H bond is not involved in the rate-determining step. Kinetic studies indicate the first-order behaviour with respect to the arene component. It is interesting that this system works without the need for any sacrificial oxidant and is highly selective for C(sp2)-H activation, whereas C(sp3)-H bonds are unaffected. This study may have significant implications for the functionalization of methylarenes which are sensitive to oxidative conditions.

Nature and kinetic analysis of carbon-carbon bond fragmentation reactions of cation radicals derived from SET-oxidation of lignin model compounds.

PubMed

Cho, Dae Won; Parthasarathi, Ramakrishnan; Pimentel, Adam S; Maestas, Gabriel D; Park, Hea Jung; Yoon, Ung Chan; Dunaway-Mariano, Debra; Gnanakaran, S; Langan, Paul; Mariano, Patrick S

2010-10-01

Features of the oxidative cleavage reactions of diastereomers of dimeric lignin model compounds, which are models of the major types of structural units found in the lignin backbone, were examined. Cation radicals of these substances were generated by using SET-sensitized photochemical and Ce(IV) and lignin peroxidase promoted oxidative processes, and the nature and kinetics of their C-C bond cleavage reactions were determined. The results show that significant differences exist between the rates of cation radical C1-C2 bond cleavage reactions of 1,2-diaryl-(β-1) and 1-aryl-2-aryloxy-(β-O-4) propan-1,3-diol structural units found in lignins. Specifically, under all conditions C1-C2 bond cleavage reactions of cation radicals of the β-1 models take place more rapidly than those of the β-O-4 counterparts. The results of DFT calculations on cation radicals of the model compounds show that the C1-C2 bond dissociation energies of the β-1 lignin model compounds are significantly lower than those of the β-O-4 models, providing clear evidence for the source of the rate differences.

Palladium-catalyzed Suzuki-Miyaura coupling of amides by carbon-nitrogen cleavage: general strategy for amide N-C bond activation.

PubMed

Meng, Guangrong; Szostak, Michal

2016-06-15

The first palladium-catalyzed Suzuki-Miyaura cross-coupling of amides with boronic acids for the synthesis of ketones by sterically-controlled N-C bond activation is reported. The transformation is characterized by operational simplicity using bench-stable, commercial reagents and catalysts, and a broad substrate scope, including substrates with electron-donating and withdrawing groups on both coupling partners, steric-hindrance, heterocycles, halides, esters and ketones. The scope and limitations are presented in the synthesis of >60 functionalized ketones. Mechanistic studies provide insight into the catalytic cycle of the cross-coupling, including the first experimental evidence for Pd insertion into the amide N-C bond. The synthetic utility is showcased by a gram-scale cross-coupling and cross-coupling at room temperature. Most importantly, this process provides a blueprint for the development of a plethora of metal catalyzed reactions of typically inert amide bonds via acyl-metal intermediates. A unified strategy for amide bond activation to enable metal insertion into N-C amide bond is outlined ().

Ethylene decomposition over Pt(100): A mechanism study from first principle calculation

NASA Astrophysics Data System (ADS)

Wang, Yuchun; Dong, Xiuqin; Yu, Yingzhe; Zhang, Minhua

2016-12-01

First principle based density functional theory was used to calculate the complete step-by-step decomposition network of ethylene (C2H4) over Pt(100) as a model for understanding the carbon deposition of olefin hydrocarbon over transition metal surface. We discussed the structural and energetic properties of all the Csbnd H and Csbnd C bond cleavage reactions in order to fully understand the formation pathway of carbon monomer. It is easier for Csbnd H bond cleavage reactions to take place, as the activation barrier of these reactions is relatively lower than that of Csbnd C bond cleavage as a whole. However, vinyl (CH2CH) is likely to be the precursor of Csbnd C bond scission, as the activation barrier of Csbnd C bond cleavage reaction of CH2CH is much lower than that of CH2CH dehydrogenation and the reaction is exothermic by 0.15 eV. CC was another form of depositional carbon on Pt(100), as it is easy to form but difficult to decompose. Finally we proposed six possible routes of carbon monomer formation.

4-alkyl-L-(Dehydro)proline biosynthesis in actinobacteria involves N-terminal nucleophile-hydrolase activity of γ-glutamyltranspeptidase homolog for C-C bond cleavage

NASA Astrophysics Data System (ADS)

Zhong, Guannan; Zhao, Qunfei; Zhang, Qinglin; Liu, Wen

2017-07-01

γ-Glutamyltranspeptidases (γ-GTs), ubiquitous in glutathione metabolism for γ-glutamyl transfer/hydrolysis, are N-terminal nucleophile (Ntn)-hydrolase fold proteins that share an autoproteolytic process for self-activation. γ-GT homologues are widely present in Gram-positive actinobacteria where their Ntn-hydrolase activities, however, are not involved in glutathione metabolism. Herein, we demonstrate that the formation of 4-Alkyl-L-(dehydro)proline (ALDP) residues, the non-proteinogenic α-amino acids that serve as vital components of many bioactive metabolites found in actinobacteria, involves unprecedented Ntn-hydrolase activity of γ-GT homologue for C-C bond cleavage. The related enzymes share a key Thr residue, which acts as an internal nucleophile for protein hydrolysis and then as a newly released N-terminal nucleophile for carboxylate side-chain processing likely through the generation of an oxalyl-Thr enzyme intermediate. These findings provide mechanistic insights into the biosynthesis of various ALDP residues/associated natural products, highlight the versatile functions of Ntn-hydrolase fold proteins, and particularly generate interest in thus far less-appreciated γ-GT homologues in actinobacteria.

Studies on the regioselectivity and kinetics of the action of trypsin on proinsulin and its derivatives using mass spectrometry.

PubMed

Gardner, Qurra-tul-Ann Afza; Younas, Hooria; Akhtar, Muhammad

2013-01-01

Human M-proinsulin was cleaved by trypsin at the R(31)R(32)-E(33) and K(64)R(65)-G(66) bonds (B/C and C/A junctions), showing the same cleavage specificity as exhibited by prohormone convertases 1 and 2 respectively. Buffalo/bovine M-proinsulin was also cleaved by trypsin at the K(59)R(60)-G(61) bond but at the B/C junction cleavage occurred at the R(31)R(32)-E(33) as well as the R(31)-R(32)E(33) bond. Thus, the human isoform in the native state, with a 31 residue connecting C-peptide, seems to have a unique structure around the B/C and C/A junctions and cleavage at these sites is predominantly governed by the structure of the proinsulin itself. In the case of both the proinsulin species the cleavage at the B/C junction was preferred (65%) over that at the C/A junction (35%) supporting the earlier suggestion of the presence of some form of secondary structure at the C/A junction. Proinsulin and its derivatives, as natural substrates for trypsin, were used and mass spectrometric analysis showed that the k(cat.)/K(m) values for the cleavage were most favourable for the scission of the bonds at the two junctions (1.02±0.08×10(5)s(-1)M(-1)) and the cleavage of the K(29)-T(30) bond of M-insulin-RR (1.3±0.07×10(5)s(-1)M(-1)). However, the K(29)-T(30) bond in M-insulin, insulin as well as M-proinsulin was shielded from attack by trypsin (k(cat.)/K(m) values around 1000s(-1)M(-1)). Hence, as the biosynthetic path follows the sequence; proinsulin→insulin-RR→insulin, the K(29)-T(30) bond becomes shielded, exposed then shielded again respectively. Copyright © 2012 Elsevier B.V. All rights reserved.

Amide-Directed Photoredox Catalyzed C-C Bond Formation at Unactivated sp3 C-H Bonds

PubMed Central

Chu, John C. K.; Rovis, Tomislav

2017-01-01

Carbon-carbon (C-C) bond formation is paramount in the synthesis of biologically relevant molecules, modern synthetic materials and commodity chemicals such as fuels and lubricants. Traditionally, the presence of a functional group is required at the site of C-C bond formation. Strategies that allow C-C bond formation at inert carbon-hydrogen (C-H) bonds allow scientists to access molecules which would otherwise be inaccessible and to develop more efficient syntheses of complex molecules.1,2 Herein we report a method for the formation of C-C bonds by directed cleavage of traditionally non-reactive C-H bonds and their subsequent coupling with readily available alkenes. Our methodology allows for the selective C-C bond formation at single C-H bonds in molecules that contain a multitude of seemingly indifferentiable such bonds. Selectivity arises through a relayed photoredox catalyzed oxidation of an N-H bond. We anticipate our findings to serve as a starting point for functionalization at inert C-H bonds through a hydrogen atom transfer strategy. PMID:27732580

Photo-assisted cyanation of transition metal nitrates coupled with room temperature C-C bond cleavage of acetonitrile.

PubMed

Zou, Shihui; Li, Renhong; Kobayashi, Hisayoshi; Liu, Juanjuan; Fan, Jie

2013-03-07

It is a challenge to use acetonitrile as a cyanating agent because of the difficulty in cleaving its C-CN bond. Herein, we report a mild photo-assisted route to conduct the cyanation of transition metal nitrates using acetonitrile as the cyanating agent coupled with room-temperature C-C bond cleavage. DFT calculations and experimental observations suggest a radical-involved reaction mechanism, which excludes toxicity from free cyanide ions.

Phenanthridine synthesis through iron-catalyzed intramolecular N-arylation of O-acetyl oxime.

PubMed

Deb, Indubhusan; Yoshikai, Naohiko

2013-08-16

O-Acetyl oximes derived from 2'-arylacetophenones undergo N-O bond cleavage/intramolecular N-arylation in the presence of a catalytic amount of iron(III) acetylacetonate in acetic acid. In combination with the conventional cross-coupling or directed C-H arylation, the reaction offers a convenient route to substituted phenanthridines.

Three different product types from reactions of lithiated cyclic aminals with trivalent organometal chlorides.

PubMed

Hellmann, Benjamin J; Kamps, Ina; Mix, Andreas; Neumann, Beate; Stammler, Hans-Georg; Mitzel, Norbert W

2010-09-21

The reaction of 2-lithio-1,3,5-trimethyl-1,3,5-triazacyclohexane with YCp(2)Cl leads to the formation of a donor-functionalised mono-anionic amide ligand, 1,3,5-trimethyl-2-(methylamidomethyl)-1,3,5-triazacyclohexane, bonded to the YCp(2) unit. The reaction involves a cleavage of the 1,3,5-triazacyclohexane ring and such a cleavage is also observed in the analogous reaction with (Me(3)C)(2)GaCl, where a MeN[double bond, length as m-dash]CH(-) fragment is formed. No such cleavage occurs in the reaction of the related dilithiated bicyclic bis(3-methyl-1,3-diazacyclohex-1-yl)methane with YCpCl(2).3thf, which affords a mixed lithium-yttrium organyl.

Flexible Xxx–Asp/Asn and Gly–Xxx Residues of Equine Cytochrome c in Matrix-Assisted Laser Desorption/Ionization In-Source Decay Mass Spectrometry

PubMed Central

Takayama, Mitsuo

2012-01-01

The backbone flexibility of a protein has been studied from the standpoint of the susceptibility of amino acid residues to in-source decay (ISD) in matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Residues more susceptible to MALDI-ISD, namely Xxx–Asp/Asn and Gly–Xxx, were identified from the discontinuous intense peak of c′-ions originating from specific cleavage at N–Cα bonds of the backbone of equine cytochrome c. The identity of the residues susceptible to ISD was consistent with the known flexible backbone amides as estimated by hydrogen/deuterium exchange (HDX) experiments. The identity of these flexible amino acid residues (Asp, Asn, and Gly) is consistent with the fact that these residues are preferred in flexible secondary structure free from intramolecular hydrogen-bonded structures such as α-helix and β-sheet. The MALDI-ISD spectrum of equine cytochrome c gave not only intense N-terminal side c′-ions originating from N–Cα bond cleavage at Xxx–Asp/Asn and Gly–Xxx residues, but also C-terminal side complement z′-ions originating from the same cleavage sites. The present study implies that MALDI-ISD can give information about backbone flexibility of proteins, comparable with the protection factors estimated by HDX. PMID:24349908

Palladium-catalyzed one-pot three- or four-component coupling of aryl iodides, alkynes, and amines through C-N bond cleavage: efficient synthesis of indole derivatives.

PubMed

Hao, Wei; Geng, Weizhi; Zhang, Wen-Xiong; Xi, Zhenfeng

2014-02-24

An efficient synthesis of N-substituted indole derivatives was realized by combining the Pd-catalyzed one-pot multicomponent coupling approach with cleavage of the C(sp(3))-N bonds. Three or four components of aryl iodides, alkynes, and amines were involved in this coupling process. The cyclopentadiene-phosphine ligand showed high efficiency. A variety of aryl iodides, including cyclic and acyclic tertiary amino aryl iodides, and substituted 1-bromo-2-iodobenzene derivatives could be used. Both symmetric and unsymmetric alkynes substituted with alkyl, aryl, or trimethylsilyl groups could be applied. Cyclic secondary amines such as piperidine, morpholine, 4-methylpiperidine, 1-methylpiperazine, 2-methylpiperidine, and acyclic amines including secondary and primary amines all showed good reactivity. Further application of the resulting indole derivatives was demonstrated by the synthesis of benzosilolo[2,3-b]indole. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Thermal decomposition of solid phase nitromethane under various heating rates and target temperatures based on ab initio molecular dynamics simulations.

PubMed

Xu, Kai; Wei, Dong-Qing; Chen, Xiang-Rong; Ji, Guang-Fu

2014-10-01

The Car-Parrinello molecular dynamics simulation was applied to study the thermal decomposition of solid phase nitromethane under gradual heating and fast annealing conditions. In gradual heating simulations, we found that, rather than C-N bond cleavage, intermolecular proton transfer is more likely to be the first reaction in the decomposition process. At high temperature, the first reaction in fast annealing simulation is intermolecular proton transfer leading to CH3NOOH and CH2NO2, whereas the initial chemical event at low temperature tends to be a unimolecular C-N bond cleavage, producing CH3 and NO2 fragments. It is the first time to date that the direct rupture of a C-N bond has been reported as the first reaction in solid phase nitromethane. In addition, the fast annealing simulations on a supercell at different temperatures are conducted to validate the effect of simulation cell size on initial reaction mechanisms. The results are in qualitative agreement with the simulations on a unit cell. By analyzing the time evolution of some molecules, we also found that the time of first water molecule formation is clearly sensitive to heating rates and target temperatures when the first reaction is an intermolecular proton transfer.

The chemical structure of macromolecular fractions of a sulfur-rich oil

NASA Astrophysics Data System (ADS)

Richnow, Hans H.; Jenisch, Angela; Michaelis, Walter

1993-06-01

A selective stepwise chemical degradation has been developed for structural studies of highmolecularweight (HMW) fractions of sulfur-rich oils. The degradation steps are: (i) desulfurization (ii) cleavage of oxygen-carbon bonds (iii) oxidation of aromatic structural units. After each step, the remaining macromolecular matter was subjected to the subsequent reaction. This degradation scheme was applied to the asphaltene, the resin and a macromolecular fraction of low polarity (LPMF) of the Rozel Point oil. Total amounts of degraded low-molecular-weight compounds increased progressively in the order asphaltene < resin < LPMF. Desulfurization yielded mainly phytane, steranes and triterpanes. Oxygen-carbon bond cleavage resulted in hydrocarbon fractions predominated by n-alkanes and acyclic isoprenoids. The oxidation step afforded high amounts of linear carboxylic acids in the range of C 11 to C 33. The released compounds provide a more complete picture of the molecular structure of the oil fractions than previously available. Labelling experiments with deuterium atoms allowed to characterize the site of bonding and the type of linkage for the released compounds. Evidence is presented that subunits of the macromolecular network are attached simultaneously by oxygen and sulfur (n-alkanes, hopanes) or by sulfur and aromatic units ( n-alkanes, steranes).

Cu(II)-catalyzed esterification reaction via aerobic oxidative cleavage of C(CO)-C(alkyl) bonds.

PubMed

Ma, Ran; He, Liang-Nian; Liu, An-Hua; Song, Qing-Wen

2016-02-04

A novel Cu(II)-catalyzed aerobic oxidative esterification of simple ketones for the synthesis of esters has been developed with wide functional group tolerance. This process is assumed to go through a tandem sequence consisting of α-oxygenation/esterification/nucleophilic addition/C-C bond cleavage and carbon dioxide is released as the only byproduct.

Copper-catalyzed aerobic oxidative C-H functionalization of substituted pyridines: synthesis of imidazopyridine derivatives.

PubMed

Yu, Jipan; Jin, Yunhe; Zhang, Hao; Yang, Xiaobo; Fu, Hua

2013-12-02

A novel, efficient, and practical method for the synthesis of imidazopyridine derivatives has been developed through the copper-catalyzed aerobic oxidative C-H functionalization of substituted pyridines with N-(alkylidene)-4H-1,2,4-triazol-4-amines. The procedure occurs by cleavage of the N-N bond in the N-(alkylidene)-4H-1,2,4-triazol-4-amines and activation of an aryl C-H bond in the substituted pyridines. This is the first example of the preparation of imidazopyridine derivatives by using pyridines as the substrates by transition-metal-catalyzed C-H functionalization. This method should provide a novel and efficient strategy for the synthesis of other nitrogen heterocycles. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cu-catalyzed esterification reaction via aerobic oxygenation and C-C bond cleavage: an approach to α-ketoesters.

PubMed

Zhang, Chun; Feng, Peng; Jiao, Ning

2013-10-09

The Cu-catalyzed novel aerobic oxidative esterification reaction of 1,3-diones for the synthesis of α-ketoesters has been developed. This method combines C-C σ-bond cleavage, dioxygen activation and oxidative C-H bond functionalization, as well as provides a practical, neutral, and mild synthetic approach to α-ketoesters which are important units in many biologically active compounds and useful precursors in a variety of functional group transformations. A plausible radical process is proposed on the basis of mechanistic studies.

Photoinduced reactions of both 2-formyl-2H-azirine and isoxazole: A theoretical study based on electronic structure calculations and nonadiabatic dynamics simulations

NASA Astrophysics Data System (ADS)

Cao, Jun

2015-06-01

In the present work, the combined electronic structure calculations and dynamics simulations have been performed to explore photocleavages of 2-formyl-2H-azirine and isoxazole in the gas phase and the subsequent rearrangement reactions. The carbonyl n → π* transition induces a cleavage of the C—N single bond of 2-formyl-2H-azirine to yield β-formylvinylnitrene in open-shell singlet state. However, the n → π* excitation of the imine chromophore results in a cleavage of the C—C single bond, producing a nitrile ylide intermediate through an internal conversion to the ground state. β-formylvinylnitrene and nitrile ylide with the carbonyl group are easily transformed into 2-formyl-2H-azirine and oxazole, respectively. The N—O bond cleavages on both S1(1ππ*) and S2(1nNπ*) of isoxazole are ultrafast processes, and they give products of 2-formyl-2H-azirine, 3-formylketenimine, HCN + CHCHO, and HCO + CHCHN. Both 2H-azirines and ketenimines were suggested to be formed from the triplet vinylnitrenes by intersystem crossing in the previous studies. However, our calculations show that the singlet β-formylvinylnitrene is responsible for the formation of 2-formyl-2H-azirine and 3-formylketenimine, and the singlet vinylnitrenes can play a key role in the photoinduced reactions of both 2H-azirines and isoxazoles.

Oxidative cleavage of the octyl side chain of 1-(3,4-dichlorobenzyl)-5-octylbiguanide (OPB-2045) in rat and dog liver preparations.

PubMed

Umehara, K; Kudo, S; Hirao, Y; Morita, S; Uchida, M; Odomi, M; Miyamoto, G

2000-08-01

The metabolism of 1-(3,4-dichlorobenzyl)-5-octylbiguanide (OPB-2045), a new potent biguanide antiseptic, was investigated using rat and dog liver preparations to elucidate the mechanism of OPB-2045 metabolite formation, in which the octyl side chain is reduced to four, five, or six carbon atoms. Chemical structures of metabolites were characterized by 1H NMR, fast atom bombardment/mass spectrometry, and liquid chromatography/electrospray ionization-tandem mass spectrometry. Three main metabolites were observed during incubation of OPB-2045 with rat liver S9: 2-octanol (M-1), 3-octanol (M-2), and 4-octanol (M-3). In the incubation of OPB-2045 with dog liver S9, eight metabolites were observed, seven of which being M-1, M-2, M-3, 2-octanone (M-4), threo-2,3-octandiol (M-5), erythro-2,3-octandiol (M-6), and 1,2-octandiol (M-7). M-5 and M-6 were further biotransformed to a ketol derivative and C-C bond cleavage metabolite (hexanoic acid derivative), an in vivo end product, in the incubation with dog liver microsomes. The reactions required NADPH as a cofactor and were significantly inhibited by the various inhibitors of cytochrome P450 (i.e., CO, n-octylamine, SKF 525-A, metyrapone, and alpha-naphthoflavone). The results indicate that the degraded products of OPB-2045 are produced by C-C bond cleavage after monohydroxylation, dihydroxylation, and ketol formation at the site of the octyl side chain with possible involvement of cytochrome P450 systems. This aliphatic C-C bond cleavage by sequential oxidative reactions may play an important role in the metabolism of other drugs or endogenous compounds that possess aliphatic chains.

Identifying the Tautomeric Form of a Deoxyguanosine-Estrogen Quinone Intermediate.

PubMed

Stack, Douglas E

2015-09-10

Mechanistic insights into the reaction of an estrogen o-quinone with deoxyguanosine has been further investigated using high level density functional calculations in addition to the use of 4-hyroxycatecholestrone (4-OHE₁) regioselectivity labeled with deuterium at the C1-position. Calculations using the M06-2X functional with large basis sets indicate the tautomeric form of an estrogen-DNA adduct present when glycosidic bonds cleavage occurs is comprised of an aromatic A ring structure. This tautomeric form was further verified by use of deuterium labelling of the catechol precursor use to form the estrogen o-quinone. Regioselective deuterium labelling at the C1-position of the estrogen A ring allows discrimination between two tautomeric forms of a reaction intermediate either of which could be present during glycosidic bond cleavage. HPLC-MS analysis indicates a reactive intermediate with a m/z of 552.22 consistent with a tautomeric form containing no deuterium. This intermediate is consistent with a reaction mechanism that involves: (1) proton assisted Michael addition; (2) re-aromatization of the estrogen A ring; and (3) glycosidic bond cleavage to form the known estrogen-DNA adduct, 4-OHE₁-1-N7Gua.

Mass spectrometric investigation of buspirone drug in comparison with thermal analyses and MO-calculations

NASA Astrophysics Data System (ADS)

Zayed, M. A.; Fahmey, M. A.; Hawash, M. A.; El-Habeeb, Abeer A.

2007-06-01

The buspirone drug is usually present as hydrochloride form of general formula C 21H 31N 5O 2·HCl, and of molecular weight (MW) = 421.96. It is an analgesic anxiolytic drug, which does not cause sedative or depression of central nervous system. In the present work it is investigated using electron impact mass spectral (EI-MS) fragmentation at 70 eV, in comparison with thermal analyses (TA) measurements (TG/DTG and DTA) and molecular orbital calculation (MOC). Semi-empirical MO calculation, PM3 procedure, has been carried out on buspirone both as neutral molecule (in TA) and the corresponding positively charged species (in MS). The calculated MOC parameters include bond length, bond order, particle charge distribution on different atoms and heats of formation. The fragmentation pathways of buspirone in EI-MS lead to the formation of important primary and secondary fragment ions. The mechanism of formation of some important daughter ions can be illuminated from comparing with that obtained using electrospray ESIMS/MS mode mass spectrometer through the accurate mass measurement determination. The losses of the intermediate aliphatic part (CH 2) 4 due to cleavage of N-C bond from both sides is the primary cleavage in both techniques (MS and TA). The PM3 provides a base for fine distinction among sites of initial bond cleavage and subsequent fragmentation of drug molecule in both TA and MS techniques; consequently the choice of the correct pathway of such fragmentation knowing this structural session of bonds can be used to decide the active sites of this drug responsible for its chemical, biological and medical reactivity.

Mechanism of C-C and C-H bond cleavage in ethanol oxidation reaction on Cu2O(111): a DFT-D and DFT+U study.

PubMed

Xu, Han; Miao, Bei; Zhang, Minhua; Chen, Yifei; Wang, Lichang

2017-10-04

The performance of transition metal catalysts for ethanol oxidation reaction (EOR) in direct ethanol fuel cells (DEFCs) may be greatly affected by their oxidation. However, the specific effect and catalytic mechanism for EOR of transition metal oxides are still unclear and deserve in-depth exploitation. Copper as a potential anode catalyst can be easily oxidized in air. Thus, in this study, we investigated C-C and C-H bond cleavage reactions of CH x CO (x = 1, 2, 3) species in EOR on Cu 2 O(111) using PBE+U calculations, as well as the specific effect of +U correction on the process of adsorption and reaction on Cu 2 O(111). It was revealed that the catalytic performance of Cu 2 O(111) for EOR was restrained compared with that of Cu(100). Except for the C-H cleavage of CH 2 CO, all the reaction barriers for C-C and C-H cleavage were higher than those on Cu(100). The most probable pathway for CH 3 CO to CHCO on Cu 2 O(111) was the continuous dehydrogenation reaction. Besides, the barrier for C-C bond cleavage increased due to the loss of H atoms in the intermediate. Moreover, by the comparison of the traditional GGA/PBE method and the PBE+U method, it could be concluded that C-C cleavage barriers would be underestimated without +U correction, while C-H cleavage barriers would be overestimated. +U correction was proved to be necessary, and the reaction barriers and the values of the Hubbard U parameter had a proper linear relationship.

Influence of secondary structure on in-source decay of protein in matrix-assisted laser desorption/ionization mass spectrometry.

PubMed

Takayama, Mitsuo; Osaka, Issey; Sakakura, Motoshi

2012-01-01

The susceptibility of the N-Cα bond of the peptide backbone to specific cleavage by in-source decay (ISD) in matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS) was studied from the standpoint of the secondary structure of three proteins. A naphthalene derivative, 5-amino-1-naphtol (5,1-ANL), was used as the matrix. The resulting c'-ions, which originate from the cleavage at N-Cα bonds in flexible secondary structures such as turn and bend, and are free from intra-molecular hydrogen-bonded α-helix structure, gave relatively intense peaks. Furthermore, ISD spectra of the proteins showed that the N-Cα bonds of specific amino acid residues, namely Gly-Xxx, Xxx-Asp, and Xxx-Asn, were more susceptible to MALDI-ISD than other amino acid residues. This is in agreement with the observation that Gly, Asp and Asn residues usually located in turns, rather than α-helix. The results obtained indicate that protein molecules embedded into the matrix crystal in the MALDI experiments maintain their secondary structures as determined by X-ray crystallography, and that MALDI-ISD has the capability for providing information concerning the secondary structure of protein.

High-valent manganese–oxo valence tautomers and the influence of Lewis/Brönsted acids on C–H bond cleavage

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

Baglia, Regina A.; Krest, Courtney M.; Yang, Tzuhsiung

The addition of Lewis or Brönsted acids (LA = Zn(OTf) 2, B(C 6F 5) 3, HBAr F, TFA) to the high-valent manganese–oxo complex Mn V(O)(TBP 8Cz) results in the stabilization of a valence tautomer Mn IV(O-LA)(TBP 8Cz •+). The Zn II and B(C 6F 5) 3 complexes were characterized by manganese K-edge X-ray absorption spectroscopy (XAS). The position of the edge energies and the intensities of the pre-edge (1s to 3d) peaks confirm that the Mn ion is in the +4 oxidation state. Fitting of the extended X-ray absorption fine structure (EXAFS) region reveals 4 N/O ligands at Mn–N avemore » = 1.89 Å and a fifth N/O ligand at 1.61 Å, corresponding to the terminal oxo ligand. This Mn–O bond length is elongated compared to the Mn V(O) starting material (Mn–O = 1.55 Å). The reactivity of Mn IV(O-LA)(TBP 8Cz •+) toward C–H substrates was examined, and it was found that H • abstraction from C–H bonds occurs in a 1:1 stoichiometry, giving a Mn IV complex and the dehydrogenated organic product. The rates of C–H cleavage are accelerated for the Mn IV(O-LA)(TBP 8Cz •+) valence tautomer as compared to the MnV(O) valence tautomer when LA = Zn II, B(C 6F 5) 3, and HBArF, whereas for LA = TFA, the C–H cleavage rate is slightly slower than when compared to MnV(O). A large, nonclassical kinetic isotope effect of k H/ k D = 25–27 was observed for LA = B(C 6F 5) 3 and HBAr F, indicating that H-atom transfer (HAT) is the rate-limiting step in the C–H cleavage reaction and implicating a potential tunneling mechanism for HAT. Furthermore, the reactivity of Mn IV(O-LA)(TBP 8Cz •+) toward C–H bonds depends on the strength of the Lewis acid. The HAT reactivity is compared with the analogous corrole complex Mn IV(O–H)(tpfc •+) recently reported.« less

High-valent manganese–oxo valence tautomers and the influence of Lewis/Brönsted acids on C–H bond cleavage

DOE PAGES

Baglia, Regina A.; Krest, Courtney M.; Yang, Tzuhsiung; ...

2016-09-30

The addition of Lewis or Brönsted acids (LA = Zn(OTf) 2, B(C 6F 5) 3, HBAr F, TFA) to the high-valent manganese–oxo complex Mn V(O)(TBP 8Cz) results in the stabilization of a valence tautomer Mn IV(O-LA)(TBP 8Cz •+). The Zn II and B(C 6F 5) 3 complexes were characterized by manganese K-edge X-ray absorption spectroscopy (XAS). The position of the edge energies and the intensities of the pre-edge (1s to 3d) peaks confirm that the Mn ion is in the +4 oxidation state. Fitting of the extended X-ray absorption fine structure (EXAFS) region reveals 4 N/O ligands at Mn–N avemore » = 1.89 Å and a fifth N/O ligand at 1.61 Å, corresponding to the terminal oxo ligand. This Mn–O bond length is elongated compared to the Mn V(O) starting material (Mn–O = 1.55 Å). The reactivity of Mn IV(O-LA)(TBP 8Cz •+) toward C–H substrates was examined, and it was found that H • abstraction from C–H bonds occurs in a 1:1 stoichiometry, giving a Mn IV complex and the dehydrogenated organic product. The rates of C–H cleavage are accelerated for the Mn IV(O-LA)(TBP 8Cz •+) valence tautomer as compared to the MnV(O) valence tautomer when LA = Zn II, B(C 6F 5) 3, and HBArF, whereas for LA = TFA, the C–H cleavage rate is slightly slower than when compared to MnV(O). A large, nonclassical kinetic isotope effect of k H/ k D = 25–27 was observed for LA = B(C 6F 5) 3 and HBAr F, indicating that H-atom transfer (HAT) is the rate-limiting step in the C–H cleavage reaction and implicating a potential tunneling mechanism for HAT. Furthermore, the reactivity of Mn IV(O-LA)(TBP 8Cz •+) toward C–H bonds depends on the strength of the Lewis acid. The HAT reactivity is compared with the analogous corrole complex Mn IV(O–H)(tpfc •+) recently reported.« less

Photoinduced reactions of both 2-formyl-2H-azirine and isoxazole: A theoretical study based on electronic structure calculations and nonadiabatic dynamics simulations

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

Cao, Jun, E-mail: caojunbnu@mail.bnu.edu.cn

2015-06-28

In the present work, the combined electronic structure calculations and dynamics simulations have been performed to explore photocleavages of 2-formyl-2H-azirine and isoxazole in the gas phase and the subsequent rearrangement reactions. The carbonyl n → π{sup *} transition induces a cleavage of the C—N single bond of 2-formyl-2H-azirine to yield β-formylvinylnitrene in open-shell singlet state. However, the n → π{sup *} excitation of the imine chromophore results in a cleavage of the C—C single bond, producing a nitrile ylide intermediate through an internal conversion to the ground state. β-formylvinylnitrene and nitrile ylide with the carbonyl group are easily transformed intomore » 2-formyl-2H-azirine and oxazole, respectively. The N—O bond cleavages on both S{sub 1}({sup 1}ππ{sup *}) and S{sub 2}({sup 1}n{sub N}π{sup *}) of isoxazole are ultrafast processes, and they give products of 2-formyl-2H-azirine, 3-formylketenimine, HCN + CHCHO, and HCO + CHCHN. Both 2H-azirines and ketenimines were suggested to be formed from the triplet vinylnitrenes by intersystem crossing in the previous studies. However, our calculations show that the singlet β-formylvinylnitrene is responsible for the formation of 2-formyl-2H-azirine and 3-formylketenimine, and the singlet vinylnitrenes can play a key role in the photoinduced reactions of both 2H-azirines and isoxazoles.« less

Transition Metal-Mediated and -Catalyzed C-F Bond Activation via Fluorine Elimination.

PubMed

Fujita, Takeshi; Fuchibe, Kohei; Ichikawa, Junji

2018-06-28

Activation of carbon-fluorine (C-F) bonds is an important topic in synthetic organic chemistry recently. Among the methods for C-F bond cleavage, metal mediated and catalyzed β- or α-fluorine elimination proceeds under mild conditions compared with oxidative addition of C-F bond. The β- or α-fluorine elimination is initiated from organometallic intermediates having fluorine substituents on carbon atoms β or α to metal centers, respectively. Transformations via these elimination processes (C-F bond cleavage), which are typically preceded by carbon-carbon (or carbon-heteroatom) bond formation, have been remarkably developed as C-F bond activation methods in the past five years. In this minireview, we summarize the applications of transition metal-mediated and -catalyzed fluorine elimination to synthetic organic chemistry from a historical perspective for early studies and from a systematic perspective for recent studies. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The unexpected mechanism underlying the high-valent mono-oxo-rhenium(V) hydride catalyzed hydrosilylation of C=N functionalities: insights from a DFT study.

PubMed

Wang, Jiandi; Wang, Wenmin; Huang, Liangfang; Yang, Xiaodi; Wei, Haiyan

2015-04-07

In this study, we theoretically investigated the mechanism underlying the high-valent mono-oxo-rhenium(V) hydride Re(O)HCl2(PPh3)2 (1) catalyzed hydrosilylation of C=N functionalities. Our results suggest that an ionic S(N)2-Si outer-sphere pathway involving the heterolytic cleavage of the Si-H bond competes with the hydride pathway involving the C=N bond inserted into the Re-H bond for the rhenium hydride (1) catalyzed hydrosilylation of the less steric C=N functionalities (phenylmethanimine, PhCH=NH, and N-phenylbenzylideneimine, PhCH=NPh). The rate-determining free-energy barriers for the ionic outer-sphere pathway are calculated to be ∼28.1 and 27.6 kcal mol(-1), respectively. These values are slightly more favorable than those obtained for the hydride pathway (by ∼1-3 kcal mol(-1)), whereas for the large steric C=N functionality of N,1,1-tri(phenyl)methanimine (PhCPh=NPh), the ionic outer-sphere pathway (33.1 kcal mol(-1)) is more favorable than the hydride pathway by as much as 11.5 kcal mol(-1). Along the ionic outer-sphere pathway, neither the multiply bonded oxo ligand nor the inherent hydride moiety participate in the activation of the Si-H bond. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Facile scission of isonitrile carbon–nitrogen triple bond using a diborane(4) reagent

PubMed Central

Asakawa, Hiroki; Lee, Ka-Ho; Lin, Zhenyang; Yamashita, Makoto

2014-01-01

Transition metal reagents and catalysts are generally effective to cleave all three bonds (one σ and two π) in a triple bond despite its high bonding energy. Recently, chemistry of single-bond cleavage by using main-group element compounds is rapidly being developed in the absence of transition metals. However, the cleavage of a triple bond using non-transition-metal compounds is less explored. Here we report that an unsymmetrical diborane(4) compound could react with carbon monoxide and tert-butyl isonitrile at room temperature. In the latter case, the carbon–nitrogen triple bond was completely cleaved in the absence of transition metal as confirmed by X-ray crystallographic analysis, 13C NMR spectroscopy with 13C labelling and DFT calculations. The DFT calculations also revealed the detailed reaction mechanism and indicated that the key for the carbon–nitrogen triple-bond cleavage could be attributed to the presence of nucleophilic nitrogen atom in one of the intermediates. PMID:24967910

Highly regioselective Lewis acid-catalyzed [3+2] cycloaddition of alkynes with donor-acceptor oxiranes by selective carbon-carbon bond cleavage of epoxides.

PubMed

Liu, Renrong; Zhang, Mei; Zhang, Junliang

2011-12-28

A novel, efficient, highly regioselective Sc(OTf)(3)-catalyzed [3+2] cycloaddition of electron-rich alkynes with donor-acceptor oxiranes via highly chemoselective C-C bond cleavage under mild conditions was developed. This journal is © The Royal Society of Chemistry 2011

Cleavage of sp3 C-O bonds via oxidative addition of C-H bonds.

PubMed

Choi, Jongwook; Choliy, Yuriy; Zhang, Xiawei; Emge, Thomas J; Krogh-Jespersen, Karsten; Goldman, Alan S

2009-11-04

(PCP)Ir (PCP = kappa(3)-C(6)H(3)-2,6-[CH(2)P(t-Bu)(2)](2)) is found to undergo oxidative addition of the methyl-oxygen bond of electron-poor methyl aryl ethers, including methoxy-3,5-bis(trifluoromethyl)benzene and methoxypentafluorobenzene, to give the corresponding aryloxide complexes (PCP)Ir(CH(3))(OAr). Although the net reaction is insertion of the Ir center into the C-O bond, density functional theory (DFT) calculations and a significant kinetic isotope effect [k(CH(3))(OAr)/k(CD(3))(OAr) = 4.3(3)] strongly argue against a simple insertion mechanism and in favor of a pathway involving C-H addition and alpha-migration of the OAr group to give a methylene complex followed by hydride-to-methylene migration to give the observed product. Ethoxy aryl ethers, including ethoxybenzene, also undergo C-O bond cleavage by (PCP)Ir, but the net reaction in this case is 1,2-elimination of ArO-H to give (PCP)Ir(H)(OAr) and ethylene. DFT calculations point to a low-barrier pathway for this reaction that proceeds through C-H addition of the ethoxy methyl group followed by beta-aryl oxide elimination and loss of ethylene. Thus, both of these distinct C-O cleavage reactions proceed via initial addition of a C(sp(3))-H bond, despite the fact that such bonds are typically considered inert and are much stronger than C-O bonds.

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

Zhang, Shaoguang; Appel, Aaron M.; Bullock, R. Morris

Controlling the heterolytic cleavage of the H-H bond of dihydrogen is critically important in catalytic hydrogenations and in the catalytic oxidation of H2. We show how the rate of reversible heterolytic cleavage of H2 can be controlled over nearly four orders of magnitude at 25 °C, from 2.1 × 103 s-1 to ≥107 s-1. Bifunctional Mo complexes, [CpMo(CO)(κ3-P2N2)]+ (P2N2 = 1,5-diaza-3,7-diphosphacyclooctane with alkyl/aryl groups on N and P), have been developed for heterolytic cleavage of H2 into a proton and a hydride, akin to Frustrated Lewis Pairs. The H-H bond cleavage is enabled by the basic amine in the secondmore » coordination sphere. The products of heterolytic cleavage of H2, Mo hydride complexes bearing protonated amines, [CpMo(H)(CO)(P2N2H)]+, were characterized by spectroscopic studies and by X-ray crystallography. Variable temperature 1H, 15N and 2-D 1H-1H ROESY NMR spectra indicated rapid exchange of the proton and hydride. The exchange rates are in the order [CpMo(H)(CO)(PPh2NPh2H)]+ > [CpMo(H)(CO)(PtBu2NPh2H)]+ > [CpMo(H)(CO)(PPh2NBn2H)]+ > [CpMo(H)(CO)(PtBu2NBn2H)]+ > [CpMo(H)(CO)(PtBu2NtBu2H)]+. The pKa values determined in acetonitrile range from 9.3 to 17.7, and show a linear correlation with the logarithm of the exchange rates. Thus the exchange dynamics are controlled through the relative acidity of the [CpMo(H)(CO)(P2N2H)]+ and [CpMo(H2)(CO)(P2N2)]+ isomers, providing a design principle for controlling heterolytic cleavage of H2.« less

Ab initio calculations of the effects of H+ and NH4+ on the initial decomposition of HMX.

PubMed

Wang, Luoxin; Tuo, Xinlin; Yi, Changhai; Wang, Xiaogong

2008-10-01

In this work, the effects of H(+) and NH(4)(+) on the initial decomposition of HMX were investigated on the basis of the B3P86/6-31G** and B3LYP/6-31G* calculations. Three initial decomposition pathways including the N-NO(2) bond fission, HONO elimination and C-N bond dissociation were considered for the complexes formed by HMX with H(+) (PHMX1 and PHMX2) or with NH(4)(+) (AHMX). We found that H(+) and NH(4)(+) did not evidently induce the HMX to trigger the N-NO(2) heterolysis because the energy barrier of N-NO(2) heterolysis was found to be higher than the bond dissociation energy of N-NO(2) homolytic cleavage. Meanwhile, the transition state barriers of the HONO elimination from the complexes were found to be similar to that from the isolated HMX, which means that the HONO elimination reaction of HMX was not affected by the H(+) and NH(4)(+). As for the ring-opening reaction of HMX due to the C-N bond dissociation, the calculated potential energy profile showed that the energy of the complex (AHMX) went uphill along the C-N bond length and no transition state existed on the curve. However, the transition state energy barriers of C-N bond dissociation were calculated to be only 5.0 kcal/mol and 5.5 kcal/mol for the PHMX1 and PHMX2 complexes, respectively, which were much lower than the C-N bond dissociation energy of isolated HMX. Moreover, among the three initial decomposition reactions, the C-N bond dissociation was also the most energetically favorable pathway for the PHMX1 and PHMX2. Our calculation results showed that the H(+) can significantly promote the initial thermal decomposition of C-N bond of HMX, which, however, is influenced by NH(4)(+) slightly.

A ReaxFF-based molecular dynamics study of the mechanisms of interactions between reactive oxygen plasma species and the Candida albicans cell wall

NASA Astrophysics Data System (ADS)

Zhao, T.; Shi, L.; Zhang, Y. T.; Zou, L.; Zhang, L.

2017-10-01

Atmospheric pressure non-equilibrium plasmas have attracted significant attention and have been widely used to inactivate pathogens, yet the mechanisms underlying the interactions between plasma-generated species and bio-organisms have not been elucidated clearly. In this paper, reactive molecular dynamics simulations are employed to investigate the mechanisms of interactions between reactive oxygen plasma species (O, OH, and O2) and β-1,6-glucan (a model for the C. albicans cell wall) from a microscopic point of view. Our simulations show that O and OH species can break structurally important C-C and C-O bonds, while O2 molecules exhibit only weak, non-bonded interactions with β-1,6-glucan. Hydrogen abstraction from hydroxyl or CH groups occurs first in all bond cleavage mechanisms. This is followed by a cascade of bond cleavage and double bond formation events. These lead to the destruction of the fungal cell wall. O and OH have similar effects related to their bond cleavage mechanisms. Our simulation results provide fundamental insights into the mechanisms underlying the interactions between reactive oxygen plasma species and the fungal cell wall of C. albicans at the atomic level.

Highly Chemoselective Reduction of Amides (Primary, Secondary, Tertiary) to Alcohols using SmI2/Amine/H2O under Mild Conditions

PubMed Central

2014-01-01

Highly chemoselective direct reduction of primary, secondary, and tertiary amides to alcohols using SmI2/amine/H2O is reported. The reaction proceeds with C–N bond cleavage in the carbinolamine intermediate, shows excellent functional group tolerance, and delivers the alcohol products in very high yields. The expected C–O cleavage products are not formed under the reaction conditions. The observed reactivity is opposite to the electrophilicity of polar carbonyl groups resulting from the nX → π*C=O (X = O, N) conjugation. Mechanistic studies suggest that coordination of Sm to the carbonyl and then to Lewis basic nitrogen in the tetrahedral intermediate facilitate electron transfer and control the selectivity of the C–N/C–O cleavage. Notably, the method provides direct access to acyl-type radicals from unactivated amides under mild electron transfer conditions. PMID:24460078

Carbon-sulfur bond formation by reductive elimination of gold(iii) thiolates.

PubMed

Currie, Lucy; Rocchigiani, Luca; Hughes, David L; Bochmann, Manfred

2018-05-08

Whereas the reaction of the gold(iii) pincer complex (C^N^C)AuCl with 1-adamantyl thiol (AdSH) in the presence of base affords (C^N^C)AuSAd, the same reaction in the absence of base leads to formation of aryl thioethers as the products of reductive elimination of the Au-C and Au-S ligands (C^N^C = dianion of 2-6-diphenylpyridine or 2-6-diphenylpyrazine). Although high chemical stability is usually taken as a characteristic of pincer complexes, results show that thiols are capable of cleaving one of the pincer Au-C bonds. This reaction is not simply a function of S-H acidity, since no cleavage takes place with other more acidic X-H compounds, such as carbazole, amides, phenols and malonates. The reductive C-S elimination follows a second-order rate law, -d[1a]/dt = k[1a][AdSH]. Reductive elimination is enabled by displacement of the N-donor by thiol; this provides the conformational flexibility necessary for C-S bond formation to occur. Alternatively, reductive C-S bond formation can be induced by reaction of pre-formed thiolates (C^N^C)AuSR with a strong Brønsted acid, followed by addition of SMe2 as base. On the other hand, treatment of (C^N^C)AuR (R = Me, aryl, alkynyl) with thiols under similar conditions leads to selective C-C rather than C-S bond formation. The reaction of (C^N^C)AuSAd with H+ in the absence of a donor ligand affords the thiolato-bridged complex [{(C^N-CH)Au(μ-SAd)}2]2+ which was crystallographically characterised.

Mechanism of the mutagenic action of hydroxylamine. IX. The UV-induced cleavage of the N-O bond in N4-hydroxy-and N4-methoxycytidine and N6-methoxyadenosine.

PubMed Central

Simukova, N A; Yakovlev, D Y; Budowsky, E I

1975-01-01

The principal UV-induced (lambda = 2546nm) reaction of N4-hydroxy- and N4methoxycytidines and N6-methoxyadenosine in neutral aqueous solutions is cleavage of the exocyclic N-O bond with the respective formation of cytidine and adenosine. Quantum yields are 2.8x10(-3) and 2.2x10(-3) M/E for the first two compounds and 9.1x10(-3) M/E for N6-methoxyadenosine. PMID:1052542

Design, Sustainable Synthesis, and Programmed Reactions of Templated N-Heteroaryl-Fused Vinyl Sultams.

PubMed

Laha, Joydev K; Sharma, Shubhra; Kirar, Seema; Banerjee, Uttam C

2017-09-15

A de novo design and synthesis of N-heteroaryl-fused vinyl sultams as templates for programming chemical reactions on vinyl sultam periphery or (hetero)aryl ring is described. The key features include rational designing and sustainable synthesis of the template, customized reactions of vinyl sultams at C═C bond or involving N-S bond cleavage, and reactions on the periphery of the heteroaryl ring for late-stage diversification. The simple, easy access to the template coupled with opportunities for the synthesis of diversely functionalized heterocyles from a single template constitutes a rare study in contemporary organic synthesis.

A cascade of acid-promoted C-O bond cleavage and redox reactions: from oxa-bridged benzazepines to benzazepinones.

PubMed

Zhang, Yuewei; Yang, Fengzhi; Zheng, Lianyou; Dang, Qun; Bai, Xu

2014-12-05

A sequence of C-O bond cleavage and redox reactions in oxa-bridged azepines was realized under acid promoted conditions. This protocol provides an atom-economical and straightforward approach to access benzo[b]azepin-5(2H)-ones in high yields. The formal synthesis of tolvaptan was achieved by exploiting this new transformation.

New Approaches to the Synthesis of Novel Organosilanes.

DTIC Science & Technology

1983-10-01

through" electrode composed of RVC ( reticulated vitreous carbon ), a highly conductive sponge of carbonized material. Both of these flow systems...effective in promoting silicon- carbon bond cleavage and reformation to give cyclic and cage compounds readily and in good yields: (tA*3-9)(CŖ). n 2-S...silicon to carbon bonds and has broad based applications in research and industrial labs. The increase in reaction rate and yield with ultrasonic waves

Rhodium-catalyzed enantioselective cyclizations of γ-alkynylaldehydes with acyl phosphonates: ligand- and substituent-controlled C-P or C-H bond cleavage.

PubMed

Masuda, Kengo; Sakiyama, Norifumi; Tanaka, Rie; Noguchi, Keiichi; Tanaka, Ken

2011-05-11

It has been established that a cationic rhodium(I)/(R)-H(8)-BINAP or (R)-Segphos complex catalyzes two modes of enantioselective cyclizations of γ-alkynylaldehydes with acyl phosphonates via C-P or C-H bond cleavage. The ligands of the Rh(I) complexes and the substitutents of both γ-alkynylaldehydes and acyl phosphonates control these two different pathways. © 2011 American Chemical Society

Distinct hydroxy-radical-induced damage of 3'-uridine monophosphate in RNA: a theoretical study.

PubMed

Zhang, Ru bo; Eriksson, Leif A

2009-01-01

RNA strand scission and base release in 3'-uridine monophosphate (UMP), induced by OH radical addition to uracil, is studied at the DFT B3LYP/6-31+G(d,p) level in the gas phase and in solution. In particular, the mechanism of hydrogen-atom transfer subsequent to radical formation, from C2' on the sugar to the C6 site on the base, is explored. The barriers of (C2'-)H2'(a) abstraction by the C6 radical site range from 11.2 to 20.0 kcal mol(-1) in the gas phase and 14.1 to 21.0 kcal mol(-1) in aqueous solution, indicating that the local surrounding governs the hydrogen-abstraction reaction in a stereoselective way. The calculated N1-C1' (N1-glycosidic bond) and beta-phosphate bond strengths show that homolytic and heterolytic bond-breaking processes are largely favored in each case, respectively. The barrier for beta-phosphate bond rupture is approximately 3.2-4.0 kcal mol(-1) and is preferred by 8-12 kcal mol(-1) over N1-glycosidic bond cleavage in both the gas phase and solution. The beta-phosphate bond-rupture reactions are exothermal in the gas phase and solution, whereas N1-C1' bond-rupture reactions require both solvation and thermal corrections at 298 K to be energetically favored. The presence of the ribose 2'-OH group and its formation of low-barrier hydrogen bonds with oxygen atoms of the 3'-phosphate linkage are highly important for hydrogen transfer and the subsequent bond-breakage reactions.

Inactivation of neurotensin by rat brain synaptic membranes. Cleavage at the Pro10-Tyr11 bond by endopeptidase 24.11 (enkephalinase) and a peptidase different from proline-endopeptidase.

PubMed

Checler, F; Emson, P C; Vincent, J P; Kitabgi, P

1984-11-01

It was shown previously that the tridecapeptide neurotensin is inactivated by rat brain synaptic membranes and that one of the primary inactivating cleavages occurs at the Pro10-Try11 peptide bond, leading to the formation of NT1-10 and NT11-13. The present study was designed to investigate the possibility that this cleavage was catalyzed by proline endopeptidase and/or endopeptidase 24.11 (enkephalinase). Purified rat brain synaptic membranes were found to contain a N-benzyloxycarbonyl-Gly-Pro-4-methyl-coumarinyl-7-amide-hydrolyzin g activity that was markedly inhibited (93%) by the proline endopeptidase inhibitor N-benzyloxycarbonyl-Pro-Prolinal and partially blocked (25%) by an antiproline endopeptidase antiserum. In contrast, the cleavage of neurotensin at the Pro10-Tyr11 bond by synaptic membranes was not affected by N-benzyloxycarbonyl-Pro-Prolinal and the antiserum. When the conversion of NT1-10 to NT1-8 by angiotensin converting enzyme was blocked by captopril and when the processing of NT11-13 by aminopeptidase(s) was inhibited by bestatin, it was found that thiorphan, a potent endopeptidase 24.11 inhibitor, partially decreased the formation of NT1-10 and NT11-13 by synaptic membranes. (1) proline endopeptidase, although it is present in synaptic membranes, is not involved in the cleavage of neurotensin at the Pro10-Tyr11 bond; (2) endopeptidase 24.11 only partially contributes to this cleavage; (3) there exists in rat brain synaptic membranes a peptidase different from proline endopeptidase and endopeptidase 24.11 that is mainly responsible for inactivating neurotensin by cleaving at the Pro10-Tyr11 bond.

Unusually short chalcogen bonds involving organoselenium: insights into the Se-N bond cleavage mechanism of the antioxidant ebselen and analogues.

PubMed

Thomas, Sajesh P; Satheeshkumar, K; Mugesh, Govindasamy; Guru Row, T N

2015-04-27

Structural studies on the polymorphs of the organoselenium antioxidant ebselen and its derivative show the potential of organic selenium to form unusually short Se⋅⋅⋅O chalcogen bonds that lead to conserved supramolecular recognition units. Se⋅⋅⋅O interactions observed in these polymorphs are the shortest such chalcogen bonds known for organoselenium compounds. The FTIR spectral evolution characteristics of this interaction from solution state to solid crystalline state further validates the robustness of this class of supramolecular recognition units. The strength and electronic nature of the Se⋅⋅⋅O chalcogen bonds were explored using high-resolution X-ray charge density analysis and atons-in-molecules (AIM) theoretical analysis. A charge density study unravels the strong electrostatic nature of Se⋅⋅⋅O chalcogen bonding and soft-metal-like behavior of organoselenium. An analysis of the charge density around Se-N and Se-C covalent bonds in conjunction with the Se⋅⋅⋅O chalcogen bonding modes in ebselen and its analogues provides insights into the mechanism of drug action in this class of organoselenium antioxidants. The potential role of the intermolecular Se⋅⋅⋅O chalcogen bonding in forming the intermediate supramolecular assembly that leads to the bond cleavage mechanism has been proposed in terms of electron density topological parameters in a series of molecular complexes of ebselen with reactive oxygen species (ROS). © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tandem MS Analysis of Selenamide-Derivatized Peptide Ions

NASA Astrophysics Data System (ADS)

Zhang, Yun; Zhang, Hao; Cui, Weidong; Chen, Hao

2011-09-01

Our previous study showed that selenamide reagents such as ebselen and N-(phenylseleno)phthalimide (NPSP) can be used for selective and rapid derivatization of protein/peptide thiols in high conversion yield. This paper reports the systematic investigation of MS/MS dissociation behaviors of selenamide-derivatized peptide ions upon collision induced dissociation (CID) and electron transfer dissociation (ETD). In the positive ion mode, derivatized peptide ions exhibit tag-dependent CID dissociation pathways. For instance, ebselen-derivatized peptide ions preferentially undergo Se-S bond cleavage upon CID to produce a characteristic fragment ion, the protonated ebselen ( m/z 276), which allows selective identification of thiol peptides from protein digest as well as selective detection of thiol proteins from protein mixture using precursor ion scan (PIS). In contrast, NPSP-derivatized peptide ions retain their phenylselenenyl tags during CID, which is useful in sequencing peptides and locating cysteine residues. In the negative ion CID mode, both types of tags are preferentially lost via the Se-S cleavage, analogous to the S-S bond cleavage during CID of disulfide-containing peptide anions. In consideration of the convenience in preparing selenamide-derivatized peptides and the similarity of Se-S of the tag to the S-S bond, we also examined ETD of the derivatized peptide ions to probe the mechanism for electron-based ion dissociation. Interestingly, facile cleavage of Se-S bond occurs to the peptide ions carrying either protons or alkali metal ions, while backbone cleavage to form c/z ions is severely inhibited. These results are in agreement with the Utah-Washington mechanism proposed for depicting electron-based ion dissociation processes.

Non-adiabatic behavior in the homolytic and heterolytic bond dissociation of protonated hydrazine: A guided ion beam and theoretical investigation

NASA Astrophysics Data System (ADS)

McNary, Christopher P.; Armentrout, P. B.

2017-09-01

Threshold collision-induced dissociation using a guided ion beam tandem mass spectrometer was performed on protonated hydrazine and its perdeuterated variant. The dominant dissociation pathways observed were endothermic homolytic and heterolytic cleavages of the N-N bond. The data were analyzed using a statistical model after accounting for internal and kinetic energy distributions, multiple collisions, and kinetic shifts to obtain 0 K bond dissociation energies. Comparison with literature thermochemistry demonstrates that both channels behave non-adiabatically. Heterolytic bond cleavage yields NH2+ + NH3 products, but the NH2+ fragment is in the spin-restricted excited 1A1 state and not in the spin-forbidden ground 3B1 state, whereas homolytic bond cleavage leads to dissociation to the NH3+ + NH2 product asymptote with NH2 in its excited 2A1 state rather than the energetically favored 2B1 state. The rationale for the non-adiabatic behavior observed in the homolytic bond cleavage is revealed by detailed theoretical calculations of the relevant potential energy surfaces and the relevant occupied valence molecular orbitals. These calculations suggest that the non-adiabatic behavior results from conservation of the σ and π character of the binding and lone pair electrons on the nitrogen atoms.

An allosteric disulfide bond is involved in enhanced activation of factor XI by protein disulfide isomerase.

PubMed

Zucker, M; Seligsohn, U; Yeheskel, A; Mor-Cohen, R

2016-11-01

Essentials Reduction of three disulfide bonds in factor (F) XI enhances chromogenic substrate cleavage. We measured FXI activity upon reduction and identified a bond involved in the enhanced activity. Reduction of FXI augments FIX cleavage, probably by faster conversion of FXI to FXIa. The Cys362-Cys482 disulfide bond is responsible for FXI enhanced activation upon its reduction. Background Reduction of factor (F) XI by protein disulfide isomerase (PDI) has been shown to enhance the ability of FXI to cleave its chromogenic substrate. Three disulfide bonds in FXI (Cys118-Cys147, Cys362-Cys482, and Cys321-Cys321) are involved in this augmented activation. Objectives To characterize the mechanisms by which PDI enhances FXI activity. Methods FXI activity was measured following PDI reduction. Thiols that were exposed in FXI after PDI reduction were labeled with 3-(N-maleimidopropionyl)-biocytin (MPB) and detected with avidin. The rate of conversion of FXI to activated FXI (FXIa) following thrombin activation was assessed with western blotting. FXI molecules harboring mutations that disrupt the three disulfide bonds (C147S, C321S, and C482S) were expressed in cells. The antigenicity of secreted FXI was measured with ELISA, and its activity was assessed by the use of a chromogenic substrate. The effect of disulfide bond reduction was analyzed by the use of molecular dynamics. Results Reduction of FXI by PDI enhanced cleavage of both its chromogenic substrate, S2366, and its physiologic substrate, FIX, and resulted in opening of the Cys362-Cys482 bond. The rate of conversion of FXI to FXIa was increased following its reduction by PDI. C482S-FXI showed enhanced activity as compared with both wild-type FXI and C321S-FXI. MD showed that disruption of the Cys362-Cys482 bond leads to a broader thrombin-binding site in FXI. Conclusions Reduction of FXI by PDI enhances its ability to cleave FIX, probably by causing faster conversion of FXI to FXIa. The Cys362-Cys482 disulfide bond is involved in enhancing FXI activation following its reduction, possibly by increasing thrombin accessibility to FXI. © 2016 International Society on Thrombosis and Haemostasis.

Dynamic Responses and Initial Decomposition under Shock Loading: A DFTB Calculation Combined with MSST Method for β-HMX with Molecular Vacancy.

PubMed

He, Zheng-Hua; Chen, Jun; Ji, Guang-Fu; Liu, Li-Min; Zhu, Wen-Jun; Wu, Qiang

2015-08-20

Despite extensive efforts on studying the decomposition mechanism of HMX under extreme condition, an intrinsic understanding of mechanical and chemical response processes, inducing the initial chemical reaction, is not yet achieved. In this work, the microscopic dynamic response and initial decomposition of β-HMX with (1 0 0) surface and molecular vacancy under shock condition, were explored by means of the self-consistent-charge density-functional tight-binding method (SCC-DFTB) in conjunction with multiscale shock technique (MSST). The evolutions of various bond lengths and charge transfers were analyzed to explore and understand the initial reaction mechanism of HMX. Our results discovered that the C-N bond close to major axes had less compression sensitivity and higher stretch activity. The charge was transferred mainly from the N-NO2 group along the minor axes and H atom to C atom during the early compression process. The first reaction of HMX primarily initiated with the fission of the molecular ring at the site of the C-N bond close to major axes. Further breaking of the molecular ring enhanced intermolecular interactions and promoted the cleavage of C-H and N-NO2 bonds. More significantly, the dynamic response behavior clearly depended on the angle between chemical bond and shock direction.

The catalytic chain of human complement subcomponent C1r. Purification and N-terminal amino acid sequences of the major cyanogen bromide-cleavage fragments.

PubMed

Arlaud, G J; Gagnon, J; Porter, R R

1982-01-01

1. The a- and b-chains of reduced and alkylated human complement subcomponent C1r were separated by high-pressure gel-permeation chromatography and isolated in good yield and in pure form. 2. CNBr cleavage of C1r b-chain yielded eight major peptides, which were purified by gel filtration and high-pressure reversed-phase chromatography. As determined from the sum of their amino acid compositions, these peptides accounted for a minimum molecular weight of 28 000, close to the value 29 100 calculated from the whole b-chain. 3. N-Terminal sequence determinations of C1r b-chain and its CNBr-cleavage peptides allowed the identification of about two-thirds of the amino acids of C1r b-chain. From our results, and on the basis of homology with other serine proteinases, an alignment of the eight CNBr-cleavage peptides from C1r b-chain is proposed. 4. The residues forming the 'charge-relay' system of the active site of serine proteinases (His-57, Asp-102 and Ser-195 in the chymotrypsinogen numbering) are found in the corresponding regions of C1r b-chain, and the amino acid sequence around these residues has been determined. 5. The N-terminal sequence of C1r b-chain has been extended to residue 60 and reveals that C1r b-chain lacks the 'histidine loop', a disulphide bond that is present in all other known serine proteinases.

Palladium-catalyzed cyclocoupling of 2-halobiaryls with isocyanides via the cleavage of carbon-hydrogen bonds.

PubMed

Tobisu, Mamoru; Imoto, Shinya; Ito, Sana; Chatani, Naoto

2010-07-16

To demonstrate the utility of isocyanides in catalytic C-H bond functionalization reactions, a palladium-catalyzed cyclocoupling reaction of 2-halobiaryls with isocyanides was developed. The reaction afforded an array of fluorenone imine derivatives via the cleavage of a C-H bond at the 2'-position of 2-halobiaryls. The use of 2,6-disubstituted phenyl isocyanide was crucial for this catalytic cyclocoupling reaction to proceed. The reaction was applicable to heterocyclic and vinylic substrates, allowing the construction of a wide range of ring system. The large kinetic isotope effect observed (k(H)/k(D) = 5.3) indicates that C-H bond activation was the turnover-limiting step in this catalysis.

On the nature of carbon-hydrogen bond activation at rhodium and related reactions.

PubMed

Jones, William D

2005-06-27

Over the past 20 years, substantial progress has been made in the understanding of the activation of C-H and other strong bonds by reactive metal complexes in low oxidation states. This paper will present an overview of the use of pentamethylcyclopentadienyl and trispyrazolylborate rhodium complexes for the activation of arene and alkane C-H bonds. Insights into bond strengths, kinetic and thermodynamic selectivities, and the nature of the intermediates involved will be reviewed. The role of eta-2 arene complexes will be shown to be critical to the C-H activation reactions. Some information about the fleeting alkane sigma-complexes will also be presented. In addition, use of these complexes with thiophenes has shown the ability to cleave C-S bonds. Mechanistic information has been obtained indicating coordination through sulfur prior to cleavage. Relevant examples of nickel-based C-S cleavage will also be given.

Raney Ni-Sn catalyst for H2 production from biomass-derived hydrocarbons.

PubMed

Huber, G W; Shabaker, J W; Dumesic, J A

2003-06-27

Hydrogen (H2) was produced by aqueous-phase reforming of biomass-derived oxygenated hydrocarbons at temperatures near 500 kelvin over a tin-promoted Raney-nickel catalyst. The performance of this non-precious metal catalyst compares favorably with that of platinum-based catalysts for production of hydrogen from ethylene glycol, glycerol, and sorbitol. The addition of tin to nickel decreases the rate of methane formation from C-O bond cleavage while maintaining the high rates of C-C bond cleavage required for hydrogen formation.

Why Nature Uses Radical SAM Enzymes so Widely: Electron Nuclear Double Resonance Studies of Lysine 2,3-Aminomutase Show the 5'-dAdo• "Free Radical" Is Never Free.

PubMed

Horitani, Masaki; Byer, Amanda S; Shisler, Krista A; Chandra, Tilak; Broderick, Joan B; Hoffman, Brian M

2015-06-10

Lysine 2,3-aminomutase (LAM) is a radical S-adenosyl-L-methionine (SAM) enzyme and, like other members of this superfamily, LAM utilizes radical-generating machinery comprising SAM anchored to the unique Fe of a [4Fe-4S] cluster via a classical five-membered N,O chelate ring. Catalysis is initiated by reductive cleavage of the SAM S-C5' bond, which creates the highly reactive 5'-deoxyadenosyl radical (5'-dAdo•), the same radical generated by homolytic Co-C bond cleavage in B12 radical enzymes. The SAM surrogate S-3',4'-anhydroadenosyl-L-methionine (anSAM) can replace SAM as a cofactor in the isomerization of L-α-lysine to L-β-lysine by LAM, via the stable allylic anhydroadenosyl radical (anAdo•). Here electron nuclear double resonance (ENDOR) spectroscopy of the anAdo• radical in the presence of (13)C, (2)H, and (15)N-labeled lysine completes the picture of how the active site of LAM from Clostridium subterminale SB4 "tames" the 5'-dAdo• radical, preventing it from carrying out harmful side reactions: this "free radical" in LAM is never free. The low steric demands of the radical-generating [4Fe-4S]/SAM construct allow the substrate target to bind adjacent to the S-C5' bond, thereby enabling the 5'-dAdo• radical created by cleavage of this bond to react with its partners by undergoing small motions, ∼0.6 Å toward the target and ∼1.5 Å overall, that are controlled by tight van der Waals contact with its partners. We suggest that the accessibility to substrate and ready control of the reactive C5' radical, with "van der Waals control" of small motions throughout the catalytic cycle, is common within the radical SAM enzyme superfamily and is a major reason why these enzymes are the preferred means of initiating radical reactions in nature.

Why Nature Uses Radical SAM Enzymes so Widely: Electron Nuclear Double Resonance Studies of Lysine 2,3-Aminomutase Show the 5′-dAdo• “Free Radical” Is Never Free

PubMed Central

Horitani, Masaki; Byer, Amanda S.; Shisler, Krista A.; Chandra, Tilak; Broderick, Joan B.; Hoffman, Brian M.

2015-01-01

Lysine 2,3-aminomutase (LAM) is a radical S-adenosyl-L-methionine (SAM) enzyme and, like other members of this superfamily, LAM utilizes radical-generating machinery comprising SAM anchored to the unique Fe of a [4Fe-4S] cluster via a classical five-membered N,O chelate ring. Catalysis is initiated by reductive cleavage of the SAM S–C5′ bond, which creates the highly reactive 5′-deoxyadenosyl radical (5′-dAdo•), the same radical generated by homolytic Co–C bond cleavage in B12 radical enzymes. The SAM surrogate S-3′,4′-anhydroadenosyl-L-methionine (anSAM) can replace SAM as a cofactor in the isomerization of L-α-lysine to L-β-lysine by LAM, via the stable allylic anhydroadenosyl radical (anAdo•). Here electron nuclear double resonance (ENDOR) spectroscopy of the anAdo• radical in the presence of 13C, 2H, and 15N-labeled lysine completes the picture of how the active site of LAM from Clostridium subterminale SB4 “tames” the 5′-dAdo• radical, preventing it from carrying out harmful side reactions: this “free radical” in LAM is never free. The low steric demands of the radical-generating [4Fe-4S]/SAM construct allow the substrate target to bind adjacent to the S–C5′ bond, thereby enabling the 5′-dAdo• radical created by cleavage of this bond to react with its partners by undergoing small motions, ~0.6 Å toward the target and ~1.5 Å overall, that are controlled by tight van der Waals contact with its partners. We suggest that the accessibility to substrate and ready control of the reactive C5′ radical, with “van der Waals control” of small motions throughout the catalytic cycle, is common within the radical SAM enzyme superfamily and is a major reason why these enzymes are the preferred means of initiating radical reactions in nature. PMID:25923449

Selective hydrodeoxygenation of biomass-derived oxygenates to unsaturated hydrocarbons using molybdenum carbide catalysts.

PubMed

Ren, Hui; Yu, Weiting; Salciccioli, Michael; Chen, Ying; Huang, Yulin; Xiong, Ke; Vlachos, Dionisios G; Chen, Jingguang G

2013-05-01

Which cleavage do you prefer? With a combination of density functional theory (DFT) calculations, surface science studies, and reactor evaluations, Mo(2)C is identified as a highly selective HDO catalyst to selectively convert biomass-derived oxygenates to unsaturated hydrocarbons through selective C-O bond scissions without C-C bond cleavage. This provides high-value HDO products for utilization as feedstocks for chemicals and fuels; this also reduces the overall consumption of H2 . Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Rhenium-Promoted C-C Bond-Cleavage Reactions of Internal Propargyl Alcohols.

PubMed

Lee, Kui Fun; Bai, Wei; Sung, Herman H Y; Williams, Ian D; Lin, Zhenyang; Jia, Guochen

2018-06-07

The first examples of C-C bond cleavage reactions of internal propargyl alcohols to give vinylidene complexes are described. Treatment of [Re(dppm) 3 ]I with RC≡CC(OH)R'R'' (R=aryl, alkyl; C(OH)R'R''=C(OH)Ph 2, C(OH)Me 2 , C(OH)HPh, C(OH)H 2 ) produced the vinylidene complexes ReI(=C=CHR)(dppm) 2 with the elimination of C(O)R'R''. Computational studies support that the reactions proceed through a β-alkynyl elimination of alkoxide intermediates Re{OC(R')(R'')C≡CR}(dppm) 2 . © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anti-Arrhenius cleavage of covalent bonds in bottlebrush macromolecules on substrate.

PubMed

Lebedeva, Natalia V; Nese, Alper; Sun, Frank C; Matyjaszewski, Krzysztof; Sheiko, Sergei S

2012-06-12

Spontaneous degradation of bottlebrush macromolecules on aqueous substrates was monitored by atomic force microscopy. Scission of C ─ C covalent bonds in the brush backbone occurred due to steric repulsion between the adsorbed side chains, which generated bond tension on the order of several nano-Newtons. Unlike conventional chemical reactions, the rate of bond scission was shown to decrease with temperature. This apparent anti-Arrhenius behavior was caused by a decrease in the surface energy of the underlying substrate upon heating, which results in a corresponding decrease of bond tension in the adsorbed macromolecules. Even though the tension dropped minimally from 2.16 to 1.89 nN, this was sufficient to overpower the increase in the thermal energy (k(B)T) in the Arrhenius equation. The rate constant of the bond-scission reaction was measured as a function of temperature and surface energy. Fitting the experimental data by a perturbed Morse potential V = V(0)(1 - e(-βx))(2) - fx, we determined the depth and width of the potential to be V(0) = 141 ± 19 kJ/mol and β(-1) = 0.18 ± 0.03 Å, respectively. Whereas the V(0) value is in reasonable agreement with the activation energy E(a) = 80-220 kJ/mol of mechanical and thermal degradation of organic polymers, it is significantly lower than the dissociation energy of a C ─ C bond D(e) = 350 kJ/mol. Moreover, the force constant K(x) = 2β(2)V(0) = 1.45 ± 0.36 kN/m of a strained bottlebrush along its backbone is markedly larger than the force constant of a C ─ C bond K(l) = 0.44 kN/m, which is attributed to additional stiffness due to deformation of the side chains.

Gas-phase conformation-specific photofragmentation of proline-containing peptide ions.

PubMed

Kim, Tae-Young; Valentine, Stephen J; Clemmer, David E; Reilly, James P

2010-08-01

Singly-protonated proline-containing peptides with N-terminal arginine are photodissociated with vacuum ultraviolet (VUV) light in an ESI linear ion trap/orthogonal-TOF (LIT/o-TOF). When proline is the nth residue from the N-terminus, unusual b(n) + 2 and a(n) + 2 ions are observed. Their formation is explained by homolytic cleavage of the C(alpha)-C bond in conjunction with a rearrangement of electrons and an amide hydrogen. The latter is facilitated by a proline-stabilized gas-phase peptide conformation. Copyright 2010 American Society for Mass Spectrometry. Published by Elsevier Inc. All rights reserved.

Trapping-mediated dissociative chemisorption of C3H8 and C3D8 on Ir(110)

NASA Astrophysics Data System (ADS)

Kelly, D.; Weinberg, W. H.

1996-07-01

We have employed molecular beam techniques to investigate the molecular trapping and trapping-mediated dissociative chemisorption of C3H8 and C3D8 on Ir(110) at low beam translational energies, Ei≤5 kcal/mol, and surface temperatures, Ts, from 85 to 1200 K. For Ts=85 K, C3H8 is molecularly adsorbed on Ir(110) with a trapping probability, ξ, equal to 0.94 at Ei=1.6 kcal/mol and ξ=0.86 at Ei=5 kcal/mol. At Ei=1.9 kcal/mol and Ts=85 K, ξ of C3D8 is equal to 0.93. From 150 K to approximately 700 K, the initial probabilities of dissociative chemisorption of propane decrease with increasing Ts. For Ts from 700 to 1200 K, however, the initial probability of dissociative chemisorption maintains the essentially constant value of 0.16. These observations are explained within the context of a kinetic model which includes both C-H (C-D) and C-C bond cleavage. Below 450 K propane chemisorption on Ir(110) arises essentially solely from C-H (C-D) bond cleavage, an unactivated mechanism (with respect to a gas-phase energy zero) for this system, which accounts for the decrease in initial probabilities of chemisorption with increasing Ts. With increasing Ts, however, C-C bond cleavage, the activation energy of which is greater than the desorption energy of physically adsorbed propane, increasingly contributes to the measured probability of dissociative chemisorption. The activation energies, referenced to the bottom of the physically adsorbed molecular well, for C-H and C-C bond cleavage for C3H8 on Ir(110) are found to be Er,CH=5.3±0.3 kcal/mol and Er,CC=9.9±0.6 kcal/mol, respectively. The activation energies for C-D and C-C bond cleavage for C3D8 on Ir(110) are 6.3±0.3 kcal/mol and 10.5±0.6 kcal/mol, respectively. The desorption activation energy of propane from Ir(110) is approximately 9.5 kcal/mol. These activation energies are compared to activation energies determined recently for ethane and propane adsorption on Ir(111), Ru(001), and Pt(110)-(1×2), and ethane activation on Ir(110).

Understanding Nitrogen Fixation

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

Paul J. Chirik

The purpose of our program is to explore fundamental chemistry relevant to the discovery of energy efficient methods for the conversion of atmospheric nitrogen (N{sub 2}) into more value-added nitrogen-containing organic molecules. Such transformations are key for domestic energy security and the reduction of fossil fuel dependencies. With DOE support, we have synthesized families of zirconium and hafnium dinitrogen complexes with elongated and activated N-N bonds that exhibit rich N{sub 2} functionalization chemistry. Having elucidated new methods for N-H bond formation from dihydrogen, C-H bonds and Broensted acids, we have since turned our attention to N-C bond construction. These reactionsmore » are particularly important for the synthesis of amines, heterocycles and hydrazines with a range of applications in the fine and commodity chemicals industries and as fuels. One recent highlight was the discovery of a new N{sub 2} cleavage reaction upon addition of carbon monoxide which resulted in the synthesis of an important fertilizer, oxamide, from the diatomics with the two strongest bonds in chemistry. Nitrogen-carbon bonds form the backbone of many important organic molecules, especially those used in the fertilizer and pharamaceutical industries. During the past year, we have continued our work in the synthesis of hydrazines of various substitution patterns, many of which are important precursors for heterocycles. In most instances, the direct functionalization of N{sub 2} offers a more efficient synthetic route than traditional organic methods. In addition, we have also discovered a unique CO-induced N{sub 2} bond cleavage reaction that simultaneously cleaves the N-N bond of the metal dinitrogen compound and assembles new C-C bond and two new N-C bonds. Treatment of the CO-functionalized core with weak Broensted acids liberated oxamide, H{sub 2}NC(O)C(O)NH{sub 2}, an important slow release fertilizer that is of interest to replace urea in many applications. The synthesis of ammonia, NH{sub 3}, from its elements, H{sub 2} and N{sub 2}, via the venerable Haber-Bosch process is one of the most significant technological achievements of the past century. Our research program seeks to discover new transition metal reagents and catalysts to disrupt the strong N {triple_bond} N bond in N{sub 2} and create new, fundamental chemical linkages for the construction of molecules with application as fuels, fertilizers and fine chemicals. With DOE support, our group has discovered a mild method for ammonia synthesis in solution as well as new methods for the construction of nitrogen-carbon bonds directly from N{sub 2}. Ideally these achievements will evolve into more efficient nitrogen fixation schemes that circumvent the high energy demands of industrial ammonia synthesis. Industrially, atmospheric nitrogen enters the synthetic cycle by the well-established Haber-Bosch process whereby N{sub 2} is hydrogenated to ammonia at high temperature and pressure. The commercialization of this reaction represents one of the greatest technological achievements of the 20th century as Haber-Bosch ammonia is responsible for supporting approximately 50% of the world's population and serves as the source of half of the nitrogen in the human body. The extreme reaction conditions required for an economical process have significant energy consequences, consuming 1% of the world's energy supply mostly in the form of pollution-intensive coal. Moreover, industrial H{sub 2} synthesis via the water gas shift reaction and the steam reforming of methane is fossil fuel intensive and produces CO{sub 2} as a byproduct. New synthetic methods that promote this thermodynamically favored transformation ({Delta}G{sup o} = -4.1 kcal/mol) under milder conditions or completely obviate it are therefore desirable. Most nitrogen-containing organic molecules are derived from ammonia (and hence rely on the Haber-Bosch and H{sub 2} synthesis processes) and direct synthesis from atmospheric nitrogen could, in principle, be more energy-efficient. This is particularly attractive given the interest in direct hydrazine fuel cells.« less

Carbon-carbon bond cleavage of 1,2-hydroxy ethers b7 vanadium(V) dipicolinate complexes

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

Hanson, Susan K; Gordon, John C; Thorn, David L

2009-01-01

The development of alternatives to current petroleum-based fuels and chemicals is becoming increasingly important due to concerns over climate change, growing world energy demand, and energy security issues. Using non-food derived biomass to produce renewable feedstocks for chemicals and fuels is a particularly attractive possibility. However, the majority of biomass is in the form of lignocellulose, which is often not fully utilized due to difficulties associated with breaking down both lignin and cellulose. Recently, a number of methods have been reported to transform cellulose directly into more valuable materials such as glucose, sorbitol, 5-(chloromethyl)furfural, and ethylene glycol. Less progress hasmore » been made with selective transformations of lignin, which is typically treated in paper and forest industries by kraft pulping (sodium hydroxide/sodium sulfide) or incineration. Our group has begun investigating aerobic oxidative C-C bond cleavage catalyzed by dipicolinate vanadium complexes, with the idea that a selective C-C cleavage reaction of this type could be used to produce valuable chemicals or intermediates from cellulose or lignin. Lignin is a randomized polymer containing methoxylated phenoxy propanol units. A number of different linkages occur naturally; one of the most prevalent is the {beta}-O-4 linkage shown in Figure 1, containing a C-C bond with 1,2-hydroxy ether substituents. While the oxidative C-C bond cleavage of 1,2-diols has been reported for a number of metals, including vanadium, iron, manganese, ruthenium, and polyoxometalate complexes, C-C bond cleavage of 1,2-hydroxy ethers is much less common. We report herein vanadium-mediated cleavage of C-C bonds between alcohol and ether functionalities in several lignin model complexes. In order to explore the scope and potential of vanadium complexes to effect oxidative C-C bond cleavage in 1,2-hydroxy ethers, we examined the reactivity of the lignin model complexes pinacol monomethyl ether (A), 2-phenoxyethanol (B), and 1,2-diphenyl-2-methoxyethanol (C) (Figure 1). Reaction of (dipic)V{sup V}(O)O{sup i}Pr (1a) or (dipic)V{sup v}(O)OEt (lb) with A, B, or C in acetonitrile yielded new vanadium(V) complexes where the alcohol-ether ligand was bound in a chelating fashion. From the reaction of 1b with pinacol monomethyl ether (A) in acetonitrile solution, (dipic)V{sup v}(O)(pinOMe) (2) (PinOMe = 2,3-dimethyl-3-methoxy-2-butanoxide) was isolated in 61 % yield. Reaction of 1b with 2-phenoxyethanol (B) in acetonitrile gave the new complex (dipic)V{sup v}(O)(OPE) (3) (OPE = 2-phenoxyethoxide), which was isolated in 76% yield. In a similar fashion, 1a reacted with 1,2-diphenyl-2-methoxyethanol (C) to give (dipic)V(O)(DPME) (4) (DPME = 1,2-diphenyl-2-methoxyethoxide), which was isolated in 39% yield. Complexes 2, 3, and 4 were characterized by {sup 1}H NMR and IR spectroscopy, elemental analysis, and X-ray crystallography. Compared to the previously reported vanadium(V) pinacolate complex (dipic)V(O)(pinOH) the X-ray structure of complex 2 reveals a slightly shorter V = O bond, 1.573(2) {angstrom} vs 1.588(2) {angstrom} for the pinOH structure. Complexes 3 and 4 display similar vanadium oxo bond distances of 1.568(2) {angstrom} and 1.576(2) {angstrom}, respectively. All three complexes show longer bonds to the ether-oxygen trans to the oxo (2.388(2) {angstrom} for 2, 2.547(2) {angstrom} for 3, and 2.438(2) {angstrom} for 4) than to the hydroxy-oxygen in the pinOH structure (2.252(2) {angstrom}).« less

Phenylselenolate Mercury Alkyl Compounds, PhSeHgMe and PhSeHgEt: Molecular Structures, Protolytic Hg–C Bond Cleavage and Phenylselenolate Exchange‡

PubMed Central

Yurkerwich, Kevin; Quinlivan, Patrick J.; Rong, Yi

2015-01-01

The phenylselenolate mercury alkyl compounds, PhSeHgMe and PhSeHgEt, have been structurally characterized by X-ray diffraction, thereby demonstrating that both compounds are monomeric with approximately linear coordination geometries; the mercury centers do, nevertheless, exhibit secondary Hg•••Se intermolecular interactions that serve to increase the coordination number in the solid state. The ethyl derivative, PhSeHgEt, undergoes facile protolytic cleavage of the Hg–C bond to release ethane at room temperature, whereas PhSeHgMe exhibits little reactivity under similar conditions. Interestingly, the cleavage of the Hg–C bond of PhSeHgEt is also more facile than that of the thiolate analogue, PhSHgEt, which demonstrates that coordination by selenium promotes protolytic cleavage of the mercury-carbon bond. The phenylselenolate compounds PhSeHgR (R = Me, Et) also undergo degenerate exchange reactions with, for example, PhSHgR and RHgCl. In each case, the alkyl groups preserve coupling to the 199Hg nuclei, thereby indicating that the exchange process involves metathesis of the Hg–SePh/Hg–X groups rather than metathesis of the Hg–R/Hg–R groups. PMID:26644634

Phenylselenolate Mercury Alkyl Compounds, PhSeHgMe and PhSeHgEt: Molecular Structures, Protolytic Hg-C Bond Cleavage and Phenylselenolate Exchange.

PubMed

Yurkerwich, Kevin; Quinlivan, Patrick J; Rong, Yi; Parkin, Gerard

2016-01-08

The phenylselenolate mercury alkyl compounds, PhSeHgMe and PhSeHgEt, have been structurally characterized by X-ray diffraction, thereby demonstrating that both compounds are monomeric with approximately linear coordination geometries; the mercury centers do, nevertheless, exhibit secondary Hg•••Se intermolecular interactions that serve to increase the coordination number in the solid state. The ethyl derivative, PhSeHgEt, undergoes facile protolytic cleavage of the Hg-C bond to release ethane at room temperature, whereas PhSeHgMe exhibits little reactivity under similar conditions. Interestingly, the cleavage of the Hg-C bond of PhSeHgEt is also more facile than that of the thiolate analogue, PhSHgEt, which demonstrates that coordination by selenium promotes protolytic cleavage of the mercury-carbon bond. The phenylselenolate compounds PhSeHgR (R = Me, Et) also undergo degenerate exchange reactions with, for example, PhSHgR and RHgCl. In each case, the alkyl groups preserve coupling to the 199 Hg nuclei, thereby indicating that the exchange process involves metathesis of the Hg-SePh/Hg-X groups rather than metathesis of the Hg-R/Hg-R groups.

Adenosylcobinamide methyl phosphate as a pseudocoenzyme for diol dehydrase.

PubMed

Ishida, A; Toraya, T

1993-02-16

Adenosylcobinamide methyl phosphate, a novel analog of adenosylcobalamin lacking the nucleotide loop moiety, was synthesized. It did not show detectable coenzymic activity but behaved as a strong competitive inhibitor against AdoCbl with relatively high affinity (Ki = 2.5 microM). When apoenzyme was incubated at 37 degrees C with this analog in the presence of substrate, the Co-C bond of the analog was almost completely and irreversibly cleaved within 10 min, forming an enzyme-bound Co(II)-containing species. The cleavage was not observed in the absence of substrate. The Co-C bond cleavage in the presence of substrate was not catalytic but stoichiometric, implying that the Co-C bond of the analog undergoes activation when the analog binds to the active site of the enzyme. 5'-Deoxyadenosine was the only product derived from the adenosyl group of the analog upon the Co-C bond cleavage. Apoenzyme did not undergo modification during this process. Therefore, it seems likely that adenosylcobinamide methyl phosphate acts as a pseudocoenzyme or a potent suicide coenzyme. Since adenosylcobinamide neither functions as coenzyme nor binds tightly to apoenzyme, it can be concluded that the phosphodiester moiety of the nucleotide loop of adenosylcobalamin is essential for tight binding to apoenzyme and therefore for subsequent activation of the Co-C bond and catalysis. It is also evident that the nucleotide loop is obligatory for the normal progress of catalytic cycle.

Oxidation of aniline aerofloat in flotation wastewater by sodium hypochlorite solution.

PubMed

Lin, Weixiong; Tian, Jing; Ren, Jie; Xu, Pingting; Dai, Yongkang; Sun, Shuiyu; Wu, Chun

2016-01-01

Aniline aerofloat (dianilinodithiophosphoric acid (C6H5NH)2PSSH) is a widely used phosphorodithioic organic flotation collector that contains aniline groups and dithiophosphate groups. In the present study, sodium hypochlorite solution was used to oxidize aniline aerofloat. The effect of operational parameters and optimum oxidation conditions on aniline aerofloat was studied, and the oxidation pathway of aniline aerofloat was proposed by analyzing its main oxidation intermediates. The results showed that NaOCl concentration had a significant influence on aniline aerofloat oxidation and at 100 mg/L aniline aerofloat, 84.54% was removed under the following optimal conditions: NaOCl concentration = 1.25 g/L, pH = 4, and reaction time = 60 min. The main reaction of aniline aerofloat by NaOCl included N-P bond cleavage, aniline group oxidation, aniline group chlorination, and dithiophosphate group oxidation. The initial reaction was the N-P bond cleavage and the anilines and dithiophosphate was further oxidized to other intermediates by five parallel reaction pathways.

A general synthesis of C8-arylpurine phosphoramidites.

PubMed

Vongsutilers, Vorasit; Daft, Jonathan R; Shaughnessy, Kevin H; Gannett, Peter M

2009-09-02

A general scheme for the synthesis of C8-arylpurine phosphoramidites has been developed. C8-Arylation of C8-bromo-2'-deoxyguanosine is the key step and has been achieved through the use of a Suzuki coupling. Since the coupling reaction is conducted under aqueous conditions, it is unnecessary to protect and then deprotect the hydroxyl groups, thus saving several steps and improving overall yields. Once the C8-arylgroup is introduced, the glycosidic bond becomes very sensitive to acid catalyzed cleavage. Protection of the amino groups as the corresponding N,N-dimethylformamidine derivative improves stability of the derivatives. Synthetic C8-arylpurines were successfully used to prepare synthetic oligonucleotides.

Ethers on Si(001): A Prime Example for the Common Ground between Surface Science and Molecular Organic Chemistry.

PubMed

Pecher, Lisa; Laref, Slimane; Raupach, Marc; Tonner, Ralf

2017-11-20

By using computational chemistry it has been shown that the adsorption of ether molecules on Si(001) under ultrahigh vacuum conditions can be understood with classical concepts of organic chemistry. Detailed analysis of the two-step reaction mechanism-1) formation of a dative bond between the ether oxygen atom and a Lewis acidic surface atom and 2) nucleophilic attack of a nearby Lewis basic surface atom-shows that it mirrors acid-catalyzed ether cleavage in solution. The O-Si dative bond is the strongest of its kind, and the reactivity in step 2 defies the Bell-Evans-Polanyi principle. Electron rearrangement during C-O bond cleavage has been visualized with a newly developed method for analyzing bonding, which shows that the mechanism of nucleophilic substitutions on semiconductor surfaces is identical to molecular S N 2 reactions. Our findings illustrate how surface science and molecular chemistry can mutually benefit from each other and unexpected insight can be gained. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural and Kinetic Isotope Effect Studies of Nicotinamidase (Pnc1) from Saccharomyces cerevisiae

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

Smith, Brian C.; Anderson, Mark A.; Hoadley, Kelly A.

2012-05-08

Nicotinamidases catalyze the hydrolysis of nicotinamide to nicotinic acid and ammonia. Nicotinamidases are absent in mammals but function in NAD{sup +} salvage in many bacteria, yeast, plants, protozoa, and metazoans. We have performed structural and kinetic investigations of the nicotinamidase from Saccharomyces cerevisiae (Pnc1). Steady-state product inhibitor analysis revealed an irreversible reaction in which ammonia is the first product released, followed by nicotinic acid. A series of nicotinamide analogues acting as inhibitors or substrates were examined, revealing that the nicotinamide carbonyl oxygen and ring nitrogen are critical for binding and reactivity. X-ray structural analysis revealed a covalent adduct between nicotinaldehydemore » and Cys167 of Pnc1 and coordination of the nicotinamide ring nitrogen to the active-site zinc ion. Using this structure as a guide, the function of several residues was probed via mutagenesis and primary {sup 15}N and {sup 13}C kinetic isotope effects (KIEs) on V/K for amide bond hydrolysis. The KIE values of almost all variants were increased, indicating that C-N bond cleavage is at least partially rate limiting; however, a decreased KIE for D51N was indicative of a stronger commitment to catalysis. In addition, KIE values using slower alternate substrates indicated that C-N bond cleavage is at least partially rate limiting with nicotinamide to highly rate limiting with thionicotinamide. A detailed mechanism involving nucleophilic attack of Cys167, followed by elimination of ammonia and then hydrolysis to liberate nicotinic acid, is discussed. These results will aid in the design of mechanism-based inhibitors to target pathogens that rely on nicotinamidase activity.« less

Copper(I)-catalyzed substitution reactions of propargylic amines: importance of C(sp)-C(sp3) bond cleavage in generation of iminium intermediates.

PubMed

Sugiishi, Tsuyuka; Kimura, Akifumi; Nakamura, Hiroyuki

2010-04-21

Substitution reactions of propargylic amines proceed in the presence of copper(I) catalysts. Mechanistic studies showed that C(sp)-C(sp(3)) bond cleavage assisted by nitrogen lone-pair electrons is essential for the reaction, and the resulting iminium intermediates undergo amine exchange, aldehyde exchange, and alkyne addition reactions. Because iminium intermediates are key to aldehyde-alkyne-amine (A(3)) coupling reactions, this transformation is effective not only for reconstruction of propargylic amines but also for chiral induction of racemic compounds in the presence of chiral catalysts.

Regioselectivity of enzymatic and photochemical single electron transfer promoted carbon-carbon bond fragmentation reactions of tetrameric lignin model compounds.

PubMed

Cho, Dae Won; Latham, John A; Park, Hea Jung; Yoon, Ung Chan; Langan, Paul; Dunaway-Mariano, Debra; Mariano, Patrick S

2011-04-15

New types of tetrameric lignin model compounds, which contain the common β-O-4 and β-1 structural subunits found in natural lignins, have been prepared and carbon-carbon bond fragmentation reactions of their cation radicals, formed by photochemical (9,10-dicyanoanthracene) and enzymatic (lignin peroxidase) SET-promoted methods, have been explored. The results show that cation radical intermediates generated from the tetrameric model compounds undergo highly regioselective C-C bond cleavage in their β-1 subunits. The outcomes of these processes suggest that, independent of positive charge and odd-electron distributions, cation radicals of lignins formed by SET to excited states of sensitizers or heme-iron centers in enzymes degrade selectively through bond cleavage reactions in β-1 vs β-O-4 moieties. In addition, the findings made in the enzymatic studies demonstrate that the sterically large tetrameric lignin model compounds undergo lignin peroxidase-catalyzed cleavage via a mechanism involving preliminary formation of an enzyme-substrate complex.

Copper-catalyzed oxidative dimerizations of 3-N-hydroxy-aminoprop-1-enes to form 1,4-dihydroxy-2,3-diaminocyclohexanes with C2  symmetry.

PubMed

Ghorpade, Satish; Liu, Rai-Shung

2014-11-17

This work describes the one-step construction of complex and important molecular frameworks through copper-catalyzed oxidations of cheap tertiary amines. Copper-catalyzed aerobic oxidations of N-hydroxyaminopropenes to form C2 -symmetric N- and O-functionalized cyclohexanes are described. Such catalytic oxidations proceed with remarkable stereocontrol and high efficiency. Reductive cleavage of the two NO bonds of these products delivers 1,4-dihydroxy-2,3-diaminocyclohexanes, which are important skeletons of several bioactive molecules. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Iron(II)-catalyzed intermolecular amino-oxygenation of olefins through the N-O bond cleavage of functionalized hydroxylamines.

PubMed

Lu, Deng-Fu; Zhu, Cheng-Liang; Jia, Zhen-Xin; Xu, Hao

2014-09-24

An iron-catalyzed diastereoselective intermolecular olefin amino-oxygenation reaction is reported, which proceeds via an iron-nitrenoid generated by the N-O bond cleavage of a functionalized hydroxylamine. In this reaction, a bench-stable hydroxylamine derivative is used as the amination reagent and oxidant. This method tolerates a range of synthetically valuable substrates that have been all incompatible with existing amino-oxygenation methods. It can also provide amino alcohol derivatives with regio- and stereochemical arrays complementary to known amino-oxygenation methods.

Forging C-C Bonds Through Decarbonylation of Aryl Ketones.

PubMed

Somerville, Rosie J; Martin, Ruben

2017-06-06

The ability of nickel to cleave strong σ-bonds is again in the spotlight after a recent report that demonstrates the feasibility of using nickel complexes to promote decarbonylation of diaryl ketones. This transformation involves the cleavage of two strong C-C(O) bonds and avoids the use of noble metals, hence reinforcing the potential of decarbonylation as a technique for forging C-C bonds. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Manolopoulou, Marika; Guo, Qing; Malito, Enrico

Insulin is a hormone vital for glucose homeostasis, and insulin-degrading enzyme (IDE) plays a key role in its clearance. IDE exhibits a remarkable specificity to degrade insulin without breaking the disulfide bonds that hold the insulin A and B chains together. Using Fourier transform ion cyclotron resonance (FTICR) mass spectrometry to obtain high mass accuracy, and electron capture dissociation (ECD) to selectively break the disulfide bonds in gas phase fragmentation, we determined the cleavage sites and composition of human insulin fragments generated by human IDE. Our time-dependent analysis of IDE-digested insulin fragments reveals that IDE is highly processive in itsmore » initial cleavage at the middle of both the insulin A and B chains. This ensures that IDE effectively splits insulin into inactive N- and C-terminal halves without breaking the disulfide bonds. To understand the molecular basis of the recognition and unfolding of insulin by IDE, we determined a 2.6-A resolution insulin-bound IDE structure. Our structure reveals that IDE forms an enclosed catalytic chamber that completely engulfs and intimately interacts with a partially unfolded insulin molecule. This structure also highlights how the unique size, shape, charge distribution, and exosite of the IDE catalytic chamber contribute to its high affinity ( approximately 100 nm) for insulin. In addition, this structure shows how IDE utilizes the interaction of its exosite with the N terminus of the insulin A chain as well as other properties of the catalytic chamber to guide the unfolding of insulin and allowing for the processive cleavages.« less

Fundamental studies of desulfurization processes: reaction of methanethiol on ZnO and Cs/ZnO

NASA Astrophysics Data System (ADS)

Dvorak, Joseph; Jirsak, Tomas; Rodriguez, José A.

2001-05-01

The reaction of methanethiol on ZnO and Cs promoted ZnO surfaces has been studied with synchrotron based photoemission and thermal desorption spectroscopy. On ZnO, methanethiol undergoes selective reaction to produce carbon monoxide (37-58%), methane (23-38%), formaldehyde (12-15%), ethane (1-11%), and a mixture of ethylene and acetylene (3-13%). At low temperatures (<100 K), methanethiol reacts to yield thiolate intermediate bound to Zn 2+ cations. The thiolate is stable to 500 K. Above this temperature, C-S bond cleavage occurs to yield methyl intermediate and atomic S. Carbon is removed from the surface as gaseous products above 500 K, and atomic sulfur remains bound to the zinc sites of the surface. Submonolayer amounts of cesium do not have a significant promotional effect on C-S bond cleavage, whereas Cs multilayers are found to significantly lower the activation barrier for C-S bond cleavage. This study illustrates the chemistry associated with the desulfurization of thiols on a catalytically relevant oxide surface.

Specific Cα-C Bond Cleavage of β-Carbon-Centered Radical Peptides Produced by Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry

NASA Astrophysics Data System (ADS)

Nagoshi, Keishiro; Yamakoshi, Mariko; Sakamoto, Kenya; Takayama, Mitsuo

2018-04-01

Radical-driven dissociation (RDD) of hydrogen-deficient peptide ions [M - H + H]·+ has been examined using matrix-assisted laser dissociation/ionization in-source decay mass spectrometry (MALDI-ISD MS) with the hydrogen-abstracting matrices 4-nitro-1-naphthol (4,1-NNL) and 5-nitrosalicylic acid (5-NSA). The preferential fragment ions observed in the ISD spectra include N-terminal [a] + ions and C-terminal [x]+, [y + 2]+, and [w]+ ions which imply that β-carbon (Cβ)-centered radical peptide ions [M - Hβ + H]·+ are predominantly produced in MALDI conditions. RDD reactions from the peptide ions [M - Hβ + H]·+ successfully explains the fact that both [a]+ and [x]+ ions arising from cleavage at the Cα-C bond of the backbone of Gly-Xxx residues are missing from the ISD spectra. Furthermore, the formation of [a]+ ions originating from the cleavage of Cα-C bond of deuterated Ala(d3)-Xxx residues indicates that the [a]+ ions are produced from the peptide ions [M - Hβ + H]·+ generated by deuteron-abstraction from Ala(d3) residues. It is suggested that from the standpoint of hydrogen abstraction via direct interactions between the nitro group of matrix and hydrogen of peptides, the generation of the peptide radical ions [M - Hβ + H]·+ is more favorable than that of the α-carbon (Cα)-centered radical ions [M - Hα + H]·+ and the amide nitrogen-centered radical ions [M - HN + H]·+, while ab initio calculations indicate that the formation of [M - Hα + H]·+ is energetically most favorable. [Figure not available: see fulltext.

Mechanistic Insights into Ring Cleavage and Contraction of Benzene over a Titanium Hydride Cluster.

PubMed

Kang, Xiaohui; Luo, Gen; Luo, Lun; Hu, Shaowei; Luo, Yi; Hou, Zhaomin

2016-09-14

Carbon-carbon bond cleavage of benzene by transition metals is of great fundamental interest and practical importance, as this transformation is involved in the production of fuels and other important chemicals in the industrial hydrocracking of naphtha on solid catalysts. Although this transformation is thought to rely on cooperation of multiple metal sites, molecular-level information on the reaction mechanism has remained scarce to date. Here, we report the DFT studies of the ring cleavage and contraction of benzene by a molecular trinuclear titanium hydride cluster. Our studies suggest that the reaction is initiated by benzene coordination, followed by H2 release, C6H6 hydrometalation, repeated C-C and C-H bond cleavage and formation to give a MeC5H4 unit, and insertion of a Ti atom into the MeC5H4 unit with release of H2 to give a metallacycle product. The C-C bond cleavage and ring contraction of toluene can also occur in a similar fashion, though some details are different due to the presence of the methyl substituent. Obviously, the facile release of H2 from the metal hydride cluster to provide electrons and to alter the charge population at the metal centers, in combination with the flexible metal-hydride connections and dynamic redox behavior of the trimetallic framework, has enabled this unusual transformation to occur. This work has not only provided unprecedented insights into the activation and transformation of benzene over a multimetallic framework but it may also offer help in the design of new molecular catalysts for the activation and transformation of inactive aromatics.

Aromatic thiol-mediated cleavage of N-O bonds enables chemical ubiquitylation of folded proteins

NASA Astrophysics Data System (ADS)

Weller, Caroline E.; Dhall, Abhinav; Ding, Feizhi; Linares, Edlaine; Whedon, Samuel D.; Senger, Nicholas A.; Tyson, Elizabeth L.; Bagert, John D.; Li, Xiaosong; Augusto, Ohara; Chatterjee, Champak

2016-09-01

Access to protein substrates homogenously modified by ubiquitin (Ub) is critical for biophysical and biochemical investigations aimed at deconvoluting the myriad biological roles for Ub. Current chemical strategies for protein ubiquitylation, however, employ temporary ligation auxiliaries that are removed under harsh denaturing conditions and have limited applicability. We report an unprecedented aromatic thiol-mediated N-O bond cleavage and its application towards native chemical ubiquitylation with the ligation auxiliary 2-aminooxyethanethiol. Our interrogation of the reaction mechanism suggests a disulfide radical anion as the active species capable of cleaving the N-O bond. The successful semisynthesis of full-length histone H2B modified by the small ubiquitin-like modifier-3 (SUMO-3) protein further demonstrates the generalizability and compatibility of our strategy with folded proteins.

Dipole and Coulomb forces in electron capture dissociation and electron transfer dissociation mass spectroscopy.

PubMed

Świerszcz, Iwona; Skurski, Piotr; Simons, Jack

2012-02-23

Ab initio electronic structure calculations were performed on a doubly charged polypeptide model H(+)-Lys(Ala)(19)-CO-CH(NH(2))-CH(2)-SS-CH(2)-(NH(2))CH-CO-(Ala)(19)-Lys-H(+) consisting of a C-terminal protonated Lys followed by a 19-Ala α-helix with a 20th Ala-like unit whose side chain is linked by a disulfide bond to a corresponding Ala-like unit connected to a second 19-Ala α-helix terminated by a second C-terminal-protonated Lys. The Coulomb potentials arising from the two charged Lys residues and dipole potentials arising from the two oppositely directed 72 D dipoles of the α-helices act to stabilize the SS bond's σ* orbital. The Coulomb potentials provide stabilization of 1 eV, while the two large dipoles generate an additional 4 eV. Such stabilization allows the SS σ* orbital to attach an electron and thereby generate disulfide bond cleavage products. Although calculations are performed only on SS bond cleavage, discussion of N-C(α) bond cleavage caused by electron attachment to amide π* orbitals is also presented. The magnitudes of the stabilization energies as well as the fact that they arise from Coulomb and dipole potentials are supported by results on a small model system consisting of a H(3)C-SS-CH(3) molecule with positive and negative fractional point charges to its left and right designed to represent (i) two positive charges ca. 32 Å distant (i.e., the two charged Lys sites of the peptide model) and (ii) two 72 D dipoles (i.e., the two α-helices). Earlier workers suggested that internal dipole forces in polypeptides could act to guide incoming free electrons (i.e., in electron capture dissociation (ECD)) toward the positive end of the dipole and thus affect the branching ratios for cleaving various bonds. Those workers argued that, because of the huge mass difference between an anion donor and a free electron, internal dipole forces would have a far smaller influence over the trajectory of a donor (i.e., in electron transfer dissociation (ETD)). The present findings suggest that, in addition to their effects on guiding electron or donor trajectories, dipole potentials (in combination with Coulomb potentials) also alter the energies of SS σ* and amide π* orbitals, which then affects the ability of these orbitals to bind an electron. Thus, both by trajectory-guiding and by orbital energy stabilization, Coulomb and dipole potentials can have significant influences on the branching ratios of ECD and ETC in which disulfide or N-C(α) bonds are cleaved. © 2012 American Chemical Society

Synthesis of [{AgO2CCH2OMe(PPh3)} n ] and theoretical study of its use in focused electron beam induced deposition.

PubMed

Tamuliene, Jelena; Noll, Julian; Frenzel, Peter; Rüffer, Tobias; Jakob, Alexander; Walfort, Bernhard; Lang, Heinrich

2017-01-01

The synthesis, chemical and physical properties of [{AgO 2 CCH 2 OMe} n ] ( 1 ) and [{AgO 2 CCH 2 OMe(PPh 3 )} n ] ( 2 ) are reported. Consecutive reaction of AgNO 3 with HO 2 CCH 2 OMe gave 1 , which upon treatment with PPh 3 produced 2 . Coordination compound 2 forms a 1D coordination polymer in the solid state as evidenced by single crystal X-ray structure analysis. The coordination geometry at Ag + is of the [3 + 1] type, whereby the carboxylate anions act as bridging ligands. The formation of PPh 3 -Ag(I) coordinative bonds results in distorted T-shaped AgPO 2 units, which are stabilized further by an additional O-Ag dative bond. TG and TG-MS measurements show that 1 and 2 decompose at 190-250 °C ( 1 ) and 260-300 °C ( 2 ) via decarboxylation, involving Ag-P ( 2 ), C-C and C-O bond cleavages to give elemental silver as confirmed by PXRD studies. In order to verify if polymeric 2 is suitable as a FEBID precursor for silver deposition, its vapor pressure was determined ( p 170 °C = 5.318 mbar, ∆H vap = 126.1 kJ mol -1 ), evincing little volatility. Also EI and ESI mass spectrometric studies were carried out. The dissociation of the silver(I) compound 2 under typical electron-driven FEBID conditions was studied by DFT (B3LYP) calculations on monomeric [AgO 2 CCH 2 OMe(PPh 3 )]. At an energy of the secondary electrons up to 0.8 eV elimination of PPh 3 occurs, giving Ag + and O 2 CCH 2 OMe - . Likewise, by release of PPh 3 from [AgO 2 CCH 2 OMe(PPh 3 )] the fragment [AgO 2 CCH 2 OMe] - is formed from which Ag + and O 2 CCH 2 OMe - is generated, further following the first fragmentation route. However, at 1.3 eV the initial step is decarboxylation giving [AgCH 2 OMe(PPh 3 )], followed by Ag-P and Ag-C bond cleavages.

Reaction of (carbonylimido)sulfur(IV) derivatives with TAS-fluoride, (Me2N)3S+Me3SiF2-.

PubMed

Lork, E; Viets, D; Mews, R; Oberhammer, H

2000-10-16

In the reaction of TAS-fluoride, (Me2N)3S+Me3SiF2-, with carbonyl sulfur difluoride imides RC(O)NSF2 (R = F, CF3), C-N bond, cleavage is observed, and TAS+RC(O)F2- and NSF are the final products. From TASF and RC(O)NS(CF3)F, the salts TAS+RC(O)NS(CF3)F2- (R = F (14), CF3 (15)), with psi-pentacoordinate sulfur centers in the anions, are formed. An X-ray structure investigation of 14 shows that the fluorine atoms occupy axial positions and CF3, NC(O)F, and the sulfur lone pair occupy equatorial positions of the trigonal bipyramid. The -C(O)F group lies in the equatorial plane with the CO bond synperiplanar to the SN bond. According to B3LYP calculations, this structure corresponds to a global minimum and the expected axial orientation of the -C(O)F group represents a transition state. Calculations for the unstable FC(O)NSF3- anion show a different geometry. The -C(O)F group deviates 40 degrees from axial orientation, and the equatorially bonded fluorine is, in contrast to the -CF3 group in 14, syn positioned.

Neurotensin-metabolizing peptidases in rat fundus plasma membranes.

PubMed

Checler, F; Barelli, H; Kwan, C Y; Kitabgi, P; Vincent, J P

1987-08-01

The mechanisms by which neurotensin (NT) was inactivated by rat fundus plasma membranes were characterized. Primary inactivating cleavages occurred at the Arg8-Arg9, Pro10-Tyr11, and Ile12-Leu13 peptidyl bonds. Hydrolysis at the Arg8-Arg9 bond was fully abolished by the use of N-[1(R,S)-carboxy-2-phenylethyl]-alanyl-alanyl-phenylalanine-p- aminobenzoate, a result indicating the involvement at this site of a recently purified soluble metallopeptidase. Hydrolysis of the Pro10-Tyr11 bond was totally resistant to N-benzyloxycarbonyl-prolyl-prolinal and thiorphan, an observation suggesting that the peptidase responsible for this cleavage was different from proline endopeptidase and endopeptidase 24.11 and might correspond to a NT-degrading neutral metallopeptidase recently isolated from rat brain synaptic membranes. The enzyme acting at the Ile12-Leu13 bond has not yet been identified. Secondary cleavages occurring on NT degradation products were mainly generated by bestatin-sensitive aminopeptidases and post-proline dipeptidyl aminopeptidase. The content in NT-metabolizing peptidases present in rat fundus plasma membranes is compared with that previously established for purified rat brain synaptic membranes.

Fragmentation of Electrospray-produced Deprotonated Ions of Oligodeoxyribonucleotides Containing an Alkylated or Oxidized Thymidine

PubMed Central

Wang, Pengcheng; Williams, Renee T.; Guerrero, Candace R.; Ji, Debin; Wang, Yinsheng

2014-01-01

Alkylation and oxidation constitute major routes of DNA damage induced by endogenous and exogenous genotoxic agents. Understanding the biological consequences of DNA lesions often necessitates the availability of oligodeoxyribonucleotide (ODN) substrates harboring these lesions, and sensitive and robust methods for validating the identities of these ODNs. Tandem mass spectrometry is well suited for meeting these latter analytical needs. In the present study, we evaluated how the incorporation of an ethyl group to different positions (i.e., O2, N3 and O4) of thymine and the oxidation of its 5-methyl carbon impact collisionally activated dissociation (CAD) pathways of electrospray-produced deprotonated ions of ODNs harboring these thymine modifications. Unlike an unmodified thymine, which often manifests poor cleavage of the C3′-O3′ bond, the incorporation of an alkyl group to the O2 position and, to a much lesser extent, the O4 position, but not the N3 position of thymine, led to facile cleavage of the C3′-O3′ bond on the 3′ side of the modified thymine. Similar efficient chain cleavage was observed when thymine was oxidized to 5-formyluracil or 5-carboxyluracil, but not 5-hydroxymethyluracil. Additionally, with the support of computational modeling, we revealed that proton affinity and acidity of the modified nucleobases govern the fragmentation of ODNs containing the alkylated and oxidized thymidine derivatives, respectively. These results provided important insights into the effects of thymine modifications on ODN fragmentation. PMID:24664806

Mono- and tri-ester hydrogenolysis using tandem catalysis. Scope and mechanism.

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

Lohr, Tracy L.; Li, Zhi; Assary, Rajeev S.

The scope and mechanism of thermodynamically leveraged ester RC(O)O-R' bond hydrogenolysis by tandem metal triflate + supported Pd catalysts are investigated both experimentally and theoretically by DFT and energy span analysis. This catalytic system has a broad scope, with relative cleavage rates scaling as, tertiary 4 secondary 4 primary ester at 1 bar H-2, yielding alkanes and carboxylic acids with high conversion and selectivity. Benzylic and allylic esters display the highest activity. The rate law is nu = k[M(OTf )(n)](1)[ester](0)[H-2](0) with an H/D kinetic isotope effect = 6.5 +/- 0.5, implying turnover-limiting C-H scission following C-O cleavage, in agreement withmore » theory. Intermediate alkene products are then rapidly hydrogenated. Applying this approach with the very active Hf(OTf)(4) catalyst to bio-derived triglycerides affords near-quantitative yields of C-3 hydrocarbons rather than glycerol. From model substrates, it is found that RC(O)O-R' cleavage rates are very sensitive to steric congestion and metal triflate identity. For triglycerides, primary/external glyceryl CH2-O cleavage predominates over secondary/internal CH-O cleavage, with the latter favored by less acidic or smaller ionic radius metal triflates, raising the diester selectivity to as high as 48% with Ce(OTf)(3).« less

Kinetics of acid-catalyzed cleavage of procyanindins

Treesearch

Richard W. Hemingway; Gerald W. McGraw

1983-01-01

Comparison of the rates of cleavage of isomeric procyanidin dimers in the presence of excess phenylmethane thiol and acetic acid showed that compounds with a C(4)-C(8) interflavanoid bond were cleaved more rapidly than their C(4)-C(6) linked isomers, that 2,3-cis isomers with an axial flavan substituent were cleaved more-rapidly than a 2,3-...

Electronic excited state paths of Stone-Wales rearrangement in pyrene: roles of conical intersections.

PubMed

Yamazaki, Kaoru; Niitsu, Naoyuki; Nakamura, Kosuke; Kanno, Manabu; Kono, Hirohiko

2012-11-26

We investigated the reaction paths of Stone-Wales rearrangement (SWR), i.e., π/2 rotation of two carbon atoms with respect to the midpoint of the bond, in graphene and carbon nanotube quantum chemically. Our particular attention is focused on the roles of electronic excitations and conical intersections (CIs) in the reaction mechanism. We used pyrene as a model system. The reaction paths were determined by constructing potential energy surfaces at the MS-CASPT2//SA-CASSCF level of theory. We found that there are no CIs involved in SWR when both of C-C bond cleavage and formation occur simultaneously (concerted mechanism). In contrast, for the reaction path with stepwise cleavage and formation of C-C bonds, C-C bond breaking and making processes proceed through two CIs. When SWR starts from the ground (S(0)) state, the concerted and stepwise paths have an equivalent reaction barrier ΔE(‡) (9.5-9.6 eV). For the reaction path starting from excited states, only the stepwise mechanism is energetically preferable. This path contains a nonadabatic transition between the S(1) and S(0) states via a CI associated with the first stage of C-C bond cleavage and has ΔE(‡) as large as in the S(0) paths. We confirmed that the main active molecular orbitals and electron configurations for the low-lying electronic states of larger nanocarbons are the same as those in pyrene. This result suggests the importance of the nonadiabatic transitions through CIs in the photochemical reactions in large nanocarbons.

New Redox Polymers that Exhibit Reversible Cleavage of Sulfur Bonds as Cathode Materials.

PubMed

Baloch, Marya; Ben Youcef, Hicham; Li, Chunmei; Garcia-Calvo, Oihane; Rodriguez, Lide M; Shanmukaraj, Devaraj; Rojo, Teofilo; Armand, Michel

2016-11-23

Two new cathode materials based on redox organosulfur polymers were synthesized and investigated for rechargeable lithium batteries as a proof-of-concept study. These cathodes offered good cycling performance owing to the absence of polysulfide solubility, which plagues Li/S systems. Herein, an aliphatic polyamine or a conjugated polyazomethine was used as the base to tether the redox-active species. The activity comes from the cleavage and formation of S-S or N-S bonds, which is made possible by the rigid conjugated backbone. The synthesized polymers were characterized through FTIR spectroscopy and thermogravimetric analysis (TGA). Galvanostatic measurements were performed to evaluate the discharge/charge cycles and characterize the performance of the lithium-based cells, which displayed initial discharge capacities of approximately 300 mA h g -1 at C/5 over 100 cycles with approximately 98 % Coulombic efficiency. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Site-Specific Imaging of Elemental Steps in Dehydration of Diols on TiO 2(110)

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

Acharya, Danda P.; Yoon, Yeohoon; Li, Zhenjun

2013-11-26

The conversion of diols on partially reduced TiO 2(110) at low coverage was studied using variable-temperature scanning tunneling microscopy, temperature programmed desorption and density functional theory calculations. We find, that below ~230 K, ethane-1,2-diol and propane-1,3-diol molecules adsorb predominantly on five-fold coordinated Ti5c atoms. The dynamic equilibrium between molecularly bound and dissociated species resulting from O-H bond scission and reformation is observed. As the diols start to diffuse on the Ti5c rows above ~230 K, they dissociate irreversibly upon encountering bridging oxygen (O b) vacancy (VO’s) defects. Two dissociation pathways, one via O-H and the other via C-O bond scissionmore » leading to identical surface intermediates, hydroxyalkoxy, O b-(CH 2)n-OH (n = 2, 3) and bridging hydroxyl, HO b, are seen. For O-H bond scission, the O b-(CH 2)n-OH is found on the position of the original VO, while for C-O scission it is found on the adjacent Ob site. Theoretical calculations suggest that the observed mixture of C-O/O-H bond breaking processes are a result of the steric factors enforced upon the diols by the second OH group that is bound to a Ti5c site. At room temperature, rich dissociation/reformation dynamics of the second, Ti5c-bound O-H leads to the formation of dioxo, Ob-(CH 2)n-OTi, species. Above ~400 K, both O b-(CH 2)n-OH and Ob-(CH 2)n-OTi species convert into a new intermediate, that is centered on Ob row. Combined experimental and theoretical evidence shows that this intermediate is most likely a new dioxo, O b-(CH 2) 2-Ob, species. Further annealing leads to sequential C-Ob bond cleavage and alkene desorption above ~ 500 K. Simulations find that the sequential C-O bond breaking process follows a homolytic diradical pathway with the first C-O bond breaking event accompanied by a non-adiabatic electron transfer within the TiO 2(110) substrate.« less

Spectroscopic Identification of the Au-C Bond Formation upon Electroreduction of an Aryl Diazonium Salt on Gold.

PubMed

Guo, Limin; Ma, Lipo; Zhang, Yelong; Cheng, Xun; Xu, Ye; Wang, Jin; Wang, Erkang; Peng, Zhangquan

2016-11-08

Electroreduction of aryl diazonium salts on gold can produce organic films that are more robust than their analogous self-assembled monolayers formed from chemical adsorption of organic thiols on gold. However, whether the enhanced stability is due to the Au-C bond formation remains debated. In this work, we report the electroreduction of an aryl diazonium salt of 4,4'-disulfanediyldibenzenediazonium on gold forming a multilayer of Au-(Ar-S-S-Ar) n , which can be further degraded to a monolayer of Au-Ar-S - by electrochemical cleavage of the S-S moieties within the multilayer. By conducting an in situ surface-enhanced Raman spectroscopic study of both the multilayer formation/degradation and the monolayer reduction/oxidation processes, coupled to density functional theory calculations, we provide compelling evidence that an Au-C bond does form upon electroreduction of aryl diazonium salts on gold and that the enhanced stability of the electrografted organic films is due to the Au-C bond being intrinsically stronger than the Au-S bond for a given phenylthiolate compound by ca. 0.4 eV.

Hydrolytic cleavage of both CS2 carbon-sulfur bonds by multinuclear Pd(II) complexes at room temperature

NASA Astrophysics Data System (ADS)

Jiang, Xuan-Feng; Huang, Hui; Chai, Yun-Feng; Lohr, Tracy Lynn; Yu, Shu-Yan; Lai, Wenzhen; Pan, Yuan-Jiang; Delferro, Massimiliano; Marks, Tobin J.

2017-02-01

Developing homogeneous catalysts that convert CS2 and COS pollutants into environmentally benign products is important for both fundamental catalytic research and applied environmental science. Here we report a series of air-stable dimeric Pd complexes that mediate the facile hydrolytic cleavage of both CS2 carbon-sulfur bonds at 25 °C to produce CO2 and trimeric Pd complexes. Oxidation of the trimeric complexes with HNO3 regenerates the dimeric starting complexes with the release of SO2 and NO2. Isotopic labelling confirms that the carbon and oxygen atoms of CO2 originate from CS2 and H2O, respectively, and reaction intermediates were observed by gas-phase and electrospray ionization mass spectrometry, as well as by Fourier transform infrared spectroscopy. We also propose a plausible mechanistic scenario based on the experimentally observed intermediates. The mechanism involves intramolecular attack by a nucleophilic Pd-OH moiety on the carbon atom of coordinated µ-OCS2, which on deprotonation cleaves one C-S bond and simultaneously forms a C-O bond. Coupled C-S cleavage and CO2 release to yield [(bpy)3Pd3(µ3-S)2](NO3)2 (bpy, 2,2‧-bipyridine) provides the thermodynamic driving force for the reaction.

Perfluorinated Ligands in Organometallic Chemistry

DTIC Science & Technology

1989-12-12

C49t00ooVER ,or C M’ AD"OV’~mDecember 12) 199IFinal 1/1/86 to 8/31/89C smuS. FUNOING NUMgIERS cJ Perfluorinated Ligands in Organometallic Chemistry 612...compounds, stabilized by tridentate perfluorinated ligands. Dinuclear rhodium complexes of OFCOT undergo a selective C-F bond activation reaction...hexafluorocyclooctatrieneyne ligand. Stereospecific cleavage of a fluorinated C-C bond,#-bond in perfluorocyclopropene by platinum and iridium complexes has been achieved

Deciphering the chemoselectivity of nickel-dependent quercetin 2,4-dioxygenase.

PubMed

Wang, Wen-Juan; Wei, Wen-Jie; Liao, Rong-Zhen

2018-06-13

The reaction mechanism and chemoselectivity of nickel-dependent quercetin 2,4-dioxygenase (2,4-QueD) have been investigated using the QM/MM approach. The protonation state of the Glu74 residue, a first-shell ligand of Ni, has been considered to be either neutral or deprotonated. QM/MM calculations predict that Glu74 must be deprotonated to rationalize the chemoselectivity and steer the 2,4-dioxygenolytic cleavage of quercetin, which harvests the experimentally-observed product, 2-protocatechuoylphloroglucinol carboxylic acid, coupled with the release of carbon monoxide. If the enzyme has a neutral Glu74 residue, the undesired 2,3-dioxygenolytic cleavage of quercetin becomes the dominant pathway, leading to the formation of α-keto acid. The calculations suggest that the reaction takes place via three major steps: (1) attack of the superoxide on the C2 of the substrate pyrone ring to generate a NiII-peroxide intermediate; (2) formation of the second C-O bond between C4 and the peroxide to produce a peroxide bridge; (3) simultaneous cleavage of the C2-C3, C3-C4, and O1-O2 bonds with the formation of 2-protocatechuoylphloroglucinol carboxylic acid and carbon monoxide. The third step was found to be rate-limiting, with a barrier of 17.4 kcal mol-1, which is in very good agreement with the experimental kinetic data. For the second C-O bond formation, an alternative pathway is that the peroxide attacks the C3 of the substrate pyrone ring, leading to the formation of a four-membered ring intermediate, which then undergoes concerted C2-C3 and O1-O2 bond cleavages to produce an α-keto acid. This pathway is associated with a barrier of 30.6 kcal mol-1, which is much higher than the major pathway. When Glu74 is protonated, the 2,3-dioxygenolytic pathway, however, has a lower barrier (21.8 kcal mol-1) than the 2,4-dioxygenolytic pathway.

Synthesis of [{AgO2CCH2OMe(PPh3)}n] and theoretical study of its use in focused electron beam induced deposition

PubMed Central

Noll, Julian; Frenzel, Peter; Rüffer, Tobias; Jakob, Alexander; Walfort, Bernhard

2017-01-01

The synthesis, chemical and physical properties of [{AgO2CCH2OMe}n] (1) and [{AgO2CCH2OMe(PPh3)}n] (2) are reported. Consecutive reaction of AgNO3 with HO2CCH2OMe gave 1, which upon treatment with PPh3 produced 2. Coordination compound 2 forms a 1D coordination polymer in the solid state as evidenced by single crystal X-ray structure analysis. The coordination geometry at Ag+ is of the [3 + 1] type, whereby the carboxylate anions act as bridging ligands. The formation of PPh3–Ag(I) coordinative bonds results in distorted T-shaped AgPO2 units, which are stabilized further by an additional O–Ag dative bond. TG and TG–MS measurements show that 1 and 2 decompose at 190–250 °C (1) and 260–300 °C (2) via decarboxylation, involving Ag–P (2), C–C and C–O bond cleavages to give elemental silver as confirmed by PXRD studies. In order to verify if polymeric 2 is suitable as a FEBID precursor for silver deposition, its vapor pressure was determined (p 170 °C = 5.318 mbar, ∆H vap = 126.1 kJ mol−1), evincing little volatility. Also EI and ESI mass spectrometric studies were carried out. The dissociation of the silver(I) compound 2 under typical electron-driven FEBID conditions was studied by DFT (B3LYP) calculations on monomeric [AgO2CCH2OMe(PPh3)]. At an energy of the secondary electrons up to 0.8 eV elimination of PPh3 occurs, giving Ag+ and O2CCH2OMe−. Likewise, by release of PPh3 from [AgO2CCH2OMe(PPh3)] the fragment [AgO2CCH2OMe]− is formed from which Ag+ and O2CCH2OMe− is generated, further following the first fragmentation route. However, at 1.3 eV the initial step is decarboxylation giving [AgCH2OMe(PPh3)], followed by Ag–P and Ag–C bond cleavages. PMID:29259876

Regulator-dependent mechanisms of C3b processing by factor I allow differentiation of immune responses.

PubMed

Xue, Xiaoguang; Wu, Jin; Ricklin, Daniel; Forneris, Federico; Di Crescenzio, Patrizia; Schmidt, Christoph Q; Granneman, Joke; Sharp, Thomas H; Lambris, John D; Gros, Piet

2017-08-01

The complement system labels microbes and host debris for clearance. Degradation of surface-bound C3b is pivotal to direct immune responses and protect host cells. How the serine protease factor I (FI), assisted by regulators, cleaves either two or three distant peptide bonds in the CUB domain of C3b remains unclear. We present a crystal structure of C3b in complex with FI and regulator factor H (FH; domains 1-4 with 19-20). FI binds C3b-FH between FH domains 2 and 3 and a reoriented C3b C-terminal domain and docks onto the first scissile bond, while stabilizing its catalytic domain for proteolytic activity. One cleavage in C3b does not affect its overall structure, whereas two cleavages unfold CUB and dislodge the thioester-containing domain (TED), affecting binding of regulators and thereby determining the number of cleavages. These data explain how FI generates late-stage opsonins iC3b or C3dg in a context-dependent manner, to react to foreign, danger or healthy self signals.

Rhodium(i)-catalyzed asymmetric [4 + 2] cycloaddition reactions of 2-alkylenecyclobutanols with cyclic enones through C–C bond cleavage: efficient access to trans-bicyclic compounds† †Electronic supplementary information (ESI) available. CCDC 1575240. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c7sc04784c

PubMed Central

Zheng, Xinxin; Guo, Rui

2018-01-01

We report a rhodium-catalyzed asymmetric formal intermolecular [4 + 2] cycloaddition reaction of 2-alkylenecyclobutanols with α,β-unsaturated cyclic ketones leading to synthetically useful trans-bicyclic molecules. Three consecutive stereogenic centers are formed in a highly enantio- and diastereoselective manner. Stepwise C–C bond cleavage and annulation are likely involved in the reaction pathway. Here, iPr-Duphos is the viable chiral ligand that promotes excellent enantio-control. PMID:29675233

Decomposition of multilayer benzene and n-hexane films on vanadium.

PubMed

Souda, Ryutaro

2015-09-21

Reactions of multilayer hydrocarbon films with a polycrystalline V substrate have been investigated using temperature-programmed desorption and time-of-flight secondary ion mass spectrometry. Most of the benzene molecules were dissociated on V, as evidenced by the strong depression in the thermal desorption yields of physisorbed species at 150 K. The reaction products dehydrogenated gradually after the multilayer film disappeared from the surface. Large amount of oxygen was needed to passivate the benzene decomposition on V. These behaviors indicate that the subsurface sites of V play a role in multilayer benzene decomposition. Decomposition of the n-hexane multilayer films is manifested by the desorption of methane at 105 K and gradual hydrogen desorption starting at this temperature, indicating that C-C bond scission precedes C-H bond cleavage. The n-hexane dissociation temperature is considerably lower than the thermal desorption temperature of the physisorbed species (140 K). The n-hexane multilayer morphology changes at the decomposition temperature, suggesting that a liquid-like phase formed after crystallization plays a role in the low-temperature decomposition of n-hexane.

Multifaceted catalytic hydrogenation of amides via diverse activation of a sterically confined bipyridine-ruthenium framework.

PubMed

Miura, Takashi; Naruto, Masayuki; Toda, Katsuaki; Shimomura, Taiki; Saito, Susumu

2017-05-16

Amides are ubiquitous and abundant in nature and our society, but are very stable and reluctant to salt-free, catalytic chemical transformations. Through the activation of a "sterically confined bipyridine-ruthenium (Ru) framework (molecularly well-designed site to confine adsorbed H 2 in)" of a precatalyst, catalytic hydrogenation of formamides through polyamide is achieved under a wide range of reaction conditions. Both C=O bond and C-N bond cleavage of a lactam became also possible using a single precatalyst. That is, catalyst diversity is induced by activation and stepwise multiple hydrogenation of a single precatalyst when the conditions are varied. The versatile catalysts have different structures and different resting states for multifaceted amide hydrogenation, but the common structure produced upon reaction with H 2 , which catalyzes hydrogenation, seems to be "H-Ru-N-H."

The fate of H atom adducts to 3'-uridine monophosphate.

PubMed

Wang, Ran; Zhang, Ru Bo; Eriksson, Leif A

2010-07-29

The stabilities of the adducts deriving from H free radical addition to the O2, O4, and C5 positions of 3'-uridine monophosphate (3'UMP) are studied by the hybrid density functional B3LYP approach. Upon H atom addition at the O2 position, a concerted low-barrier proton-transfer process will initially occur, followed by the potential ruptures of the N-glycosidic or beta-phosphate bonds. The rupture barriers are strongly influenced by the rotational configuration of the phosphate group at the 3' terminal, and are influenced by bulk solvation effects. The O4-H adduct has the highest thermal stability, as the localization of the unpaired electron does not enable cleavage of either the C1'-N1 or the C3'-O(P) bonds. For the most stable adduct, with H atom added to the C5 position, the rate-controlled step is the H2'a abstraction by the C6 radical site, after which the subsequent strand rupture reactions proceed with low barriers. The main unpaired electron densities are presented for the transient species. Combined with previous results, it is concluded that the H atom adducts are more facile to drive the strand scission rather than N-glycosidic bond ruptures within the nucleic acid bases.

Base Release and Modification in Solid-Phase DNA Exposed to Low-Energy Electrons.

PubMed

Choofong, Surakarn; Cloutier, Pierre; Sanche, Léon; Wagner, J Richard

2016-11-01

Ionization generates a large number of secondary low-energy electrons (LEEs) with a most probable energy of approximately 10 eV, which can break DNA bonds by dissociative electron attachment (DEA) and lead to DNA damage. In this study, we investigated radiation damage to dry DNA induced by X rays (1.5 keV) alone on a glass substrate or X rays combined with extra LEEs (average energy of 5.8 eV) emitted from a tantalum (Ta) substrate under an atmosphere of N 2 and standard ambient conditions of temperature and pressure. The targets included calf-thymus DNA and double-stranded synthetic oligonucleotides. We developed analytical methods to measure the release of non-modified DNA bases from DNA and the formation of several base modifications by LC-MS/MS with isotopic dilution for precise quantification. The results show that the yield of non-modified bases as well as base modifications increase by 20-30% when DNA is deposited on a Ta substrate compared to that on a glass substrate. The order of base release (Gua > Ade > Thy ∼ Cyt) agrees well with several theoretical studies indicating that Gua is the most susceptible site toward sugar-phosphate cleavage. The formation of DNA damage by LEEs is explained by DEA leading to the release of non-modified bases involving the initial cleavage of N1-C1', C3'-O3' or C5'-O5' bonds. The yield of base modifications was lower than the release of non-modified bases. The main LEE-induced base modifications include 5,6-dihydrothymine (5,6-dHT), 5,6-dihydrouracil (5-dHU), 5-hydroxymethyluracil (5-HmU) and 5-formyluracil (5-ForU). The formation of base modifications by LEEs can be explained by DEA and cleavage of the C-H bond of the methyl group of Thy (giving 5-HmU and 5-ForU) and by secondary reactions of H atoms and hydride anions that are generated by primary LEE reactions followed by subsequent reaction with Cyt and Thy (giving 5,6-dHU and 5,6-dHT).

Catalytic activation of carbon-carbon bonds in cyclopentanones.

PubMed

Xia, Ying; Lu, Gang; Liu, Peng; Dong, Guangbin

2016-11-24

In the chemical industry, molecules of interest are based primarily on carbon skeletons. When synthesizing such molecules, the activation of carbon-carbon single bonds (C-C bonds) in simple substrates is strategically important: it offers a way of disconnecting such inert bonds, forming more active linkages (for example, between carbon and a transition metal) and eventually producing more versatile scaffolds. The challenge in achieving such activation is the kinetic inertness of C-C bonds and the relative weakness of newly formed carbon-metal bonds. The most common tactic starts with a three- or four-membered carbon-ring system, in which strain release provides a crucial thermodynamic driving force. However, broadly useful methods that are based on catalytic activation of unstrained C-C bonds have proven elusive, because the cleavage process is much less energetically favourable. Here we report a general approach to the catalytic activation of C-C bonds in simple cyclopentanones and some cyclohexanones. The key to our success is the combination of a rhodium pre-catalyst, an N-heterocyclic carbene ligand and an amino-pyridine co-catalyst. When an aryl group is present in the C3 position of cyclopentanone, the less strained C-C bond can be activated; this is followed by activation of a carbon-hydrogen bond in the aryl group, leading to efficient synthesis of functionalized α-tetralones-a common structural motif and versatile building block in organic synthesis. Furthermore, this method can substantially enhance the efficiency of the enantioselective synthesis of some natural products of terpenoids. Density functional theory calculations reveal a mechanism involving an intriguing rhodium-bridged bicyclic intermediate.

Low energy electron induced cytosine base release in 2′-deoxycytidine-3′-monophosphate via glycosidic bond cleavage: A time-dependent wavepacket study

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

Bhaskaran, Renjith; Sarma, Manabendra, E-mail: msarma@iitg.ernet.in

2014-09-14

Low energy electron (LEE) induced cytosine base release in a selected pyrimidine nucleotide, viz., 2′-deoxycytidine-3′-monophosphate is investigated using ab initio electronic structure methods and time dependent quantum mechanical calculations. It has been noted that the cytosine base scission is comparatively difficult process than the 3′ C–O bond cleavage from the lowest π{sup *} shape resonance in energy region <1 eV. This is mainly due to the high activation energy barrier associated with the electron transfer from the π{sup *} orbital of the base to the σ{sup *} orbital of the glycosidic N–C bond. In addition, the metastable state formed aftermore » impinging LEE (0–1 eV) has very short lifetime (10 fs) which may decay in either of the two competing auto-detachment or dissociation process simultaneously. On the other hand, the selected N–C mode may cleave to form the cytosine base anion at higher energy regions (>2 eV) via tunneling of the glycosidic bond. Resonance states generated within this energy regime will exist for a duration of ∼35–55 fs. Comparison of salient features of the two dissociation events, i.e., 3′ C–O single strand break and glycosidic N–C bond cleavage in 3′-dCMPH molecule are also provided.« less

Structural and Molecular Basis for the Novel Catalytic Mechanism and Evolution of DddP, an Abundant Peptidase-Like Bacterial Dimethylsulfoniopropionate Lyase: A New Enzyme from an Old Fold

NASA Astrophysics Data System (ADS)

Zhang, Y. Z.; Wang, P.; Chen, X. L.; Li, C. Y.; Gao, X.; Zhu, D.; Xie, B. B.; Qin, Q. L.; Zhang, X. Y.; Su, H. N.; Zhou, B. C.; Xun, L.

2015-12-01

The microbial cleavage of dimethylsulfoniopropionate (DMSP) generates volatile dimethyl sulfide (DMS) and is an important step in global sulfur and carbon cycles. DddP is a DMSP lyase in marine bacteria and the deduced dddP gene product is abundant in marine metagenomic data sets. However, DddP belongs to the M24 peptidase family according to sequence alignment. Peptidases hydrolyze C-N bonds but DddP is deduced to cleave C-S bonds. Mechanisms responsible for this striking functional shift are currently unknown. We determined the structures of DMSP lyase RlDddP (the DddP from Ruegeria lacuscaerulensis ITI_1157) bound to inhibitory 2-(N-morpholino) ethanesulfonic acid or PO43- and of two mutants of RlDddP bound to acrylate. Based on structural, mutational and biochemical analyses, we characterized a new ion-shift catalytic mechanism of RlDddP for DMSP cleavage. Further, we suggested the structural mechanism leading to the loss of peptidase activity and the subsequent development of DMSP lyase activity in DddP. This study sheds light on the catalytic mechanism and the divergent evolution of DddP, leading to a better understanding of marine bacterial DMSP catabolism and global DMS production.

Transition-metal-catalyzed direct arylation of (hetero)arenes by C-H bond cleavage.

PubMed

Ackermann, Lutz; Vicente, Rubén; Kapdi, Anant R

2009-01-01

The area of transition-metal-catalyzed direct arylation through cleavage of C-H bonds has undergone rapid development in recent years, and is becoming an increasingly viable alternative to traditional cross-coupling reactions with organometallic reagents. In particular, palladium and ruthenium catalysts have been described that enable the direct arylation of (hetero)arenes with challenging coupling partners--including electrophilic aryl chlorides and tosylates as well as simple arenes in cross-dehydrogenative arylations. Furthermore, less expensive copper, iron, and nickel complexes were recently shown to be effective for economically attractive direct arylations.

Enhanced photocatalytic degradation of Amaranth dye on mesoporous anatase TiO2: evidence of C-N, N[double bond, length as m-dash]N bond cleavage and identification of new intermediates.

PubMed

Naik, Amarja P; Salkar, Akshay V; Majik, Mahesh S; Morajkar, Pranay P

2017-07-01

The photocatalytic degradation mechanism of Amaranth, a recalcitrant carcinogenic azo dye, was investigated using mesoporous anatase TiO 2 under sunlight. Mesoporous anatase TiO 2 of a high photocatalytic activity has been synthesized using a sol-gel method and its photocatalytic activity for the degradation of Amaranth dye has been evaluated with respect to Degussa P25. The effect of bi-dentate complexing agents like oxalic acid, ethylene glycol and urea on the surface properties of TiO 2 catalyst has been investigated using TG-DTA, FTIR, HR-TEM, SAED, PXRD, EDS, UV-DRS, PL, BET N 2 adsorption-desorption isotherm studies and BJH analysis. The influence of catalyst properties such as the mesoporous network, pore volume and surface area on the kinetics of degradation of Amaranth as a function of irradiation time under natural sunlight has been monitored using UV-Vis spectroscopy. The highest rate constant value of 0.069 min -1 was obtained for the photocatalytic degradation of Amaranth using TiO 2 synthesized via a urea assisted sol-gel synthesis method. The effect of the reaction conditions such as pH, TiO 2 concentration and Amaranth concentration on the photodegradation rate has been investigated. The enhanced photocatalytic activity of synthesized TiO 2 in comparison with P25 is attributed to the mesoporous nature of the catalyst leading to increased pore diameter, pore volume, surface area and enhanced charge carrier separation efficiency. New intermediates of photocatalytic degradation of Amaranth, namely, sodium-3-hydroxynaphthalene-2,7-disulphonate, 3-hydroxynaphthalene, sodium-4-aminonaphthalenesulphonate and sodium-4-aminobenzenesulphonate have been identified using LC-ESI-MS for the very first time, providing direct evidence for simultaneous bond cleavage pathways (-C-N-) and (-N[double bond, length as m-dash]N-). A new plausible mechanism of TiO 2 catalysed photodegradation of Amaranth along with the comparison of its toxicity to that of its degradation intermediates and products is proposed.

Multiple C-H Bond Activations and Ring-Opening C-S Bond Cleavage of Thiophene by Dirhenium Carbonyl Complexes.

PubMed

Adams, Richard D; Dhull, Poonam; Tedder, Jonathan D

2018-06-14

The reaction of Re 2 (CO) 8 (μ-C 6 H 5 )(μ-H) (1) with thiophene in CH 2 Cl 2 at 40 °C yielded the new compound Re 2 (CO) 8 (μ-η 2 -SC 4 H 3 )(μ-H) (2), which contains a bridging σ-π-coordinated thienyl ligand formed by the activation of the C-H bond at the 2 position of the thiophene. Compound 2 exhibits dynamical activity on the NMR time scale involving rearrangements of the bridging thienyl ligand. The reaction of compound 2 with a second 1 equiv of 1 at 45 °C yielded the doubly metalated product [Re 2 (CO) 8 (μ-H)] 2 (μ-η 2 -2,3-μ-η 2 -4,5-C 4 H 2 S) (3), formed by the activation of the C-H bond at the 5 position of the thienyl ligand in 2. Heating 3 in a hexane solvent to reflux transformed it into the ring-opened compound Re(CO) 4 [μ-η 5 -η 2 -SCC(H)C(H)C(H)][Re(CO) 3 ][Re 2 (CO) 8 (μ-H)] (4) by the loss of one CO ligand. Compound 4 contains a doubly metalated 1-thiapentadienyl ligand formed by the cleavage of one of the C-S bonds. When heated to reflux (125 °C) in an octane solvent in the presence of H 2 O, the new compound Re(CO) 4 [η 5 -μ-η 2 -SC(H)C(H)C(H)C(H)]Re(CO) 3 (5) was obtained by cleavage of the Re 2 (CO) 8 (μ-H) group from 4 with formation of the known coproduct [Re(CO) 3 (μ 3 -OH)] 4 . All new products were characterized by single-crystal X-ray diffraction analyses.

Site-specific Phosphorylation Protects Glycogen Synthase Kinase-3β from Calpain-mediated Truncation of Its N and C Termini*

PubMed Central

Ma, Shanshan; Liu, Shaojun; Huang, Qiaoying; Xie, Bo; Lai, Bingquan; Wang, Chong; Song, Bin; Li, Mingtao

2012-01-01

Glycogen synthase kinase-3β (GSK-3β), a key regulator of neuronal apoptosis, is inhibited by the phosphorylation of Ser-9/Ser-389 and was recently shown to be cleaved by calpain at the N terminus, leading to its subsequent activation. In this study calpain was found to cleave GSK-3β not only at the N terminus but also at the C terminus, and cleavage sites were identified at residues Thr-38–Thr-39 and Ile-384–Gln-385. Furthermore, the cleavage of GSK-3β occurred in tandem with Ser-9 dephosphorylation during cerebellar granule neuron apoptosis. Increasing Ser-9 phosphorylation of GSK-3β by inhibiting phosphatase 1/2A or pretreating with purified active Akt inhibited calpain-mediated cleavage of GSK-3β at both N and C termini, whereas non-phosphorylatable mutant GSK-3β S9A facilitated its cleavage. In contrast, Ser-389 phosphorylation selectively inhibited the cleavage of GSK-3β at the C terminus but not the N terminus. Calpain-mediated cleavage resulted in three truncated products, all of which contained an intact kinase domain: ΔN-GSK-3β (amino acids 39–420), ΔC-GSK-3β (amino acids 1–384), and ΔN/ΔC-GSK-3β (amino acids 39–384). All three truncated products showed increased kinase and pro-apoptotic activity, with ΔN/ΔC-GSK-3β being the most active form. This observation suggests that the GSK-3β C terminus acts as an autoinhibitory domain similar to the N terminus. Taken together, these findings demonstrate that calpain-mediated cleavage activates GSK-3β by removing its N- and C-terminal autoinhibitory domains and that Ser-9 phosphorylation inhibits the cleavage of GSK-3β at both termini. In contrast, Ser-389 phosphorylation inhibits only C-terminal cleavage but not N-terminal cleavage. These findings also identify a mechanism by which site-specific phosphorylation and calpain-mediated cleavage operate in concert to regulate GSK-3β activity. PMID:22496446

Site-specific phosphorylation protects glycogen synthase kinase-3β from calpain-mediated truncation of its N and C termini.

PubMed

Ma, Shanshan; Liu, Shaojun; Huang, Qiaoying; Xie, Bo; Lai, Bingquan; Wang, Chong; Song, Bin; Li, Mingtao

2012-06-29

Glycogen synthase kinase-3β (GSK-3β), a key regulator of neuronal apoptosis, is inhibited by the phosphorylation of Ser-9/Ser-389 and was recently shown to be cleaved by calpain at the N terminus, leading to its subsequent activation. In this study calpain was found to cleave GSK-3β not only at the N terminus but also at the C terminus, and cleavage sites were identified at residues Thr-38-Thr-39 and Ile-384-Gln-385. Furthermore, the cleavage of GSK-3β occurred in tandem with Ser-9 dephosphorylation during cerebellar granule neuron apoptosis. Increasing Ser-9 phosphorylation of GSK-3β by inhibiting phosphatase 1/2A or pretreating with purified active Akt inhibited calpain-mediated cleavage of GSK-3β at both N and C termini, whereas non-phosphorylatable mutant GSK-3β S9A facilitated its cleavage. In contrast, Ser-389 phosphorylation selectively inhibited the cleavage of GSK-3β at the C terminus but not the N terminus. Calpain-mediated cleavage resulted in three truncated products, all of which contained an intact kinase domain: ΔN-GSK-3β (amino acids 39-420), ΔC-GSK-3β (amino acids 1-384), and ΔN/ΔC-GSK-3β (amino acids 39-384). All three truncated products showed increased kinase and pro-apoptotic activity, with ΔN/ΔC-GSK-3β being the most active form. This observation suggests that the GSK-3β C terminus acts as an autoinhibitory domain similar to the N terminus. Taken together, these findings demonstrate that calpain-mediated cleavage activates GSK-3β by removing its N- and C-terminal autoinhibitory domains and that Ser-9 phosphorylation inhibits the cleavage of GSK-3β at both termini. In contrast, Ser-389 phosphorylation inhibits only C-terminal cleavage but not N-terminal cleavage. These findings also identify a mechanism by which site-specific phosphorylation and calpain-mediated cleavage operate in concert to regulate GSK-3β activity.

Chelation-assisted carbon-hydrogen and carbon-carbon bond activation by transition metal catalysts.

PubMed

Jun, Chul-Ho; Moon, Choong Woon; Lee, Dae-Yon

2002-06-03

Herein we describe the chelation-assisted C-H and C-C bond activation of carbonyl compounds by Rh1 catalysts. Hydroacylation of olefins was accomplished by utilizing 2-amino-3-picoline as a chelation auxiliary. The same strategy was employed for the C-C bond activation of unstrained ketones. Allylamine 24 was devised as a synthon of formaldehyde. Hydroiminoacylation of alkynes with allylamine 24 was applied to the alkyne cleavage by the aid of cyclohexylamine.

NiCu single atom alloys catalyze the C—H bond activation in the selective non- oxidative ethanol dehydrogenation reaction

DOE PAGES

Shan, Junjun; Liu, Jilei; Li, Mengwei; ...

2017-12-29

Here, NiCu single atom alloy (SAA) nanoparticles supported on silica are reported to catalyze the non-oxidative dehydrogenation of ethanol, selectively to acetaldehyde and hydrogen products by facilitating the C—H bond cleavage. The activity and selectivity of the NiCu SAA catalysts were compared to monometallic copper and to PtCu and PdCu single atom alloys, in a flow reactor at moderate temperatures. In-situ DRIFTS showed that the silica support facilitates the O—H bond cleavage of ethanol to form ethoxy intermediates over all the supported alloy catalysts. However, these remain unreactive up to 250°C for the Cu/SiO 2 monometallic nanoparticles, while in themore » NiCu SAA, acetaldehyde is formed at much lower temperatures, below 150°C. In situ DRIFTS was also used to identify the C—H activation step as the rate determining step of this reaction on all the copper catalysts we examined. The presence of atomically dispersed Ni in Cu significantly lowers the C—H bond activation barrier, whereas Pt and Pd atoms were found less effective. This work provides direct evidence that the C—H bond cleavage is the rate determining step in ethanol dehydrogenation over this type catalyst.« less

NiCu single atom alloys catalyze the C—H bond activation in the selective non- oxidative ethanol dehydrogenation reaction

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

Shan, Junjun; Liu, Jilei; Li, Mengwei

Here, NiCu single atom alloy (SAA) nanoparticles supported on silica are reported to catalyze the non-oxidative dehydrogenation of ethanol, selectively to acetaldehyde and hydrogen products by facilitating the C—H bond cleavage. The activity and selectivity of the NiCu SAA catalysts were compared to monometallic copper and to PtCu and PdCu single atom alloys, in a flow reactor at moderate temperatures. In-situ DRIFTS showed that the silica support facilitates the O—H bond cleavage of ethanol to form ethoxy intermediates over all the supported alloy catalysts. However, these remain unreactive up to 250°C for the Cu/SiO 2 monometallic nanoparticles, while in themore » NiCu SAA, acetaldehyde is formed at much lower temperatures, below 150°C. In situ DRIFTS was also used to identify the C—H activation step as the rate determining step of this reaction on all the copper catalysts we examined. The presence of atomically dispersed Ni in Cu significantly lowers the C—H bond activation barrier, whereas Pt and Pd atoms were found less effective. This work provides direct evidence that the C—H bond cleavage is the rate determining step in ethanol dehydrogenation over this type catalyst.« less

Characterization of CMPO and its radiolysis products by Direct Infusion ESI-MS

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

G. S. Groenewold; G. Elias; B. J. Mincher

2012-09-01

Direct infusion electrospray ionization-mass spectrometry (ESI-MS) approaches were developed for rapid identification of octyl,phenyl,(N,N-(diisobutyl)carbamoylmethyl) phosphine oxide (CMPO) and impurity compounds formed during alpha and gamma irradiation experiments. CMPO is an aggressive Lewis base, and produces extremely abundant metal complex ions in the ESI-MS analysis that make identification of low abundance compounds that are less nucleophilic challenging. Radiolysis products were identified using several approaches including restricting ion trapping so as to exclude the abundant natiated CMPO ions, extraction of acidic products using aqueous NaOH, and extraction of basic products using HNO3. These approaches generated protonated, natiated and deprotonated species derived frommore » CMPO degradation products formed via radiolytic cleavages of several different bonds. Cleavages of the amide and methylene-phosphoryl bonds appear to be favored by both forms of irradiation, while alpha irradiation also appears to induce cleavage of the methylene-carbonyl bond. The degradation products observed are formed from recombination of the initially formed radicals with hydrogen, methyl, isopropyl and hydroxyl radicals that are derived either from CMPO, or the dodecane solvent.« less

Palladium-Catalyzed Reductive Insertion of Alcohols into Aryl Ether Bonds

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

Wang, Meng; Gutiérrez, Oliver Y.; Camaioni, Donald M.

Pd/C catalyzes C-O bond cleavage of aryl ethers (diphenyl ether and cyclohexyl phenyl ether) by methanol in H2. The aromatic C-O bond is cleaved by reductive methanolysis, which is initiated by Pd-catalyzed partial hydrogenation of one phenyl ring to form an enol ether. The enol ether reacts rapidly with methanol to form a ketal, which generates methoxycyclohexene by eliminating phenol or an alkanol. Subsequent hydrogenation leads to methoxycyclohexane.

From ketones to esters by a Cu-catalyzed highly selective C(CO)-C(alkyl) bond cleavage: aerobic oxidation and oxygenation with air.

PubMed

Huang, Xiaoqiang; Li, Xinyao; Zou, Miancheng; Song, Song; Tang, Conghui; Yuan, Yizhi; Jiao, Ning

2014-10-22

The Cu-catalyzed aerobic oxidative esterification of simple ketones via C-C bond cleavage has been developed. Varieties of common ketones, even inactive aryl long-chain alkyl ketones, are selectively converted into esters. The reaction tolerates a wide range of alcohols, including primary and secondary alcohols, chiral alcohols with retention of the configuration, electron-deficient phenols, as well as various natural alcohols. The usage of inexpensive copper catalyst, broad substrate scope, and neutral and open air conditions make this protocol very practical. (18)O labeling experiments reveal that oxygenation occurs during this transformation. Preliminary mechanism studies indicate that two novel pathways are mainly involved in this process.

Computational Study of Pincer Iridium Catalytic Systems: C-H, N-H, and C-C Bond Activation and C-C Coupling Reactions

NASA Astrophysics Data System (ADS)

Zhou, Tian

Computational chemistry has achieved vast progress in the last decades in the field, which was considered to be only experimental before. DFT (density functional theory) calculations have been proven to be able to be applied to large systems, while maintaining high accuracy. One of the most important achievements of DFT calculations is in exploring the mechanism of bond activation reactions catalyzed by organometallic complexes. In this dissertation, we discuss DFT studies of several catalytic systems explored in the lab of Professor Alan S. Goldman. Headlines in the work are: (1) (R4PCP)Ir alkane dehydrogenation catalysts are highly selective and different from ( R4POCOP)Ir catalysts, predicting different rate-/selectivity-determining steps; (2) The study of the mechanism for double C-H addition/cyclometalation of phenanthrene or biphenyl by (tBu4PCP)Ir(I) and ( iPr4PCP)Ir illustrates that neutral Ir(III) C-H addition products can undergo a very facile second C-H addition, particularly in the case of sterically less-crowded Ir(I) complexes; (3) (iPr4PCP)Ir pure solid phase catalyst is highly effective in producing high yields of alpha-olefin products, since the activation enthalpy for dehydrogenation is higher than that for isomerization via an allyl pathway; higher temperatures favor the dehydrogenation/isomerization ratio; (4) (PCP)Ir(H)2(N2H4) complex follows a hydrogen transfer mechanism to undergo both dehydrogenation to form N 2 and H2, as well as hydrogen transfer followed by N-N bond cleavage to form NH3, N2, and H2; (5) The key for the catalytic effect of solvent molecule in CO insertion reaction for RMn(CO)5 is hydrogen bond assisted interaction. The basicity of the solvent determines the strength of the hydrogen bond interaction during the catalytic path and determines the catalytic power of the solvent; and (6) Dehydrogenative coupling of unactivated C-H bonds (intermolecular vinyl-vinyl, intramolecular vinyl-benzyl) is catalyzed by precursors of the (iPr4 PCP)Ir fragment. The key step for this mechanism is a Ir(III) vinyl hydride complex undergoing addition of a styrenyl ortho C-H bond to give an Ir(III) metalloindene plus H2.

On the mechanism of peptidoglycan binding and cleavage by the endo-specific lytic transglycosylase MltE from Escherichia coli.

PubMed

Fibriansah, Guntur; Gliubich, Francesca I; Thunnissen, Andy-Mark W H

2012-11-13

The lytic transglycosylase MltE from Escherichia coli is a periplasmic, outer membrane-attached enzyme that cleaves the β-1,4-glycosidic bonds between N-acetylmuramic acid and N-acetylglucosamine residues in the cell wall peptidoglycan, producing 1,6-anhydromuropeptides. Here we report three crystal structures of MltE: in a substrate-free state, in a binary complex with chitopentaose, and in a ternary complex with the glycopeptide inhibitor bulgecin A and the murodipeptide N-acetylglucosaminyl-N-acetylmuramyl-l-Ala-d-Glu. The substrate-bound structures allowed a detailed analysis of the saccharide-binding interactions in six subsites of the peptidoglycan-binding groove (subsites -4 to +2) and, combined with site-directed mutagenesis analysis, confirmed the role of Glu64 as catalytic acid/base. The structures permitted the precise modeling of a short glycan strand of eight saccharide residues, providing evidence for two additional subsites (+3 and +4) and revealing the productive conformational state of the substrate at subsites -1 and +1, where the glycosidic bond is cleaved. Full accessibility of the peptidoglycan-binding groove and preferential binding of an N-acetylmuramic acid residue in a (4)C(1) chair conformation at subsite +2 explain why MltE shows only endo- and no exo-specific activity toward glycan strands. The results further indicate that catalysis of glycosidic bond cleavage by MltE proceeds via distortion toward a sofa-like conformation of the N-acetylmuramic acid sugar ring at subsite -1 and by anchimeric assistance of the sugar's N-acetyl group, as shown previously for the lytic transglycosylases Slt70 and MltB.

Compositional effects in Ru, Pd, Pt, and Rh-doped mesoporous tantalum oxide catalysts for ammonia synthesis.

PubMed

Yue, Chaoyang; Qiu, Longhui; Trudeau, Michel; Antonelli, David

2007-06-11

A series of early metal-promoted Ru-, Pd-, Pt-, and Rh-doped mesoporous tantalum oxide catalysts were synthesized using a variety of dopant ratios and dopant precursors, and the effects of these parameters on the catalytic activity of NH3 synthesis from H2 and N2 were explored. Previous studies on this system supported an unprecedented mechanism in which N-N cleavage occurred at the Ta sites rather than on Ru. The results of the present study showed, for all systems, that Ba is a better promoter than Cs or La and that the nitrate is a superior precursor for Ba than the isopropoxide or the hydroxide. 15N-labeling studies showed that residual nitrate functions as the major ammonia source in the first hour but that it does not account for the ammonia produced after the nitrate is completely consumed. Ru3(CO)12 proved to be a better Ru precursor than RuCl(3).3H2O, and an almost linear increase in activity with increasing Ru loading level was observed at 350 degrees C (623 K). However, at 175 degrees C (448 K), the increase in Ru had no effect on the reaction rate. Pd functioned with comparable rates to Ru, while Pt and Rh functioned far less efficiently. The surprising activities for the Pd-doped catalysts, coupled with XPS evidence for low-valent Ta in this catalyst system, support a mechanism in which cleavage of the N-N triple bond occurs on Ta rather than the precious metal because the Ea value for N-N cleavage on Pd is 2.5 times greater than that for Ru, and the 9.3 kJ mol-1 Ea value measured previously for the Ru system suggests that N-N cleavage cannot occur at the Ru surface.

Improvement and mechanism of interfacial adhesion in PBO fiber/bismaleimide composite by oxygen plasma treatment

NASA Astrophysics Data System (ADS)

Liu, Dong; Chen, Ping; Mu, Jujie; Yu, Qi; Lu, Chun

2011-05-01

The improved interfacial adhesion of PBO fiber-reinforced bismaleimide composite by oxygen plasma processing was investigated in this paper. After treatment, the maximum value of interlaminar shear strength was 57.5 MPa, with an increase of 28.9%. The oxygen concentration of the fiber surface increased, as did the surface roughness, resulting in improvement of the surface wettability. The cleavage and rearrangement of surface bonds created new functional groups O dbnd C sbnd O, N sbnd C dbnd O and N sbnd O, thereby activating the fiber surface. And long-time treatment increased the reaction degree of surface groups while destroyed the newly-created physical structures. The enhancement of adhesion relied primarily on the strengthening of chemical bonding and mechanical interlocking between the fiber and the matrix. The composite rupture planes indicated that the fracture failure shifted from the interface to the matrix or the fiber.

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

Huang, Yingying; Triscari, Joseph M.; Tseng, George C.

Data mining was performed on 28 330 unique peptide tandem mass spectra for which sequences were assigned with high confidence. By dividing the spectra into different sets based on structural features and charge states of the corresponding peptides, chemical interactions involved in promoting specific cleavage patterns in gas-phase peptides were characterized. Pairwise fragmentation maps describing cleavages at all Xxx-Zzz residue combinations for b and y ions reveal that the difference in basicity between Arg and Lys results in different dissociation patterns for singly charged Arg- and Lys-ending tryptic peptides. While one dominant protonation form (proton localized) exists for Arg-ending peptides,more » a heterogeneous population of different protonated forms or more facile interconversion of protonated forms (proton partially mobile) exists for Lys-ending peptides. Cleavage C-terminal to acidic residues dominates spectra from peptides that have a localized proton and cleavage N-terminal to Pro dominates those that have a mobile or partially mobile proton. When Pro is absent from peptides that have a mobile or partially mobile proton, cleavage at each peptide bond becomes much more prominent. Whether the above patterns can be found in b ions, y ions, or both depends on the location of the proton holder(s). Enhanced cleavages C-terminal to branched aliphatic residues (Ile, Val, Leu) are observed in both b and y ions from peptides that have a mobile proton, as well as in y ions from peptides that have a partially mobile proton; enhanced cleavages N-terminal to these residues are observed in b ions from peptides that have a partially mobile proton. Statistical tools have been designed to visualize the fragmentation maps and measure the similarity between them. The pairwise cleavage patterns observed expand our knowledge of peptide gas-phase fragmentation behaviors and should be useful in algorithm development that employs improved models to predict fragment ion intensities.« less

Heterobimetallic Ti/Co Complexes That Promote Catalytic N-N Bond Cleavage.

PubMed

Wu, Bing; Gramigna, Kathryn M; Bezpalko, Mark W; Foxman, Bruce M; Thomas, Christine M

2015-11-16

Treatment of the tris(phosphinoamide) titanium precursor ClTi(XylNP(i)Pr2)3 (1) with CoI2 leads to the heterobimetallic complex (η(2)-(i)Pr2PNXyl)Ti(XylNP(i)Pr2)2(μ-Cl)CoI (2). One-electron reduction of 2 affords (η(2)-(i)Pr2PNXyl)Ti(XylNP(i)Pr2)2CoI (3), which can be reduced by another electron under dinitrogen to generate the reduced diamagnetic complex (THF)Ti(XylNP(i)Pr2)3CoN2 (4). The removal of the dinitrogen ligand from 4 under vacuum affords (THF)Ti(XylNP(i)Pr2)3Co (5), which features a Ti-Co triple bond. Treatment of 4 with hydrazine or methyl hydrazine results in N-N bond cleavage and affords the new diamagnetic complexes (L)Ti(XylNP(i)Pr2)3CoN2 (L = NH3 (6), MeNH2 (7)). Complexes 4, 5, and 6 have been shown to catalyze the disproportionation of hydrazine into ammonia and dinitrogen gas through a mechanism involving a diazene intermediate.

Mechanistic Insights on C-O and C-C Bond Activation and Hydrogen Insertion during Acetic Acid Hydrogenation Catalyzed by Ruthenium Clusters in Aqueous Medium

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

Shangguan, Junnan; Olarte, Mariefel V.; Chin, Ya-Huei

Catalytic pathways for acetic acid (CH3COOH) and hydrogen (H2) reactions on dispersed Ru clusters in the aqueous medium and the associated kinetic requirements for C-O and C-C bond cleavages and hydrogen insertion are established from rate and isotopic assessments. CH3COOH reacts with H2 in steps that either retain its carbon backbone and lead to ethanol, ethyl acetate, and ethane (47-95 %, 1-23 %, and 2-17 % carbon selectivities, respectively) or break its C-C bond and form methane (1-43 % carbon selectivities) at moderate temperatures (413-523 K) and H2 pressures (10-60 bar, 298 K). Initial CH3COOH activation is the kinetically relevantmore » step, during which CH3C(O)-OH bond cleaves on a metal site pair at Ru cluster surfaces nearly saturated with adsorbed hydroxyl (OH*) and acetate (CH3COO*) intermediates, forming an adsorbed acetyl (CH3CO*) and hydroxyl (OH*) species. Acetic acid turnover rates increase proportionally with both H2 (10-60 bar) and CH3COOH concentrations at low CH3COOH concentrations (<0.83 M), but decrease from first to zero order as the CH3COOH concentration and the CH3COO* coverages increase and the vacant Ru sites concomitantly decrease. Beyond the initial CH3C(O)-OH bond activation, sequential H-insertions on the surface acetyl species (CH3CO*) lead to C2 products and their derivative (ethanol, ethane, and ethyl acetate) and the competitive C-C bond cleavage of CH3CO* causes the eventual methane formation. The instantaneous carbon selectivities towards C2 species (ethanol, ethane, and ethyl acetate) increase linearly with the concentration of proton-type Hδ+ (derived from carboxylic acid dissociation) and chemisorbed H*. The selectivities towards C2 products decrease with increasing temperature, because of higher observed barriers for C-C bond cleavage than H-insertion. This study offers an interpretation of mechanism and energetics and provides kinetic evidence of carboxylic acid assisted proton-type hydrogen (Hδ+) shuffling during H-insertion steps in the aqueous phase, unlike those in the vapor phase, during the hydrogenation of acetic acid on Ru clusters.« less

Structural and Mechanistic Insights into C-P Bond Hydrolysis by Phosphonoacetate Hydrolase

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

Agarwal, Vinayak; Borisova, Svetlana A.; Metcalf, William W.

2011-12-22

Bacteria have evolved pathways to metabolize phosphonates as a nutrient source for phosphorus. In Sinorhizobium meliloti 1021, 2-aminoethylphosphonate is catabolized to phosphonoacetate, which is converted to acetate and inorganic phosphate by phosphonoacetate hydrolase (PhnA). Here we present detailed biochemical and structural characterization of PhnA that provides insights into the mechanism of C-P bond cleavage. The 1.35 {angstrom} resolution crystal structure reveals a catalytic core similar to those of alkaline phosphatases and nucleotide pyrophosphatases but with notable differences, such as a longer metal-metal distance. Detailed structure-guided analysis of active site residues and four additional cocrystal structures with phosphonoacetate substrate, acetate, phosphonoformatemore » inhibitor, and a covalently bound transition state mimic provide insight into active site features that may facilitate cleavage of the C-P bond. These studies expand upon the array of reactions that can be catalyzed by enzymes of the alkaline phosphatase superfamily.« less

Negative Ion In-Source Decay Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry for Sequencing Acidic Peptides

NASA Astrophysics Data System (ADS)

McMillen, Chelsea L.; Wright, Patience M.; Cassady, Carolyn J.

2016-05-01

Matrix-assisted laser desorption/ionization (MALDI) in-source decay was studied in the negative ion mode on deprotonated peptides to determine its usefulness for obtaining extensive sequence information for acidic peptides. Eight biological acidic peptides, ranging in size from 11 to 33 residues, were studied by negative ion mode ISD (nISD). The matrices 2,5-dihydroxybenzoic acid, 2-aminobenzoic acid, 2-aminobenzamide, 1,5-diaminonaphthalene, 5-amino-1-naphthol, 3-aminoquinoline, and 9-aminoacridine were used with each peptide. Optimal fragmentation was produced with 1,5-diaminonphthalene (DAN), and extensive sequence informative fragmentation was observed for every peptide except hirudin(54-65). Cleavage at the N-Cα bond of the peptide backbone, producing c' and z' ions, was dominant for all peptides. Cleavage of the N-Cα bond N-terminal to proline residues was not observed. The formation of c and z ions is also found in electron transfer dissociation (ETD), electron capture dissociation (ECD), and positive ion mode ISD, which are considered to be radical-driven techniques. Oxidized insulin chain A, which has four highly acidic oxidized cysteine residues, had less extensive fragmentation. This peptide also exhibited the only charged localized fragmentation, with more pronounced product ion formation adjacent to the highly acidic residues. In addition, spectra were obtained by positive ion mode ISD for each protonated peptide; more sequence informative fragmentation was observed via nISD for all peptides. Three of the peptides studied had no product ion formation in ISD, but extensive sequence informative fragmentation was found in their nISD spectra. The results of this study indicate that nISD can be used to readily obtain sequence information for acidic peptides.

Negative Ion In-Source Decay Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry for Sequencing Acidic Peptides.

PubMed

McMillen, Chelsea L; Wright, Patience M; Cassady, Carolyn J

2016-05-01

Matrix-assisted laser desorption/ionization (MALDI) in-source decay was studied in the negative ion mode on deprotonated peptides to determine its usefulness for obtaining extensive sequence information for acidic peptides. Eight biological acidic peptides, ranging in size from 11 to 33 residues, were studied by negative ion mode ISD (nISD). The matrices 2,5-dihydroxybenzoic acid, 2-aminobenzoic acid, 2-aminobenzamide, 1,5-diaminonaphthalene, 5-amino-1-naphthol, 3-aminoquinoline, and 9-aminoacridine were used with each peptide. Optimal fragmentation was produced with 1,5-diaminonphthalene (DAN), and extensive sequence informative fragmentation was observed for every peptide except hirudin(54-65). Cleavage at the N-Cα bond of the peptide backbone, producing c' and z' ions, was dominant for all peptides. Cleavage of the N-Cα bond N-terminal to proline residues was not observed. The formation of c and z ions is also found in electron transfer dissociation (ETD), electron capture dissociation (ECD), and positive ion mode ISD, which are considered to be radical-driven techniques. Oxidized insulin chain A, which has four highly acidic oxidized cysteine residues, had less extensive fragmentation. This peptide also exhibited the only charged localized fragmentation, with more pronounced product ion formation adjacent to the highly acidic residues. In addition, spectra were obtained by positive ion mode ISD for each protonated peptide; more sequence informative fragmentation was observed via nISD for all peptides. Three of the peptides studied had no product ion formation in ISD, but extensive sequence informative fragmentation was found in their nISD spectra. The results of this study indicate that nISD can be used to readily obtain sequence information for acidic peptides.

New Insight into the Cleavage Reaction of Nostoc sp. Strain PCC 7120 Carotenoid Cleavage Dioxygenase in Natural and Nonnatural Carotenoids

PubMed Central

Heo, Jinsol; Kim, Se Hyeuk

2013-01-01

Carotenoid cleavage dioxygenases (CCDs) are enzymes that catalyze the oxidative cleavage of carotenoids at a specific double bond to generate apocarotenoids. In this study, we investigated the activity and substrate preferences of NSC3, a CCD of Nostoc sp. strain PCC 7120, in vivo and in vitro using natural and nonnatural carotenoid structures. NSC3 cleaved β-apo-8′-carotenal at 3 positions, C-13C-14, C-15C-15′, and C-13′C-14′, revealing a unique cleavage pattern. NSC3 cleaves the natural structure of carotenoids 4,4′-diaponeurosporene, 4,4′-diaponeurosporen-4′-al, 4,4′-diaponeurosporen-4′-oic acid, 4,4′-diapotorulene, and 4,4′-diapotorulen-4′-al to generate novel cleavage products (apo-14′-diaponeurosporenal, apo-13′-diaponeurosporenal, apo-10′-diaponeurosporenal, apo-14′-diapotorulenal, and apo-10′-diapotorulenal, respectively). The study of carotenoids with natural or nonnatural structures produced by using synthetic modules could provide information valuable for understanding the cleavage reactions or substrate preferences of other CCDs in vivo and in vitro. PMID:23524669

Isolation of an oxomanganese(V) porphyrin intermediate in the reaction of a manganese(III) porphyrin complex and H2O2 in aqueous solution.

PubMed

Nam, Wonwoo; Kim, Inwoo; Lim, Mi Hee; Choi, Hye Jin; Lee, Je Seung; Jang, Ho G

2002-05-03

The reaction of [Mn(TF(4)TMAP)](CF(3)SO(3))(5) (TF(4)TMAP=meso-tetrakis(2,3,5,6-tetrafluoro-N,N,N-trimethyl-4-aniliniumyl)porphinato dianion) with H(2)O(2) (2 equiv) at pH 10.5 and 0 degrees C yielded an oxomanganese(V) porphyrin complex 1 in aqueous solution, whereas an oxomanganese(IV) porphyrin complex 2 was generated in the reactions of tert-alkyl hydroperoxides such as tert-butyl hydroperoxide and 2-methyl-1-phenyl-2-propyl hydroperoxide. Complex 1 was capable of epoxidizing olefins and exchanging its oxygen with H(2) (18)O, whereas 2 did not epoxidize olefins. From the reactions of [Mn(TF(4)TMAP)](5+) with various oxidants in the pH range 3-11, the O-O bond cleavage of hydroperoxides was found to be sensitive to the hydroperoxide substituent and the pH of the reaction solution. Whereas the O-O bond of hydroperoxides containing an electron-donating tert-alkyl group is cleaved homolytically, an electron-withdrawing substituent such as an acyl group in m-chloroperoxybenzoic acid (m-CPBA) facilitates O-O bond heterolysis. The mechanism of the O-O bond cleavage of H(2)O(2) depends on the pH of the reaction solution: O-O bond homolysis prevails at low pH and O-O bond heterolysis becomes a predominant pathway at high pH. The effect of pH on (18)O incorporation from H(2) (18)O into oxygenated products was examined over a wide pH range, by carrying out the epoxidation of carbamazepine (CBZ) with [Mn(TF(4)TMAP)](5+) and KHSO(5) in buffered H(2) (18)O solutions. A high proportion of (18)O was incorporated into the CBZ-10,11-oxide product at all pH values but this proportion was not affected significantly by the pH of the reaction solution.

Catalytic hydrolysis of carbonyl sulphide and carbon disulphide over Fe2O3 cluster: Competitive adsorption and reaction mechanism.

PubMed

Ning, Ping; Song, Xin; Li, Kai; Wang, Chi; Tang, Lihong; Sun, Xin

2017-10-31

The competitive adsorption and reaction mechanism for the catalytic hydrolysis of carbonyl sulphide (COS) and carbon disulphide (CS 2 ) over Fe 2 O 3 cluster was investigated. Compared with experimental results, the theoretical study was used to further investigate the competitive adsorption and effect of H 2 S in the hydrolysis reaction of COS and CS 2 . Experimental results showed that Fe 2 O 3 cluster enhanced the catalytic hydrolysis effect. Meanwhile, H 2 S was not conducive to the hydrolysis of COS and CS 2 . Theoretical calculations indicated that the order of competitive adsorption on Fe 2 O 3 is as follows: H 2 O (strong) >CS 2 (medium) >COS (weak). In the hydrolysis process, the C=S bond cleavage occurs easier than C=O bond cleavage. The hydrolysis reaction is initiated via the migration of an H-atom, which triggers C=S bond cleavage and S-H bond formation. Additionally, we find the first step of CS 2 hydrolysis to be rate limiting. The presence of H 2 S increases the reaction energy barrier, which is not favourable for COS hydrolysis. Fe 2 O 3 can greatly decrease the maximum energy barrier, which decreases the minimum energy required for hydrolysis, making it relatively facile to occur. In general, the theoretical results were consistent with experimental results, which proved that the theoretical study was reliable.

The effect of anatase TiO2 surface structure on the behavior of ethanol adsorption and its initial dissociation step: A DFT study

NASA Astrophysics Data System (ADS)

Zhang, Riguang; Liu, Zhixue; Ling, Lixia; Wang, Baojun

2015-10-01

The perfect and defective surfaces of anatase TiO2 including (1 0 1) and (0 0 1) surfaces have been chosen to probe into the effect of anatase TiO2 surface structure on the behavior of ethanol adsorption and initial dissociation step. Here, the results are obtained by density functional theory (DFT) calculation together with the periodic slab model. Our results show that the surface structure of anatase TiO2 can obviously affect the behavior of ethanol adsorption and the catalytic activity of its initial dissociation step; firstly, on the perfect and defective surfaces of anatase (1 0 1), ethanol dominantly exists in the form of molecule adsorption; however, ethanol is the dissociative adsorption on the hydroxylated anatase (0 0 1), and the coexistences of molecular and dissociation adsorption modes on the perfect anatase (0 0 1). On the other hand, the initial dissociation step of ethanol with molecule adsorption prefers to begin with its O-H bond cleavage leading to CH3CH2O and H species rather than the cleavage of its α-C-H, β-C-H, C-C and C-O bonds, namely, the preferable O-H bond cleavage for the initial dissociation step of ethanol is independent of the surface structure of anatase TiO2; however, the corresponding catalytic activity of ethanol initial dissociation step with the O-H bond cleavage on different anatase TiO2 surfaces is in the following order: hydroxylated (0 0 1) > perfect (0 0 1) > defective (1 0 1) > perfect (1 0 1), suggesting that the catalytic activity for the initial dissociation step of ethanol is sensitive to the surface structure of anatase TiO2, and the hydroxylated (0 0 1) is the most favorable surface. Among these surfaces, the most favorable product for the initial dissociation step of ethanol is CH3CH2O species.

Complexes of a dianionic bis(diphosphinomethanide) with lithium, sodium, potassium and zirconium. Effect of substitution on the Schlenk dimerisation of vinylidene phosphines.

PubMed

Izod, Keith; McFarlane, William; Tyson, Brent V; Clegg, William; Harrington, Ross W

2004-12-07

The vinylidene phosphine (Pr(n)(2)P)(2)C=CH(2) (1) undergoes Schlenk dimerisation on treatment with an excess of any of the alkali metals Li, Na or K to give the butane-1,4-diide complexes [(L)M{(Pr(n)(2)P)(2)CCH(2)}](2)[(L)M =(THF)(2)Li (6), (THF)(3)Na (7b), (DME)(2)K (8b)], after recrystallisation. Whereas the reaction between the analogous phenyl derivative (Ph(2)P)(2)C=CH(2) and K results in cleavage of a P-C bond, 1 reacts smoothly with K to give 8, with no evidence for P-C cleavage. Compound 6 is an excellent ligand transfer reagent: metathesis reactions between either 6 or its phenyl analogue [(THF)(2)Li{(Ph(2)P)(2)CCH(2)}](2) (2) and two equivalents of Cp(2)ZrCl(2) in THF give the corresponding dinuclear zirconocene derivatives [Cp(2)Zr(Cl){(R(2)P)(2)CCH(2)}](2) in good yields [R = Ph (11), Pr(n)(12)]. Compounds 6, 7b, 8b, 11 and 12 have been characterised by multi-element NMR spectroscopy and, where possible, by elemental analysis; compounds 6, 7b, 11 and 12 have additionally been characterised by X-ray crystallography.

Heme-bound nitroxyl, hydroxylamine, and ammonia ligands as intermediates in the reaction cycle of cytochrome c nitrite reductase: a theoretical study.

PubMed

Bykov, Dmytro; Plog, Matthias; Neese, Frank

2014-01-01

In this article, we consider, in detail, the second half-cycle of the six-electron nitrite reduction mechanism catalyzed by cytochrome c nitrite reductase. In total, three electrons and four protons must be provided to reach the final product, ammonia, starting from the HNO intermediate. According to our results, the first event in this half-cycle is the reduction of the HNO intermediate, which is accomplished by two PCET reactions. Two isomeric radical intermediates, HNOH(•) and H2NO(•), are formed. Both intermediates are readily transformed into hydroxylamine, most likely through intramolecular proton transfer from either Arg114 or His277. An extra proton must enter the active site of the enzyme to initiate heterolytic cleavage of the N-O bond. As a result of N-O bond cleavage, the H2N(+) intermediate is formed. The latter readily picks up an electron, forming H2N(+•), which in turn reacts with Tyr218. Interestingly, evidence for Tyr218 activity was provided by the mutational studies of Lukat (Biochemistry 47:2080, 2008), but this has never been observed in the initial stages of the overall reduction process. According to our results, an intramolecular reaction with Tyr218 in the final step of the nitrite reduction process leads directly to the final product, ammonia. Dissociation of the final product proceeds concomitantly with a change in spin state, which was also observed in the resonance Raman investigations of Martins et al. (J Phys Chem B 114:5563, 2010).

C=C bond cleavage on neutral VO3(V2O5)n clusters.

PubMed

Dong, Feng; Heinbuch, Scott; Xie, Yan; Bernstein, Elliot R; Rocca, Jorge J; Wang, Zhe-Chen; Ding, Xun-Lei; He, Sheng-Gui

2009-01-28

The reactions of neutral vanadium oxide clusters with alkenes (ethylene, propylene, 1-butene, and 1,3-butadiene) are investigated by experiments and density function theory (DFT) calculations. Single photon ionization through extreme ultraviolet radiation (EUV, 46.9 nm, 26.5 eV) is used to detect neutral cluster distributions and reaction products. In the experiments, we observe products (V(2)O(5))(n)VO(2)CH(2), (V(2)O(5))(n)VO(2)C(2)H(4), (V(2)O(5))(n)VO(2)C(3)H(4), and (V(2)O(5))(n)VO(2)C(3)H(6), for neural V(m)O(n) clusters in reactions with C(2)H(4), C(3)H(6), C(4)H(6), and C(4)H(8), respectively. The observation of these products indicates that the C=C bonds of alkenes can be broken on neutral oxygen rich vanadium oxide clusters with the general structure VO(3)(V(2)O(5))(n=0,1,2...). DFT calculations demonstrate that the reaction VO(3) + C(3)H(6) --> VO(2)C(2)H(4) + H(2)CO is thermodynamically favorable and overall barrierless at room temperature. They also provide a mechanistic explanation for the general reaction in which the C=C double bond of alkenes is broken on VO(3)(V(2)O(5))(n=0,1,2...) clusters. A catalytic cycle for alkene oxidation on vanadium oxide is suggested based on our experimental and theoretical investigations. The reactions of V(m)O(n) with C(6)H(6) and C(2)F(4) are also investigated by experiments. The products VO(2)(V(2)O(5))(n)C(6)H(4) are observed for dehydration reactions between V(m)O(n) clusters and C(6)H(6). No product is detected for V(m)O(n) clusters reacting with C(2)F(4). The mechanisms of the reactions between VO(3) and C(2)F(4)/C(6)H(6) are also investigated by calculations at the B3LYP/TZVP level.

Anti-Arrhenius cleavage of covalent bonds in bottlebrush macromolecules on substrate

PubMed Central

Lebedeva, Natalia V.; Nese, Alper; Sun, Frank C.; Matyjaszewski, Krzysztof; Sheiko, Sergei S.

2012-01-01

Spontaneous degradation of bottlebrush macromolecules on aqueous substrates was monitored by atomic force microscopy. Scission of C─C covalent bonds in the brush backbone occurred due to steric repulsion between the adsorbed side chains, which generated bond tension on the order of several nano-Newtons. Unlike conventional chemical reactions, the rate of bond scission was shown to decrease with temperature. This apparent anti-Arrhenius behavior was caused by a decrease in the surface energy of the underlying substrate upon heating, which results in a corresponding decrease of bond tension in the adsorbed macromolecules. Even though the tension dropped minimally from 2.16 to 1.89 nN, this was sufficient to overpower the increase in the thermal energy (kBT) in the Arrhenius equation. The rate constant of the bond-scission reaction was measured as a function of temperature and surface energy. Fitting the experimental data by a perturbed Morse potential V = V0(1 - e-βx)2 - fx, we determined the depth and width of the potential to be V0 = 141 ± 19 kJ/mol and β-1 = 0.18 ± 0.03 Å, respectively. Whereas the V0 value is in reasonable agreement with the activation energy Ea = 80–220 kJ/mol of mechanical and thermal degradation of organic polymers, it is significantly lower than the dissociation energy of a C─C bond De = 350 kJ/mol. Moreover, the force constant Kx = 2β2V0 = 1.45 ± 0.36 kN/m of a strained bottlebrush along its backbone is markedly larger than the force constant of a C─C bond Kl = 0.44 kN/m, which is attributed to additional stiffness due to deformation of the side chains. PMID:22645366

Cationized Carbohydrate Gas-Phase Fragmentation Chemistry

NASA Astrophysics Data System (ADS)

Bythell, Benjamin J.; Abutokaikah, Maha T.; Wagoner, Ashley R.; Guan, Shanshan; Rabus, Jordan M.

2017-04-01

We investigate the fragmentation chemistry of cationized carbohydrates using a combination of tandem mass spectrometry, regioselective labeling, and computational methods. Our model system is D-lactose. Barriers to the fundamental glyosidic bond cleavage reactions, neutral loss pathways, and structurally informative cross-ring cleavages are investigated. The most energetically favorable conformations of cationized D-lactose were found to be similar. In agreement with the literature, larger group I cations result in structures with increased cation coordination number which require greater collision energy to dissociate. In contrast with earlier proposals, the B n -Y m fragmentation pathways of both protonated and sodium-cationized analytes proceed via protonation of the glycosidic oxygen with concerted glycosidic bond cleavage. Additionally, for the sodiated congeners our calculations support sodiated 1,6-anhydrogalactose B n ion structures, unlike the preceding literature. This affects the subsequent propensity of formation and prediction of B n /Y m branching ratio. The nature of the anomeric center (α/β) affects the relative energies of these processes, but not the overall ranking. Low-energy cross-ring cleavages are observed for the metal-cationized analytes with a retro-aldol mechanism producing the 0,2 A 2 ion from the sodiated forms . Theory and experiment support the importance of consecutive fragmentation processes, particularly for the protonated congeners at higher collision energies.

Towards Understanding the Tandem Mass Spectra of Protonated Oligopeptides. 2: The Proline Effect in Collision-Induced Dissociation of Protonated Ala-Ala-Xxx-Pro-Ala (Xxx = Ala, Ser, Leu, Val, Phe, and Trp)

NASA Astrophysics Data System (ADS)

Bleiholder, Christian; Suhai, Sándor; Harrison, Alex G.; Paizs, Béla

2011-06-01

The product ion spectra of proline-containing peptides are commonly dominated by y n ions generated by cleavage at the N-terminal side of proline residues. This proline effect is investigated in the current work by collision-induced dissociation (CID) of protonated Ala-Ala-Xxx-Pro-Ala (Xxx includes Ala, Ser, Leu, Val, Phe, and Trp) in an electrospray/quadrupole/time-of-flight (QqTOF) mass spectrometer and by quantum chemical calculations on protonated Ala-Ala-Ala-Pro-Ala. The CID spectra of all investigated peptides show a dominant y 2 ion (Pro-Ala sequence). Our computational results show that the proline effect mainly arises from the particularly low threshold energy for the amide bond cleavage N-terminal to the proline residue, and from the high proton affinity of the proline-containing C-terminal fragment produced by this cleavage. These theoretical results are qualitatively supported by the experimentally observed y 2 / b 3 abundance ratios for protonated Ala-Ala-Xxx-Pro-Ala (Xxx = Ala, Ser, Leu, Val, Phe, and Trp). In the post-cleavage phase of fragmentation the N-terminal oxazolone fragment with the Ala-Ala-Xxx sequence and Pro-Ala compete for the ionizing proton for these peptides. As the proton affinity of the oxazolone fragment increases, the y 2 / b 3 abundance ratio decreases.

Towards understanding the tandem mass spectra of protonated oligopeptides. 2: The proline effect in collision-induced dissociation of protonated Ala-Ala-Xxx-Pro-Ala (Xxx = Ala, Ser, Leu, Val, Phe, and Trp).

PubMed

Bleiholder, Christian; Suhai, Sándor; Harrison, Alex G; Paizs, Béla

2011-06-01

The product ion spectra of proline-containing peptides are commonly dominated by y(n) ions generated by cleavage at the N-terminal side of proline residues. This proline effect is investigated in the current work by collision-induced dissociation (CID) of protonated Ala-Ala-Xxx-Pro-Ala (Xxx includes Ala, Ser, Leu, Val, Phe, and Trp) in an electrospray/quadrupole/time-of-flight (QqTOF) mass spectrometer and by quantum chemical calculations on protonated Ala-Ala-Ala-Pro-Ala. The CID spectra of all investigated peptides show a dominant y(2) ion (Pro-Ala sequence). Our computational results show that the proline effect mainly arises from the particularly low threshold energy for the amide bond cleavage N-terminal to the proline residue, and from the high proton affinity of the proline-containing C-terminal fragment produced by this cleavage. These theoretical results are qualitatively supported by the experimentally observed y(2)/b(3) abundance ratios for protonated Ala-Ala-Xxx-Pro-Ala (Xxx = Ala, Ser, Leu, Val, Phe, and Trp). In the post-cleavage phase of fragmentation the N-terminal oxazolone fragment with the Ala-Ala-Xxx sequence and Pro-Ala compete for the ionizing proton for these peptides. As the proton affinity of the oxazolone fragment increases, the y(2)/b(3) abundance ratio decreases.

UV photolysis of 4-iodo-, 4-bromo-, and 4-chlorophenol: Competition between C-Y (Y = halogen) and O-H bond fission

NASA Astrophysics Data System (ADS)

Sage, Alan G.; Oliver, Thomas A. A.; King, Graeme A.; Murdock, Daniel; Harvey, Jeremy N.; Ashfold, Michael N. R.

2013-04-01

The wavelength dependences of C-Y and O-H bond fission following ultraviolet photoexcitation of 4-halophenols (4-YPhOH) have been investigated using a combination of velocity map imaging, H Rydberg atom photofragment translational spectroscopy, and high level spin-orbit resolved electronic structure calculations, revealing a systematic evolution in fragmentation behaviour across the series Y = I, Br, Cl (and F). All undergo O-H bond fission following excitation at wavelengths λ ≲ 240 nm, on repulsive ((n/π)σ*) potential energy surfaces (PESs), yielding fast H atoms with mean kinetic energies ˜11 000 cm-1. For Y = I and Br, this process occurs in competition with prompt C-I and C-Br bond cleavage on another (n/π)σ* PES, but no Cl/Cl* products unambiguously attributable to one photon induced C-Cl bond fission are observed from 4-ClPhOH. Differences in fragmentation behaviour at longer excitation wavelengths are more marked. Prompt C-I bond fission is observed following excitation of 4-IPhOH at all λ ≤ 330 nm; the wavelength dependent trends in I/I* product branching ratio, kinetic energy release, and recoil anisotropy suggest that (with regard to C-I bond fission) 4-IPhOH behaves like a mildly perturbed iodobenzene. Br atoms are observed when exciting 4-BrPhOH at long wavelengths also, but their velocity distributions suggest that dissociation occurs after internal conversion to the ground state. O-H bond fission, by tunnelling (as in phenol), is observed only in the cases of 4-FPhOH and, more weakly, 4-ClPhOH. These observed differences in behaviour can be understood given due recognition of (i) the differences in the vertical excitation energies of the C-Y centred (n/π)σ* potentials across the series Y = I < Br < Cl and the concomitant reduction in C-Y bond strength, cf. that of the rival O-H bond, and (ii) the much increased spin-orbit coupling in, particularly, 4-IPhOH. The present results provide (another) reminder of the risks inherent in extrapolating photochemical behaviour measured for one molecule at one wavelength to other (related) molecules and to other excitation energies.

Rh(I) -Catalyzed Intramolecular Carbonylative C-H/C-I Coupling of 2-Iodobiphenyls Using Furfural as a Carbonyl Source.

PubMed

Furusawa, Takuma; Morimoto, Tsumoru; Nishiyama, Yasuhiro; Tanimoto, Hiroki; Kakiuchi, Kiyomi

2016-08-19

Synthesis of fluoren-9-ones by a Rh-catalyzed intramolecular C-H/C-I carbonylative coupling of 2-iodobiphenyls using furfural as a carbonyl source is presented. The findings indicate that the rate-determining step is not a C-H bond cleavage but, rather, the oxidative addition of the C-I bond to a Rh(I) center. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Role and mechanism of the maturation cleavage of VP0 in poliovirus assembly: structure of the empty capsid assembly intermediate at 2.9 A resolution.

PubMed Central

Basavappa, R.; Syed, R.; Flore, O.; Icenogle, J. P.; Filman, D. J.; Hogle, J. M.

1994-01-01

The crystal structure of the P1/Mahoney poliovirus empty capsid has been determined at 2.9 A resolution. The empty capsids differ from mature virions in that they lack the viral RNA and have yet to undergo a stabilizing maturation cleavage of VP0 to yield the mature capsid proteins VP4 and VP2. The outer surface and the bulk of the protein shell are very similar to those of the mature virion. The major differences between the 2 structures are focused in a network formed by the N-terminal extensions of the capsid proteins on the inner surface of the shell. In the empty capsids, the entire N-terminal extension of VP1, as well as portions corresponding to VP4 and the N-terminal extension of VP2, are disordered, and many stabilizing interactions that are present in the mature virion are missing. In the empty capsid, the VP0 scissile bond is located some 20 A away from the positions in the mature virion of the termini generated by VP0 cleavage. The scissile bond is located on the rim of a trefoil-shaped depression in the inner surface of the shell that is highly reminiscent of an RNA binding site in bean pod mottle virus. The structure suggests plausible (and ultimately testable) models for the initiation of encapsidation, for the RNA-dependent autocatalytic cleavage of VP0, and for the role of the cleavage in establishing the ordered N-terminal network and in generating stable virions. PMID:7849583

Role of water in aging of human butyrylcholinesterase inhibited by echothiophate: the crystal structure suggests two alternative mechanisms of aging.

PubMed

Nachon, Florian; Asojo, Oluwatoyin A; Borgstahl, Gloria E O; Masson, Patrick; Lockridge, Oksana

2005-02-01

Organophosphorus poisons (OP) bind covalently to the active-site serine of cholinesterases. The inhibited enzyme can usually be reactivated with powerful nucleophiles such as oximes. However, the covalently bound OP can undergo a suicide reaction (termed aging) yielding nonreactivatable enzyme. In human butyrylcholinesterase (hBChE), aging involves the residues His438 and Glu197 that are proximal to the active-site serine (Ser198). The mechanism of aging is known in detail for the nerve gases soman, sarin, and tabun as well as the pesticide metabolite isomalathion. Aging of soman- and sarin-inhibited acetylcholinesterase occurs by C-O bond cleavage, whereas that of tabun- and isomalathion-inhibited acetylcholinesterase occurs by P-N and P-S bond cleavage, respectively. In this work, the crystal structures of hBChE inhibited by the ophthalmic reagents echothiophate (nonaged and aged) and diisopropylfluorophosphate (aged) were solved and refined to 2.1, 2.25, and 2.2 A resolution, respectively. No appreciable shift in the position of the catalytic triad histidine was observed between the aged and nonaged conjugates of hBChE. This absence of shift contrasts with the aged and nonaged crystal structures of Torpedo californica acetylcholinesterase inhibited by the nerve agent VX. The nonaged hBChE structure shows one water molecule interacting with Glu197 and the catalytic triad histidine (His438). Interestingly, this water molecule is ideally positioned to promote aging by two mechanisms: breaking either a C-O bond or a P-O bond. Pesticides and certain stereoisomers of nerve agents are expected to undergo aging by breaking the P-O bond.

On the Reaction Mechanism of Acetaldehyde Decomposition on Mo(110)

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

Mei, Donghai; Karim, Ayman M.; Wang, Yong

2012-02-16

The strong Mo-O bond strength provides promising reactivity of Mo-based catalysts for the deoxygenation of biomass-derived oxygenates. Combining the novel dimer saddle point searching method with periodic spin-polarized density functional theory calculations, we investigated the reaction pathways of a acetaldehyde decomposition on the clean Mo(110) surface. Two reaction pathways were identified, a selective deoxygenation and a nonselective fragmentation pathways. We found that acetaldehyde preferentially adsorbs at the pseudo 3-fold hollow site in the η2(C,O) configuration on Mo(110). Among four possible bond (β-C-H, γ-C-H, C-O and C-C) cleavages, the initial decomposition of the adsorbed acetaldehyde produces either ethylidene via the C-Omore » bond scission or acetyl via the β-C-H bond scission while the C-C and the γ-C-H bond cleavages of acetaldehyde leading to the formation of methyl (and formyl) and formylmethyl are unlikely. Further dehydrogenations of ethylidene into either ethylidyne or vinyl are competing and very facile with low activation barriers of 0.24 and 0.31 eV, respectively. Concurrently, the formed acetyl would deoxygenate into ethylidyne via the C-O cleavage rather than breaking the C-C or the C-H bonds. The selective deoxygenation of acetaldehyde forming ethylene is inhibited by relatively weaker hydrogenation capability of the Mo(110) surface. Instead, the nonselective pathway via vinyl and vinylidene dehydrogenations to ethynyl as the final hydrocarbon fragment is kinetically favorable. On the other hand, the strong interaction between ethylene and the Mo(110) surface also leads to ethylene decomposition instead of desorption into the gas phase. This work was financially supported by the National Advanced Biofuels Consortium (NABC). Computing time was granted by a user project (emsl42292) at the Molecular Science Computing Facility in the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL). This work was financially supported by the National Advanced Biofuels Consortium (NABC). Computing time was granted by a user project (emsl42292) at the Molecular Science Computing Facility in the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL). The EMSL is a U.S. Department of Energy (DOE) national scientific user facility located at Pacific Northwest National Laboratory (PNNL) and supported by the DOE Office of Biological and Environmental Research. Pacific Northwest National Laboratory is operated by Battelle for the U.S. Department of Energy.« less

Specificity and kinetics of haloalkane dehalogenase.

PubMed

Schanstra, J P; Kingma, J; Janssen, D B

1996-06-21

Haloalkane dehalogenase converts halogenated alkanes to their corresponding alcohols. The active site is buried inside the protein and lined with hydrophobic residues. The reaction proceeds via a covalent substrate-enzyme complex. This paper describes a steady-state and pre-steady-state kinetic analysis of the conversion of a number of substrates of the dehalogenase. The kinetic mechanism for the "natural" substrate 1,2-dichloroethane and for the brominated analog and nematocide 1,2-dibromoethane are given. In general, brominated substrates had a lower Km, but a similar kcat than the chlorinated analogs. The rate of C-Br bond cleavage was higher than the rate of C-Cl bond cleavage, which is in agreement with the leaving group abilities of these halogens. The lower Km for brominated compounds therefore originates both from the higher rate of C-Br bond cleavage and from a lower Ks for bromo-compounds. However, the rate-determining step in the conversion (kcat) of 1, 2-dibromoethane and 1,2-dichloroethane was found to be release of the charged halide ion out of the active site cavity, explaining the different Km but similar kcat values for these compounds. The study provides a basis for the analysis of rate-determining steps in the hydrolysis of various environmentally important substrates.

Thermal Decomposition of the Solid Phase of Nitromethane: Ab Initio Molecular Dynamics Simulations

NASA Astrophysics Data System (ADS)

Chang, Jing; Lian, Peng; Wei, Dong-Qing; Chen, Xiang-Rong; Zhang, Qing-Ming; Gong, Zi-Zheng

2010-10-01

The Car-Parrinello molecular dynamics simulations were employed to investigate thermal decomposition of the solid nitromethane. It is found that it undergoes chemical decomposition at about 2200 K under ambient pressure. The initiation of reactions involves both proton transfer and commonly known C-N bond cleavage. About 75 species and 100 elementary reactions were observed with the final products being H2O, CO2, N2, and CNCNC. It represents the first complete simulation of solid-phase explosive reactions reported to date, which is of far-reaching implication for design and development of new energetic materials.

Structural basis for activation of the complement system by component C4 cleavage

PubMed Central

Kidmose, Rune T.; Laursen, Nick S.; Dobó, József; Kjaer, Troels R.; Sirotkina, Sofia; Yatime, Laure; Sottrup-Jensen, Lars; Thiel, Steffen; Gál, Péter; Andersen, Gregers R.

2012-01-01

An essential aspect of innate immunity is recognition of molecular patterns on the surface of pathogens or altered self through the lectin and classical pathways, two of the three well-established activation pathways of the complement system. This recognition causes activation of the MASP-2 or the C1s serine proteases followed by cleavage of the protein C4. Here we present the crystal structures of the 203-kDa human C4 and the 245-kDa C4⋅MASP-2 substrate⋅enzyme complex. When C4 binds to MASP-2, substantial conformational changes in C4 are induced, and its scissile bond region becomes ordered and inserted into the protease catalytic site in a manner canonical to serine proteases. In MASP-2, an exosite located within the CCP domains recognizes the C4 C345C domain 60 Å from the scissile bond. Mutations in C4 and MASP-2 residues at the C345C–CCP interface inhibit the intermolecular interaction and C4 cleavage. The possible assembly of the huge in vivo enzyme–substrate complex consisting of glycan-bound mannan-binding lectin, MASP-2, and C4 is discussed. Our own and prior functional data suggest that C1s in the classical pathway of complement activated by, e.g., antigen–antibody complexes, also recognizes the C4 C345C domain through a CCP exosite. Our results provide a unified structural framework for understanding the early and essential step of C4 cleavage in the elimination of pathogens and altered self through two major pathways of complement activation. PMID:22949645

Mechanisms of catalytic cleavage of benzyl phenyl ether in aqueous and apolar phases

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

He, Jiayue; Lu, Lu; Zhao, Chen

2014-03-01

Catalytic pathways for the cleavage of ether bonds in benzyl phenyl ether (BPE) in liquid phase using Ni- and zeolite-based catalysts are explored. In the absence of catalysts, the C-O bond is selectively cleaved in water by hydrolysis, forming phenol and benzyl alcohol as intermediates, followed by alkylation. The hydronium ions catalyzing the reactions are provided by the dissociation of water at 523 K. Upon addition of HZSM-5, rates of hydrolysis and alkylation are markedly increased in relation to proton concentrations. In the presence of Ni/SiO 2, the selective hydrogenolysis dominates for cleaving the C aliphatic-O bond. Catalyzed by themore » dual-functional Ni/HZSM-5, hydrogenolysis occurs as the major route rather than hydrolysis (minor route). In apolar undecane, the non-catalytic thermal pyrolysis route dominates. Hydrogenolysis of BPE appears to be the major reaction pathway in undecane in the presence of Ni/SiO 2 or Ni/HZSM-5, almost completely suppressing radical reactions. Density functional theory (DFT) calculations strongly support the proposed C-O bond cleavage mechanisms on BPE in aqueous and apolar phases. These calculations show that BPE is initially protonated and subsequently hydrolyzed in the aqueous phase. Finally, DFT calculations suggest that the radical reactions in non-polar solvents lead to primary benzyl and phenoxy radicals in undecane, which leads to heavier condensation products as long as metals are absent for providing dissociated hydrogen.« less

Catalytic activation of carbon–carbon bonds in cyclopentanones

PubMed Central

Xia, Ying; Lu, Gang; Liu, Peng; Dong, Guangbin

2017-01-01

In the chemical industry, molecules of interest are based primarily on carbon skeletons. When synthesizing such molecules, the activation of carbon–carbon single bonds (C–C bonds) in simple substrates is strategically important: it offers a way of disconnecting such inert bonds, forming more active linkages (for example, between carbon and a transition metal) and eventually producing more versatile scaffolds1–13. The challenge in achieving such activation is the kinetic inertness of C–C bonds and the relative weakness of newly formed carbon–metal bonds6,14. The most common tactic starts with a three- or four-membered carbon-ring system9–13, in which strain release provides a crucial thermodynamic driving force. However, broadly useful methods that are based on catalytic activation of unstrained C–C bonds have proven elusive, because the cleavage process is much less energetically favourable. Here we report a general approach to the catalytic activation of C–C bonds in simple cyclopentanones and some cyclohexanones. The key to our success is the combination of a rhodium pre-catalyst, an N-heterocyclic carbene ligand and an amino-pyridine co-catalyst. When an aryl group is present in the C3 position of cyclopentanone, the less strained C–C bond can be activated; this is followed by activation of a carbon–hydrogen bond in the aryl group, leading to efficient synthesis of functionalized α-tetralones—a common structural motif and versatile building block in organic synthesis. Furthermore, this method can substantially enhance the efficiency of the enantioselective synthesis of some natural products of terpenoids. Density functional theory calculations reveal a mechanism involving an intriguing rhodium-bridged bicyclic intermediate. PMID:27806379

Side reactions of nitroxide-mediated polymerization: N-O versus O-C cleavage of alkoxyamines.

PubMed

Hodgson, Jennifer L; Roskop, Luke B; Gordon, Mark S; Lin, Ching Yeh; Coote, Michelle L

2010-09-30

Free energies for the homolysis of the NO-C and N-OC bonds were compared for a large number of alkoxyamines at 298 and 393 K, both in the gas phase and in toluene solution. On this basis, the scope of the N-OC homolysis side reaction in nitroxide-mediated polymerization was determined. It was found that the free energies of NO-C and N-OC homolysis are not correlated, with NO-C homolysis being more dependent upon the properties of the alkyl fragment and N-OC homolysis being more dependent upon the structure of the aminyl fragment. Acyclic alkoxyamines and those bearing the indoline functionality have lower free energies of N-OC homolysis than other cyclic alkoxyamines, with the five-membered pyrrolidine and isoindoline derivatives showing lower free energies than the six-membered piperidine derivatives. For most nitroxides, N-OC homolysis is normally favored above NO-C homolysis only when a heteroatom that is α to the NOC carbon center stabilizes the NO-C bond and/or the released alkyl radical is not sufficiently stabilized. As part of this work, accurate methods for the calculation of free energies for the homolysis of alkoxyamines were determined. Accurate thermodynamic parameters to within 4.5 kJ mol(-1) of experimental values were found using an ONIOM approximation to G3(MP2)-RAD combined with PCM solvation energies at the B3-LYP/6-31G(d) level.

Characterization and Modeling of the Collision Induced Dissociation Patterns of Deprotonated Glycosphingolipids: Cleavage of the Glycosidic Bond

NASA Astrophysics Data System (ADS)

Rožman, Marko

2016-01-01

Glycosphingolipid fragmentation behavior was investigated by combining results from analysis of a series of negative ion tandem mass spectra and molecular modeling. Fragmentation patterns extracted from 75 tandem mass spectra of mainly acidic glycosphingolipid species (gangliosides) suggest prominent cleavage of the glycosidic bonds with retention of the glycosidic oxygen atom by the species formed from the reducing end (B and Y ion formation). Dominant product ions arise from dissociation of sialic acids glycosidic bonds whereas product ions resulting from cleavage of other glycosidic bonds are less abundant. Potential energy surfaces and unimolecular reaction rates of several low-energy fragmentation pathways leading to cleavage of glycosidic bonds were estimated in order to explain observed dissociation patterns. Glycosidic bond cleavage in both neutral (unsubstituted glycosyl group) and acidic glycosphingolipids was the outcome of the charge-directed intramolecular nucleophilic substitution (SN2) mechanism. According to the suggested mechanism, the nucleophile in a form of carboxylate or oxyanion attacks the carbon at position one of the sugar ring, simultaneously breaking the glycosidic bond and yielding an epoxide. For gangliosides, unimolecular reaction rates suggest that dominant product ions related to the cleavage of sialic acid glycosidic bonds are formed via direct dissociation channels. On the other hand, low abundant product ions related to the dissociation of other glycosidic bonds are more likely to be the result of sequential dissociation. Although results from this study mainly contribute to the understanding of glycosphingolipid fragmentation chemistry, some mechanistic findings regarding cleavage of the glycosidic bond may be applicable to other glycoconjugates.

Proton-driven amide bond-cleavage pathways of gas-phase peptide ions lacking mobile protons.

PubMed

Bythell, Benjamin J; Suhai, Sándor; Somogyi, Arpád; Paizs, Béla

2009-10-07

The mobile proton model (Dongre, A. R., Jones, J. L., Somogyi, A. and Wysocki, V. H. J. Am. Chem. Soc. 1996, 118 , 8365-8374) of peptide fragmentation states that the ionizing protons play a critical role in the gas-phase fragmentation of protonated peptides upon collision-induced dissociation (CID). The model distinguishes two classes of peptide ions, those with or without easily mobilizable protons. For the former class mild excitation leads to proton transfer reactions which populate amide nitrogen protonation sites. This enables facile amide bond cleavage and thus the formation of b and y sequence ions. In contrast, the latter class of peptide ions contains strongly basic functionalities which sequester the ionizing protons, thereby often hindering formation of sequence ions. Here we describe the proton-driven amide bond cleavages necessary to produce b and y ions from peptide ions lacking easily mobilizable protons. We show that this important class of peptide ions fragments by different means from those with easily mobilizable protons. We present three new amide bond cleavage mechanisms which involve salt-bridge, anhydride, and imine enol intermediates, respectively. All three new mechanisms are less energetically demanding than the classical oxazolone b(n)-y(m) pathway. These mechanisms offer an explanation for the formation of b and y ions from peptide ions with sequestered ionizing protons which are routinely fragmented in large-scale proteomics experiments.

Unexpected mechanochemical complexity in the mechanistic scenarios of disulfide bond reduction in alkaline solution

NASA Astrophysics Data System (ADS)

Dopieralski, Przemyslaw; Ribas-Arino, Jordi; Anjukandi, Padmesh; Krupicka, Martin; Marx, Dominik

2017-02-01

The reduction of disulfides has a broad importance in chemistry, biochemistry and materials science, particularly those methods that use mechanochemical activation. Here we show, using isotensional simulations, that strikingly different mechanisms govern disulfide cleavage depending on the external force. Desolvation and resolvation processes are found to be crucial, as they have a direct impact on activation free energies. The preferred pathway at moderate forces, a bimolecular SN2 attack of OH- at sulfur, competes with unimolecular C-S bond rupture at about 2 nN, and the latter even becomes barrierless at greater applied forces. Moreover, our study unveils a surprisingly rich reactivity scenario that also includes the transformation of concerted SN2 reactions into pure bond-breaking processes at specific forces. Given that these forces are easily reached in experiments, these insights will fundamentally change our understanding of mechanochemical activation in general, which is now expected to be considerably more intricate than previously thought.

Pd/Nb2O5/SiO2 catalyst for the direct hydrodeoxygenation of biomass-related compounds to liquid alkanes under mild conditions.

PubMed

Shao, Yi; Xia, Qineng; Liu, Xiaohui; Lu, Guanzhong; Wang, Yanqin

2015-05-22

A simple Pd-loaded Nb2 O5 /SiO2 catalyst was prepared for the hydrodeoxygenation of biomass-related compounds to alkanes under mild conditions. Niobium oxide dispersed in silica (Nb2 O5 /SiO2 ) as the support was prepared by the sol-gel method and characterized by various techniques, including N2 adsorption, XRD, NH3 temperature-programmed desorption (TPD), TEM, and energy-dispersive X-ray spectroscopy (EDAX) atomic mapping. The characterization results showed that the niobium oxide species were amorphous and well dispersed in silica. Compared to commercial Nb2 O5 , Nb2 O5 /SiO2 has significantly more active niobium oxide species exposed on the surface. Under mild conditions (170 °C, 2.5 MPa), Pd/10 %Nb2 O5 /SiO2 was effective for the hydrodeoxygenation reactions of 4-(2-furyl)-3-buten-2-one (aldol adduct of furfural with acetone), palmitic acid, tristearin, and diphenyl ether (model compounds of microalgae oils, vegetable oils, and lignin), which gave high yields (>94 %) of alkanes with little CC bond cleavage. More importantly, owing to the significant promotion effect of NbOx species on CO bond cleavage and the mild reaction conditions, the CC cleavage was considerably restrained, and the catalyst showed an excellent activity and stability for the hydrodeoxygenation of palmitic acid with almost no decrease in hexadecane yield (94-95 %) in a 150 h time-on-stream test. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical Cleavage of an Asp-Cys Sequence Allows Efficient Production of Recombinant Peptides with an N-Terminal Cysteine Residue.

PubMed

Pane, Katia; Verrillo, Mariavittoria; Avitabile, Angela; Pizzo, Elio; Varcamonti, Mario; Zanfardino, Anna; Di Maro, Antimo; Rega, Camilla; Amoresano, Angela; Izzo, Viviana; Di Donato, Alberto; Cafaro, Valeria; Notomista, Eugenio

2018-04-18

Peptides with an N-terminal cysteine residue allow site-specific modification of proteins and peptides and chemical synthesis of proteins. They have been widely used to develop new strategies for imaging, drug discovery, diagnostics, and chip technologies. Here we present a method to produce recombinant peptides with an N-terminal cysteine residue as a convenient alternative to chemical synthesis. The method is based on the release of the desired peptide from a recombinant fusion protein by mild acid hydrolysis of an Asp-Cys sequence. To test the general validity of the method we prepared four fusion proteins bearing three different peptides (20-37 amino acid long) at the C-terminus of a ketosteroid isomerase-derived and two Onconase-derived carriers for the production of toxic peptides in E. coli. The chosen peptides were (C)GKY20, an antimicrobial peptide from the C-terminus of human thrombin, (C)ApoB L , an antimicrobial peptide from an inner region of human Apolipoprotein B, and (C)p53pAnt, an anticancer peptide containing the C-terminal region of the p53 protein fused to the cell penetrating peptide Penetratin. Cleavage efficiency of Asp-Cys bonds in the four fusion proteins was studied as a function of pH, temperature, and incubation time. In spite of the differences in the amino acid sequence (GTGDCGKY, GTGDCHVA, GSGTDCGSR, SQGSDCGSR) we obtained for all the proteins a cleavage efficiency of about 70-80% after 24 h incubation at 60 °C and pH 2. All the peptides were produced with very good yield (5-16 mg/L of LB cultures), high purity (>96%), and the expected content of free thiol groups (1 mol per mole of peptide). Furthermore, (C)GKY20 was modified with PyMPO-maleimide, a commercially available fluorophore bearing a thiol reactive group, and with 6-hydroxy-2-cyanobenzothiazole, a reagent specific for N-terminal cysteines, with yields of 100% thus demonstrating that our method is very well suited for the production of fully reactive peptides with an N-terminal cysteine residue.

Periodic trends in bond dissociation energies. A theoretical study.

PubMed

Mó, Otilia; Yáñez, Manuel; Eckert-Maksić, Mirjana; Maksić, Zvonimir B; Alkorta, Ibón; Elguero, José

2005-05-19

Bond dissociation energies (BDEs) of all possible A-X single bonds involving the first- and second-row atoms, from Li to Cl, where the free valences are saturated by hydrogens, have been estimated through the use of the G3-theory and at the B3LYP/6-311+G(3df,2pd)//B3LYP/6-31G(2df,p) DFT level of theory. BDEs exhibit a periodical behavior. The A-X (A = Li, Be, B, Na, Mg, Al, and Si) BDEs show a steady increase along the first and the second row of the periodic table as a function of the atomic number Z(X). For A-X bonds involving electronegative atoms (A = C, N, O, F, P, S, and Cl) the bond energies achieve a maximum around Z(X) = 5. The same behavior is observed when BDEs are plotted against the electronegativity chi(X) of the atom X. Thus, for A-X bonds (A = Li, Be, B, Na, Mg, Al, Si), the BDEs for a fixed A increases, grosso modo, as the electronegativity differences between X and A increase, with some exceptions, which reflect the differences in the relaxation energies of the radicals produced upon the bond cleavage. A similar trend, albeit less pronounced, is found for single A-X bonds, where A = C, N, O, F, P, S, and Cl. However, there is an additional feature embodied in the enhancement of the strength of the A-boron bonds due to the ability of boron to act as a strong electron acceptor. The trends in bond lengths and charge densities at the bond critical points are in line with the aforementioned behavior.

Ruthenium-catalyzed oxidation of alkenes, alkynes, and alcohols to organic acids with aqueous hydrogen peroxide.

PubMed

Che, Chi-Ming; Yip, Wing-Ping; Yu, Wing-Yiu

2006-09-18

A protocol that adopts aqueous hydrogen peroxide as a terminal oxidant and [(Me3tacn)(CF3CO2)2Ru(III)(OH2)]CF3CO2 (1; Me3tacn = 1,4,7-trimethyl-1,4,7-triazacyclononane) as a catalyst for oxidation of alkenes, alkynes, and alcohols to organic acids in over 80% yield is presented. For the oxidation of cyclohexene to adipic acid, the loading of 1 can be lowered to 0.1 mol %. On the one-mole scale, the oxidation of cyclohexene, cyclooctene, and 1-octanol with 1 mol % of 1 produced adipic acid (124 g, 85% yield), suberic acid (158 g, 91% yield), and 1-octanoic acid (129 g, 90% yield), respectively. The oxidative C=C bond-cleavage reaction proceeded through the formation of cis- and trans-diol intermediates, which were further oxidized to carboxylic acids via C-C bond cleavage.

Estimation of the degree of hydrogen bonding between quinoline and water by ultraviolet-visible absorbance spectroscopy in sub- and supercritical water

NASA Astrophysics Data System (ADS)

Osada, Mitsumasa; Toyoshima, Katsunori; Mizutani, Takakazu; Minami, Kimitaka; Watanabe, Masaru; Adschiri, Tadafumi; Arai, Kunio

2003-03-01

UV-visible spectra of quinoline was measured in sub- and supercritical water (25 °C

Site-targeted mutagenesis for stabilization of recombinant monoclonal antibody expressed in tobacco (Nicotiana tabacum) plants

PubMed Central

Hehle, Verena K.; Paul, Matthew J.; Roberts, Victoria A.; van Dolleweerd, Craig J.; Ma, Julian K.-C.

2016-01-01

This study examined the degradation pattern of a murine IgG1κ monoclonal antibody expressed in and extracted from transformed Nicotiana tabacum. Gel electrophoresis of leaf extracts revealed a consistent pattern of recombinant immunoglobulin bands, including intact and full-length antibody, as well as smaller antibody fragments. N-terminal sequencing revealed these smaller fragments to be proteolytic cleavage products and identified a limited number of protease-sensitive sites in the antibody light and heavy chain sequences. No strictly conserved target sequence was evident, although the peptide bonds that were susceptible to proteolysis were predominantly and consistently located within or near to the interdomain or solvent-exposed regions in the antibody structure. Amino acids surrounding identified cleavage sites were mutated in an attempt to increase resistance. Different Guy’s 13 antibody heavy and light chain mutant combinations were expressed transiently in N. tabacum and demonstrated intensity shifts in the fragmentation pattern, resulting in alterations to the full-length antibody-to-fragment ratio. The work strengthens the understanding of proteolytic cleavage of antibodies expressed in plants and presents a novel approach to stabilize full-length antibody by site-directed mutagenesis.—Hehle, V. K., Paul, M. J., Roberts, V. A., van Dolleweerd, C. J., Ma, J. K.-C. Site-targeted mutagenesis for stabilization of recombinant monoclonal antibody expressed in tobacco (Nicotiana tabacum) plants. PMID:26712217

Asymmetric NHC-catalyzed redox α-amination of α-aroyloxyaldehydes.

PubMed

Taylor, James E; Daniels, David S B; Smith, Andrew D

2013-12-06

Asymmetric α-amination through an N-heterocyclic carbene (NHC)-catalyzed redox reaction of α-aroyloxyaldehydes with N-aryl-N-aroyldiazenes to form α-hydrazino esters with high enantioselectivity (up to 99% ee) is reported. The hydrazide products are readily converted into enantioenriched N-aryl amino esters through samarium(II) iodide mediated N-N bond cleavage.

Combined Experimental and Computational Study on the Unimolecular Decomposition of JP-8 Jet Fuel Surrogates. I. n-Decane (n-C10H22).

PubMed

Zhao, Long; Yang, Tao; Kaiser, Ralf I; Troy, Tyler P; Ahmed, Musahid; Belisario-Lara, Daniel; Ribeiro, Joao Marcelo; Mebel, Alexander M

2017-02-16

Exploiting a high temperature chemical reactor, we explored the pyrolysis of helium-seeded n-decane as a surrogate of the n-alkane fraction of Jet Propellant-8 (JP-8) over a temperature range of 1100-1600 K at a pressure of 600 Torr. The nascent products were identified in situ in a supersonic molecular beam via single photon vacuum ultraviolet (VUV) photoionization coupled with a mass spectroscopic analysis of the ions in a reflectron time-of-flight mass spectrometer (ReTOF). Our studies probe, for the first time, the initial reaction products formed in the decomposition of n-decane-including radicals and thermally labile closed-shell species effectively excluding mass growth processes. The present study identified 18 products: molecular hydrogen (H 2 ), C2 to C7 1-alkenes [ethylene (C 2 H 4 ) to 1-heptene (C 7 H 14 )], C1-C3 radicals [methyl (CH 3 ), vinyl (C 2 H 3 ), ethyl (C 2 H 5 ), propargyl (C 3 H 3 ), allyl (C 3 H 5 )], small C1-C3 hydrocarbons [methane (CH 4 ), acetylene (C 2 H 2 ), allene (C 3 H 4 ), methylacetylene (C 3 H 4 )], along with higher-order reaction products [1,3-butadiene (C 4 H 6 ), 2-butene (C 4 H 8 )]. On the basis of electronic structure calculations, n-decane decomposes initially by C-C bond cleavage (excluding the terminal C-C bonds) producing a mixture of alkyl radicals from ethyl to octyl. These alkyl radicals are unstable under the experimental conditions and rapidly dissociate by C-C bond β-scission to split ethylene (C 2 H 4 ) plus a 1-alkyl radical with the number of carbon atoms reduced by two and 1,4-, 1,5-, 1,6-, or 1,7-H shifts followed by C-C β-scission producing alkenes from propene to 1-octene in combination with smaller 1-alkyl radicals. The higher alkenes become increasingly unstable with rising temperature. When the C-C β-scission continues all the way to the propyl radical (C 3 H 7 ), it dissociates producing methyl (CH 3 ) plus ethylene (C 2 H 4 ). Also, at higher temperatures, hydrogen atoms can abstract hydrogen from C 10 H 22 to yield n-decyl radicals, while methyl (CH 3 ) can also abstract hydrogen or recombine with hydrogen to form methane. These n-decyl radicals can decompose via C-C-bond β-scission to C3 to C9 alkenes.

β-Lactam Ring Opening: A Useful Entry to Amino Acids and Relevant Nitrogen-Containing Compounds

NASA Astrophysics Data System (ADS)

Palomo, C.; Oiarbide, M.

The main strategies for the ring opening of β-lactams by chemical means are described. The discovery of each approach is put into context, sometimes in connection to processes occurring in biological systems, and the synthetic opportunities each approach offers are shown. Thus, this β-lactam route affords a number of synthetically relevant building-blocks, including α-amino acids, β-amino acids, their derived peptides, and other nitrogen containing heterocycles and open chain molecules. The content, which encompases references to initial work, further major development, and the most relevant recent literature contributions, is categorized according to the ring bond cleavaged (N 1-C 2, C 2-C 3, C 3 -C 4 , N 1-C 4), to finish with ring opening strategies leading to large heterocyclic compounds. Within each category, distinction has been made according to the type of nucleophilic agent employed, principally O-, N-, and C-nucleophiles. Also, a variety of applications of the strategy to the synthesis of interesting target compounds are shown.

Synthesis, structure, and catalytic activity of novel trinuclear rare-earth metal amido complexes incorporating μ-η5:η1 bonding indolyl and μ3-oxo groups.

PubMed

Yang, Song; Zhu, Xiancui; Zhou, Shuangliu; Wang, Shaowu; Feng, Zhijun; Wei, Yun; Miao, Hui; Guo, Liping; Wang, Fenhua; Zhang, Guangchao; Gu, Xiaoxia; Mu, Xiaolong

2014-02-14

The reactions of different pyrrolyl-functionalized indoles with rare-earth metal(III) amides [(Me3Si)2N]3RE(III)(μ-Cl)Li(THF)3 (RE = Yb, Er, Dy, Eu, Y) produced different kinds of rare-earth metal amido complexes. Reactions of N-((1H-pyrrol-2-yl)methylene)-2-(1H-indol-3-yl)ethanamine with rare-earth metal amides [(Me3Si)2N]3RE(III)(μ-Cl)Li(THF)3 (RE = Yb, Er, Dy, Eu, Y) in toluene or THF at temperatures of 75-80 °C afforded the novel trinuclear rare-earth metal amido complexes incorporating the indolyl ligand in μ-η(5):η(1) bonding modes and a μ3-O group, which is believed to originate from cleavage of the THF ring based on experimental results. Reactions of 2-(1H-indol-3-yl)-N-((1-methyl-1H-pyrrol-2-yl)methylene)ethanamine with rare-earth metal(III) amides [(Me3Si)2N]3RE(III)(μ-Cl)Li(THF)3 (RE = Yb, Dy) produced mononuclear ytterbium and dysprosium amides having the indolyl ligand in an η(1) bonding fashion. The results indicate that substituents not only have an influence on reactivity, but also have an influence on the bonding of the indolyl ligands with metals. The catalytic activities of the novel lanthanide amido complexes for the hydrophosphonylation of both aromatic and aliphatic aldehydes and ketones were explored. The results indicate that these complexes display a high catalytic activity for the C-P bond formation under mild conditions when using low catalyst loadings (0.1 mol% for aldehydes and ketones). Thus, it provides a potential way to prepare α-hydroxy phosphonates.

Reduction of [Cp*Sb]4 with Subvalent Main-Group Metal Reductants: Syntheses and Structures of [(L1 Mg)4 (Sb4 )] and [(L2 Ga)2 (Sb4 )] Containing Edge-Missing Sb4 Units.

PubMed

Ganesamoorthy, Chelladurai; Krüger, Julia; Wölper, Christoph; Nizovtsev, Anton S; Schulz, Stephan

2017-02-16

[Cp*Sb] 4 (Cp*=C 5 Me 5 ) reacts with [L 1 Mg] 2 and L 2 Ga with formation of [(L 1 Mg) 4 (μ 4 ,η 1:2:2:2 -Sb 4 )] (L 1 =iPr 2 NC[N(2,6-iPr 2 C 6 H 3 )] 2 , 1) and [(L 2 Ga) 2 (μ,η 2:2 -Sb 4 )] (L 2 =HC[C(Me)N(2,6-iPr 2 C 6 H 3 )] 2 , 2). The cleavage of the Sb-Sb and Sb-C bonds in [Cp*Sb] 4 are the crucial steps in both reactions. The formation of 1 occurred by elimination of the Cp* anion and formation of Cp*MgL 1 , while 2 was formed by reductive elimination of Cp* 2 and oxidative addition of L 2 Ga to the Sb 4 unit. 1 and 2 were characterized by heteronuclear NMR spectroscopy and single-crystal X-ray diffraction, and their bonding situation was studied by quantum chemical calculations. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A density functional theory study on peptide bond cleavage at aspartic residues: direct vs cyclic intermediate hydrolysis.

PubMed

Sang-aroon, Wichien; Amornkitbamrung, Vittaya; Ruangpornvisuti, Vithaya

2013-12-01

In this work, peptide bond cleavages at carboxy- and amino-sides of the aspartic residue in a peptide model via direct (concerted and step-wise) and cyclic intermediate hydrolysis reaction pathways were explored computationally. The energetics, thermodynamic properties, rate constants, and equilibrium constants of all hydrolysis reactions, as well as their energy profiles were computed at the B3LYP/6-311++G(d,p) level of theory. The result indicated that peptide bond cleavage of the Asp residue occurred most preferentially via the cyclic intermediate hydrolysis pathway. In all reaction pathways, cleavage of the peptide bond at the amino-side occurred less preferentially than at the carboxy-side. The overall reaction rate constants of peptide bond cleavage of the Asp residue at the carboxy-side for the assisted system were, in increasing order: concerted < step-wise < cyclic intermediate.

Metabolism of Hydrocarbons in n-Alkane-Utilizing Anaerobic Bacteria.

PubMed

Wilkes, Heinz; Buckel, Wolfgang; Golding, Bernard T; Rabus, Ralf

2016-01-01

The glycyl radical enzyme-catalyzed addition of n-alkanes to fumarate creates a C-C-bond between two concomitantly formed stereogenic carbon centers. The configurations of the two diastereoisomers of the product resulting from n-hexane activation by the n-alkane-utilizing denitrifying bacterium strain HxN1, i.e. (1-methylpentyl)succinate, were assigned as (2S,1'R) and (2R,1'R). Experiments with stereospecifically deuterated n-(2,5-2H2)hexanes revealed that exclusively the pro-S hydrogen atom is abstracted from C2 of the n-alkane by the enzyme and later transferred back to C3 of the alkylsuccinate formed. These results indicate that the alkylsuccinate-forming reaction proceeds with an inversion of configuration at the carbon atom (C2) of the n-alkane forming the new C-C-bond, and thus stereochemically resembles a SN2-type reaction. Therefore, the reaction may occur in a concerted manner, which may avoid the highly energetic hex-2-yl radical as an intermediate. The reaction is associated with a significant primary kinetic isotope effect (kH/kD ≥3) for hydrogen, indicating that the homolytic C-H-bond cleavage is involved in the first irreversible step of the reaction mechanism. The (1-methylalkyl)succinate synthases of n-alkane-utilizing anaerobic bacteria apparently have very broad substrate ranges enabling them to activate not only aliphatic but also alkyl-aromatic hydrocarbons. Thus, two denitrifiers and one sulfate reducer were shown to convert the nongrowth substrate toluene to benzylsuccinate and further to the dead-end product benzoyl-CoA. For this purpose, however, the modified β-oxidation pathway known from alkylbenzene-utilizing bacteria was not employed, but rather the pathway used for n-alkane degradation involving CoA ligation, carbon skeleton rearrangement and decarboxylation. Furthermore, various n-alkane- and alkylbenzene-utilizing denitrifiers and sulfate reducers were found to be capable of forming benzyl alcohols from diverse alkylbenzenes, putatively via dehydrogenases. The thermophilic sulfate reducer strain TD3 forms n-alkylsuccinates during growth with n-alkanes or crude oil, which, based on the observed patterns of homologs, do not derive from a terminal activation of n-alkanes. © 2016 S. Karger AG, Basel.

Snapshots of C-S Cleavage in Egt2 Reveals Substrate Specificity and Reaction Mechanism.

PubMed

Irani, Seema; Naowarojna, Nathchar; Tang, Yang; Kathuria, Karan R; Wang, Shu; Dhembi, Anxhela; Lee, Norman; Yan, Wupeng; Lyu, Huijue; Costello, Catherine E; Liu, Pinghua; Zhang, Yan Jessie

2018-05-17

Sulfur incorporation in the biosynthesis of ergothioneine, a histidine thiol derivative, differs from other well-characterized transsulfurations. A combination of a mononuclear non-heme iron enzyme-catalyzed oxidative C-S bond formation and a subsequent pyridoxal 5'-phosphate (PLP)-mediated C-S lyase reaction leads to the net transfer of a sulfur atom from a cysteine to a histidine. In this study, we structurally and mechanistically characterized a PLP-dependent C-S lyase Egt2, which mediates the sulfoxide C-S bond cleavage in ergothioneine biosynthesis. A cation-π interaction between substrate and enzyme accounts for Egt2's preference of sulfoxide over thioether as a substrate. Using mutagenesis and structural biology, we captured three distinct states of the Egt2 C-S lyase reaction cycle, including a labile sulfenic intermediate captured in Egt2 crystals. Chemical trapping and high-resolution mass spectrometry were used to confirm the involvement of the sulfenic acid intermediate in Egt2 catalysis. Copyright © 2018 Elsevier Ltd. All rights reserved.

Rhodium-catalyzed synthesis of silafluorene derivatives via cleavage of silicon-hydrogen and carbon-hydrogen bonds.

PubMed

Ureshino, Tomonari; Yoshida, Takuya; Kuninobu, Yoichiro; Takai, Kazuhiko

2010-10-20

The rhodium-catalyzed synthesis of silafluorenes from biphenylhydrosilanes is described. This highly efficient reaction proceeds via both Si-H and C-H bond activation, producing only H(2) as a side product. Using this method, a ladder-type bis-silicon-bridged p-terphenyl could also be synthesized.

Gas-Phase Chemistry of Arylimido-Functionalized Hexamolybdates [Mo6O19]2-

NASA Astrophysics Data System (ADS)

Cao, Jie; Wang, QianQian; Liu, Chang; An, ShuQi

2018-04-01

The gas-phase fragmentations of a series of arylimido derivatives of hexamolybdate [Mo6O18(NC6H5-n R n )]2- (2-10, where R = CH3, i-C3H7, OCH3, NO2; n = 1 or 2) versus the parent species [Mo6O19]2- (1) were systematically studied using electrospray tandem mass spectrometry (ESI). Fragmentation of 1 generates two molybdate fragments only, [Mo3O10]2- and [Mo4O13]2-, whereas decomposition of 2-10 went through two dissociation pathways in which path A generates a variety of molybdate fragments via breaking the Mo-N bond followed by the cleavages of the multiple Mo-O bonds, whereas path B produces a range of molybdate fragments with arylimido group via breaking the multiple Mo-O bonds on POM framework. Moreover, the presences of mixed-oxidation-state molybdate fragments are characteristic for the fragmentation. The gas-phase stability order obtained by energy-variable collision-induced dissociation (CID) experiment reveals that 2-10 are generally less stable than 1 and substitution on the benzene ring exerts a considerable effect on the stabilization of the hybrid clusters. [Figure not available: see fulltext.

Thermal decomposition of the solid phase of nitromethane: ab initio molecular dynamics simulations.

PubMed

Chang, Jing; Lian, Peng; Wei, Dong-Qing; Chen, Xiang-Rong; Zhang, Qing-Ming; Gong, Zi-Zheng

2010-10-29

The Car-Parrinello molecular dynamics simulations were employed to investigate thermal decomposition of the solid nitromethane. It is found that it undergoes chemical decomposition at about 2200 K under ambient pressure. The initiation of reactions involves both proton transfer and commonly known C-N bond cleavage. About 75 species and 100 elementary reactions were observed with the final products being H2O, CO2, N2, and CNCNC. It represents the first complete simulation of solid-phase explosive reactions reported to date, which is of far-reaching implication for design and development of new energetic materials.

Selective Cleavage of the Aryl Ether Bonds in Lignin for Depolymerization by Acidic Lithium Bromide Molten Salt Hydrate under Mild Conditions.

PubMed

Yang, Xiaohui; Li, Ning; Lin, Xuliang; Pan, Xuejun; Zhou, Yonghong

2016-11-09

The present study demonstrates that the concentrated lithium bromide (LiBr) solution with acid as catalyst was able to selectively cleave the β-O-4 aryl ether bond and lead to lignin depolymerization under mild conditions (e.g., in 60% LiBr with 0.3 M HCl at 110 °C for 2 h). Four industrial lignins from different pulping and biorefining processes, including softwood kraft lignin (SKL), hardwood kraft lignin (HKL), softwood ethanol organosolv lignin (EOL), and acid corncob lignin (ACL), were treated in the LiBr solution. The molecular weight, functional group, and interunit linkages of the lignins were characterized using GPC, FTIR, and NMR. The results indicated that the β-O-4 aryl ether bonds of the lignins were selectively cleaved, and both LiBr and HCl played crucial roles in catalyzing the cleavage of the ether bonds.

Gold(I) and Gold(III) Complexes of Cyclic (Alkyl)(amino)carbenes

PubMed Central

2016-01-01

The chemistry of Au(I) complexes with two types of cyclic (alkyl)(amino)carbene (CAAC) ligands has been explored, using the sterically less demanding dimethyl derivative Me2CAAC and the 2-adamantyl ligand AdCAAC. The conversion of (AdCAAC)AuCl into (AdCAAC)AuOH by treatment with KOH is significantly accelerated by the addition of tBuOH. (AdCAAC)AuOH is a convenient starting material for the high-yield syntheses of (AdCAAC)AuX complexes by acid/base and C–H activation reactions (X = OAryl, CF3CO2, N(Tf)2, C2Ph, C6F5, C6HF4, C6H2F3, CH2C(O)C6H4OMe, CH(Ph)C(O)Ph, CH2SO2Ph), while the cationic complexes [(AdCAAC)AuL]+ (L = CO, CNtBu) and (AdCAAC)AuCN were obtained by chloride substitution from (AdCAAC)AuCl. The reactivity toward variously substituted fluoroarenes suggests that (AdCAAC)AuOH is able to react with C–H bonds with pKa values lower than about 31.5. This, together with the spectroscopic data, confirm the somewhat stronger electron-donor properties of CAAC ligands in comparison to imidazolylidene-type N-heterocyclic carbenes (NHCs). In spite of this, the oxidation of Me2CAAC and AdCAAC gold compounds is much less facile. Oxidations proceed with C–Au cleavage by halogens unless light is strictly excluded. The oxidation of (AdCAAC)AuCl with PhICl2 in the dark gives near-quantitative yields of (AdCAAC)AuCl3, while [Au(Me2CAAC)2]Cl leads to trans-[AuCl2(Me2CAAC)2]Cl. In contrast to the chemistry of imidazolylidene-type gold NHC complexes, oxidation products containing Au–Br or Au–I bonds could not be obtained; whereas the reaction with CsBr3 cleaves the Au–C bond to give mixtures of [AdCAAC-Br]+[AuBr2]− and [(AdCAAC-Br)]+ [AuBr4]−, the oxidation of (AdCAAC)AuI with I2 leads to the adduct (AdCAAC)AuI·I2. Irrespective of the steric demands of the CAAC ligands, their gold complexes proved more resistant to oxidation and more prone to halogen cleavage of the Au–C bonds than gold(I) complexes of imidazole-based NHC ligands. PMID:26146436

Using ambient ozone for assignment of double bond position in unsaturated lipids.

PubMed

Ellis, Shane R; Hughes, Jessica R; Mitchell, Todd W; in het Panhuis, Marc; Blanksby, Stephen J

2012-03-07

Unsaturated lipids deposited onto a range of materials are observed to react with the low concentrations of ozone present in normal laboratory air. Parent lipids and ozonolysis cleavage products are both detected directly from surfaces by desorption electrospray ionisation mass spectrometry (DESI-MS) with the resulting mass spectra providing clear evidence of the double bond position within these molecules. This serendipitous process has been coupled with thin-layer chromatography (TLC) to provide a simple but powerful approach for the detailed structural elucidation of lipids present in complex biological extracts. Lipid extracts from human lens were deposited onto normal phase TLC plates and then developed to separate components according to lipid class. Exposure of the developed plates to laboratory air for ca. 1 h prior to DESI-MS analysis gave rise to ozonolysis products allowing for the unambiguous identification of double bond positions in even low abundant, unsaturated lipids. In particular, the co-localization of intact unsaturated lactosylceramides (LacCer) with products from their oxidative cleavage provide the first evidence for the presence of three isomeric LacCer (d18:0/24:1) species in the ocular lens lipidome, i.e., variants with double bonds at the n-9, n-7 and n-5 positions.

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols.

PubMed

Tait, Katrina; Horvath, Alysia; Blanchard, Nicolas; Tam, William

2017-01-01

The acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicylic alkene using alcohol nucleophiles were investigated. Although this acid-catalyzed ring-opening reaction did not cleave the cyclopropane unit as planned, this represent the first examples of ring-openings of cyclopropanated 3-aza-2-oxabicyclo[2.2.1]alkenes that lead to the cleavage of the C-O bond instead of the N-O bond. Different acid catalysts were tested and it was found that pyridinium toluenesulfonate in methanol gave the best yields in the ring-opening reactions. The scope of the reaction was successfully expanded to include primary, secondary, and tertiary alcohol nucleophiles. Through X-ray crystallography, the stereochemistry of the product was determined which confirmed an S N 2-like mechanism to form the ring-opened product.

Enhancing Protein Disulfide Bond Cleavage by UV Excitation and Electron Capture Dissociation for Top-Down Mass Spectrometry.

PubMed

Wongkongkathep, Piriya; Li, Huilin; Zhang, Xing; Loo, Rachel R Ogorzalek; Julian, Ryan R; Loo, Joseph A

2015-11-15

The application of ion pre-activation with 266 nm ultraviolet (UV) laser irradiation combined with electron capture dissociation (ECD) is demonstrated to enhance top-down mass spectrometry sequence coverage of disulfide bond containing proteins. UV-based activation can homolytically cleave a disulfide bond to yield two separated thiol radicals. Activated ECD experiments of insulin and ribonuclease A containing three and four disulfide bonds, respectively, were performed. UV-activation in combination with ECD allowed the three disulfide bonds of insulin to be cleaved and the overall sequence coverage to be increased. For the larger sized ribonuclease A with four disulfide bonds, irradiation from an infrared laser (10.6 µm) to disrupt non-covalent interactions was combined with UV-activation to facilitate the cleavage of up to three disulfide bonds. Preferences for disulfide bond cleavage are dependent on protein structure and sequence. Disulfide bonds can reform if the generated radicals remain in close proximity. By varying the time delay between the UV-activation and the ECD events, it was determined that disulfide bonds reform within 10-100 msec after their UV-homolytic cleavage.

Activation of carbon-hydrogen bonds and dihydrogen by 1,2-CH-addition across metal-heteroatom bonds.

PubMed

Webb, Joanna R; Burgess, Samantha A; Cundari, Thomas R; Gunnoe, T Brent

2013-12-28

The controlled conversion of hydrocarbons to functionalized products requires selective C-H bond cleavage. This perspective provides an overview of 1,2-CH-addition of hydrocarbons across d(0) transition metal imido complexes and compares and contrasts these to examples of analogous reactions that involve later transition metal amide, hydroxide and alkoxide complexes with d(6) and d(8) metals.

Increasing the Aromatic Selectivity of Quinoline Hydrogenolysis Using Pd/MOx–Al2O3

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

Bachrach, Mark; Morlanes-Sanchez, Natalia; Canlas, Christian P.

2014-09-11

Catalysts consisting of Pd nanoparticles supported on highly dispersed TiOx–Al2O3, TaOx–Al2O3, and MoOx–Al2O3 are studied for catalytic quinoline hydrogenation and selective C–N bond cleavage at 275 °C and 20 bar H2. The Pd/MOx–Al2O3 materials exhibit significantly greater aromatic product selectivity and thus 10–15 % less required H2 for a given level of denitrogenation relative to an unmodified Pd/Al2O3 catalyst.

O2-dependent Aliphatic Carbon-carbon Bond Cleavage Reactivity in a Ni(II) Enolate Complex Having a Hydrogen Bond Donor Microenvironment; Comparison with a Hydrophobic Analog

PubMed Central

Grubel, Katarzyna; Fuller, Amy L.; Chambers, Bonnie M.; Arif, Atta M.; Berreau, Lisa M.

2010-01-01

A mononuclear Ni(II) complex having an acireductone type ligand, and supported by the bnpapa (N,N-bis((6-neopentylamino-2-pyridyl)methyl-N-((2-pyridyl)methyl)amine ligand, [(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (14), has been prepared and characterized by elemental analysis, 1H NMR, FTIR, and UV-vis. To gain insight into the 1H NMR features of 14, the air stable analog complexes [(bnpapa)Ni(CH3C(O)CHC(O)CH3)]ClO4 (16) and [(bnpapa)Ni(ONHC(O)CH3)]ClO4 (17) were prepared and characterized by X-ray crystallography, 1H NMR, FTIR, UV-vis, mass spectrometry, and solution conductivity measurements. Compounds 16 and 17 are 1:1 electrolyte species in CH3CN. 1H and 2H NMR studies of 14, 16, and 17 and deuterated analogs revealed that the complexes having six-membered chelate rings for the exogenous ligand (14 and 16) do not have a plane of symmetry within the solvated cation and thus exhibit more complicated 1H NMR spectra. Compound 17, as well as other simple Ni(II) complexes of the bnpapa ligand (e.g. [(bnpapa)Ni(ClO4)(CH3CN)]ClO4 (18) and [(bnpapaNi)2(μ-Cl)2](ClO4)2 (19)), exhibit 1H NMR spectra consistent with the presence of a plane of symmetry within the cation. Treatment of [(bnpapa)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (14) with O2 results in aliphatic carbon-carbon bond cleavage within the acireductone-type ligand and the formation of [(bnpapa)Ni(O2CPh)]ClO4 (9), benzoic acid, benzil, and CO. Use of 18O2 in the reaction gives high levels of incorporation (>80%) of one labeled oxygen atom into 9 and benzoic acid. The product mixture and level of 18O incorporation in this reaction is different than that exhibited by the analog supported the hydrophobic 6-Ph2TPA ligand, [(6-Ph2TPA)Ni(PhC(O)C(OH)C(O)Ph)]ClO4 (2). We propose that this difference is due to variations in the reactivity of bnpapa- and 6-Ph2TPA-ligated Ni(II) complexes with triketone and/or peroxide species produced in the reaction pathway. PMID:20039645

Intramolecular hydrogen bonding in malonaldehyde and its radical analogues.

PubMed

Lin, Chen; Kumar, Manoj; Finney, Brian A; Francisco, Joseph S

2017-09-28

High level Brueckner doubles with triples correction method-based ab initio calculations have been used to investigate the nature of intramolecular hydrogen bonding and intramolecular hydrogen atom transfer in cis-malonaldehyde (MA) and its radical analogues. The radicals considered here are the ones that correspond to the homolytic cleavage of C-H bonds in cis-MA. The results suggest that cis-MA and its radical analogues, cis-MA RS , and cis-MA RA , both exist in planar geometry. The calculated intramolecular O-H⋯O=C bond in cis-MA is shorter than that in the radical analogues. The intramolecular hydrogen bond in cis-MA is stronger than in its radicals by at least 3.0 kcal/mol. The stability of a cis-malonaldehyde radical correlates with the extent of electron spin delocalization; cis-MA RA , in which the radical spin is more delocalized, is the most stable MA radical, whereas cis-MA RS , in which the radical spin is strongly localized, is the least stable radical. The natural bond orbital analysis indicates that the intramolecular hydrogen bonding (O⋯H⋯O) in cis-malonaldehyde radicals is stabilized by the interaction between the lone pair orbitals of donor oxygen and the σ * orbital of acceptor O-H bond (n → σ * OH ). The calculated barriers indicate that the intramolecular proton transfer in cis-MA involves 2.2 kcal/mol lower barrier than that in cis-MA RS .

Water-Soluble Fe(II)−H2O Complex with a Weak O−H Bond Transfers a Hydrogen Atom via an Observable Monomeric Fe(III)−OH

PubMed Central

Brines, Lisa M.; Coggins, Michael K.; Poon, Penny Chaau Yan; Toledo, Santiago; Kaminsky, Werner; Kirk, Martin L.

2015-01-01

Understanding the metal ion properties that favor O−H bond formation versus cleavage should facilitate the development of catalysts tailored to promote a specific reaction, e.g., C−H activation or H2O oxidation. The first step in H2O oxidation involves the endothermic cleavage of a strong O−H bond (BDFE = 122.7 kcal/mol), promoted by binding the H2O to a metal ion, and by coupling electron transfer to proton transfer (PCET). This study focuses on details regarding how a metal ion’s electronic structure and ligand environment can tune the energetics of M(HO−H) bond cleavage. The synthesis and characterization of an Fe(II)−H2O complex, 1, that undergoes PCET in H2O to afford a rare example of a monomeric Fe(III)−OH, 7, is described. High-spin 7 is also reproducibly generated via the addition of H2O to {[FeIII(OMe2N4(tren))]2-(µ-O)}2+ (8). The O−H bond BDFE of Fe(II)−H2O (1) (68.6 kcal/mol) is calculated using linear fits to its Pourbaix diagram and shown to be 54.1 kcal/mol less than that of H2O and 10.9 kcal/mol less than that of [Fe(II)(H2O)6]2+. The O−H bond of 1 is noticeably weaker than the majority of reported Mn+(HxO−H) (M = Mn, Fe; n+ = 2+, 3+; x = 0, 1) complexes. Consistent with their relative BDFEs, Fe(II)−H2O (1) is found to donate a H atom to TEMPO•, whereas the majority of previously reported Mn+−O(H) complexes, including [MnIII(SMe2N4(tren))(OH)]+ (2), have been shown to abstract H atoms from TEMPOH. Factors responsible for the weaker O−H bond of 1, such as differences in the electron-donating properties of the ligand, metal ion Lewis acidity, and electronic structure, are discussed. PMID:25611075

UV Photofragmentation Dynamics of Protonated Cystine: Disulfide Bond Rupture.

PubMed

Soorkia, Satchin; Dehon, Christophe; Kumar, S Sunil; Pedrazzani, Mélanie; Frantzen, Emilie; Lucas, Bruno; Barat, Michel; Fayeton, Jacqueline A; Jouvet, Christophe

2014-04-03

Disulfide bonds (S-S) play a central role in stabilizing the native structure of proteins against denaturation. Experimentally, identification of these linkages in peptide and protein structure characterization remains challenging. UV photodissociation (UVPD) can be a valuable tool in identifying disulfide linkages. Here, the S-S bond acts as a UV chromophore and absorption of one UV photon corresponds to a σ-σ* transition. We have investigated the photodissociation dynamics of protonated cystine, which is a dimer of two cysteines linked by a disulfide bridge, at 263 nm (4.7 eV) using a multicoincidence technique in which fragments coming from the same fragmentation event are detected. Two types of bond cleavages are observed corresponding to the disulfide (S-S) and adjacent C-S bond ruptures. We show that the S-S cleavage leads to three different fragment ions via three different fragmentation mechanisms. The UVPD results are compared to collision-induced dissociation (CID) and electron-induced dissociation (EID) studies.

Synthesis and structural characterization of (C sub 5 Me sub 5 )Zr(R) sub 2 (L) sub n sup + complexes

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

Crowther, D.J.; Jordan, R.F.; Baenziger, N.C.

1990-09-01

The reaction of (C{sub 5}Me{sub 5})Zr(CH{sub 3}){sub 3} with ((C{sub 5}H{sub 4}Me){sub 2}Fe)(BPh{sub 4}) in THF yields ((C{sub 5}Me{sub 5})Zr(CH{sub 3}){sub 2}(THF){sub 2})(BPh{sub 4}) (1) via oxidative cleavage of a Zr-CH{sub 3} bond. X-ray diffraction reveals that the cation of 1 adopts a square-pyramidal/four-legged piano-stool structure with cis CH{sub 3} groups. The orientations of the THF ligands and the Zr-O bond distances suggest that Zr-O {pi}-bonding is important for at least one of the THF ligands. Data for 1: a = 14.551 (2) {angstrom}, b = 15.191 (4) {angstrom}, c = 17.852 (19) {angstrom}, {beta} = 92.26 (3){degree}, V =more » 3,943 (6) {angstrom}{sup 3}, Z = 4 in space group P2{sub 1}/c. Reaction of 1 with excess dmpe in THF solution yields ((C{sub 5}Me{sub 5})Zr(CH{sub 3}){sub 2}(dmpe)(THF))(BPh{sub 4}) (2), which also has been characterized by X-ray diffraction.« less

The Generation of Dehydroalanine Residues in Protonated Polypeptides: Ion/Ion Reactions for Introducing Selective Cleavages

NASA Astrophysics Data System (ADS)

Peng, Zhou; Bu, Jiexun; McLuckey, Scott A.

2017-09-01

We examine a gas-phase approach for converting a subset of amino acid residues in polypeptide cations to dehydroalanine (Dha). Subsequent activation of the modified polypeptide ions gives rise to specific cleavage N-terminal to the Dha residue. This process allows for the incorporation of selective cleavages in the structural characterization of polypeptide ions. An ion/ion reaction within the mass spectrometer between a multiply protonated polypeptide and the sulfate radical anion introduces a radical site into the multiply protonated polypeptide reactant. Subsequent collisional activation of the polypeptide radical cation gives rise to radical side chain loss from one of several particular amino acid side chains (e.g., leucine, asparagine, lysine, glutamine, and glutamic acid) to yield a Dha residue. The Dha residues facilitate preferential backbone cleavages to produce signature c- and z-ions, demonstrated with cations derived from melittin, mechano growth factor (MGF), and ubiquitin. The efficiencies for radical side chain loss and for subsequent generation of specific c- and z-ions have been examined as functions of precursor ion charge state and activation conditions using cations of ubiquitin as a model for a small protein. It is noted that these efficiencies are not strongly dependent on ion trap collisional activation conditions but are sensitive to precursor ion charge state. Moderate to low charge states show the greatest overall yields for the specific Dha cleavages, whereas small molecule losses (e.g., water/ammonia) dominate at the lowest charge states and proton catalyzed amide bond cleavages that give rise to b- and y-ions tend to dominate at high charge states. [Figure not available: see fulltext.

Degradation chemistry of gemcitabine hydrochloride, a new antitumor agent.

PubMed

Anliker, S L; McClure, M S; Britton, T C; Stephan, E A; Maple, S R; Cooke, G G

1994-05-01

The anti-tumor agent gemcitabine hydrochloride, a beta-difluoronucleoside, is remarkably stable in the solid state. In 0.1 N HCI solution at 40 degrees C, deamination of gemcitabine occurs, yielding its uridine analogue. Approximately 86% of the initial gemcitabine remains after 4 weeks under these conditions. Cleavage of the N-glycosidic bond of gemcitabine or conversion to its alpha-anomer in 0.1 N HCI solution is not observed over a 4-week period. However, this work has shown that gemcitabine hydrochloride anomerizes in 0.1 N NaOH at 40 degrees C. Approximately 72% of the initial gemcitabine remains after 4 weeks under the basic conditions used. Uridine hydrolysis products are also formed under these conditions. The anormerization reaction, which is unusual under basic conditions, has been confirmed by characterization of the chromatographically isolated alpha-anomer by NMR and mass spectrometry. A mechanism involving an acyclic intermediate is proposed.

Diagnostic cyclisation reactions which follow phosphate transfer to carboxylate anion centres for energised [M-H]- anions of pTyr-containing peptides.

PubMed

Tran, T T Nha; Wang, Tianfang; Hack, Sandra; Bowie, John H

2011-09-15

The low-energy negative ion phosphoTyr to C-terminal -CO(2)PO(3)H(2) rearrangement occurs for energised peptide [M-H](-) anions even when there are seven amino acid residues between the pTyr and C-terminal amino acid residues. The rearranged C-terminal -CO(2)PO(2)H(O(-)) group effects characteristic S(N)i cyclisation/cleavage reactions. The most pronounced of these involves the electrophilic central backbone carbon of the penultimate amino acid residue. This reaction is aided by the intermediacy of an H-bonded intermediate in which the nucleophilic and electrophilic reaction centres are held in proximity in order for the S(N)i cyclisation/cleavage to proceed. The ΔG(reaction) is +184 kJ mol(-1) with the barrier to the S(N)i transition state being +240 kJ mol(-1) at the HF/6-31 + G(d)//AM1 level of theory. A similar phosphate rearrangement from pTyr to side chain CO(2)(-) (of Asp or Glu) may also occur for energised peptide [M-H](-) anions. The reaction is favourable: ΔG(reaction) is -44 kJ mol(-1) with a maximum barrier of +21 kJ mol(-1) (to the initial transition state) when Asp and Tyr are adjacent. The rearranged species R(1)-Tyr-NHCH(CH(2)CO(2)PO(3)H(-))COR(2) (R(1)  = CHO; R(2)  = OCH(3)) may undergo an S(N)i six-centred cyclisation/cleavage reaction to form the product anion R(1)-Tyr(NH(-)). This process has a high energy requirement [ΔG(reaction)  = +224 kJ mol(-1), with the barrier to the S(N)i transition state being +299 kJ mol(-1)]. Copyright © 2011 John Wiley & Sons, Ltd.

Acid/base-regulated reversible electron transfer disproportionation of N–N linked bicarbazole and biacridine derivatives† †Electronic supplementary information (ESI) available: Experimental information, synthesis and characterization data, NMR spectra, solid state NMR data, X-ray data, ESR spectra, UV-Vis-NIR spectra, fluorescence spectra, kinetic experiments, theoretical calculations, Tables S1–S8, Scheme S1, Fig. S1–12, References. CCDC 1025063, 1038914, 1049677 and 1040722. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5sc00946d

PubMed Central

Pandit, Palash; Yamamoto, Koji; Nakamura, Toshikazu; Nishimura, Katsuyuki; Kurashige, Yuki; Yanai, Takeshi; Nakamura, Go; Masaoka, Shigeyuki; Furukawa, Ko; Yakiyama, Yumi; Kawano, Masaki

2015-01-01

Regulation of electron transfer on organic substances by external stimuli is a fundamental issue in science and technology, which affects organic materials, chemical synthesis, and biological metabolism. Nevertheless, acid/base-responsive organic materials that exhibit reversible electron transfer have not been well studied and developed, owing to the difficulty in inventing a mechanism to associate acid/base stimuli and electron transfer. We discovered a new phenomenon in which N–N linked bicarbazole (BC) and tetramethylbiacridine (TBA) derivatives undergo electron transfer disproportionation by acid stimulus, forming their stable radical cations and reduced species. The reaction occurs through a biradical intermediate generated by the acid-triggered N–N bond cleavage reaction of BC or TBA, which acts as a two electron acceptor to undergo electron transfer reactions with two equivalents of BC or TBA. In addition, in the case of TBA the disproportionation reaction is highly reversible through neutralization with NEt3, which recovers TBA through back electron transfer and N–N bond formation reactions. This highly reversible electron transfer reaction is possible due to the association between the acid stimulus and electron transfer via the acid-regulated N–N bond cleavage/formation reactions which provide an efficient switching mechanism, the ability of the organic molecules to act as multi-electron donors and acceptors, the extraordinary stability of the radical species, the highly selective reactivity, and the balance of the redox potentials. This discovery provides new design concepts for acid/base-regulated organic electron transfer systems, chemical reagents, or organic materials. PMID:29218181

A QM/MM study of the reaction mechanism of (R)-hydroxynitrile lyases from Arabidopsis thaliana (AtHNL).

PubMed

Zhu, Wenyou; Liu, Yongjun; Zhang, Rui

2015-01-01

Hydroxynitrile lyases (HNLs) catalyze the conversion of chiral cyanohydrins to hydrocyanic acid (HCN) and aldehyde or ketone. Hydroxynitrile lyase from Arabidopsis thaliana (AtHNL) is the first R-selective HNL enzyme containing an α/β-hydrolases fold. In this article, the catalytic mechanism of AtHNL was theoretically studied by using QM/MM approach based on the recently obtained crystal structure in 2012. Two computational models were constructed, and two possible reaction pathways were considered. In Path A, the calculation results indicate that the proton transfer from the hydroxyl group of cyanohydrin occurs firstly, and then the cleavage of C1-C2 bond and the rotation of the generated cyanide ion (CN(-)) follow, afterwards, CN(-) abstracts a proton from His236 via Ser81. The C1-C2 bond cleavage and the protonation of CN(-) correspond to comparable free energy barriers (12.1 vs. 12.2 kcal mol(-1)), suggesting that both of the two processes contribute a lot to rate-limiting. In Path B, the deprotonation of the hydroxyl group of cyanohydrin and the cleavage of C1-C2 bond take place in a concerted manner, which corresponds to the highest free energy barrier of 13.2 kcal mol(-1). The free energy barriers of Path A and B are very similar and basically agree well with the experimental value of HbHNL, a similar enzyme of AtHNL. Therefore, both of the two pathways are possible. In the reaction, the catalytic triad (His236, Ser81, and Asp208) acts as the general acid/base, and the generated CN(-) is stabilized by the hydroxyl group of Ser81 and the main-chain NH-groups of Ala13 and Phe82. © 2014 Wiley Periodicals, Inc.

Elucidation of the mechanism of N-demethylation catalyzed by cytochrome P450 monooxygenase is facilitated by exploiting nitrogen-15 heavy isotope effects.

PubMed

Kwiecień, Renata A; Molinié, Roland; Paneth, Piotr; Silvestre, Virginie; Lebreton, Jacques; Robins, Richard J

2011-06-01

(15)N heavy isotope effects are especially useful when detail is sought pertaining to the reaction mechanism for the cleavage of a C-N bond. Their potential in assisting to describe the mechanism of N-demethylation of tertiary amines by the action of cytochrome P450 monooxygenase has been investigated. As a working model for the first step, oxidation of the N-methyl group to N-methoxyl, tropine and a cytochrome P450 monooxygenase reaction centre composed of a truncated heme with sulfhydryl as the axial ligand were used. It is apparent that this first step of the reaction proceeds via a hydrogen atom transfer mechanism. Transition states for this step are described for both the high spin ((4)TS(H)) and low spin ((2)TS(H)) pathways in both gas and solvation states. Hence, overall normal secondary (15)N KIE could be calculated for the reaction path modeled in the low spin state, and inverse for the reaction modeled in the high spin state. This partial reaction has been identified as the probable rate limiting step. The model for the second step, fission of the C-N bond, consisted of N-methoxylnortropine and two molecules of water. A transition state described for this step, TS(CN), gives a strongly inverse overall theoretical (15)N KIE. Copyright © 2011 Elsevier Inc. All rights reserved.

Collision induced dissociation of protonated N-nitrosodimethylamine by ion trap mass spectrometry: Ultimate carcinogens in gas phase

NASA Astrophysics Data System (ADS)

Kulikova, Natalia; Baker, Michael; Gabryelski, Wojciech

2009-12-01

Collision induced dissociation of protonated N-nitrosodimethylamine (NDMA) and isotopically labeled N-nitrosodimethyl-d6-amine (NDMA-d6) was investigated by sequential ion trap mass spectrometry to establish mechanisms of gas phase reactions leading to intriguing products of this potent carcinogen. The fragmentation of (NDMA + H+) occurs via two dissociation pathways. In the alkylation pathway, homolytic cleavage of the N-O bond of N-dimethyl, N'-hydroxydiazenium ion generates N-dimethyldiazenium distonic ion which reacts further by a CH3 radical loss to form methanediazonium ion. Both methanediazonium ion and its precursor are involved in ion/molecule reactions. Methanediazonium ion showed to be capable of methylating water and methanol molecules in the gas phase of the ion trap and N-dimethyldiazenium distonic ion showed to abstract a hydrogen atom from a solvent molecule. In the denitrosation pathway, a tautomerization of N-dimethyl, N'-hydroxydiazenium ion to N-nitrosodimethylammonium intermediate ion results in radical cleavage of the N-N bond of the intermediate ion to form N-dimethylaminium radical cation which reacts further through [alpha]-cleavage to generate N-methylmethylenimmonium ion. Although the reactions of NDMA in the gas phase are different to those for enzymatic conversion of NDMA in biological systems, each activation method generates the same products. We will show that collision induced dissociation of N-nitrosodiethylamine (NDEA) and N-nitrosodipropylamine (NDPA) is also a feasible approach to gain information on formation, stability, and reactivity of alkylating agents originating from NDEA and NDPA. Investigating such biologically relevant, but highly reactive intermediates in the condensed phase is hampered by the short life-times of these transient species.

Affinity cleavage at the putative metal-binding site of pigeon liver malic enzyme by the Fe(2+)-ascorbate system.

PubMed

Wei, C H; Chou, W Y; Huang, S M; Lin, C C; Chang, G G

1994-06-28

Pigeon liver malic enzyme was rapidly inactivated by micromolar concentrations of ferrous sulfate in the presence of ascorbate at neutral pH and 0 or 25 degrees C. Omitting the ascorbate or replacing the ferrous ion with manganese ion did not lead to any inactivation. Manganese, magnesium, zinc, cobalt, or calcium ion at 200 molar excess over ferrous ion offered complete protection of the enzyme from Fe(2+)-induced inactivation. Ni2+ provided partial protection, while Ba2+ or imidazole was ineffective in protection. Addition of 4 mM Mn2+ or 5 mM EDTA into a partially modified enzyme stopped further inactivation of the enzyme. Inclusion of substrates (L-malate or NADP+, singly or in combination) in the incubation mixture did not affect the inactivation rate. The enzyme inactivation was demonstrated to be followed by protein cleavage. Native pigeon liver malic enzyme had a subunit M(r) of 65,000. The inactivated enzyme with residual activity of only 0.3% was cleaved into two fragments with M(r) of 31,000 and 34,000, respectively. The cleavage site was identified as the peptide bond between Asp258 and Ile259. Native pigeon liver malic enzyme was blocked at the N-terminus. Cleavage at the putative metal-binding site exposed a new N-terminus, which was identified to be at the 34-kDa fragment containing the C-terminal half of original sequence 259-557. Our results indicated that Fe2+ catalyzed a specific oxidation of pigeon liver malic enzyme at Asp258 and/or some other essential amino acid residues that caused enzyme inactivation. The modified enzyme was then affinity cleaved at the Mn(2+)-binding site.

Ab Initio energetics of SiO bond cleavage.

PubMed

Hühn, Carolin; Erlebach, Andreas; Mey, Dorothea; Wondraczek, Lothar; Sierka, Marek

2017-10-15

A multilevel approach that combines high-level ab initio quantum chemical methods applied to a molecular model of a single, strain-free SiOSi bridge has been used to derive accurate energetics for SiO bond cleavage. The calculated SiO bond dissociation energy and the activation energy for water-assisted SiO bond cleavage of 624 and 163 kJ mol -1 , respectively, are in excellent agreement with values derived recently from experimental data. In addition, the activation energy for H 2 O-assisted SiO bond cleavage is found virtually independent of the amount of water molecules in the vicinity of the reaction site. The estimated reaction energy for this process including zero-point vibrational contribution is in the range of -5 to 19 kJ mol -1 . © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Molecular Basis of C–N Bond Cleavage by the Glycyl Radical Enzyme Choline Trimethylamine-Lyase

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

Bodea, Smaranda; Funk, Michael A.; Balskus, Emily P.

We report that deamination of choline catalyzed by the glycyl radical enzyme choline trimethylamine-lyase (CutC) has emerged as an important route for the production of trimethylamine, a microbial metabolite associated with both human disease and biological methane production. Here, we have determined five high-resolution X-ray structures of wild-type CutC and mechanistically informative mutants in the presence of choline. Within an unexpectedly polar active site, CutC orients choline through hydrogen bonding with a putative general base, and through close interactions between phenolic and carboxylate oxygen atoms of the protein scaffold and the polarized methyl groups of the trimethylammonium moiety. These structuralmore » data, along with biochemical analysis of active site mutants, support a mechanism that involves direct elimination of trimethylamine. Lastly, this work broadens our understanding of radical-based enzyme catalysis and will aid in the rational design of inhibitors of bacterial trimethylamine production.« less

Spectroscopy and formation of lanthanum-hydrocarbon radicals formed by association and carbon-carbon bond cleavage of isoprene

NASA Astrophysics Data System (ADS)

Cao, Wenjin; Hewage, Dilrukshi; Yang, Dong-Sheng

2018-05-01

La atom reaction with isoprene is carried out in a laser-vaporization molecular beam source. The reaction yields an adduct as the major product and C—C cleaved and dehydrogenated species as the minor ones. La(C5H8), La(C2H2), and La(C3H4) are characterized with mass-analyzed threshold ionization (MATI) spectroscopy and quantum chemical computations. The MATI spectra of all three species exhibit a strong origin band and several weak vibronic bands corresponding to La-ligand stretch and ligand-based bend excitations. La(C5H8) is a five-membered metallacycle, whereas La(C2H2) and La(C3H4) are three-membered rings. All three metallacycles prefer a doublet ground state with a La 6s1-based valence electron configuration and a singlet ion. The five-membered metallacycle is formed through La addition and isoprene isomerization, whereas the two three-membered rings are produced by La addition and insertion, hydrogen migration, and carbon-carbon bond cleavage.

Mechanisms of selective cleavage of C–O bonds in di-aryl ethers in aqueous phase

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

He, Jiayue; Zhao, Chen; Mei, Donghai

2014-01-01

A novel route for cleaving the C-O aryl ether bonds of p-substituted H-, CH 3-, and OH- diphenyl ethers has been explored over Ni/SiO 2 catalysts at very mild conditions. The C-O bond of diphenyl ether is cleaved by parallel hydrogenolysis and hydrolysis (hydrogenolysis combined with HO* addition) on Ni. The rates as a function of H 2 pressure from 0 to 10 MPa indicate that the rate-determining step is the C-O bond cleavage on Ni. H* atoms compete with the organic reactant for adsorption leading to a maximum in the rate with increasing H 2 pressure. In contrast tomore » diphenyl ether, hydrogenolysis is the exclusive route for cleaving an ether C-O bond of di-p-tolyl ether to form p-cresol and toluene. 4,4'-dihydroxydiphenyl ether undergoes sequential surface hydrogenolysis, first to phenol and HOC 6H 4O* (adsorbed), which is then cleaved to phenol (C 6H 5O* with added H*) and H 2O (O* with two added H*) in a second step. Density function theory supports the operation of this pathway. Notably, addition of H* to HOC 6H 4O* is less favorable than a further hydrogenolytic C-O bond cleavage. The TOFs of three aryl ethers with Ni/SiO 2 in water followed the order 4,4'-dihydroxydiphenyl ether (69 h -1) > diphenyl ether (26 h -1) > di-p-tolyl ether (1.3 h -1), in line with the increasing apparent activation energies, ranging from 93 kJ∙mol -1 (4,4'-dihydroxydiphenyl ether) < diphenyl ether (98 kJ∙mol -1) to di-p-tolyl ether (105 kJ∙mol -1). D.M. thanks the support from the US Department of Energy, Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences & Biosciences. Pacific Northwest National Laboratory (PNNL) is a multiprogram national laboratory operated for DOE by Battelle. Computing time was granted by the grand challenge of computational catalysis of the William R. Wiley Environmental Molecular Sciences Laboratory (EMSL) and by the National Energy Research Scientific Computing Center (NERSC). EMSL is a national scientific user facility located at Pacific Northwest National Laboratory (PNNL) and sponsored by DOE’s Office of Biological and Environmental Research.« less

Active site remodeling during the catalytic cycle in metal-dependent fructose-1,6-bisphosphate aldolases.

PubMed

Jacques, Benoit; Coinçon, Mathieu; Sygusch, Jurgen

2018-03-28

Crystal structures of two bacterial metal (Zn) dependent D-fructose 1,6-bisphosphate (FBP) aldolases in complex with substrate, analogues, and triose-P reaction products were determined to 1.5-2.0 Å resolution. The ligand complexes cryotrapped in native or mutant H. pylori aldolase crystals enabled a novel mechanistic description of FBP C 3 -C 4 bond cleavage. The reaction mechanism uses active site remodelling during the catalytic cycle implicating relocation of the Zn cofactor that is mediated by conformational changes of active site loops. Substrate binding initiates conformational changes, triggered upon P 1 -phosphate binding, which liberates the Zn chelating His180, allowing it to act as a general base for the proton abstraction at the FBP C 4 -hydroxyl group. A second zinc chelating His83 hydrogen bonds the substrate C 4 - hydroxyl group and assists cleavage by stabilizing the developing negative charge during proton abstraction. Cleavage is concerted with relocation of the metal cofactor from an interior to a surface exposed site, thereby stabilizing the nascent enediolate form. Conserved residue Glu142 is essential for protonation of the enediolate form, prior to product release. A D-tagatose 1,6-bisphosphate enzymatic complex reveals how His180 mediated proton abstraction controls stereospecificity of the cleavage reaction. Recognition and discrimination of the reaction products, dihydroxyacetone-P and D-glyceraldehyde-3-P, occurs via charged hydrogen bonds between hydroxyl groups of the triose-Ps and conserved residues, Asp82 and Asp255, respectively, and are crucial aspects of the enzyme's role in gluconeogenesis. Conformational changes in mobile loops β5-α7 and β6-α8 (containing catalytic residues Glu142 and His180, respectively) drive active site remodelling enabling the relocation of the metal cofactor. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

Initial decomposition of the condensed-phase β-HMX under shock waves: molecular dynamics simulations.

PubMed

Ge, Ni-Na; Wei, Yong-Kai; Ji, Guang-Fu; Chen, Xiang-Rong; Zhao, Feng; Wei, Dong-Qing

2012-11-26

We have performed quantum-based multiscale simulations to study the initial chemical processes of condensed-phase octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) under shock wave loading. A self-consistent charge density-functional tight-binding (SCC-DFTB) method was employed. The results show that the initial decomposition of shocked HMX is triggered by the N-NO(2) bond breaking under the low velocity impact (8 km/s). As the shock velocity increases (11 km/s), the homolytic cleavage of the N-NO(2) bond is suppressed under high pressure, the C-H bond dissociation becomes the primary pathway for HMX decomposition in its early stages. It is accompanied by a five-membered ring formation and hydrogen transfer from the CH(2) group to the -NO(2) group. Our simulations suggest that the initial chemical processes of shocked HMX are dependent on the impact velocity, which gain new insights into the initial decomposition mechanism of HMX upon shock loading at the atomistic level, and have important implications for understanding and development of energetic materials.

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

Zhao, D.; Ladipo, F.T.; Braddock-Wilking, J.

Low temperature crystal structures of (DABCO)H{sup +}Co(CO){sub 4}{sup -} (1) and (DABCO)H{sup +}Co(CO){sub 3}PPh{sub 3}{sup -} (2) (DABCO = 1,4-diazabicyclooctane) indicate that both salts exhibit N-H...Co hydrogen bonding. IR and NMR data indicate that these hydrogen bonded species persist in nonpolar solvents such as toluene, but exist as solvent separated ions in more polar solvents. Replacement of the axial CO ligand by PPh{sub 3} leads to a shortening of the N...Co separation in the solid state from 3.437(3) to 3.294(6) A. This change is accompanied by an increase in the angle between the equatorial carbonyl ligands. Thus, the crystallographic resultsmore » suggest a strengthening of the N-H...Co hydrogen bond upon increasing the basicity of the metal center, the first observation of this type in the solid state. This assertion is supported by variable-temperature {sup 1}H and {sup 13}C NMR data in toluene-d{sub 8} solution which, discussed in the light of ab initio calculations, indicate that the barrier to a fluxional process involving cleavage of the N-H...Co hydrogen bond is greater in 2 than in 1. The crystal structures of 1 and 2 have been determined by X-ray diffraction at 135(5) and 123(5) K, respectively. 19 refs., 2 figs., 5 tabs.« less

Copper-induced ammonia N-H functionalization.

PubMed

Álvarez, María; Álvarez, Eleuterio; Fructos, Manuel R; Urbano, Juan; Pérez, Pedro J

2016-10-07

The activation of ammonia has been achieved with the aid of the Tp(Ms)Cu core (Tp(Ms) = hydrotris(3-mesityl-pyrazolyl)borate). Complexes of the general composition Tp(Ms)Cu(amine) (1-4) including the ammonia adduct Tp(Ms)Cu(NH3) (1) have been synthesized and fully spectroscopical- and structurally characterized. Coordinated ammonia in 1 has been reacted with Ph3CPF6 yielding Tp(Ms)Cu(NH2CPh3) (5) as a result of N-H cleavage and N-C bond formation. In a parallel manner the catalytic functionalization of ammonia with ethyl diazoacetate leading to glycinate derivatives has been developed with Tp(Ms)Cu(THF) as the catalyst, in the first example of this transformation with ammonia and a copper-based system.

Truncated cystatin C in cerebrospiral fluid: Technical [corrected] artefact or biological process?

PubMed

Carrette, Odile; Burkhard, Pierre R; Hughes, Severine; Hochstrasser, Denis F; Sanchez, Jean-Charles

2005-08-01

Cystatin C, a low molecular weight cysteine proteinase inhibitor present in human body fluids at physiological concentrations, is more expressed in cerebrospinal fluid (CSF) than in plasma. Mass spectrometric characterization showed that after 3 months of storage of human CSF at -20 degrees C, cystatin C was cleaved in the peptide bond between R8 and L9 and lost its eight N-termini amino acids, whereas this cleavage did not occur when stored at -80 degrees C. This truncation occurred in all CSF samples studied irrespective of the underlying neurological status, indicating a storage-related artefact rather than a physiological or pathological processing of the protein. These results stress the importance of optimal preanalytical storage conditions of any sample prior to proteomics studies.

Photodegradation of Polyfluorinated Dibenzo-p-Dioxins in Organic Solvents: Experimental and Theoretical Studies.

PubMed

Zeng, Xiaolan; Qu, Ruijuan; Feng, Mingbao; Chen, Jing; Wang, Liansheng; Wang, Zunyao

2016-08-02

Eighteen polyfluorinated dibenzo-p-dioxins (PFDDs) were synthesized by pyrolysis of fluorophenols. Using a 500 W Xe lamp as the light source, the PFDDs photodegradation kinetics in n-hexane were investigated. The photolysis reactions obeyed the pseudo-first-order rate equation, and higher fluorinated PFDDs tended to photolyze more slowly. Theoretically calculated parameters reflecting the molecular structural properties were used to develop a new model of PFDDs photolysis rates. The results indicated that the substitution pattern for fluorine atoms and the C-O bond length were major factors in the photolysis of PFDDs. We selected octafluorinated dibenzo-p-dioxin (OFDD) as a representative PFDDs to explore the influence of solvent on the photolysis rate of PFDDs, and the results indicated that neither the polarity nor donor hydrogen of organic solvents are independent influencing factors. Mechanistic pathways for the photolysis of OFDD in n-hexane were first studied. The results indicated that photodegradation of OFDD produces octafluorinated dihydroxybiphenyls, octafluorinated phenoxyphenols, and fluorinated phenols. The major pathway for photodegradation of OFDD was C-O bond cleavage. Defluorination reactions did not occur during the photolysis process.

Structural Determinants of Autoproteolysis of the Haemophilus influenzae Hap Autotransporter▿

PubMed Central

Kenjale, Roma; Meng, Guoyu; Fink, Doran L.; Juehne, Twyla; Ohashi, Tomoo; Erickson, Harold P.; Waksman, Gabriel; St. Geme, Joseph W.

2009-01-01

Haemophilus influenzae is a gram-negative bacterium that initiates infection by colonizing the upper respiratory tract. The H. influenzae Hap autotransporter protein mediates adherence, invasion, and microcolony formation in assays with respiratory epithelial cells and presumably facilitates colonization. The serine protease activity of Hap is associated with autoproteolytic cleavage and extracellular release of the HapS passenger domain, leaving the Hapβ C-terminal domain embedded in the outer membrane. Cleavage occurs most efficiently at the LN1036-37 peptide bond and to a lesser extent at three other sites. In this study, we utilized site-directed mutagenesis, homology modeling, and assays with a peptide library to characterize the structural determinants of Hap proteolytic activity and cleavage specificity. In addition, we used homology modeling to predict the S1, S2, and S4 subsite residues of the Hap substrate groove. Our results indicate that the P1 and P2 positions at the Hap cleavage sites are critical for cleavage, with leucine preferred over larger hydrophobic residues or other amino acids in these positions. The substrate groove is formed by L263 and N274 at the S1 subsite, R264 at the S2 subsite, and E265 at the S4 subsite. This information may facilitate design of approaches to block Hap activity and interfere with H. influenzae colonization. PMID:19687208

Novel Functional Complexity of Polycystin-1 by GPS Cleavage In Vivo: Role in Polycystic Kidney Disease

PubMed Central

Kurbegovic, Almira; Kim, Hyunho; Xu, Hangxue; Yu, Shengqiang; Cruanès, Julie; Maser, Robin L.; Boletta, Alessandra; Trudel, Marie

2014-01-01

Polycystin-1 (Pc1) cleavage at the G protein-coupled receptor (GPCR) proteolytic site (GPS) is required for normal kidney morphology in humans and mice. We found a complex pattern of endogenous Pc1 forms by GPS cleavage. GPS cleavage generates not only the heterodimeric cleaved full-length Pc1 (Pc1cFL) in which the N-terminal fragment (NTF) remains noncovalently associated with the C-terminal fragment (CTF) but also a novel (Pc1) form (Pc1deN) in which NTF becomes detached from CTF. Uncleaved Pc1 (Pc1U) resides primarily in the endoplasmic reticulum (ER), whereas both Pc1cFL and Pc1deN traffic through the secretory pathway in vivo. GPS cleavage is not a prerequisite, however, for Pc1 trafficking in vivo. Importantly, Pc1deN is predominantly found at the plasma membrane of renal epithelial cells. By functional genetic complementation with five Pkd1 mouse models, we discovered that CTF plays a crucial role in Pc1deN trafficking. Our studies support GPS cleavage as a critical regulatory mechanism of Pc1 biogenesis and trafficking for proper kidney development and homeostasis. PMID:24958103

Partial De Novo Sequencing and Unusual CID Fragmentation of a 7 kDa, Disulfide-Bridged Toxin

NASA Astrophysics Data System (ADS)

Medzihradszky, Katalin F.; Bohlen, Christopher J.

2012-05-01

A 7 kDa toxin isolated from the venom of the Texas coral snake ( Micrurus tener tener) was subjected to collision-induced dissociation (CID) and electron-transfer dissociation (ETD) analyses both before and after reduction at low pH. Manual and automated approaches to de novo sequencing are compared in detail. Manual de novo sequencing utilizing the combination of high accuracy CID and ETD data and an acid-related cleavage yielded the N-terminal half of the sequence from the reduced species. The intact polypeptide, containing 3 disulfide bridges produced a series of unusual fragments in ion trap CID experiments: abundant internal amino acid losses were detected, and also one of the disulfide-linkage positions could be determined from fragments formed by the cleavage of two bonds. In addition, internal and c-type fragments were also observed.

Tertiary to secondary reduction of aminomethylphosphane derived from 1-ethylpiperazine as a result of its coordination to ruthenium(II) centre - The first insight into the nature of process

NASA Astrophysics Data System (ADS)

Płotek, Michał; Starosta, Radosław; Komarnicka, Urszula K.; Skórska-Stania, Agnieszka; Kołoczek, Przemysław; Dudek, Karol; Kyzioł, Agnieszka

2016-10-01

Introduction of tertiary aminomethylphosphane P{CH2N(CH2CH2)2NCH2CH3}3 (B; tris{1-[4-ethyl(tetrahydro-1,4-diazino)]methyl}phosphane) to methanolic solution of [Ru(η5-C5H5)Cl(PPh3)2] (1) and NaBF4, instead of straightforward substitution of the chloride leads to concomitant cleavage of aminomethylphosphane's Psbnd CH2 bond. The obtained complex [Ru(η5-C5H5)PH{CH2N(CH2CH2)2NCH2CH3}2(PPh3)2]BF4 (2B‧) was fully characterized by spectroscopic methods ((NMR, IR, ESI-MS) and its solid state structure was determined with single crystal X-ray diffraction method. It was proven that the structure of 2B‧ is similar to the previously synthesized morpholine counterpart [Ru(η5-C5H5)PH{CH2N(CH2CH2)2O}2(PPh3)2]BF4 (2A‧). DFT calculations (B3LYP with the D95V(d,p) basis set for C, N, H and O and LanL2DZ with Los Alamos ECPs for Ru, P and Cl) revealed that the binding of aminomethylphosphanes to the ruthenium centre leads to the Psbnd C bonds elongation, which may finally result in breaking one of them and phosphane's reduction from tertiary to secondary ones.

Catalytic routes and oxidation mechanisms in photoreforming of polyols

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

Sanwald, Kai E.; Berto, Tobias F.; Eisenreich, Wolfgang

2016-12-01

Photocatalytic reforming of biomass-derived oxygenates leads to H 2 generation and evolution of CO 2 via parallel formation of organic intermediates through anodic oxidations on a Rh/TiO 2 photocatalyst. The reaction pathways and kinetics in the photoreforming of C 3–C 6 polyols were explored. Polyols are converted via direct and indirect hole transfer pathways resulting in (i) oxidative rupture of C–C bonds, (ii) oxidation to a-oxygen functionalized aldoses and ketoses (carbonyl group formation) and (iii) light-driven dehydration. Direct hole transfer to chemisorbed oxygenates on terminal Ti(IV)-OH groups, generating alkoxy-radicals that undergo ß-C–C-cleavage, is proposed for the oxidative C–C rupture. Carbonylmore » group formation and dehydration are attributed to indirect hole transfer at surface lattice oxygen sites [Ti_ _ _O_ _ _Ti] followed by the generation of carbon-centered radicals. Polyol chain length impacts the contribution of the oxidation mechanisms favoring the C–C bond cleavage (internal preferred over terminal) as the dominant pathway with higher polyol carbon number.« less

An enantioselective route to alpha-methyl carboxylic acids via metal and enzyme catalysis.

PubMed

Norinder, Jakob; Bogár, Krisztián; Kanupp, Lisa; Bäckvall, Jan-E

2007-11-22

Dynamic kinetic resolution of allylic alcohols to allylic acetates followed by copper-catalyzed allylic substitution gave alkenes in high yields and high optical purity. Subsequent oxidative C-C double bond cleavage afforded pharmaceutically important alpha-methyl substituted carboxylic acids in high ee.

Imidazoline ring cleavage in 1,3,6,10-tetraazatetracyclo-(7. 3. 1. 0/sup 2,7/. 0/sup 6,13/)trideca-4,11-dienes, leading to the formation of diquinoxalino(1,2-. cap alpha. :2',3'-d)pyrrole derivatives

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

Charushin, V.N.; Petrova, G.M.; Aleksandrov, G.G.

1987-10-01

Dibenzo(d,k)-1,3,6,10-tetraazatetracyclo(7.3.1.0/sup 2,7/.0/sup 6,13/) trideca-4,11-dienes undergo addition reactions at the C/sub (2)/ carbon atom with alcohols and thiols, accompanied by cleavage of the C-N bond of the imidazoline ring, to generate diquinoxalino(1,2-..cap alpha..:2',3'-d)pyrrole derivatives. /sup 1/H NMR spectra were recorded on Perkin-Elmer R 12B (60 MHz) and Bruker WH-90 spectrometer for CDCl/sub 3/ solutions at 40/sup 0/C and with TMS as internal standard. /sup 13/C NMR spectra were obtained on a Bruker WH-90 (22.62 MHz) spectrometer. /sup 13/C chemical shifts were measured relative to solvent signals (deltaCDCl/sub 3/ 77.0 ppm). /sup 13/C NMR spectra of compounds IIa and g were takenmore » using full spin-spin carbon-proton decoupling. In order to measure SSCC the spectrum was recorded both with proton coupling and also with selective decoupling of individual protons and their attached /sup 13/C carbon nuclei.« less

Structural And Biochemical Studies of Botulinum Neurotoxin Serotype C1 Light Chain Protease: Implications for Dual Substrate Specificity

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

Jin, R.; Sikorra, S.; Stegmann, C.M.

2009-06-01

Clostridial neurotoxins are the causative agents of the neuroparalytic disease botulism and tetanus. They block neurotransmitter release through specific proteolysis of one of the three soluble N-ethylmaleimide-sensitive-factor attachment protein receptors (SNAREs) SNAP-25, syntaxin, and synaptobrevin, which constitute part of the synaptic vesicle fusion machinery. The catalytic component of the clostridial neurotoxins is their light chain (LC), a Zn2+ endopeptidase. There are seven structurally and functionally related botulinum neurotoxins (BoNTs), termed serotype A to G, and tetanus neurotoxin (TeNT). Each of them exhibits unique specificity for their target SNAREs and peptide bond(s) they cleave. The mechanisms of action for substrate recognitionmore » and target cleavage are largely unknown. Here, we report structural and biochemical studies of BoNT/C1-LC, which is unique among BoNTs in that it exhibits dual specificity toward both syntaxin and SNAP-25. A distinct pocket (S1') near the active site likely achieves the correct register for the cleavage site by only allowing Ala as the P1' residue for both SNAP-25 and syntaxin. Mutations of this SNAP-25 residue dramatically reduce enzymatic activity. The remote a-exosite that was previously identified in the complex of BoNT/A-LC and SNAP-25 is structurally conserved in BoNT/C1. However, mutagenesis experiments show that the a-exosite of BoNT/C1 plays a less stringent role in substrate discrimination in comparison to that of BoNT/A, which could account for its dual substrate specificity.« less

Assignment of the Stereochemistry and Anomeric Configuration of Sugars within Oligosaccharides Via Overlapping Disaccharide Ladders Using MSn

NASA Astrophysics Data System (ADS)

Konda, Chiharu; Londry, Frank A.; Bendiak, Brad; Xia, Yu

2014-08-01

A systematic approach is described that can pinpoint the stereo-structures (sugar identity, anomeric configuration, and location) of individual sugar units within linear oligosaccharides. Using a highly modified mass spectrometer, dissociation of linear oligosaccharides in the gas phase was optimized along multiple-stage tandem dissociation pathways (MSn, n = 4 or 5). The instrument was a hybrid triple quadrupole/linear ion trap mass spectrometer capable of high-efficiency bidirectional ion transfer between quadrupole arrays. Different types of collision-induced dissociation (CID), either on-resonance ion trap or beam-type CID could be utilized at any given stage of dissociation, enabling either glycosidic bond cleavages or cross-ring cleavages to be maximized when wanted. The approach first involves optimizing the isolation of disaccharide units as an ordered set of overlapping substructures via glycosidic bond cleavages during early stages of MSn, with explicit intent to minimize cross-ring cleavages. Subsequently, cross-ring cleavages were optimized for individual disaccharides to yield key diagnostic product ions ( m/ z 221). Finally, fingerprint patterns that establish stereochemistry and anomeric configuration were obtained from the diagnostic ions via CID. Model linear oligosaccharides were derivatized at the reducing end, allowing overlapping ladders of disaccharides to be isolated from MSn. High confidence stereo-structural determination was achieved by matching MSn CID of the diagnostic ions to synthetic standards via a spectral matching algorithm. Using this MSn ( n = 4 or 5) approach, the stereo-structures, anomeric configurations, and locations of three individual sugar units within two pentasaccharides were successfully determined.

Molecular electrocatalysts for oxidation of hydrogen using earth-abundant metals: shoving protons around with proton relays.

PubMed

Bullock, R Morris; Helm, Monte L

2015-07-21

Sustainable, carbon-neutral energy is needed to supplant the worldwide reliance on fossil fuels in order to address the persistent problem of increasing emissions of CO2. Solar and wind energy are intermittent, highlighting the need to develop energy storage on a huge scale. Electrocatalysts provide a way to convert between electrical energy generated by renewable energy sources and chemical energy in the form of chemical bonds. Oxidation of hydrogen to give two electrons and two protons is carried out in fuel cells, but the typical catalyst is platinum, a precious metal of low earth abundance and high cost. In nature, hydrogenases based on iron or iron/nickel reversibly oxidize hydrogen with remarkable efficiencies and rates. Functional models of these enzymes have been synthesized with the goal of achieving electrocatalytic H2 oxidation using inexpensive, earth-abundant metals along with a key feature identified in the [FeFe]-hydrogenase: an amine base positioned near the metal. The diphosphine ligands P(R)2N(R')2 (1,5-diaza-3,7-diphosphacyclooctane with alkyl or aryl groups on the P and N atoms) are used as ligands in Ni, Fe, and Mn complexes. The pendant amines facilitate binding and heterolytic cleavage of H2, placing the hydride on the metal and the proton on the amine. The pendant amines also serve as proton relays, accelerating intramolecular and intermolecular proton transfers. Electrochemical oxidations and deprotonations by an exogeneous amine base lead to catalytic cycles for oxidation of H2 (1 atm) at room temperature for catalysts derived from [Ni(P(Cy)2N(R')2)2](2+), Cp(C6F5)Fe(P(tBu)2N(Bn)2)H, and MnH(P(Ph)2N(Bn)2)(bppm)(CO) [bppm = (PAr(F)2)2CH2]. In the oxidation of H2 catalyzed by [Ni(P(Cy)2N(R')2)2](2+), the initial product observed experimentally is a Ni(0) complex in which two of the pendant amines are protonated. Two different pathways can occur from this intermediate; deprotonation followed by oxidation occurs with a lower overpotential than the alternate pathway involving oxidation followed by deprotonation. The Mn cation [Mn(P(Ph)2N(Bn)2)(bppm)(CO)](+) mediates the rapid (>10(4) s(-1) at -95 °C), reversible heterolytic cleavage of H2. Obtaining the optimal benefit of pendant amines incorporated into the ligand requires that the pendant amine be properly positioned to interact with a M-H or M(H2) bond. In addition, ligands are ideally selected such that the hydride-acceptor ability of the metal and the basicity of a pendant are tuned to give low barriers for heterolytic cleavage of the H-H bond and subsequent proton transfer reactions. Using these principles allows the rational design of electrocatalysts for H2 oxidation using earth-abundant metals.

Increasing the Aromatic Selectivity of Quinoline Hydrogenolysis Using Pd/MO x–Al 2O 3

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

Bachrach, Mark; Morlanes-Sanchez, Natalia; Canlas, Christian P.

2014-09-11

Catalysts consisting of Pd nanoparticles supported on highly dispersed TiO x–Al 2O 3, TaO x–Al 2O 3, and MoO x–Al 2O 3 are studied for catalytic quinoline hydrogenation and selective C–N bond cleavage at 275 °C and 20 bar H 2. Lastly, the Pd/MO x–Al 2O 3 materials exhibit significantly greater aromatic product selectivity and thus 10–15 % less required H 2 for a given level of denitrogenation relative to an unmodified Pd/Al 2O 3 catalyst.

Kinetic Control in the Cleavage of Unsymmetrical Disilanes.

PubMed

Hevesi, Làszlò; Dehon, Michael; Crutzen, Raphael; Lazarescu-Grigore, Adriana

1997-04-04

A series of 12 phenyl-substituted arylpentamethyldisilanes 1a-l have been synthesized in order to examine the regioselectivity of their nucleophilic Si,Si bond cleavage reactions under Still's conditions (MeLi/HMPA/0 degrees C). It has been found that the sensitivity of these reactions to the electronic effects of the substituents in the phenyl ring could be described by the Hammett-type equation log(k(A)/k(B)) = 0.4334 + 2.421(Sigmasigma); (correlation coefficient R = 0.983). The k(A)/k(B) ratio represents the relative rate of attack at silicon atom A (linked to the aryl ring) or at silicon atom B (away from the aryl ring) of the unsymmetrical disilanes. Thus, the present investigation shows that the earlier belief according to which the nucleophilic cleavage of unsymmetrical disilanes always produces the more stable silyl anionic species (thermodynamic control) should be abandoned, or at least seriously amended: kinetic factors appear to exert a primary influence on the regioselectivity of such reactions. Since the two major kinetic factors (i.e., electrophilic character of and steric hindrance at a given silicon atom) have opposite effects on the orientation of the reaction, it may happen that kinetic and thermodynamic control lead to the same result. For some of the unsymmetrical disilanes studied, the major reaction path was not the Si,Si bond cleavage; instead, Si-aryl bond breaking occurred, producing the corresponding aryl anions.

Blackbody infrared radiative dissociation of oligonucleotide anions.

PubMed

Klassen, J S; Schnier, P D; Williams, E R

1998-11-01

The dissociation kinetics of a series of doubly deprotonated oligonucleotide 7-mers [d(A)7(2-), d(AATTAAT)2-, d(TTAATTA)2-, and d(CCGGCCG)2-] were measured using blackbody infrared radiative dissociation in a Fourier-transform mass spectrometer. The oligonucleotides dissociate first by cleavage at the glycosidic bond leading to the loss of a neutral nucleobase, followed by cleavage at the adjacent (5') phosphodiester bond to produce structurally informative a-base and w type ions. From the temperature dependence of the unimolecular dissociation rate constants, Arrhenius activation parameters in the zero-pressure limit are obtained for the loss of base. The measured Arrhenius parameters are dependent on the identity of the nucleobase. The process involving the loss of an adenine base from the dianions, d(A)7(2-), d(AATTAAT)2-, and d(TTAATTA)2- has an average activation energy (Ea) of approximately 1.0 eV and a preexponential factor (A) of 10(10) s-1. Both guanine and cytosine base loss occurs for d(CCGGCCG)2-. The average Arrhenius parameters for the loss of cytosine and guanine are Ea = 1.32 +/- 0.03 eV and A = 10(13.3 +/- 0.3) s-1. No loss of thymine was observed for mixed adenine-thymine oligonucleotides. Neither base loss nor any other fragmentation reactions occur for d(T)7(2-) over a 600 s reaction delay at 207 degrees C, a temperature close to the upper limit accessible with our instrument. The Arrhenius parameters indicate that the preferred cleavage sites for mixed oligonucleotides of similar mass-to-charge ratio will be strongly dependent on the internal energy of the precursor ions. At low internal energies (effective temperatures below 475 K), loss of adenine and subsequent cleavage of the adjacent phosphoester bonds will dominate, whereas at higher energies, preferential cleavage at C and G residues will occur. The magnitude of the A factors < or = 10(13) s-1 measured for the loss of the three nucleobases (A, G, and C) is indicative of an entropically neutral or disfavored process as the rate limiting step for this reaction.

Blackbody Infrared Radiative Dissociation of Oligonucleotide Anions

PubMed Central

Klassen, John S.; Schnier, Paul D.; Williams, Evan R.

2005-01-01

The dissociation kinetics of a series of doubly deprotonated oligonucleotide 7-mers [ d(A)72-, d(AATTAAT)2−, d(TTAATTA)2−, and d(CCGGCCG)2−] were measured using blackbody infrared radiative dissociation in a Fourier-transform mass spectrometer. The oligonucleotides dissociate first by cleavage at the glycosidic bond leading to the loss of a neutral nucleobase, followed by cleavage at the adjacent (5′) phosphodiester bond to produce structurally informative a-base and w type ions. From the temperature dependence of the unimolecular dissociation rate constants, Arrhenius activation parameters in the zero-pressure limit are obtained for the loss of base. The measured Arrhenius parameters are dependent on the identity of the nucleobase. The process involving the loss of an adenine base from the dianions, d(A)72-, d(AATTAAT)2−, and d(TTAATTA)2− has an average activation energy (Ea) of ~1.0 eV and a preexponential factor (A) of 1010 s−1. Both guanine and cytosine base loss occurs for d(CCGGCCG)2−. The average Arrhenius parameters for the loss of cytosine and guanine are Ea = 1.32 ± 0.03 eV and A = 1013.3±0.3 s−1. No loss of thymine was observed for mixed adenine–thymine oligonucleotides. Neither base loss nor any other fragmentation reactions occur for d(T)72- over a 600 s reaction delay at 207 °C, a temperature close to the upper limit accessible with our instrument. The Arrhenius parameters indicate that the preferred cleavage sites for mixed oligonucleotides of similar mass-to-charge ratio will be strongly dependent on the internal energy of the precursor ions. At low internal energies (effective temperatures below 475 K), loss of adenine and subsequent cleavage of the adjacent phosphoester bonds will dominate, whereas at higher energies, preferential cleavage at C and G residues will occur. The magnitude of the A factors ≤1013 s−1 measured for the loss of the three nucleobases (A, G, and C) is indicative of an entropically neutral or disfavored process as the rate limiting step for this reaction. PMID:9794082

Sweet siblings with different faces: the mechanisms of FBP and F6P aldolase, transaldolase, transketolase and phosphoketolase revisited in light of recent structural data.

PubMed

Tittmann, Kai

2014-12-01

Nature has evolved different strategies for the reversible cleavage of ketose phosphosugars as essential metabolic reactions in all domains of life. Prominent examples are the Schiff-base forming class I FBP and F6P aldolase as well as transaldolase, which all exploit an active center lysine to reversibly cleave the C3-C4 bond of fructose-1,6-bisphosphate or fructose-6-phosphate to give two 3-carbon products (aldolase), or to shuttle 3-carbon units between various phosphosugars (transaldolase). In contrast, transketolase and phosphoketolase make use of the bioorganic cofactor thiamin diphosphate to cleave the preceding C2-C3 bond of ketose phosphates. While transketolase catalyzes the reversible transfer of 2-carbon ketol fragments in a reaction analogous to that of transaldolase, phosphoketolase forms acetyl phosphate as final product in a reaction that comprises ketol cleavage, dehydration and phosphorolysis. In this review, common and divergent catalytic principles of these enzymes will be discussed, mostly, but not exclusively, on the basis of crystallographic snapshots of catalysis. These studies in combination with mutagenesis and kinetic analysis not only delineated the stereochemical course of substrate binding and processing, but also identified key catalytic players acting at the various stages of the reaction. The structural basis for the different chemical fates and lifetimes of the central enamine intermediates in all five enzymes will be particularly discussed, in addition to the mechanisms of substrate cleavage, dehydration and ring-opening reactions of cyclic substrates. The observation of covalent enzymatic intermediates in hyperreactive conformations such as Schiff-bases with twisted double-bond linkages in transaldolase and physically distorted substrate-thiamin conjugates with elongated substrate bonds to be cleaved in transketolase, which probably epitomize a canonical feature of enzyme catalysis, will be also highlighted. Copyright © 2014 Elsevier Inc. All rights reserved.

Microsolvation effect and hydrogen-bonding pattern of taurine-water TA-(H2O)n (n = 1-3) complexes.

PubMed

Dai, Yumei; Wang, Yuhua; Huang, Zhengguo; Wang, Hongke; Yu, Lei

2012-01-01

The microsolvation of taurine (TA) with one, two or three water molecules was investigated by a density functional theory (DFT) approach. Quantum theory of atoms in molecules (QTAIM) analyses were employed to elucidate the hydrogen bond (H-bond) interaction characteristics in TA-(H(2)O)(n) (n = 1-3) complexes. The results showed that the intramolecular H-bond formed between the hydroxyl and the N atom of TA are retained in most TA-(H(2)O)(n) (n = 1-3) complexes, and are strengthened via cooperative effects among multiple H-bonds from n = 1-3. A trend of proton transformation exists from the hydroxyl to the N atom, which finally results in the cleavage of the origin intramolecular H-bond and the formation of a new intramolecular H-bond between the amino and the O atom of TA. Therefore, the most stable TA-(H(2)O)(3) complex becomes a zwitterionic complex rather than a neutral type. A many-body interaction analysis showed that the major contributors to the binding energies for complexes are the two-body energies, while three-body energies and relaxation energies make significant contributions to the binding energies for some complexes, whereas the four-body energies are too small to be significant.

Metal-organic cooperative catalysis in C-H and C-C bond activation and its concurrent recovery.

PubMed

Park, Young Jun; Park, Jung-Woo; Jun, Chul-Ho

2008-02-01

The development of an efficient catalytic activation (cleavage) system for C-H and C-C bonds is an important challenge in organic synthesis, because these bonds comprise a variety of organic molecules such as natural products, petroleum oils, and polymers on the earth. Among many elegant approaches utilizing transition metals to activate C-H and C-C bonds facilely, chelation-assisted protocols based on the coordinating ability of an organic moiety have attracted great attention, though they have often suffered from the need for an intact coordinating group in a substrate. In this Account, we describe our entire efforts to activate C-H or C-C bonds adjacent to carbonyl groups by employing a new concept of metal-organic cooperative catalysis (MOCC), which enables the temporal installation of a 2-aminopyridyl group into common aldehydes or ketones in a catalytic way. Consequently, a series of new catalytic reactions such as alcohol hydroacylation, oxo-ester synthesis, C-C triple bond cleavage, hydrative dimerization of alkynes, and skeletal rearrangements of cyclic ketones was realized through MOCC. In particular, in the quest for an optimized MOCC system composed of a Wilkinson's catalyst (Ph 3P) 3RhCl and an organic catalyst (2-amino-3-picoline), surprising efficiency enhancements could be achieved when benzoic acid and aniline were introduced as promoters for the aldimine formation process. Furthermore, a notable accomplishment of C-C bond activation has been made using 2-amino-3-picoline as a temporary chelating auxiliary in the reactions of unstrained ketones with various terminal olefins and Wilkinson's catalyst. In the case of seven-membered cyclic ketones, an interesting ring contraction to five- or six-membered ones takes place through skeletal rearrangements initiated by the C-C bond activation of MOCC. On the other hand, the fundamental advances of these catalytic systems into recyclable processes could be achieved by immobilizing both metal and organic components using a hydrogen-bonded self-assembled system as a catalyst support. This catalyst-recovery system provides a homogeneous phase at high temperature during the reaction and a heterogeneous phase at room temperature after the reaction. The product could be separated conveniently from the self-assembly support system by decanting the upper layer. The immobilized catalysts of both 2-aminopyridine and rhodium metal species sustained high catalytic activity for up to the eight catalytic reactions. In conclusion, the successful incorporation of an organocatalytic cycle into a transition metal catalyzed reaction led us to find MOCC for C-H and C-C bond activation. In addition, the hydrogen-bonded self-assembled support has been developed for an efficient and effective recovery system of homogeneous catalysts and could be successful in immobilizing both metal and organic catalysts.

An Unusual Carbon-Carbon Bond Cleavage Reaction During Phosphinothricin Biosynthesis

PubMed Central

Cicchillo, Robert M.; Zhang, Houjin; Blodgett, Joshua A.V.; Whitteck, John T.; Li, Gongyong; Nair, Satish K.; van der Donk, Wilfred A.; Metcalf, William W.

2010-01-01

Natural products containing phosphorus-carbon bonds have found widespread use in medicine and agriculture1. One such compound, phosphinothricin tripeptide (PTT), contains the unusual amino acid phosphinothricin (PT) attached to two alanine residues (Fig. 1). Synthetic PT (glufosinate) is a component of two top-selling herbicides (Basta® and Liberty®), and is widely used with resistant transgenic crops including corn, cotton and canola. Recent genetic and biochemical studies showed that during PTT biosynthesis 2-hydroxyethylphosphonate (HEP) is converted to hydroxymethylphosphonate (HMP) (Fig. 1)2. Reported here are the in vitro reconstitution of this unprecedented C(sp3)-C(sp3) bond cleavage reaction and X-ray crystal structures of the enzyme. The protein is a mononuclear non-heme iron(II)-dependent dioxygenase that converts HEP to HMP and formate. In contrast to most other members of this family, the oxidative consumption of HEP does not require additional cofactors or the input of exogenous electrons. The current study expands the scope of reactions catalyzed by the 2-His-1-carboxylate mononuclear non-heme iron family of enzymes. PMID:19516340

NMR analysis of cleaved Escherichia coli thioredoxin (1-73/74-108) and its P76A variant: cis/trans peptide isomerization.

PubMed Central

Yu, W. F.; Tung, C. S.; Wang, H.; Tasayco, M. L.

2000-01-01

Inspection of high resolution three-dimensional (3D) structures from the protein database reveals an increasing number of cis-Xaa-Pro and cis-Xaa-Yaa peptide bonds. However, we are still far from being able to predict whether these bonds will remain cis upon single-site substitution of Pro or Yaa and/or cleavage of a peptide bond close to it in the sequence. We have chosen oxidized Escherichia coli thioredoxin (Trx), a member of the Trx superfamily with a single alpha/beta domain and cis P76 to determine the effect of single-site substitution and/or cleavage on this isomer. Standard two-dimensional (2D) NMR analysis were performed on cleaved Trx (1-73/74-108) and its P76A variant. Analysis of the NOE connectivities indicates remarkable similarity between the secondary and supersecondary structure of the noncovalent complexes and Trx. Analysis of the 2D version of the HCCH-TOCSY and HMQC-NOESY-HMQC and 13C-filtered HMQC-NOESY spectra of cleaved Trx with uniformly 13C-labeled 175 and P76 shows surprising conservation of both cis P76 and packing of 175 against W31. A similar NMR analysis of its P76A variant provides no evidence for cis A76 and shows only subtle local changes in both the packing of 175 and the interstrand connectivities between its most protected hydrophobic strands (beta2 and beta4). Indeed, a molecular simulation model for the trans P76A variant of Trx shows only subtle local changes around the substitution site. In conclusion, cleavage of R73 is insufficient to provoke cis/trans isomerization of P76, but cleavage and single-site substitution (P76A) favors the trans isomer. PMID:10739243

ATP-Dependent C–F Bond Cleavage Allows the Complete Degradation of 4-Fluoroaromatics without Oxygen

PubMed Central

Tiedt, Oliver; Mergelsberg, Mario; Boll, Kerstin; Müller, Michael; Adrian, Lorenz; Jehmlich, Nico; von Bergen, Martin

2016-01-01

ABSTRACT Complete biodegradation of the abundant and persistent fluoroaromatics requires enzymatic cleavage of an arylic C–F bond, probably the most stable single bond of a biodegradable organic molecule. While in aerobic microorganisms defluorination of fluoroaromatics is initiated by oxygenases, arylic C–F bond cleavage has never been observed in the absence of oxygen. Here, an oxygen-independent enzymatic aryl fluoride bond cleavage is described during the complete degradation of 4-fluorobenzoate or 4-fluorotoluene to CO2 and HF in the denitrifying Thauera aromatica: the ATP-dependent defluorination of 4-fluorobenzoyl-coenzyme A (4-F-BzCoA) to benzoyl-coenzyme A (BzCoA) and HF, catalyzed by class I BzCoA reductase (BCR). Adaptation to growth with the fluoroaromatics was accomplished by the downregulation of a promiscuous benzoate-CoA ligase and the concomitant upregulation of 4-F-BzCoA-defluorinating/dearomatizing BCR on the transcriptional level. We propose an unprecedented mechanism for reductive arylic C–F bond cleavage via a Birch reduction-like mechanism resulting in a formal nucleophilic aromatic substitution. In the proposed anionic 4-fluorodienoyl-CoA transition state, fluoride elimination to BzCoA is favored over protonation to a fluorinated cyclic dienoyl-CoA. PMID:27507824

Chemoselective room temperature E1cB N-N cleavage of oxazolidinone hydrazides from enantioselective aldehyde α-hydrazination: synthesis of (+)-1,4-dideoxyallonojirimycin.

PubMed

Ferreira, Jasmin; Rees-Jones, Sophie C M; Ramaotsoa, Valerie; Msutu, Ath'enkosi; Hunter, Roger

2016-02-07

Room temperature E1cB N-N cleavage of oxazolidinone hydrazides via N-alkylation with diethyl bromomalonate and potassium or caesium carbonate as base in acetonitrile is presented. The new method has a much improved chemoselectivity, which is illustrated by a concise total synthesis of the piperidine iminosugar (+)-1,4-dideoxyallonojirimycin.

Characterization of choline trimethylamine-lyase expands the chemistry of glycyl radical enzymes.

PubMed

Craciun, Smaranda; Marks, Jonathan A; Balskus, Emily P

2014-07-18

The recently identified glycyl radical enzyme (GRE) homologue choline trimethylamine-lyase (CutC) participates in the anaerobic conversion of choline to trimethylamine (TMA), a widely distributed microbial metabolic transformation that occurs in the human gut and is linked to disease. The proposed biochemical function of CutC, C-N bond cleavage, represents new reactivity for the GRE family. Here we describe the in vitro characterization of CutC and its activating protein CutD. We have observed CutD-mediated formation of a glycyl radical on CutC using EPR spectroscopy and have demonstrated that activated CutC processes choline to trimethylamine and acetaldehyde. Surveys of potential alternate CutC substrates uncovered a strict specificity for choline. Homology modeling and mutagenesis experiments revealed essential CutC active site residues. Overall, this work establishes that CutC is a GRE of unique function and a molecular marker for anaerobic choline metabolism.

Current-Assisted Diffusion Bonding of Extruded Ti-22Al-25Nb Alloy by Spark Plasma Sintering: Interfacial Microstructure and Mechanical Properties

NASA Astrophysics Data System (ADS)

Yang, Jianlei; Wang, Guofeng; Jiao, Xueyan; Gu, Yibin; Liu, Qing; Li, You

2018-05-01

Spark plasma sintering (SPS) technology was used to current-assisted bond extruded Ti-22Al-25Nb alloy. The effects of bonding temperature (920-980 °C) and bonding time (10-30 min) on the microstructure evolution and shear strength of this alloy were investigated systematically. The temperature distribution in the specimen during the current-assisted bonding process was also analyzed by numerical simulation. It is noted that the highest temperature was obtained at the bonding interface. As the bonding temperature and bonding time increased, the voids in the interface shrank increasingly until they vanished. A complete metallurgical bonding interface could be produced at 960 °C/20 min/10 MPa, exhibiting the highest shear strength of 269.3 MPa. In addition, the shear strength of the bonded specimen depended on its interfacial microstructure. With increased bonding temperature, the fracture mode transformed from the intergranular fracture at the bonding interface to the cleavage fracture in the substrate.

Dissociation Behavior of a TEMPO-Active Ester Cross-Linker for Peptide Structure Analysis by Free Radical Initiated Peptide Sequencing (FRIPS) in Negative ESI-MS.

PubMed

Hage, Christoph; Ihling, Christian H; Götze, Michael; Schäfer, Mathias; Sinz, Andrea

2017-01-01

We have synthesized a homobifunctional amine-reactive cross-linking reagent, containing a TEMPO (2,2,6,6-tetramethylpiperidine-1-oxy) and a benzyl group (Bz), termed TEMPO-Bz-linker, to derive three-dimensional structural information of proteins. The aim for designing this novel cross-linker was to facilitate the mass spectrometric analysis of cross-linked products by free radical initiated peptide sequencing (FRIPS). In an initial study, we had investigated the fragmentation behavior of TEMPO-Bz-derivatized peptides upon collision activation in (+)-electrospray ionization collision-induced dissociation tandem mass spectrometry (ESI-CID-MS/MS) experiments. In addition to the homolytic NO-C bond cleavage FRIPS pathway delivering the desired odd-electron product ions, an alternative heterolytic NO-C bond cleavage, resulting in even-electron product ions mechanism was found to be relevant. The latter fragmentation route clearly depends on the protonation of the TEMPO-Bz-moiety itself, which motivated us to conduct (-)-ESI-MS, CID-MS/MS, and MS 3 experiments of TEMPO-Bz-cross-linked peptides to further clarify the fragmentation behavior of TEMPO-Bz-peptide molecular ions. We show that the TEMPO-Bz-linker is highly beneficial for conducting FRIPS in negative ionization mode as the desired homolytic cleavage of the NO-C bond is the major fragmentation pathway. Based on characteristic fragments, the isomeric amino acids leucine and isoleucine could be discriminated. Interestingly, we observed pronounced amino acid side chain losses in cross-linked peptides if the cross-linked peptides contain a high number of acidic amino acids. Graphical Abstract ᅟ.

Yeast ribonuclease III uses a network of multiple hydrogen bonds for RNA binding and cleavage.

PubMed

Lavoie, Mathieu; Abou Elela, Sherif

2008-08-19

Members of the bacterial RNase III family recognize a variety of short structured RNAs with few common features. It is not clear how this group of enzymes supports high cleavage fidelity while maintaining a broad base of substrates. Here we show that the yeast orthologue of RNase III (Rnt1p) uses a network of 2'-OH-dependent interactions to recognize substrates with different structures. We designed a series of bipartite substrates permitting the distinction between binding and cleavage defects. Each substrate was engineered to carry a single or multiple 2'- O-methyl or 2'-fluoro ribonucleotide substitutions to prevent the formation of hydrogen bonds with a specific nucleotide or group of nucleotides. Interestingly, introduction of 2'- O-methyl ribonucleotides near the cleavage site increased the rate of catalysis, indicating that 2'-OH are not required for cleavage. Substitution of nucleotides in known Rnt1p binding site with 2'- O-methyl ribonucleotides inhibited cleavage while single 2'-fluoro ribonucleotide substitutions did not. This indicates that while no single 2'-OH is essential for Rnt1p cleavage, small changes in the substrate structure are not tolerated. Strikingly, several nucleotide substitutions greatly increased the substrate dissociation constant with little or no effect on the Michaelis-Menten constant or rate of catalysis. Together, the results indicate that Rnt1p uses a network of nucleotide interactions to identify its substrate and support two distinct modes of binding. One mode is primarily mediated by the dsRNA binding domain and leads to the formation of stable RNA/protein complex, while the other requires the presence of the nuclease and N-terminal domains and leads to RNA cleavage.

Structural and functional analyses reveal the contributions of the C- and N-lobes of Argonaute protein to selectivity of RNA target cleavage.

PubMed

Dayeh, Daniel M; Kruithoff, Bradley C; Nakanishi, Kotaro

2018-04-27

Some gene transcripts have cellular functions as regulatory noncoding RNAs. For example, ∼23-nucleotide (nt)-long siRNAs are loaded into Argonaute proteins. The resultant ribonucleoprotein assembly, the RNA-induced silencing complex (RISC), cleaves RNAs that are extensively base-paired with the loaded siRNA. To date, base complementarity is recognized as the major determinant of specific target cleavage (or slicing), but little is known about how Argonaute inspects base pairing before cleavage. A hallmark of Argonaute proteins is their bilobal structure, but despite the significance of this structure for curtailing slicing activity against mismatched targets, the molecular mechanism remains elusive. Here, our structural and functional studies of a bilobed yeast Argonaute protein and its isolated catalytic C-terminal lobe (C-lobe) revealed that the C-lobe alone retains almost all properties of bilobed Argonaute: siRNA-duplex loading, passenger cleavage/ejection, and siRNA-dependent RNA cleavage. A 2.1 Å-resolution crystal structure revealed that the catalytic C-lobe mirrors the bilobed Argonaute in terms of guide-RNA recognition and that all requirements for transitioning to the catalytically active conformation reside in the C-lobe. Nevertheless, we found that in the absence of the N-terminal lobe (N-lobe), target RNAs are scanned for complementarity only at positions 5-14 on a 23-nt guide RNA before endonucleolytic cleavage, thereby allowing for some off-target cleavage. Of note, acquisition of an N-lobe expanded the range of the guide RNA strand used for inspecting target complementarity to positions 2-23. These findings offer clues to the evolution of the bilobal structure of catalytically active Argonaute proteins. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Abundance and diversity of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX)-metabolizing bacteria in UXO-contaminated marine sediments.

PubMed

Zhao, Jian-Shen; Manno, Dominic; Hawari, Jalal

2007-03-01

Octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX) is a toxic explosive known to be resistant to biodegradation. In this study, we found that sediment collected from two unexploded ordnance (UXO) disposal sites (UXO-3, UXO-5) and one nearby reference site (midref) in Hawaii contained anaerobic bacteria capable of removing HMX. Two groups of HMX-removing bacteria were found in UXO-5: group I contained aerotolerant anaerobes and microaerophiles, and group II contained facultative anaerobes. In UXO-3 and midref sediments, HMX-metabolizing bacteria were strictly anaerobic (group III and group IV). Using 16S rRNA sequencing, group I was assigned to a novel phylogenetic cluster of Clostridiales, and groups II and III were related to Paenibacillus and Tepidibacter of Firmicutes, respectively. Group IV bacteria were identified as Desulfovibrio of Deltaproteobacteria. Using [UL-(14)C]-HMX, group IV isolates were found to mineralize HMX (26.8% in 308 d) as determined by liberated (14)CO(2), but negligible mineralization was observed in groups I-III. Resting cells of isolates metabolized HMX to N(2)O and HCHO via the intermediary formation of 1-nitroso-octahydro-3,5,7-trinitro-1,3,5,7-tetrazocine together with methylenedinitramine. These experimental findings suggest that HMX biotransformation occurred either via initial denitration followed by ring cleavage or via reduction of one or more of the N-NO(2) group(s) to the corresponding N-NO bond(s) prior to ring cleavage.

Characterization of Long-Chain Fatty Acid as N-(4-Aminomethylphenyl) Pyridinium Derivative by MALDI LIFT-TOF/TOF Mass Spectrometry

NASA Astrophysics Data System (ADS)

Frankfater, Cheryl; Jiang, Xuntian; Hsu, Fong-Fu

2018-05-01

Charge remote fragmentation (CRF) elimination of CnH2n+2 residues along the aliphatic tail of long chain fatty acid is hall mark of keV high-energy CID fragmentation process. It is an important fragmentation pathway leading to structural characterization of biomolecules by CID tandem mass spectrometry. In this report, we describe MALDI LIFT TOF-TOF mass spectrometric approach to study a wide variety of fatty acids (FAs), which were derivatized to N-(4-aminomethylphenyl) pyridinium (AMPP) derivative, and desorbed as M+ ions by laser with or without matrix. The high-energy MALDI LIFT TOF-TOF mass spectra of FA-AMPP contain fragment ions mainly deriving from CRF cleavages of CnH2n+2 residues, as expected. These ions together with ions from specific cleavages of the bond(s) involving the functional group within the molecule provide more complete structural identification than those produced by low-energy CID/HCD using a linear ion-trap instrument. However, this LIFT TOF-TOF mass spectrometric approach inherits low sensitivity, a typical feature of high-energy CID tandem mass spectrometry. Because of the lack of unit mass precursor ion selection with sufficient sensitivity of the current LIFT TOF-TOF technology, product ion spectra from same chain length fatty acids with difference in one or two double bonds in a mixture are not distinguishable.

Why Does Alkylation of the N-H Functionality within M/NH Bifunctional Noyori-Type Catalysts Lead to Turnover?

PubMed

Dub, Pavel A; Scott, Brian L; Gordon, John C

2017-01-25

Molecular metal/NH bifunctional Noyori-type catalysts are remarkable in that they are among the most efficient artificial catalysts developed to date for the hydrogenation of carbonyl functionalities (loadings up to ∼10 -5 mol %). In addition, these catalysts typically exhibit high C═O/C═C chemo- and enantioselectivities. This unique set of properties is traditionally associated with the operation of an unconventional mechanism for homogeneous catalysts in which the chelating ligand plays a key role in facilitating the catalytic reaction and enabling the aforementioned selectivities by delivering/accepting a proton (H + ) via its N-H bond cleavage/formation. A recently revised mechanism of the Noyori hydrogenation reaction (Dub, P. A. et al. J. Am. Chem. Soc. 2014, 136, 3505) suggests that the N-H bond is not cleaved but serves to stabilize the turnover-determining transition states (TDTSs) via strong N-H···O hydrogen-bonding interactions (HBIs). The present paper shows that this is consistent with the largely ignored experimental fact that alkylation of the N-H functionality within M/NH bifunctional Noyori-type catalysts leads to detrimental catalytic activity. The purpose of this work is to demonstrate that decreasing the strength of this HBI, ultimately to the limit of its complete absence, are conditions under which the same alkylation may lead to beneficial catalytic activity.

Formation of unexpected silicon- and disiloxane-bridged multiferrocenyl derivatives bearing Si-O-CH[double bond, length as m-dash]CH2 and Si-(CH2)2C(CH3)3 substituents via cleavage of tetrahydrofuran and trapping of its ring fragments.

PubMed

Bruña, Sonia; González-Vadillo, Ana Mª; Ferrández, Marta; Perles, Josefina; Montero-Campillo, M Merced; Mó, Otilia; Cuadrado, Isabel

2017-09-12

The formation of a family of silicon- and siloxane-bridged multiferrocenyl derivatives carrying different functional groups attached to silicon, including Fc 2 (CH 3 ) 3 C(CH 2 ) 2 SiCH[double bond, length as m-dash]CH 2 (5), Fc 2 (CH 2 [double bond, length as m-dash]CH-O)SiCH[double bond, length as m-dash]CH 2 (6), Fc 2 (OH)SiCH[double bond, length as m-dash]CH 2 (7), Fc 2 (CH 2 [double bond, length as m-dash]CH-O)Si-O-Si(O-CH[double bond, length as m-dash]CH 2 )Fc 2 (8) and Fc 2 (CH 2 [double bond, length as m-dash]CH-O)Si-O-SiFc 3 (9) is described. Silyl vinyl ether molecules 6, 8 and 9 and the heteroleptic vinylsilane 5 resulted from the competing metathesis reaction of lithioferrocene (FcLi), CH 2 [double bond, length as m-dash]CH-OLi or (CH 3 ) 3 C(CH 2 ) 2 Li with the corresponding multifunctional chlorosilane, Cl 3 SiCH[double bond, length as m-dash]CH 2 or Cl 3 Si-O-SiCl 3 . The last two organolithium species have been likely formed in situ by fragmentation of the tetrahydrofuran solvent. Diferrocenylvinyloxyvinylsilane 6 is noteworthy since it represents a rare example of a redox-active silyl mononomer in which two different C[double bond, length as m-dash]C polymerisable groups are directly connected to silicon. The molecular structures of the silicon-containing multiferrocenyl species 5, 6, 8 and 9 have been investigated by single-crystal X-ray diffraction studies, demonstrating the capture and storage processes of two ring fragments resulting from the cleavage of cyclic THF in redox-active and stable crystalline organometallic compounds. From electrochemical studies we found that by changing the anion of the supporting electrolyte from [PF 6 ] - to [B(C 6 F 5 ) 4 ] - , the redox behaviour of tetrametallic disiloxane 8 can be switched from a poorly resolved multistep redox process to four consecutive well-separated one-electron oxidations, corresponding to the sequential oxidation of the four ferrocenyl moieties.

Atomic resolution structure of the cytoplasmic domain of Yersinia pestis YscU, a regulatory switch involved in type III secretion

PubMed Central

Lountos, George T; Austin, Brian P; Nallamsetty, Sreedevi; Waugh, David S

2009-01-01

Crystal structures of cleaved and uncleaved forms of the YscU cytoplasmic domain, an essential component of the type III secretion system (T3SS) in Yersinia pestis, have been solved by single-wavelength anomolous dispersion and refined with X-ray diffraction data extending up to atomic resolution (1.13 Å). These crystallographic studies provide structural insights into the conformational changes induced upon auto-cleavage of the cytoplasmic domain of YscU. The structures indicate that the cleaved fragments remain bound to each other. The conserved NPTH sequence that contains the site of the N263-P264 peptide bond cleavage is found on a β-turn which, upon cleavage, undergoes a major reorientation of the loop away from the catalytic N263, resulting in altered electrostatic surface features at the site of cleavage. Additionally, a significant conformational change was observed in the N-terminal linker regions of the cleaved and noncleaved forms of YscU which may correspond to the molecular switch that influences substrate specificity. The YscU structures determined here also are in good agreement with the auto-cleavage mechanism described for the flagellar homolog FlhB and E. coli EscU. PMID:19165725

Does a higher metal oxidation state necessarily imply higher reactivity toward H-atom transfer? A computational study of C-H bond oxidation by high-valent iron-oxo and -nitrido complexes.

PubMed

Geng, Caiyun; Ye, Shengfa; Neese, Frank

2014-04-28

In this work, the reactions of C-H bond activation by two series of iron-oxo ( (Fe(IV)), (Fe(V)), (Fe(VI))) and -nitrido model complexes ( (Fe(IV)), (Fe(V)), (Fe(VI))) with a nearly identical coordination geometry but varying iron oxidation states ranging from iv to vi were comprehensively investigated using density functional theory. We found that in a distorted octahedral coordination environment, the iron-oxo species and their isoelectronic nitrido analogues feature totally different intrinsic reactivities toward C-H bond cleavage. In the case of the iron-oxo complexes, the reaction barrier monotonically decreases as the iron oxidation state increases, consistent with the gradually enhanced electrophilicity across the series. The iron-nitrido complex is less reactive than its isoelectronic iron-oxo species, and more interestingly, a counterintuitive reactivity pattern was observed, i.e. the activation barriers essentially remain constant independent of the iron oxidation states. The detailed analysis using the Polanyi principle demonstrates that the different reactivities between these two series originate from the distinct thermodynamic driving forces, more specifically, the bond dissociation energies (BDEE-Hs, E = O, N) of the nascent E-H bonds in the FeE-H products. Further decomposition of the BDEE-Hs into the electron and proton affinity components shed light on how the oxidation states modulate the BDEE-Hs of the two series.

A novel carotenoid cleavage activity involved in the biosynthesis of Citrus fruit-specific apocarotenoid pigments

PubMed Central

Rodrigo, María J.; Alquézar, Berta; Al-Babili, Salim

2013-01-01

Citrus is the first tree crop in terms of fruit production. The colour of Citrus fruit is one of the main quality attributes, caused by the accumulation of carotenoids and their derivative C30 apocarotenoids, mainly β-citraurin (3-hydroxy-β-apo-8′-carotenal), which provide an attractive orange-reddish tint to the peel of oranges and mandarins. Though carotenoid biosynthesis and its regulation have been extensively studied in Citrus fruits, little is known about the formation of C30 apocarotenoids. The aim of this study was to the identify carotenoid cleavage enzyme(s) [CCD(s)] involved in the peel-specific C30 apocarotenoids. In silico data mining revealed a new family of five CCD4-type genes in Citrus. One gene of this family, CCD4b1, was expressed in reproductive and vegetative tissues of different Citrus species in a pattern correlating with the accumulation of C30 apocarotenoids. Moreover, developmental processes and treatments which alter Citrus fruit peel pigmentation led to changes of β-citraurin content and CCD4b1 transcript levels. These results point to the involvement of CCD4b1 in β-citraurin formation and indicate that the accumulation of this compound is determined by the availability of the presumed precursors zeaxanthin and β-cryptoxanthin. Functional analysis of CCD4b1 by in vitro assays unequivocally demonstrated the asymmetric cleavage activity at the 7′,8′ double bond in zeaxanthin and β-cryptoxanthin, confirming its role in C30 apocarotenoid biosynthesis. Thus, a novel plant carotenoid cleavage activity targeting the 7′,8′ double bond of cyclic C40 carotenoids has been identified. These results suggest that the presented enzyme is responsible for the biosynthesis of C30 apocarotenoids in Citrus which are key pigments in fruit coloration. PMID:24006419

Mo(CO)/sub 6/-promoted reductive cleavage of the carbon-sulfur bond

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

Luh, T.Y.; Wong, C.S.

1985-12-13

In order to study the reductive cleavage of carbon-sulfur bonds by Mo(CO/sub 6/, various organosulfur compounds are reacted with Mo(CO)/sub 6/ in THF. Results of these experiments demonstrate that benzylic-, aryl-, or ..cap alpha..-acyl-activated carbon-sulfur bonds are reduced by treatment with Mo(CO)/sub 6/. 1 table.

Fluoroalkenylphosphonates

NASA Astrophysics Data System (ADS)

Kadyrov, A. A.; Rokhlin, E. M.

1988-09-01

In this review we survey the methods for the preparation of derivatives of fluoroalkenylphosphonic acid and their reactions. The main methods for obtaining these compounds are based on the reactions of fluoroolefins with phosphites and also on the elimination of halogens, hydrogen halides and alkyl halides from fluoroalkylphosphonates or fluorine-containing phosphorus ylides. The chemical properties of fluoroalkenylphosphonates are due to the combined effect of the fluorine atoms and the phosphonate group. Their reactions with different reagents leads to modifications of the phosphonate group, addition to the C=C bond, replacement of the vinyl halogen atom, and cleavage of the C-P bond. The bibliography includes 96 references.

Characterization of a high-spin non-heme Fe(III)-OOH intermediate and its quantitative conversion to an Fe(IV)═O complex.

PubMed

Li, Feifei; Meier, Katlyn K; Cranswick, Matthew A; Chakrabarti, Mrinmoy; Van Heuvelen, Katherine M; Münck, Eckard; Que, Lawrence

2011-05-18

We have generated a high-spin Fe(III)-OOH complex supported by tetramethylcyclam via protonation of its conjugate base and characterized it in detail using various spectroscopic methods. This Fe(III)-OOH species can be converted quantitatively to an Fe(IV)═O complex via O-O bond cleavage; this is the first example of such a conversion. This conversion is promoted by two factors: the strong Fe(III)-OOH bond, which inhibits Fe-O bond lysis, and the addition of protons, which facilitates O-O bond cleavage. This example provides a synthetic precedent for how O-O bond cleavage of high-spin Fe(III)-peroxo intermediates of non-heme iron enzymes may be promoted. © 2011 American Chemical Society

Distinct requirements for signal peptidase processing and function in the stable signal peptide subunit of the Junin virus envelope glycoprotein

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

York, Joanne; Nunberg, Jack H.

2007-03-01

The arenavirus envelope glycoprotein (GP-C) retains a cleaved and stable signal peptide (SSP) as an essential subunit of the mature complex. This 58-amino-acid residue peptide serves as a signal sequence and is additionally required to enable transit of the assembled GP-C complex to the Golgi, and for pH-dependent membrane fusion activity. We have investigated the C-terminal region of the Junin virus SSP to study the role of the cellular signal peptidase (SPase) in generating SSP. Site-directed mutagenesis at the cleavage site (positions - 1 and - 3) reveals a pattern of side-chain preferences consistent with those of SPase. Although positionmore » - 2 is degenerate for SPase cleavage, this residue in the arenavirus SSP is invariably a cysteine. In the Junin virus, this cysteine is not involved in disulfide bonding. We show that replacement with alanine or serine is tolerated for SPase cleavage but prevents the mutant SSP from associating with GP-C and enabling transport to the cell surface. Conversely, an arginine mutation at position - 1 that prevents SPase cleavage is fully compatible with GP-C-mediated membrane fusion activity when the mutant SSP is provided in trans. These results point to distinct roles of SSP sequences in SPase cleavage and GP-C biogenesis. Further studies of the unique structural organization of the GP-C complex will be important in identifying novel opportunities for antiviral intervention against arenaviral hemorrhagic disease.« less

Effect of varying polyglutamate chain length on the structure and stability of ferricytochrome c.

PubMed

Antalík, Marián; Bágel'ová, Jaroslava; Gazová, Zuzana; Musatov, Andrej; Fedunová, Diana

2003-03-21

The effect of varying polyglutamate chain length on local and global stability of horse heart ferricytochrome c was studied using scanning calorimetry and spectroscopy methods. Spectral data indicate that polyglutamate chain lengths equal or greater than eight monomer units significantly change the apparent pK(a) for the alkaline transition of cytochrome c. The change in pK(a) is comparable to the value when cytochrome c is complexed with cytochrome bc(1). Glutamate and diglutamate do not significantly alter the temperature transition for cleavage of the Met(80)-heme iron bond of cytochrome c. At low ionic strength, polyglutamates consisting of eight or more glutamate monomers increase midpoint of the temperature transition from 57.3+/-0.2 to 66.9+/-0.2 degrees C. On the other hand, the denaturation temperature of cytochrome c decreases from 85.2+/-0.2 to 68.8+/-0.2 degrees C in the presence of polyglutamates with number of glutamate monomers n >or approximately equal 8. The rate constant for cyanide binding to the heme iron of cytochrome c of cytochrome c-polyglutamate complex also decreases by approximately 42.5% with n>or approximately equal 8. The binding constant for the binding of octaglutamate (m.w. approximately 1000) to cyt c was found to be 1.15 x 10(5) M(-1) at pH 8.0 and low ionic strength. The results indicate that the polyglutamate (n>or approximately equal 8) is able to increase the stability of the methionine sulfur-heme iron bond of cytochrome c in spite of structural differences that weaken the overall stability of the cyt c at neutral and slightly alkaline pH.

Extending the cleavage rules for the hammerhead ribozyme: mutating adenosine15.1 to inosine15.1 changes the cleavage site specificity from N16.2U16.1H17 to N16.2C16.1H17.

PubMed Central

Ludwig, J; Blaschke, M; Sproat, B S

1998-01-01

In this paper, we show that an adenosine to inosine mutation at position 15.1 changes the substrate specificity of the hammerhead ribozyme from N16.2U16.1H17to N16.2C16.1H17(H represents A, C or U). This result extends the hammerhead cleavage triplet definition from N16.2U16.1H17to the more general N16.2Y16.1H17. Comparison of cleavage rates using I15.1ribozymes for NCH triplets and standard A15.1 ribozymes for NUH triplets under single turnover conditions shows similar or slightly enhanced levels of reactivity for the I15. 1-containing structures. The effect of I15.1 substitution was also tested in nuclease-resistant 2'- O -alkyl substituted derivatives (oligozymes), showing a similar level of activity for the NUH and NCH cleaving structures. The availability of NCH triplets that can be targeted without loss of efficiency increases the flexibility of ribozyme targeting strategies. This was demonstrated by an efficient cleavage of an HCV transcript at a previously inaccessible GCA site in codon 2. PMID:9580675

Competitive fragmentation pathways of acetic acid dimer explored by synchrotron VUV photoionization mass spectrometry and electronic structure calculations.

PubMed

Guan, Jiwen; Hu, Yongjun; Zou, Hao; Cao, Lanlan; Liu, Fuyi; Shan, Xiaobin; Sheng, Liusi

2012-09-28

In present study, photoionization and dissociation of acetic acid dimers have been studied with the synchrotron vacuum ultraviolet photoionization mass spectrometry and theoretical calculations. Besides the intense signal corresponding to protonated cluster ions (CH(3)COOH)(n)·H(+), the feature related to the fragment ions (CH(3)COOH)H(+)·COO (105 amu) via β-carbon-carbon bond cleavage is observed. By scanning photoionization efficiency spectra, appearance energies of the fragments (CH(3)COOH)·H(+) and (CH(3)COOH)H(+)·COO are obtained. With the aid of theoretical calculations, seven fragmentation channels of acetic acid dimer cations were discussed, where five cation isomers of acetic acid dimer are involved. While four of them are found to generate the protonated species, only one of them can dissociate into a C-C bond cleavage product (CH(3)COOH)H(+)·COO. After surmounting the methyl hydrogen-transfer barrier 10.84 ± 0.05 eV, the opening of dissociative channel to produce ions (CH(3)COOH)(+) becomes the most competitive path. When photon energy increases to 12.4 eV, we also found dimer cations can be fragmented and generate new cations (CH(3)COOH)·CH(3)CO(+). Kinetics, thermodynamics, and entropy factors for these competitive dissociation pathways are discussed. The present report provides a clear picture of the photoionization and dissociation processes of the acetic acid dimer in the range of the photon energy 9-15 eV.

Effects of pre- and pro-sequence of thaumatin on the secretion by Pichia pastoris.

PubMed

Ide, Nobuyuki; Masuda, Tetsuya; Kitabatake, Naofumi

2007-11-23

Thaumatin is a 22-kDa sweet-tasting protein containing eight disulfide bonds. When thaumatin is expressed in Pichia pastoris using the thaumatin cDNA fused with both the alpha-factor signal sequence and the Kex2 protease cleavage site from Saccharomyces cerevisiae, the N-terminal sequence of the secreted thaumatin molecule is not processed correctly. To examine the role of the thaumatin cDNA-encoded N-terminal pre-sequence and C-terminal pro-sequence on the processing of thaumatin and efficiency of thaumatin production in P. pastoris, four expression plasmids with different pre-sequence and pro-sequence were constructed and transformed into P. pastoris. The transformants containing pre-thaumatin gene that has the native plant signal, secreted thaumatin molecules in the medium. The N-terminal amino acid sequence of the secreted thaumatin molecule was processed correctly. The production yield of thaumatin was not affected by the C-terminal pro-sequence, and the pro-sequence was not processed in P. pastoris, indicating that pro-sequence is not necessary for thaumatin synthesis.

Metal-Free Multiple Carbon-Carbon and Carbon-Hydrogen Bond Activations via Charge-Switching Mechanism in Unstrained Diindolylmethanes.

PubMed

Challa, Chandrasekhar; Varughese, Sunil; Suresh, Cherumuttathu H; Lankalapalli, Ravi S

2017-08-18

A transformation of the unstrained phenol substituted 3,3'-diindolylmethanes (DIPMs) to 2,3'-diindolylketones (DIKs) by double C-C single bond cleavage with associated rearrangements, triggered by phenyliodine(III) diacetate (PIDA), is reported. Density functional theory studies reveal a mechanism involving multiple "charge-switching" steps by synergistic involvement of the two indole units with overall low activation energy. The indole 'charge-switching' mechanism in DIPMs was further extended toward synthesis of a natural product motif cyclohepta[b]indole from biaryl appended DIBM.

Nitrogenase of Klebsiella pneumoniae. Hydrazine is a product of azide reduction.

PubMed Central

Dilworth, M J; Thorneley, R N

1981-01-01

Klebsiella pneumoniae nitrogenase reduced azide, at 30 degrees C and pH 6.8-8.2, to yield ammonia (NH3), dinitrogen (N2) and hydrazine (N2H4). Reduction of (15N = 14N = 14N)-followed by mass-spectrometric analysis showed that no new nitrogen-nitrogen bonds were formed. During azide reduction, added 15N2H4 did not contribute 15N to NH3, indicating lack of equilibration between enzyme-bound intermediates giving rise to N2H4 and N2H4 in solution. When azide reduction to N2H4 was partially inhibited by 15N2, label appeared in NH3 but not in N2H4. Product balances combined with the labelling data indicate that azide is reduced according to the following equations: (formula: see text); N2 was a competitive inhibitor and CO a non-competitive inhibitor of azide reduction to N2H4. The percentage of total electron flux used for H2 evolution concomitant with azide reduction fell from 26% at pH 6.8 to 0% at pH 8.2. Pre-steady-state kinetic data suggest that N2H4 is formed by the cleavage of the alpha-beta nitrogen-nitrogen bond to bound azide to leave a nitride (= N) intermediate that subsequently yields NH3. PMID:7030315

Synthesis, X-ray crystal structures, and phosphate ester cleavage properties of bis(2-pyridylmethyl)amine copper(II) complexes with guanidinium pendant groups.

PubMed

Belousoff, Matthew J; Tjioe, Linda; Graham, Bim; Spiccia, Leone

2008-10-06

Three new derivatives of bis(2-pyridylmethyl)amine (DPA) featuring ethylguanidinium (L (1)), propylguanidinium (L (2)), or butylguanidinium (L (3)) pendant groups have been prepared by the reaction of N, N- bis(2-pyridylmethyl)alkane-alpha,omega-diamines with 1 H-pyrazole-1-carboxamidine hydrochloride. The corresponding mononuclear copper(II) complexes were prepared by reacting the ligands with copper(II) nitrate and were isolated as [Cu(LH (+))(OH 2)](ClO 4) 3. xNaClO 4. yH 2O ( C1: L = L (1), x = 2, y = 3; C2: L = L (2), x = 2, y = 4; C3: L = L (3), x = 1, y = 0) following cation exchange purification. Recrystallization yielded crystals of composition [Cu(LH (+))(X)](ClO 4) 3.X ( C1': L = L (1), X = MeOH; C2': L = L (2), X = H 2O; C3': L = L (3), X = H 2O), which were suitable for X-ray crystallography. The crystal structures of C1', C2', and C3' indicate that the DPA moieties of the ligands coordinate to the copper(II) centers in a meridional fashion, with a water or methanol molecule occupying the fourth basal position. Weakly bound perchlorate anions located in the axial positions complete the distorted octahedral coordination spheres. The noncoordinating, monoprotonated guanidinium groups project away from the Cu(II)-DPA units and are involved in extensive charge-assisted hydrogen-bonding interactions with cocrystallized water/methanol molecules and perchlorate anions within the crystal lattices. The copper(II) complexes were tested for their ability to promote the cleavage of two model phosphodiesters, bis( p-nitrophenyl)phosphate (BNPP) and uridine-3'- p-nitrophenylphosphate (UpNP), as well as supercoiled plasmid DNA (pBR 322). While the presence of the guanidine pendants was found to be detrimental to BNPP cleavage efficiency, the functionalized complexes were found to cleave plasmid DNA and, in some cases, the model ribose phosphate diester, UpNP, at a faster rate than the parent copper(II) complex of DPA.

Metal-organic framework catalysts for selective cleavage of aryl-ether bonds

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

Allendorf, Mark D.; Stavila, Vitalie

The present invention relates to methods of employing a metal-organic framework (MOF) as a catalyst for cleaving chemical bonds. In particular instances, the MOF results in selective bond cleavage that results in hydrogenolyzis. Furthermore, the MOF catalyst can be reused in multiple cycles. Such MOF-based catalysts can be useful, e.g., to convert biomass components.

Protonation switching to the least-basic heteroatom of carbamate through cationic hydrogen bonding promotes the formation of isocyanate cations.

PubMed

Kurouchi, Hiroaki; Sumita, Akinari; Otani, Yuko; Ohwada, Tomohiko

2014-07-07

We found that phenethylcarbamates that bear ortho-salicylate as an ether group (carbamoyl salicylates) dramatically accelerate OC bond dissociation in strong acid to facilitate generation of isocyanate cation (N-protonated isocyanates), which undergo subsequent intramolecular aromatic electrophilic cyclization to give dihydroisoquinolones. To generate isocyanate cations from carbamates in acidic media as electrophiles for aromatic substitution, protonation at the ether oxygen, the least basic heteroatom, is essential to promote CO bond cleavage. However, the carbonyl oxygen of carbamates, the most basic site, is protonated exclusively in strong acids. We found that the protonation site can be shifted to an alternative basic atom by linking methyl salicylate to the ether oxygen of carbamate. The methyl ester oxygen ortho to the phenolic (ether) oxygen of salicylate is as basic as the carbamate carbonyl oxygen, and we found that monoprotonation at the methyl ester oxygen in strong acid resulted in the formation of an intramolecular cationic hydrogen bond (>CO(+) H⋅⋅⋅O<) with the phenolic ether oxygen. This facilitates OC bond dissociation of phenethylcarbamates, thereby promoting isocyanate cation formation. In contrast, superacid-mediated diprotonation at the methyl ester oxygen of the salicylate and the carbonyl oxygen of the carbamate afforded a rather stable dication, which did not readily undergo CO bond dissociation. This is an unprecedented and unknown case in which the monocation has greater reactivity than the dication. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

C-terminal N-alkylated peptide amides resulting from the linker decomposition of the Rink amide resin: a new cleavage mixture prevents their formation.

PubMed

Stathopoulos, Panagiotis; Papas, Serafim; Tsikaris, Vassilios

2006-03-01

Decomposition of the resin linkers during TFA cleavage of the peptides in the Fmoc strategy leads to alkylation of sensitive amino acids. The C-terminal amide alkylation, reported for the first time, is shown to be a major problem in peptide amides synthesized on the Rink amide resin. This side reaction occurs as a result of the Rink amide linker decomposition under TFA treatment of the peptide resin. The use of 1,3-dimethoxybenzene in a cleavage cocktail prevents almost quantitatively formation of C-terminal N-alkylated peptide amides. Oxidized by-product in the tested Cys- and Met-containing peptides were not observed, even if thiols were not used in the cleavage mixture. Copyright (c) 2005 European Peptide Society and John Wiley & Sons, Ltd.

Insertion reactions into Pd[bond]O and Pd[bond]N bonds: preparation of alkoxycarbonyl, carbonato, carbamato, thiocarbamate, and thioureide complexes of palladium(II).

PubMed

Ruiz, José; Martínez, M Teresa; Florenciano, Félix; Rodríguez, Venancio; López, Gregorio; Pérez, José; Chaloner, Penny A; Hitchcock, Peter B

2003-06-02

Mononuclear palladium hydroxo complexes of the type [Pd(N[bond]N)(C(6)F(5))(OH)] [(N[bond]N = 2,2'-bipyridine (bipy), 4,4'-dimethyl-2,2'-bipyridine (Me(2)bipy), 1,10-phenanthroline (phen), or N,N,N',N'-tetramethylethylenediamine (tmeda)] have been prepared by reaction of [Pd(N[bond]N)(C(6)F(5))(acetone)]ClO(4) with KOH in methanol. These hydroxo complexes react, in methanol, with CO (1 atm, room temperature) to yield the corresponding methoxycarbonyl complexes [Pd(N[bond]N)(C(6)F(5))(CO(2)Me)]. Similar alkoxycarbonyl complexes [Pd(N[bond]N)(C(6)F(5))(CO(2)R)] (N[bond]N = bis(3,5-dimethylpyrazol-1-yl)methane); R = Me, Et, or (i)Pr) are obtained when [Pd(N[bond]N)(C(6)F(5))Cl] is treated with KOH in the corresponding alcohol ROH and CO is bubbled through the solution. The reactions of [Pd(N[bond]N)(C(6)F(5))(OH)] (N[bond]N = bipy or Me(2)bipy) with CO(2), in tetrahydrofuran, lead to the formation of the binuclear carbonate complexes [(N[bond]N)(C(6)F(5))Pd(mu-eta(2)-CO(3))Pd(C(6)F(5))(N[bond]N)]. Complexes [Pd(N[bond]N)(C(6)F(5))(OH)] react in alcohol with PhNCS to yield the corresponding N-phenyl-O-alkylthiocarbamate complexes [Pd(N[bond]N)(C(6)F(5))[SC(OR)NPh

Carbon-Hydrogen (C-H) Bond Activation at PdIV: A Frontier in C-H Functionalization Catalysis.

PubMed

Topczewski, Joseph J; Sanford, Melanie S

2015-01-01

The direct functionalization of carbon-hydrogen (C-H) bonds has emerged as a versatile strategy for the synthesis and derivatization of organic molecules. Among the methods for C-H bond activation, catalytic processes that utilize a Pd II /Pd IV redox cycle are increasingly common. The C-H activation step in most of these catalytic cycles is thought to occur at a Pd II centre. However, a number of recent reports have suggested the feasibility of C-H cleavage occurring at Pd IV complexes. Importantly, these latter processes often result in complementary reactivity and selectivity relative to analogous transformations at Pd II . This Mini Review highlights proposed examples of C-H activation at Pd IV centres. Applications of this transformation in catalysis as well as mechanistic details obtained from stoichiometric model studies are discussed. Furthermore, challenges and future perspectives for the field are reviewed.

Chemical Constraints Governing the Origin of Metabolism: The Thermodynamic Landscape of Carbon Group Transformations

NASA Technical Reports Server (NTRS)

Weber, Arthur L.; Fonda, Mark (Technical Monitor)

2001-01-01

The thermodynamics of organic chemistry under mild aqueous conditions was examined in order to begin to understand its influence on the structure and operation of metabolism and its antecedents. Free energies were estimated for four types reactions of biochemical importance carbon-carbon bond cleavage and synthesis, hydrogen transfer between carbon groups, dehydration of alcohol groups, and aldo-keto isomerization. The energies were calculated for mainly aliphatic groups composed of carbon, hydrogen, and oxygen. The energy values showed that (1) when carbon-carbon bond cleavage involves two different types of functional groups, transfer of the shared electron-pair to the more reduced carbon group is energetically favored over transfer to the more oxidized carbon group, and (2) the energy of carbon-carbon bond transformation is strongly dependent on the type of functional group that donates the shared electron-pair during cleavage, and the group that accepts the shared electron-pair during synthesis, and (3) the energetics of C-C bond transformation is determined primarily by the half-reaction energies of the couples: carbonyl/carboxylic acid, carboxylic acid/carbon dioxide, alcohol/carbonyl, and hydrocarbon/alcohol. The energy of hydrogen-transfer between carbon groups was found to depend on the functional group class of both the hydrogen-donor and hydrogen-acceptor. From these and other observations we concluded that the chemistry of the origin of metabolism (and to a lesser degree modem metabolism) is strongly constrained by the (1) limited disproportionation energy of organic substrates that can be dissipated in a few irreversible reactions, (2) the energy-dominance of few half-reaction couples in carbon-carbon bond transformation that establishes whether a chemical reaction is energetically irreversible, reversible or unfeasible, and (3) the dependence of the transformation-energy on the oxidation state of carbon groups (functional group type) which is contingent on prior reactions in the synthetic pathway.

Engineering Environmentally-Stable Proteases to Specifically Neutralize Protein Toxins

DTIC Science & Technology

2013-10-01

acids. These sites constitute a variable environment, with the effect of mutations largely isolated to effects on interactions with the P4 side chain. 2...desires to cut. We observe, however, sequence-specific cleavage is much more subtle, depending upon how side chain interactions influence not only...first five substrate amino acids on the acyl side of the scissile bond (denoted P1 through P5, numbering from the scissile bond toward the N-terminus

Engineering Environmentally-Stable Proteases to Specifically Neutralize Protein Toxins

DTIC Science & Technology

2012-10-14

effect of mutations largely isolated to effects on interactions with the P4 side chain. 2) Most mutations at some sites (e.g. 126, 128) decrease...to cut. We observe, however, sequence-specific cleavage is much more subtle, depending upon how side chain interactions influence not only ground...five substrate amino acids on the acyl side of the scissile bond (denoted P1 through P5, numbering from the scissile bond toward the N-terminus of the

Computational Study of Low-Temperature Catalytic C-C Bond Activation of Alkanes for Portable Power

DTIC Science & Technology

2013-06-05

inhibiting the reaction. We found that Fluorinated phosphines are sufficiently π-accepting to satisfy this role. In our next step, we wanted to determine...of butane by Sen’s catalyst, Chepaikin et al. [5] proposed that CH cleavage occurs first. But the resulting catalyst fragment “X” is so electrophilic

Studies toward the oxidative and reductive activation of C-S bonds in 2'-S-aryl-2'-thiouridine derivatives.

PubMed

Rayala, Ramanjaneyulu; Giuglio-Tonolo, Alain; Broggi, Julie; Terme, Thierry; Vanelle, Patrice; Theard, Patricia; Médebielle, Maurice; Wnuk, Stanislaw F

2016-04-21

Studies directed toward the oxidative and reductive desulfurization of readily available 2'- S -aryl-2'-thiouridine derivatives were investigated with the prospect to functionalize the C2'-position of nucleosides. The oxidative desulfurization-difluorination strategy was successful on 2-(arylthio)alkanoate surrogates, while extension of the combination of oxidants and fluoride sources was not an efficient fluorination protocol when applied to 2'- S -aryl-2'-thiouridine derivatives, resulting mainly in C5-halogenation of the pyrimidine ring and C2'-monofluorination without desulfurization. Cyclic voltammetry of 2'-arylsulfonyl-2'-deoxyuridines and their 2'-fluorinated analogues showed that cleavage of the arylsulfone moiety could occur, although at relatively high cathodic potentials. While reductive-desulfonylation of 2'-arylsulfonyl-2'-deoxyuridines with organic electron donors (OEDs) gave predominantly base-induced furan type products, chemical (OED) and electrochemical reductive-desulfonylation of the α-fluorosulfone derivatives yielded the 2'-deoxy-2'-fluorouridine and 2',3'-didehydro-2',3'-dideoxy-2'-fluorouridine derivatives. These results provided good evidence of the generation of a C2'-anion through carbon-sulfur bond cleavage, opening new horizons for the reductive-functionalization approaches in nucleosides.

Studies toward the oxidative and reductive activation of C-S bonds in 2'-S-aryl-2'-thiouridine derivatives

PubMed Central

Rayala, Ramanjaneyulu; Giuglio-Tonolo, Alain; Broggi, Julie; Terme, Thierry; Vanelle, Patrice; Theard, Patricia; Médebielle, Maurice; Wnuk, Stanislaw F.

2016-01-01

Studies directed toward the oxidative and reductive desulfurization of readily available 2'-S-aryl-2'-thiouridine derivatives were investigated with the prospect to functionalize the C2'-position of nucleosides. The oxidative desulfurization-difluorination strategy was successful on 2-(arylthio)alkanoate surrogates, while extension of the combination of oxidants and fluoride sources was not an efficient fluorination protocol when applied to 2'-S-aryl-2'-thiouridine derivatives, resulting mainly in C5-halogenation of the pyrimidine ring and C2'-monofluorination without desulfurization. Cyclic voltammetry of 2'-arylsulfonyl-2'-deoxyuridines and their 2'-fluorinated analogues showed that cleavage of the arylsulfone moiety could occur, although at relatively high cathodic potentials. While reductive-desulfonylation of 2'-arylsulfonyl-2'-deoxyuridines with organic electron donors (OEDs) gave predominantly base-induced furan type products, chemical (OED) and electrochemical reductive-desulfonylation of the α-fluorosulfone derivatives yielded the 2'-deoxy-2'-fluorouridine and 2',3'-didehydro-2',3'-dideoxy-2'-fluorouridine derivatives. These results provided good evidence of the generation of a C2'-anion through carbon-sulfur bond cleavage, opening new horizons for the reductive-functionalization approaches in nucleosides. PMID:27019535

Oxidative metabolism of phenanthrene and anthracene by soil pseudomonads. The ring-fission mechanism

PubMed Central

Evans, W. C.; Fernley, H. N.; Griffiths, E.

1965-01-01

1. Phenanthrene is oxidatively metabolized by soil pseudomonads through trans-3,4-dihydro-3,4-dihydroxyphenanthrene to 3,4-dihydroxyphenanthrene, which then undergoes cleavage. 2. Some properties of the ring-fission product, cis-4-(1-hydroxynaphth-2-yl)-2-oxobut-3-enoic acid, are described. The Fe2+-dependent oxygenase therefore disrupts the bond between C-4 and the angular C of the phenanthrene nucleus. 3. An enzyme of the aldolase type converts the fission product into 1-hydroxy-2-naphthaldehyde (2-formyl-1-hydroxynaphthalene). An NAD-specific dehydrogenase is also present in the cell-free extract, which oxidizes the aldehyde to 1-hydroxy-2-naphthoic acid. This is then oxidatively decarboxylated to 1,2-dihydroxynaphthalene, thus allowing continuation of metabolism via the naphthalene pathway. 4. Anthracene is similarly metabolized, through 1,2-dihydro-1,2-dihydroxyanthracene to 1,2-dihydroxyanthracene, in which ring-fission occurs to give cis-4-(2-hydroxynaphth-3-yl)-2-oxobut-3-enoic acid. The position of cleavage is again at the bond between the angular C and C-1 of the anthracene nucleus. 5. Enzymes that convert the fission product through 2-hydroxy-3-naphthaldehyde into 2-hydroxy-3-naphthoic acid were demonstrated. The further metabolism of this acid is discussed. 6. The Fe2+-dependent oxygenase responsible for cleavage of all the o-dihydroxyphenol derivatives appears to be catechol 2,3-oxygenase, and is a constitutive enzyme in the Pseudomonas strains used. PMID:14342521

Hydrolysis of VX on Concrete: Rate of Degradation by Direct Surface Interrogation using an Ion Trap Secondary Ion Mass Spectrometer

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

Groenewold, Gary Steven; Appelhans, Anthony David; Gresham, Garold Linn

2002-09-01

The nerve agent VX (O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate) is lethal at very low levels of exposure, which can occur by dermal contact with contaminated surfaces. Hence, behavior of VX in contact with common urban or industrial surfaces is a subject of acute interest. In the present study, VX was found to undergo complete degradation when in contact with concrete surfaces. The degradation was directly interrogated at submonolayer concentrations by periodically performing secondary ion mass spectrometry (SIMS) analyses after exposure of the concrete to VX. The abundance of the [VX + H]+ ion in the SIMS spectra was observed to decrease inmore » an exponential fashion, consistent with first-order or pseudo-first-order behavior. This phenomenon enabled the rate constant to be determined at 0.005 min-1 at 25 C, which corresponds to a half-life of about 3 h on the concrete surface. The decrease in [VX + H]+ was accompanied by an increase in the abundance of the principal degradation product diisopropylaminoethanethiol (DESH), which arises by cleavage of the P-S bond. Degradation to form DESH is accompanied by the formation of ethyl methylphosphonic acid, which is observable only in the negative ion spectrum. A second degradation product was also implicated, which corresponded to a diisopropylvinylamine isomer (perhaps N,N-diisopropyl aziridinium) that arose via cleavage of the S-C bond. No evidence was observed for the formation of the toxic S-2-diisopropylaminoethyl methylphosphonothioic acid. The degradation rate constants were measured at four different temperatures (24-50 C), which resulted in a linear Arrhenius relationship and an activation energy of 52 kJ mol-1. This value agrees with previous values observed for VX hydrolysis in alkaline solutions, which suggests that the degradation of submonolayer VX is dominated by alkaline hydrolysis within the adventitious water film on the concrete surface.« less

Hydrolysis of VX on concrete: rate of degradation by direct surface interrogation using an ion trap secondary ion mass spectrometer.

PubMed

Groenewold, Gary S; Williams, John M; Appelhans, Anthony D; Gresham, Garold L; Olson, John E; Jeffery, Mark T; Rowland, Brad

2002-11-15

The nerve agent VX (O-ethyl S-2-diisopropylaminoethyl methylphosphonothiolate) is lethal at very low levels of exposure, which can occur by dermal contact with contaminated surfaces. Hence, behavior of VX in contact with common urban or industrial surfaces is a subject of acute interest. In the present study, VX was found to undergo complete degradation when in contact with concrete surfaces. The degradation was directly interrogated at submonolayer concentrations by periodically performing secondary ion mass spectrometry (SIMS) analyses after exposure of the concrete to VX. The abundance of the [VX + H]+ ion in the SIMS spectra was observed to decrease in an exponential fashion, consistent with first-order or pseudo-first-order behavior. This phenomenon enabled the rate constant to be determined at 0.005 min(-1) at 25 degrees C, which corresponds to a half-life of about 3 h on the concrete surface. The decrease in [VX + H]+ was accompanied by an increase in the abundance of the principal degradation product diisopropylaminoethanethiol (DESH), which arises by cleavage of the P-S bond. Degradation to form DESH is accompanied by the formation of ethyl methylphosphonic acid, which is observable only in the negative ion spectrum. A second degradation product was also implicated, which corresponded to a diisopropylvinylamine isomer (perhaps N,N-diisopropyl aziridinium) that arose via cleavage of the S-C bond. No evidence was observed for the formation of the toxic S-2-diisopropylaminoethyl methylphosphonothioic acid. The degradation rate constants were measured at four different temperatures (24-50 degrees C), which resulted in a linear Arrhenius relationship and an activation energy of 52 kJ mol(-1). This value agrees with previous values observed for VX hydrolysis in alkaline solutions, which suggests that the degradation of submonolayer VX is dominated by alkaline hydrolysis within the adventitious water film on the concrete surface.

A new family of nucleophiles for photoinduced, copper-catalyzed cross-couplings via single-electron transfer: reactions of thiols with aryl halides under mild conditions (O °C).

PubMed

Uyeda, Christopher; Tan, Yichen; Fu, Gregory C; Peters, Jonas C

2013-06-26

Building on the known photophysical properties of well-defined copper-carbazolide complexes, we have recently described photoinduced, copper-catalyzed N-arylations and N-alkylations of carbazoles. Until now, there have been no examples of the use of other families of heteroatom nucleophiles in such photoinduced processes. Herein, we report a versatile photoinduced, copper-catalyzed method for coupling aryl thiols with aryl halides, wherein a single set of reaction conditions, using inexpensive CuI as a precatalyst without the need for an added ligand, is effective for a wide range of coupling partners. As far as we are aware, copper-catalyzed C-S cross-couplings at 0 °C have not previously been achieved, which renders our observation of efficient reaction of an unactivated aryl iodide at -40 °C especially striking. Mechanistic investigations are consistent with these photoinduced C-S cross-couplings following a SET/radical pathway for C-X bond cleavage (via a Cu(I)-thiolate), which contrasts with nonphotoinduced, copper-catalyzed processes wherein a concerted mechanism is believed to occur.

Leveraging Electron Transfer Dissociation for Site Selective Radical Generation: Applications for Peptide Epimer Analysis

NASA Astrophysics Data System (ADS)

Lyon, Yana A.; Beran, Gregory; Julian, Ryan R.

2017-07-01

Traditional electron-transfer dissociation (ETD) experiments operate through a complex combination of hydrogen abundant and hydrogen deficient fragmentation pathways, yielding c and z ions, side-chain losses, and disulfide bond scission. Herein, a novel dissociation pathway is reported, yielding homolytic cleavage of carbon-iodine bonds via electronic excitation. This observation is very similar to photodissociation experiments where homolytic cleavage of carbon-iodine bonds has been utilized previously, but ETD activation can be performed without addition of a laser to the mass spectrometer. Both loss of iodine and loss of hydrogen iodide are observed, with the abundance of the latter product being greatly enhanced for some peptides after additional collisional activation. These observations suggest a novel ETD fragmentation pathway involving temporary storage of the electron in a charge-reduced arginine side chain. Subsequent collisional activation of the peptide radical produced by loss of HI yields spectra dominated by radical-directed dissociation, which can be usefully employed for identification of peptide isomers, including epimers.

Unexpected Hydrolytic Instability of N-Acylated Amino Acid Amides and Peptides

PubMed Central

2015-01-01

Remote amide bonds in simple N-acyl amino acid amide or peptide derivatives 1 can be surprisingly unstable hydrolytically, affording, in solution, variable amounts of 3 under mild acidic conditions, such as trifluoroacetic acid/water mixtures at room temperature. This observation has important implications for the synthesis of this class of compounds, which includes N-terminal-acylated peptides. We describe the factors contributing to this instability and how to predict and control it. The instability is a function of the remote acyl group, R2CO, four bonds away from the site of hydrolysis. Electron-rich acyl R2 groups accelerate this reaction. In the case of acyl groups derived from substituted aromatic carboxylic acids, the acceleration is predictable from the substituent’s Hammett σ value. N-Acyl dipeptides are also hydrolyzed under typical cleavage conditions. This suggests that unwanted peptide truncation may occur during synthesis or prolonged standing in solution when dipeptides or longer peptides are acylated on the N-terminus with electron-rich aromatic groups. When amide hydrolysis is an undesired secondary reaction, as can be the case in the trifluoroacetic acid-catalyzed cleavage of amino acid amide or peptide derivatives 1 from solid-phase resins, conditions are provided to minimize that hydrolysis. PMID:24617596

A comparison of flavonoid glycosides by electrospray tandem mass spectrometry

NASA Astrophysics Data System (ADS)

March, Raymond E.; Lewars, Errol G.; Stadey, Christopher J.; Miao, Xiu-Sheng; Zhao, Xiaoming; Metcalfe, Chris D.

2006-01-01

A comparison is presented of product ion mass spectra of protonated and deprotonated molecules of kaempferol-3-O-glucoside, quercitin-3-O-glucoside (isoquercitrin), quercitin-3-O-galactoside (hyperoin), apigenin-7-O-glucoside, luteolin-7-O-glucoside, genistein-7-O-glucoside, naringenin-7-O-glucoside (prunin), luteolin-4'-O-glucoside, luteolin-6-C-glucoside (homoorientin, known also as isoorientin), apigenin-8-C-glucoside (vitexin), and luteolin-8-C-glucoside (orientin) together with the product ion mass spectrum of deprotonated kaempferol-7-O-glucoside. All isomeric ions were distinguishable on the basis of their product ion mass spectra. For protonated 3-O-, 7-O-, and 4'-O-glycosides at a collision energy of 46-47 eV, homolytic cleavage of the O-glycosidic bond yielded aglycon Y+ ions, whereas in deprotonated 3-O-, 7-O-, and 4'-O-glycosides, heterolytic and homolytic cleavage of the O-glycosidic bond yielded radical aglycon (Y-H)- and aglycon (Y-) ions. In each case, fragmentation of either the glycan or the aglycon or both was observed. For 6-C- and 8-C-glycosides at a collision energy of 46-47 eV, fragmentation was restricted almost exclusively to the glycan. For luteolin-6-C-glucoside, the integrity of the aglycon structure is preserved at the expense of the glycan for which some 30 fragmentations were observed. Breakdown curves were determined as a function of collision energy for protonated and deprotonated luteolin-6-C-glucoside. An attempt has been made to rationalize the product ion mass spectra derived from C-O- and C-C-luteolin glucosides in terms of computed structures that indicate significant intramolecular hydrogen bonding and rotation of the B-ring to form a coplanar luteolin structure. It is proposed that protonated and deprotonated luteolin-6-C-glucoside may afford examples of cooperative interactive bonding that plays a major role in directing fragmentation.

Cysteine-Rich Peptide Family with Unusual Disulfide Connectivity from Jasminum sambac.

PubMed

Kumari, Geeta; Serra, Aida; Shin, Joon; Nguyen, Phuong Q T; Sze, Siu Kwan; Yoon, Ho Sup; Tam, James P

2015-11-25

Cysteine-rich peptides (CRPs) are natural products with privileged peptidyl structures that represent a potentially rich source of bioactive compounds. Here, the discovery and characterization of a novel plant CRP family, jasmintides from Jasminum sambac of the Oleaceae family, are described. Two 27-amino acid jasmintides (jS1 and jS2) were identified at the gene and protein levels. Disulfide bond mapping of jS1 by mass spectrometry and its confirmation by NMR spectroscopy revealed disulfide bond connectivity of C-1-C-5, C-2-C-4, and C-3-C-6, a cystine motif that has not been reported in plant CRPs. Structural determination showed that jS1 displays a well-defined structure framed by three short antiparallel β-sheets. Genomic analysis showed that jasmintides share a three-domain precursor arrangement with a C-terminal mature domain preceded by a long pro-domain of 46 residues and an intron cleavage site between the signal sequence and pro-domain. The compact cysteine-rich structure together with an N-terminal pyroglutamic acid residue confers jasmintides high resistance to heat and enzymatic degradation, including exopeptidase treatment. Collectively, these results reveal a new plant CRP structure with an unusual cystine connectivity, which could be useful as a scaffold for designing peptide drugs.

Photoredox Catalysis in a Complex Pharmaceutical Setting: Toward the Preparation of JAK2 Inhibitor LY2784544

PubMed Central

2015-01-01

We report a detailed investigation into the application of visible light-mediated photocatalysis to a challenging bond construction in a complex pharmaceutical target. The optimized reaction allowed the direct coupling of N-methylmorpholine with an unfunctionalized pyridazine in good yield and selectivity, and with high purity of the product isolated via crystallization. The reaction also facilitated the expedient synthesis of a range of analogues via the use of other commercially available N-methyl substituted tertiary amines, and therefore it represents an attractive tool for medicinal chemistry. Furthermore, a number of other interesting photoredox reactions were discovered during the course of this investigation, such as a formal methylation reaction via C–N bond cleavage, functionalization of C–H bonds alpha to amides, and a visible light-mediated iminium ion reduction. PMID:25356724

Transition metal catalyzed manipulation of non-polar carbon–hydrogen bonds for synthetic purpose

PubMed Central

MURAI, Shinji

2011-01-01

The direct addition of ortho C–H bonds in various aromatic compounds such as ketones, esters, imines, imidates, nitriles, and aldehydes to olefins and acetylenes can be achieved with the aid of transition metal catalysts. The ruthenium catalyzed reaction is usually highly efficient and useful as a general synthetic method. The coordination to the metal center by a heteroatom in a directing group such as carbonyl and imino groups in aromatic compounds is the key step in this process. Mechanistically, the reductive elimination to form a C–C bond is the rate-determining step, while the C–H bond cleavage step is not. PMID:21558759

Identification of surface-exposed domains on the reducing side of photosystem I

NASA Technical Reports Server (NTRS)

Xu, Q.; Guikema, J. A.; Chitnis, P. R.; Spooner, B. S. (Principal Investigator)

1994-01-01

Photosystem I (PSI) is a multisubunit enzyme that catalyzes the light-driven oxidation of plastocyanin or cytochrome c6 and the concomitant photoreduction of ferredoxin or flavodoxin. To identify the surface-exposed domains in PSI of the cyanobacterium Synechocystis sp. PCC 6803, we mapped the regions in PsaE, PsaD, and PsaF that are accessible to proteases and N-hydroxysuccinimidobiotin (NHS-biotin). Upon exposure of PSI complexes to a low concentration of endoproteinase glutamic acid (Glu)-C, PsaE was cleaved to 7.1- and 6.6-kD N-terminal fragments without significant cleavage of other subunits. Glu63 and Glu67, located near the C terminus of PsaE, were the most likely cleavage sites. At higher protease concentrations, the PsaE fragments were further cleaved and an N-terminal 9.8-kD PsaD fragment accumulated, demonstrating the accessibility of Glu residue(s) in the C-terminal domain of PsaD to the protease. Besides these major, primary cleavage products, several secondary cleavage sites on PsaD, PsaE, and PsaF were also identified. PsaF resisted proteolysis when PsaD and PsaE were intact. Glu88 and Glu124 of PsaF became susceptible to endoproteinase Glu-C upon extensive cleavage of PsaD and PsaE. Modification of PSI proteins with NHS-biotin and subsequent cleavage by endoproteinase Glu-C or thermolysin showed that the intact PsaE and PsaD, but not their major degradation products lacking C-terminal domains, were heavily biotinylated. Therefore, lysine-74 at the C terminus of PsaE was accessible for biotinylation. Similarly, lysine-107, or lysine-118, or both in PsaD could be modified by NHS-biotin.

Hydrogen Isotope Fractionation during the Biodegradation of 1,2-Dichloroethane: Potential for Pathway Identification Using a Multi-element (C, Cl, and H) Isotope Approach.

PubMed

Palau, Jordi; Shouakar-Stash, Orfan; Hatijah Mortan, Siti; Yu, Rong; Rosell, Monica; Marco-Urrea, Ernest; Freedman, David L; Aravena, Ramon; Soler, Albert; Hunkeler, Daniel

2017-09-19

Even though multi-element isotope fractionation patterns provide crucial information with which to identify contaminant degradation pathways in the field, those involving hydrogen are still lacking for many halogenated groundwater contaminants and degradation pathways. This study investigates for the first time hydrogen isotope fractionation during both aerobic and anaerobic biodegradation of 1,2-dichloroethane (1,2-DCA) using five microbial cultures. Transformation-associated isotope fractionation values (ε bulk H ) were -115 ± 18‰ (aerobic C-H bond oxidation), -34 ± 4‰ and -38 ± 4‰ (aerobic C-Cl bond cleavage via hydrolytic dehalogenation), and -57 ± 3‰ and -77 ± 9‰ (anaerobic C-Cl bond cleavage via reductive dihaloelimination). The dual-element C-H isotope approach (Λ C-H = Δδ 2 H/Δδ 13 C ≈ ε bulk H /ε bulk C , where Δδ 2 H and Δδ 13 C are changes in isotope ratios during degradation) resulted in clearly different Λ C-H values: 28 ± 4 (oxidation), 0.7 ± 0.1 and 0.9 ± 0.1 (hydrolytic dehalogenation), and 1.76 ± 0.05 and 3.5 ± 0.1 (dihaloelimination). This result highlights the potential of this approach to identify 1,2-DCA degradation pathways in the field. In addition, distinct trends were also observed in a multi- (i.e., Δδ 2 H versus Δδ 37 Cl versus Δδ 13 C) isotope plot, which opens further possibilities for pathway identification in future field studies. This is crucial information to understand the mechanisms controlling natural attenuation of 1,2-DCA and to design appropriate strategies to enhance biodegradation.

Palladium-Catalyzed Formal Cross-Coupling of Diaryl Ethers with Amines: Slicing the 4-O-5 Linkage in Lignin Models.

PubMed

Zeng, Huiying; Cao, Dawei; Qiu, Zihang; Li, Chao-Jun

2018-03-26

Lignin is the second most abundant organic matter on Earth, and is an underutilized renewable source for valuable aromatic chemicals. For future sustainable production of aromatic compounds, it is highly desirable to convert lignin into value-added platform chemicals instead of using fossil-based resources. Lignins are aromatic polymers linked by three types of ether bonds (α-O-4, β-O-4, and 4-O-5 linkages) and other C-C bonds. Among the ether bonds, the bond dissociation energy of the 4-O-5 linkage is the highest and the most challenging to cleave. To date, 4-O-5 ether linkage model compounds have been cleaved to obtain phenol, cyclohexane, cyclohexanone, and cyclohexanol. The first example of direct formal cross-coupling of diaryl ether 4-O-5 linkage models with amines is reported, in which dual C(Ar)-O bond cleavages form valuable nitrogen-containing derivatives. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural and Mechanistic Analysis of the Choline Sulfatase from Sinorhizobium melliloti: A Class I Sulfatase Specific for an Alkyl Sulfate Ester.

PubMed

van Loo, Bert; Schober, Markus; Valkov, Eugene; Heberlein, Magdalena; Bornberg-Bauer, Erich; Faber, Kurt; Hyvönen, Marko; Hollfelder, Florian

2018-03-30

Hydrolysis of organic sulfate esters proceeds by two distinct mechanisms, water attacking at either sulfur (S-O bond cleavage) or carbon (C-O bond cleavage). In primary and secondary alkyl sulfates, attack at carbon is favored, whereas in aromatic sulfates and sulfated sugars, attack at sulfur is preferred. This mechanistic distinction is mirrored in the classification of enzymes that catalyze sulfate ester hydrolysis: arylsulfatases (ASs) catalyze S-O cleavage in sulfate sugars and arylsulfates, and alkyl sulfatases break the C-O bond of alkyl sulfates. Sinorhizobium meliloti choline sulfatase (SmCS) efficiently catalyzes the hydrolysis of alkyl sulfate choline-O-sulfate (k cat /K M =4.8×10 3 s -1 M -1 ) as well as arylsulfate 4-nitrophenyl sulfate (k cat /K M =12s -1 M -1 ). Its 2.8-Å resolution X-ray structure shows a buried, largely hydrophobic active site in which a conserved glutamate (Glu386) plays a role in recognition of the quaternary ammonium group of the choline substrate. SmCS structurally resembles members of the alkaline phosphatase superfamily, being most closely related to dimeric ASs and tetrameric phosphonate monoester hydrolases. Although >70% of the amino acids between protomers align structurally (RMSDs 1.79-1.99Å), the oligomeric structures show distinctly different packing and protomer-protomer interfaces. The latter also play an important role in active site formation. Mutagenesis of the conserved active site residues typical for ASs, H 2 18 O-labeling studies and the observation of catalytically promiscuous behavior toward phosphoesters confirm the close relation to alkaline phosphatase superfamily members and suggest that SmCS is an AS that catalyzes S-O cleavage in alkyl sulfate esters with extreme catalytic proficiency. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Structure and Specificity of the Type III Secretion System Effector NleC Suggest a DNA Mimicry Mechanism of Substrate Recognition

PubMed Central

2015-01-01

Many pathogenic bacteria utilize the type III secretion system (T3SS) to translocate effector proteins directly into host cells, facilitating colonization. In enterohemmorhagic Escherichia coli (EHEC), a subset of T3SS effectors is essential for suppression of the inflammatory response in hosts, including humans. Identified as a zinc protease that cleaves NF-κB transcription factors, NleC is one such effector. Here, we investigate NleC substrate specificity, showing that four residues around the cleavage site in the DNA-binding loop of the NF-κB subunit RelA strongly influence the cleavage rate. Class I NF-κB subunit p50 is cleaved at a reduced rate consistent with conservation of only three of these four residues. However, peptides containing 10 residues on each side of the scissile bond were not efficiently cleaved by NleC, indicating that elements distal from the cleavage site are also important for substrate recognition. We present the crystal structure of NleC and show that it mimics DNA structurally and electrostatically. Consistent with this model, mutation of phosphate-mimicking residues in NleC reduces the level of RelA cleavage. We propose that global recognition of NF-κB subunits by DNA mimicry combined with a high sequence selectivity for the cleavage site results in exquisite NleC substrate specificity. The structure also shows that despite undetectable similarity of its sequence to those of other Zn2+ proteases beyond its conserved HExxH Zn2+-binding motif, NleC is a member of the Zincin protease superfamily, albeit divergent from its structural homologues. In particular, NleC displays a modified Ψ-loop motif that may be important for folding and refolding requirements implicit in T3SS translocation. PMID:25040221

Solar photochemical oxidation of alcohols using catalytic hydroquinone and copper nanoparticles under oxygen: oxidative cleavage of lignin models.

PubMed

Mitchell, Lorna J; Moody, Christopher J

2014-11-21

Alcohols are converted into to their corresponding carbonyl compounds using catalytic amounts of 1,4-hydroquinone with a copper nanoparticle electron transfer mediator with oxygen as the terminal oxidant in acetone as solvent under visible light irradiation. These conditions employing biorenewable hydroquinone as reagent were developed from initial experiments using stoichiometric amounts of 1,4-benzoquinone as oxidant. A range of benzylic and aliphatic primary and secondary alcohols are oxidized, affording the corresponding aldehydes or ketones in moderate to excellent yields. The methodology is also applicable to the oxidative degradation of lignin model compounds that undergo C-C bond cleavage to give simple aromatic compounds.

Selective cleavage of the C(α)-C(β) linkage in lignin model compounds via Baeyer-Villiger oxidation.

PubMed

Patil, Nikhil D; Yao, Soledad G; Meier, Mark S; Mobley, Justin K; Crocker, Mark

2015-03-21

Lignin is an amorphous aromatic polymer derived from plants and is a potential source of fuels and bulk chemicals. Herein, we present a survey of reagents for selective stepwise oxidation of lignin model compounds. Specifically, we have targeted the oxidative cleavage of Cα-Cβ bonds as a means to depolymerize lignin and obtain useful aromatic compounds. In this work, we prepared several lignin model compounds that possess structures, characteristic reactivity, and linkages closely related to the parent lignin polymer. We observed that selective oxidation of benzylic hydroxyl groups, followed by Baeyer-Villiger oxidation of the resulting ketones, successfully cleaves the Cα-Cβ linkage in these model compounds.

Theoretical and experimental studies on the mechanism of norbornadiene Pauson-Khand cycloadducts photorearrangement. Is there a pathway on the excited singlet potential energy surface?

PubMed

Olivella, Santiago; Solé, Albert; Lledó, Agustí; Ji, Yining; Verdaguer, Xavier; Suau, Rafael; Riera, Antoni

2008-12-17

The intermolecular Pauson-Khand reaction (PKR), a carbonylative cycloaddition between an alkyne and an alkene, is a convenient method to prepare cyclopentenones. Using norbornadiene as alkene, a myriad of tricyclo[5.2.1.0(2,6)]deca-4,8-dien-3-ones 1 can be easily prepared. The mechanism of the photochemical rearrangement of these adducts 1 into tricyclo[5.2.1.0(2,6)]deca-3,8-dien-10-ones 2 has been studied. The ground state (S(0)) and the three lowest excited states ((3)(pi pi*), (1)(n pi*), and (3)(n pi*)) potential energy surfaces (PESs) concerning the prototypical rearrangement of 1a (the cycloadduct of the PK carbonylative cycloaddition of norbornadiene and ethyne) to 2a have been thoroughly explored by means of CASSCF and CASPT2 calculations. From this study, two possible nonadiabatic pathways for the photochemical rearrangement arise: one starting on the (3)(pi pi*) PES and the other on the (1)(n pi*) PES. Both involve initial C-C gamma-bond cleavage of the enone, which leads to the formation of a bis-allyl or an allyl-butadienyloxyl diradical, respectively, that then decays to the S(0) PES through a (3)(pi pi*)/S(0) surface crossing or a (1)(n pi*)/S(0) conical intersection, each one lying in the vicinity of the corresponding diradical minimum. Once on the S(0) PES, the ring-closure to 2a occurs with virtually no energy barrier. The viability of both pathways was experimentally studied by means of triplet sensitization and quenching studies on the photorearrangement of the substituted Pauson-Khand cycloadduct 1b (R = TMS, R' = H) to 2b. Using high concentrations of either piperylene as a triplet quencher, or benzophenone as a triplet sensitizer, the reaction rate significantly slowed down. A Stern-Volmer type plot of product 2b concentration vs triplet quencher concentration showed an excellent linear correlation, thus indicating that only one excited state is involved in the photorearrangement. We conclude that, though there is a nonadiabatic pathway starting on the (1)(n pi*) PES, the reaction product is formed through the (3)(pi pi*) state because the energy barrier involved in the initial C-C gamma-bond cleavage of the enone is much lower in the (3)(pi pi*) PES than in the (1)(n pi*) PES.

Protonation of a peroxodiiron(III) complex and conversion to a diiron(III/IV) intermediate: implications for proton-assisted O-O bond cleavage in nonheme diiron enzymes.

PubMed

Cranswick, Matthew A; Meier, Katlyn K; Shan, Xiaopeng; Stubna, Audria; Kaizer, Jószef; Mehn, Mark P; Münck, Eckard; Que, Lawrence

2012-10-01

Oxygenation of a diiron(II) complex, [Fe(II)(2)(μ-OH)(2)(BnBQA)(2)(NCMe)(2)](2+) [2, where BnBQA is N-benzyl-N,N-bis(2-quinolinylmethyl)amine], results in the formation of a metastable peroxodiferric intermediate, 3. The treatment of 3 with strong acid affords its conjugate acid, 4, in which the (μ-oxo)(μ-1,2-peroxo)diiron(III) core of 3 is protonated at the oxo bridge. The core structures of 3 and 4 are characterized in detail by UV-vis, Mössbauer, resonance Raman, and X-ray absorption spectroscopies. Complex 4 is shorter-lived than 3 and decays to generate in ~20% yield of a diiron(III/IV) species 5, which can be identified by electron paramagnetic resonance and Mössbauer spectroscopies. This reaction sequence demonstrates for the first time that protonation of the oxo bridge of a (μ-oxo)(μ-1,2-peroxo)diiron(III) complex leads to cleavage of the peroxo O-O bond and formation of a high-valent diiron complex, thereby mimicking the steps involved in the formation of intermediate X in the activation cycle of ribonucleotide reductase.

Activatable iRGD-based peptide monolith: Targeting, internalization, and fluorescence activation for precise tumor imaging.

PubMed

Cho, Hong-Jun; Lee, Sung-Jin; Park, Sung-Jun; Paik, Chang H; Lee, Sang-Myung; Kim, Sehoon; Lee, Yoon-Sik

2016-09-10

A disulfide-bridged cyclic RGD peptide, named iRGD (internalizing RGD, c(CRGDK/RGPD/EC)), is known to facilitate tumor targeting as well as tissue penetration. After the RGD motif-induced targeting on αv integrins expressed near tumor tissue, iRGD encounters proteolytic cleavage to expose the CendR motif that promotes penetration into cancer cells via the interaction with neuropilin-1. Based on these proteolytic cleavage and internalization mechanism, we designed an iRGD-based monolithic imaging probe that integrates multiple functions (cancer-specific targeting, internalization and fluorescence activation) within a small peptide framework. To provide the capability of activatable fluorescence signaling, we conjugated a fluorescent dye to the N-terminal of iRGD, which was linked to the internalizing sequence (CendR motif), and a quencher to the opposite C-terminal. It turned out that fluorescence activation of the dye/quencher-conjugated monolithic peptide probe requires dual (reductive and proteolytic) cleavages on both disulfide and amide bond of iRGD peptide. Furthermore, the cleavage of the iRGD peptide leading to fluorescence recovery was indeed operative depending on the tumor-related angiogenic receptors (αvβ3 integrin and neuropilin-1) in vitro as well as in vivo. Compared to an 'always fluorescent' iRGD control probe without quencher conjugation, the dye/quencher-conjugated activatable monolithic peptide probe visualized tumor regions more precisely with lower background noise after intravenous injection, owing to the multifunctional responses specific to tumor microenvironment. All these results, along with minimal in vitro and in vivo toxicity profiles, suggest potential of the iRGD-based activatable monolithic peptide probe as a promising imaging agent for precise tumor diagnosis. Copyright © 2016 Elsevier B.V. All rights reserved.

Neutron structure and inelastic-neutron-scattering and theoretical studies of Mo(CO)(H[sub 2])[(C[sub 6]D[sub 5])[sub 2]PC[sub 2]H[sub 4]P(C[sub 6]D[sub 5])[sub 2

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

Kubas, G.J.; Burns, C.J.; Eckert, J.

1993-01-27

The synthesis and characterization of derivatives of Mo(CO)(R[sub 2]PC[sub 2]H[sub 4]PR[sub 2])[sub 2] (R = Et, i-Bu, Ph, Et-Ph) and their reactions with H[sub 2], N[sub 2], and SO[sub 2] are reported. For R = Et and i-Bu, the H[sub 2] oxidatively adds to give dihydrides, but for R = Ph, a [eta][sup 2]-H[sub 2] complex is formed. Single-crystal neutron diffraction of Mo(CO)(H[sub 2])(Ph[sub 2]PC[sub 2]H[sub 4]PPh[sub 2])[sub 2] (as a 4.5-benzene solvate with all Ph groups deuterated) at 12 K showed the H-H bond to be oriented trans to the CO and parallel to a P-Mo-P axis, with amore » length close to that of free H[sub 2] (0.74 [Angstrom]). However, the thermal ellipsoids were very large, and inelastic neutron scattering showed that the barrier to rotation of the H[sub 2] is the lowest yet measured, ca. 0.7 kcal/mol. These observations indicate that librational motion of the H[sub 2] is artificially foreshortening the H-H bond length. Application of a correction procedure gave a distance of 0.80-0.85 [Angstrom] as being more likely. Extended Huckel calculations successfully modeled the H[sub 2] coordination and also showed a low rotational barrier (1.4 kcal/mol). Theoretical considerations suggest that the degree of distortion of the MP[sub 4] skeleton is largely responsible for the ability of the complex to bind molecular hydrogen and controls the amount of back-bonding from the metal d-orbital to H[sub 2] [sigma][sup *]. The lack of an elongated H-H bond length or equilibrium with a dihydride tautomer, despite the apparent nearness of the H[sub 2] to cleavage, leads to the conclusion that the reaction coordinate for oxidative addition of H[sub 2] is rather flat until relatively precipitous cleavage of the H[sub 2]. Mo(CO)(H[sub 2])[(C[sub 6]D[sub 5])[sub 2]PC[sub 2]H[sub 4]P(C[sub 6]D[sub 5])[sub 2

Density-dependent liquid nitromethane decomposition: molecular dynamics simulations based on ReaxFF.

PubMed

Rom, Naomi; Zybin, Sergey V; van Duin, Adri C T; Goddard, William A; Zeiri, Yehuda; Katz, Gil; Kosloff, Ronnie

2011-09-15

The decomposition mechanism of hot liquid nitromethane at various compressions was studied using reactive force field (ReaxFF) molecular dynamics simulations. A competition between two different initial thermal decomposition schemes is observed, depending on compression. At low densities, unimolecular C-N bond cleavage is the dominant route, producing CH(3) and NO(2) fragments. As density and pressure rise approaching the Chapman-Jouget detonation conditions (∼30% compression, >2500 K) the dominant mechanism switches to the formation of the CH(3)NO fragment via H-transfer and/or N-O bond rupture. The change in the decomposition mechanism of hot liquid NM leads to a different kinetic and energetic behavior, as well as products distribution. The calculated density dependence of the enthalpy change correlates with the change in initial decomposition reaction mechanism. It can be used as a convenient and useful global parameter for the detection of reaction dynamics. Atomic averaged local diffusion coefficients are shown to be sensitive to the reactions dynamics, and can be used to distinguish between time periods where chemical reactions occur and diffusion-dominated, nonreactive time periods. © 2011 American Chemical Society

An expedient procedure for the oxidative cleavage of olefinic bonds with PhI(OAc)2, NMO, and catalytic OsO4.

PubMed

Nicolaou, K C; Adsool, Vikrant A; Hale, Christopher R H

2010-04-02

PhI(OAc)(2) in the presence of OsO(4) (cat.) and 2,6-lutidine cleaves olefinic bonds to yield the corresponding carbonyl compounds, albeit, in some cases, with alpha-hydroxy ketones as byproduct. A more practical and clean protocol to effect oxidative cleavage of olefinic bonds involves NMO, OsO(4) (cat.), 2,6-lutidine, and PhI(OAc)(2).

Metabolic inactivation of the circadian transmitter, pigment dispersing factor (PDF), by neprilysin-like peptidases in Drosophila.

PubMed

Isaac, R Elwyn; Johnson, Erik C; Audsley, Neil; Shirras, Alan D

2007-12-01

Recent studies have firmly established pigment dispersing factor (PDF), a C-terminally amidated octodecapeptide, as a key neurotransmitter regulating rhythmic circadian locomotory behaviours in adult Drosophila melanogaster. The mechanisms by which PDF functions as a circadian peptide transmitter are not fully understood, however; in particular, nothing is known about the role of extracellular peptidases in terminating PDF signalling at synapses. In this study we show that PDF is susceptible to hydrolysis by neprilysin, an endopeptidase that is enriched in synaptic membranes of mammals and insects. Neprilysin cleaves PDF at the internal Ser7-Leu8 peptide bond to generate PDF1-7 and PDF8-18. Neither of these fragments were able to increase intracellular cAMP levels in HEK293 cells cotransfected with the Drosophila PDF receptor cDNA and a firefly luciferase reporter gene, confirming that such cleavage results in PDF inactivation. The Ser7-Leu8 peptide bond was also the principal cleavage site when PDF was incubated with membranes prepared from heads of adult Drosophila. This endopeptidase activity was inhibited by the neprilysin inhibitors phosphoramidon (IC(50,) 0.15 micromol l(-1)) and thiorphan (IC(50,) 1.2 micromol l(-1)). We propose that cleavage by a member of the Drosophila neprilysin family of endopeptidases is the most likely mechanism for inactivating synaptic PDF and that neprilysin might have an important role in regulating PDF signals within circadian neural circuits.

Redox Potential and C-H Bond Cleaving Properties of a Nonheme FeIV=O Complex in Aqueous Solution

PubMed Central

Wang, Dong; Zhang, Mo; Bühlmann, Philippe; Que, Lawrence

2010-01-01

High-valent iron-oxo intermediates have been identified as the key oxidants in the catalytic cycles of many nonheme enzymes. Among the large number of synthetic FeIV=O complexes characterized to date, [FeIV(O)(N4Py)]2+ (1) exhibits the unique combination of thermodynamic stability, allowing its structural characterization by X-ray crystallography, and oxidative reactivity sufficient to cleave C-H bonds as strong as those in cyclohexane (DC-H = 99.3 kcal mol-1). However, its redox properties are not yet well understood. In this work, the effect of protons on the redox properties of 1 has been investigated electrochemically in nonaqueous and aqueous solutions. While the cyclic voltammetry of 1 in CH3CN is complicated by coupling of several chemical and redox processes, the FeIV/III couple is reversible in aqueous solution with E1/2 = +0.41 V vs. SCE at pH 4 and involves the transfer of one electron and one proton to give the FeIII-OH species. This is in fact the first example of reversible electrochemistry to be observed for this family of nonheme oxoiron(IV) complexes. C-H bond oxidations by 1 have been studied in H2O and found to have reactions rates that depend on the C-H bond strength but not on the solvent. Furthermore, our electrochemical results have allowed a DO-H value of 78(2) kcal mol-1 to be calculated for the FeIII-OH unit derived from 1. Interestingly, although this DO-H value is 6-11 kcal mol-1 lower than those corresponding to oxidants such as [FeIV(O)(TMP)] (TMP = tetramesitylporphinate), [RuIV(O)(bpy)2(py)]2+ (bpy = bipyridine, py = pyridine) and the tert-butylperoxyl radical, the oxidation of dihydroanthracene by 1 occurs at a rate comparable to those for these other oxidants. This comparison suggests that the nonheme N4Py ligand environment confers a kinetic advantage over the others that enhances the C-H bond cleavage ability of 1. PMID:20476758

ZnCl 2 induced catalytic conversion of softwood lignin to aromatics and hydrocarbons

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

Wang, Hongliang; Zhang, Libing; Deng, Tiansheng

2016-01-01

Selective cleavage of C-O-C bonds in lignin without disrupting C-C linkages can result in releasing aromatic monomers and dimers that can be subsequently converted into chemicals and fuels. Results showed that both biomass-derived lignin and lignin model compounds were depolymerized in a highly concentrated ZnCl2 solution. Zn2+ ions in highly concentrated ZnCl2 solutions appeared to selectively coordinate with C-O-C bonds to cause key linkages of lignin much easier to cleave. In 63 wt.% ZnCl2 solution at 200 °C for 6 h, nearly half of the softwood technical lignin was converted to liquid products, of which the majority was alkylphenols. Resultsmore » indicated that most β-O-4 and Cmethyl-OAr bonds of model compounds were cleaved undersame conditions, providing a foundation towards understanding lignin depolymerization in a concentrated ZnCl2 solution. The phenolic products were further converted into cyclic hydrocarbons via hydrodeoxygenation and coupling reactions by co-catalyst Ru/C.« less

Catalysis and co-catalysis of bond cleavages in coal and coal analogs. Final report, August 1, 1990--January 31, 1994

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

Miller, B.

1994-05-01

In work prior to the inception of this project, the authors observed that mixtures of phenolic materials and polyalkoxyaromatic molecules were appreciably more effective in catalyzing the decompositions of di-2-naphthyl ether and of di-1-naphthyl sulfide in tetralin solutions at 450{degrees}C than were the phenols by themselves, even though the polyalkoxyaromatic molecules, in the absence of phenolic co- catalysts, show essentially no catalytic activity. This was of appreciable interest in coal research because dinapthyl ether and dinapthyl sulfide have been employed as model compounds for coals in studies aimed at cleaving ether and sulfide bonds similar to those in coals. Themore » authors proposed (R. K. Sharma, K. P. Raman, and B. Miller) that the mixed catalysts used in these studies catalyze cleavages of ether and sulfide bonds by means of a mechanism involving electron transfer from the polyalkoxyaromatics to the substrates, which are activated as electron acceptors by hydrogen bonding to phenols. Since phenols themselves are electron donors, they also proposed that the well known effects of phenols in catalyzing the conversion of coals are due to similar electron transfer mechanisms.« less

Novel activity of angiotensin-converting enzyme. Hydrolysis of cholecystokinin and gastrin analogues with release of the amidated C-terminal dipeptide.

PubMed Central

Dubreuil, P; Fulcrand, P; Rodriguez, M; Fulcrand, H; Laur, J; Martinez, J

1989-01-01

ACE (angiotensin-converting enzyme; peptidyl dipeptidase A; EC 3.4.15.1), cleaves C-terminal dipeptides from active peptides containing a free C-terminus. We investigated the hydrolysis of cholecystokinin-8 [CCK-8; Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2] and of various gastrin analogues by purified rabbit lung ACE. Although these peptides are amidated at their C-terminal end, they were metabolized by ACE to several peptide fragments. These fragments were analysed by h.p.l.c., isolated and identified by comparison with synthetic fragments, and by amino acid analysis. The initial and major site of hydrolysis was the penultimate peptide bond, which generated a major product, the C-terminal amidated dipeptide Asp-Phe-NH2. As a secondary cleavage, ACE subsequently released di- or tri-peptides from the C-terminal end of the remaining N-terminal fragments. The cleavage of CCK-8 and gastrin analogues was inhibited by ACE inhibitors (Captopril and EDTA), but not by other enzyme inhibitors (phosphoramidon, thiorphan, bestatin etc.). Hydrolysis of [Leu15]gastrin-(14-17)-peptide [Boc (t-butoxycarbonyl)-Trp-Leu-Asp-Phe-NH2] in the presence of ACE was found to be dependent on the chloride-ion concentration. Km values for the hydrolysis of CCK-8, [Leu15]gastrin-(11-17)-peptide and Boc-[Leu15]gastrin-(14-17)-peptide at an NaCl concentration of 300 mM were respectively 115, 420 and 3280 microM, and the catalytic constants were about 33, 115 and 885 min-1. The kcat/Km for the reactions at 37 degrees C was approx. 0.28 microM-1.min-1, which is approx. 35 times less than that reported for the cleavage of angiotensin I. These results suggest that ACE might be involved in the metabolism in vivo of CCK and gastrin short fragments. PMID:2554881

Generalized Two-Dimensional Perturbation Correlation Infrared Spectroscopy reveals Mechanisms for the Development of Surface Charge and Recalcitrance in Plant-derived Biochars

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

Harvey, Omar R.; Herbert, Bruce; Kuo, Li-Jung

2012-09-05

Fundamental knowledge of how biochars develop surface-charge and resistance to environmental degradation (or recalcitrance) is crucial to their production for customized applications or, understanding their functions in the environment. Two-dimensional perturbation-based correlation infrared spectroscopy (2D-PCIS) was used to study the biochar formation process in three taxonomically-different plant biomass, under oxygen-limited conditions along a heat-treatment-temperature gradient (HTT; 200-650 oC). Results from 2D-PCIS pointed to the systematic, HTT-induced defragmenting of lignocellulose H-bonding network, and demethylenation/demethylation, oxidation or dehydroxylation/dehydrogenation of lignocellulose fragments as the primary reactions controlling biochar properties along the HTT gradient. The cleavage of OH O-type H-bonds, oxidation of free primarymore » hydroxyls (HTT≤500 oC), and their subsequent dehydrogenation/dehydroxylation (HTT>500 oC) controlled surface charge on the biochars; while the dehydrogenation of methylene groups, which yielded increasingly condensed structures (R-CH2-R →R=CH-R →R=C=R), controlled biochar recalcitrance. Variations in biochar properties across plant biomass type were attributable to taxa-specific transformations. For example, apparent inefficiencies in the cleavage of wood-specific H-bonds, and their subsequent oxidation to carboxyls, lead to lower surface charge in wood biochars (compared to grass biochars). Both non-taxa and taxa-specific transformations highlighted by 2D-PCIS could have significant implications for biochar functioning in fire-impacted or biochar-amended systems.« less

Ligand-to-ligand charge-transfer transitions of platinum(II) complexes with arylacetylide ligands with different chain lengths: spectroscopic characterization, effect of molecular conformations, and density functional theory calculations.

PubMed

Tong, Glenna So Ming; Law, Yuen-Chi; Kui, Steven C F; Zhu, Nianyong; Leung, King Hong; Phillips, David Lee; Che, Chi-Ming

2010-06-11

The complexes [Pt(tBu(3)tpy){C[triple bond]C(C(6)H(4)C[triple bond]C)(n-1)R}](+) (n = 1: R = alkyl and aryl (Ar); n = 1-3: R = phenyl (Ph) or Ph-N(CH(3))(2)-4; n = 1 and 2, R = Ph-NH(2)-4; tBu(3)tpy = 4,4',4''-tri-tert-butyl-2,2':6',2''-terpyridine) and [Pt(Cl(3)tpy)(C[triple bond]CR)](+) (R = tert-butyl (tBu), Ph, 9,9'-dibutylfluorene, 9,9'-dibutyl-7-dimethyl-amine-fluorene; Cl(3)tpy = 4,4',4''-trichloro-2,2':6',2''-terpyridine) were prepared. The effects of substituent(s) on the terpyridine (tpy) and acetylide ligands and chain length of arylacetylide ligands on the absorption and emission spectra were examined. Resonance Raman (RR) spectra of [Pt(tBu(3)tpy)(C[triple bond]CR)](+) (R = n-butyl, Ph, and C(6)H(4)-OCH(3)-4) obtained in acetonitrile at 298 K reveal that the structural distortion of the C[triple bond]C bond in the electronic excited state obtained by 502.9 nm excitation is substantially larger than that obtained by 416 nm excitation. Density functional theory (DFT) and time-dependent DFT (TDDFT) calculations on [Pt(H(3)tpy)(C[triple bond]CR)](+) (R = n-propyl (nPr), 2-pyridyl (Py)), [Pt(H(3)tpy){C[triple bond]C(C(6)H(4)C[triple bond]C)(n-1)Ph}](+) (n = 1-3), and [Pt(H(3)tpy){C[triple bond]C(C(6)H(4)C[triple bond]C)(n-1)C(6)H(4)-N(CH(3))(2)-4}](+)/+H(+) (n = 1-3; H(3)tpy = nonsubstituted terpyridine) at two different conformations were performed, namely, with the phenyl rings of the arylacetylide ligands coplanar ("cop") with and perpendicular ("per") to the H(3)tpy ligand. Combining the experimental data and calculated results, the two lowest energy absorption peak maxima, lambda(1) and lambda(2), of [Pt(Y(3)tpy)(C[triple bond]CR)](+) (Y = tBu or Cl, R = aryl) are attributed to (1)[pi(C[triple bond]CR)-->pi*(Y(3)tpy)] in the "cop" conformation and mixed (1)[d(pi)(Pt)-->pi*(Y(3)tpy)]/(1)[pi(C[triple bond]CR)-->pi*(Y(3)tpy)] transitions in the "per" conformation. The lowest energy absorption peak lambda(1) for [Pt(tBu(3)tpy){C[triple bond]C(C(6)H(4)C[triple bond]C)(n-1)C(6)H(4)-H-4}](+) (n = 1-3) shows a redshift with increasing chain length. However, for [Pt(tBu(3)tpy){C[triple bond]C(C6H4C[triple bond]C)(n-1)C(6)H(4)-N(CH(3))(2)-4}](+) (n = 1-3), lambda(1) shows a blueshift with increasing chain length n, but shows a redshift after the addition of acid. The emissions of [Pt(Y(3)tpy)(C[triple bond]CR)](+) (Y = tBu or Cl) at 524-642 nm measured in dichloromethane at 298 K are assigned to the (3)[pi(C[triple bond]CAr)-->pi*(Y(3)tpy)] excited states and mixed (3)[d(pi)(Pt)-->pi*(Y(3)tpy)]/(3)[pi(C[triple bond]C)-->pi*(Y(3)tpy)] excited states for R = aryl and alkyl groups, respectively. [Pt(tBu(3)tpy){C[triple bond]C(C(6)H(4)C[triple bond]C)(n-1)C(6)H(4)-N(CH(3))(2)-4}](+) (n = 1 and 2) are nonemissive, and this is attributed to the small energy gap between the singlet ground state (S(0)) and the lowest triplet excited state (T(1)).

TREM2 shedding by cleavage at the H157-S158 bond is accelerated for the Alzheimer's disease-associated H157Y variant.

PubMed

Thornton, Peter; Sevalle, Jean; Deery, Michael J; Fraser, Graham; Zhou, Ye; Ståhl, Sara; Franssen, Elske H; Dodd, Roger B; Qamar, Seema; Gomez Perez-Nievas, Beatriz; Nicol, Louise Sc; Eketjäll, Susanna; Revell, Jefferson; Jones, Clare; Billinton, Andrew; St George-Hyslop, Peter H; Chessell, Iain; Crowther, Damian C

2017-10-01

We have characterised the proteolytic cleavage events responsible for the shedding of triggering receptor expressed on myeloid cells 2 (TREM2) from primary cultures of human macrophages, murine microglia and TREM2-expressing human embryonic kidney (HEK293) cells. In all cell types, a soluble 17 kDa N-terminal cleavage fragment was shed into the conditioned media in a constitutive process that is inhibited by G1254023X and metalloprotease inhibitors and siRNA targeting ADAM10. Inhibitors of serine proteases and matrix metalloproteinases 2/9, and ADAM17 siRNA did not block TREM2 shedding. Peptidomimetic protease inhibitors highlighted a possible cleavage site, and mass spectrometry confirmed that shedding occurred predominantly at the H157-S158 peptide bond for both wild-type and H157Y human TREM2 and for the wild-type murine orthologue. Crucially, we also show that the Alzheimer's disease-associated H157Y TREM2 variant was shed more rapidly than wild type from HEK293 cells, possibly by a novel, batimastat- and ADAM10-siRNA-independent, sheddase activity. These insights offer new therapeutic targets for modulating the innate immune response in Alzheimer's and other neurological diseases. © 2017 MedImmune Ltd. Published under the terms of the CC BY 4.0 license.

Characterization of clade 2.3.4.4 H5N8 highly pathogenic avian influenza viruses from wild birds possessing atypical hemagglutinin polybasic cleavage sites.

PubMed

Usui, Tatsufumi; Soda, Kosuke; Tomioka, Yukiko; Ito, Hiroshi; Yabuta, Toshiyo; Takakuwa, Hiroki; Otsuki, Koichi; Ito, Toshihiro; Yamaguchi, Tsuyoshi

2017-02-01

Since 2014, clade 2.3.4.4 H5 subtype highly pathogenic avian influenza viruses (HPAIVs) have been distributed worldwide. These viruses, which were reported to be highly virulent in chickens by intravenous inoculation, have a consensus HPAI motif PLRERRRKR at the HA cleavage site. However, two-clade 2.3.4.4 H5N8 viruses which we isolated from wild migratory birds in late 2014 in Japan possessed atypical HA cleavage sequences. A swan isolate, Tottori/C6, had a novel polybasic cleavage sequence, PLGERRRKR, and another isolate from a dead mandarin duck, Gifu/01, had a heterogeneous mixture of consensus PLRERRRKR and variant PLRERRRRKR sequences. The polybasic HA cleavage site is the prime virulence determinant of AIVs. Therefore, in the present study, we examined the pathogenicity of these H5N8 isolates in chickens by intravenous inoculation. When 10 6 EID 50 of these viruses were intravenously inoculated into chickens, the mean death time associated with Tottori/C6 was substantially longer (>6.1 days) than that associated with Gifu/01 (2.5 days). These viruses had comparable abilities to replicate in tissue culture cells in the presence and absence of exogenous trypsin, but the growth of Tottori/C6 was hampered. These results indicate that the novel cleavage motif of Tottori/C6 did not directly affect the infectivity of the virus, but Tottori/C6 caused attenuated pathogenicity in chickens because of hampered replication efficiency. It is important to test for the emergence of diversified HPAIVs, because introduction of HPAIVs with a lower virulence like Tottori/C6 might hinder early detection of affected birds in poultry farms.

alpha-1,4-Glucan lyase, a new class of starch/glycogen degrading enzyme. III. Substrate specificity, mode of action, and cleavage mechanism.

PubMed

Yu, S; Ahmad, T; Kenne, L; Pedersén, M

1995-05-11

The alpha-1,4-glucan lyase (EC 4.2.2.-), purified from the red alga Gracilariopsis lemaneiformis, is a single polypeptide with a molecular mass of 116,654 Da as determined by matrix-assisted laser-desorption mass spectrometry. It degraded maltose, maltosaccharides, amylose, amylopectin and glycogen, forming 1,5-anhydro-D-fructose from the non-reducing end groups. The substrate specificity, mode of action, and cleavage mechanism of the enzyme were studied by using various naturally occurring and synthesized substrates. This enzyme was highly specific for the alpha-1,4-D-glucosidic bond. When a linear alpha-1,4-glucan was used as substrate, the enzyme split the substrate from the non-reducing end and released 1,5-anhydro-D-fructose successively until only one glucose unit was left. When a branched pentasaccharide of 6(2)-alpha-maltosylmaltotriose, obtained from glycogen by alpha-amylase limitation, was used as substrate, the glucose group in the 4-position of the 4,6-branched residue was not cleaved off. Using maltoheptaose as substrate and following the reaction with HPLC and 1H-NMR spectroscopy, it was found that the action mode of the lyase followed a multichain attack mechanism. 1H- and 13C-NMR spectroscopic studies on unlabelled and labelled amylose (1-2H, 2-2H, 1-13C) as substrates indicated that the lyase cleaved the C-(1')-O(4) bond forming a double bond between C-1' and C-2', thus forming the enol form of 1,5-anhydro-D-fructose. It also indicated that the catalytic process of the lyase involved proton exchanges among C-1, C-2, C-3 and the solvent.

PrP(C) homodimerization stimulates the production of PrPC cleaved fragments PrPN1 and PrPC1.

PubMed

Béland, Maxime; Motard, Julie; Barbarin, Alice; Roucou, Xavier

2012-09-19

An endoproteolytic cleavage termed α-cleavage between residues 111/112 is a characteristic feature of the cellular prion protein (PrP(C)). This cleavage generates a soluble N-terminal fragment (PrPN1) and a glycosylphosphatidylinositol-anchored C-terminal fragment (PrPC1). Independent studies demonstrate that modulating PrP(C) α-cleavage represents a potential therapeutic strategy in prion diseases. The regulation of PrP(C) α-cleavage is unclear. The only known domain that is essential for the α-cleavage to occur is a hydrophobic domain (HD). Importantly, the HD is also essential for the formation of PrP(C) homodimers. To explore the role of PrP(C) homodimerization on the α-cleavage, we used a well described inducible dimerization strategy whereby a chimeric PrP(C) composed of a modified FK506-binding protein (Fv) fused with PrP(C) and termed Fv-PrP is incubated in the presence of a dimerizer AP20187 ligand. We show that homodimerization leads to a considerable increase of PrP(C) α-cleavage in cultured cells and release of PrPN1 and PrPC1. Interestingly, enforced homodimerization increased PrP(C) levels at the plasma membrane, and preventing PrP(C) trafficking to the cell surface inhibited dimerization-induced α-cleavage. These observations were confirmed in primary hippocampal neurons from transgenic mice expressing Fv-PrP. The proteases responsible for the α-cleavage are still elusive, and in contrast to initial studies we confirm more recent investigations that neither ADAM10 nor ADAM17 are involved. Importantly, PrPN1 produced after PrP(C) homodimerization protects against toxic amyloid-β (Aβ) oligomers. Thus, our results show that PrP(C) homodimerization is an important regulator of PrP(C) α-cleavage and may represent a potential therapeutic avenue against Aβ toxicity in Alzheimer's disease.

Glutamic Acid Selective Chemical Cleavage of Peptide Bonds.

PubMed

Nalbone, Joseph M; Lahankar, Neelam; Buissereth, Lyssa; Raj, Monika

2016-03-04

Site-specific hydrolysis of peptide bonds at glutamic acid under neutral aqueous conditions is reported. The method relies on the activation of the backbone amide chain at glutamic acid by the formation of a pyroglutamyl (pGlu) imide moiety. This activation increases the susceptibility of a peptide bond toward hydrolysis. The method is highly specific and demonstrates broad substrate scope including cleavage of various bioactive peptides with unnatural amino acid residues, which are unsuitable substrates for enzymatic hydrolysis.

An Expedient Procedure for the Oxidative Cleavage of Olefinic Bonds with PhI(OAc)2, NMO, and Catalytic OsO4

PubMed Central

Nicolaou, K. C.; Adsool, Vikrant A.; Hale, Christopher R. H.

2010-01-01

PhI(OAc)2 in the presence of OsO4 (cat.) and 2,6-lutidine cleaves olefinic bonds to yield the corresponding carbonyl compounds, albeit, in some cases, with α-hydroxy ketones as by-products. A more practical and clean protocol to effect oxidative cleavage of olefinic bonds involves NMO, OsO4 (cat.), 2,6-lutidine, and PhI(OAc)2. PMID:20192259

Catabolism of gastrin releasing peptide and substance P by gastric membrane-bound peptidases.

PubMed

Bunnett, N W; Kobayashi, R; Orloff, M S; Reeve, J R; Turner, A J; Walsh, J H

1985-01-01

The catabolism of two gastric neuropeptides, the C-terminal decapeptide of gastrin releasing peptide-27 (GRP10) and substance P (SP), by membrane-bound peptidases of the porcine gastric corpus and by porcine endopeptidase-24.11 ("enkephalinase") has been investigated. GRP10 was catabolized by gastric muscle peptidases (specific activity 1.8 nmol min-1 mg-1 protein) by hydrolysis of the His8-Leu9 bond and catabolism was inhibited by phosphoramidon (I50 approx. 10(-8) M), a specific inhibitor of endopeptidase-24.11. The same bond in GRP10 was cleaved by purified endopeptidase-24.11, and hydrolysis was equally sensitive to inhibition by phosphoramidon. SP was catabolized by gastric muscle peptidases (specific activity 1.7 nmol min-1 mg-1 protein) by hydrolysis of the Gln6-Phe7, Phe7-Phe8 and Gly9-Leu10 bonds, which is identical to the cleavage of SP by purified endopeptidase-24.11. The C-terminal cleavage of GRP10 and SP would inactivate the peptides. It is concluded that a membrane-bound peptidase in the stomach wall catabolizes and inactivates GRP10 and SP and that, in its specificity and sensitivity to phosphoramidon, this peptidase resembles endopeptidase-24.11.

Reversible Twisting of Primary Amides via Ground State N-C(O) Destabilization: Highly Twisted Rotationally Inverted Acyclic Amides.

PubMed

Meng, Guangrong; Shi, Shicheng; Lalancette, Roger; Szostak, Roman; Szostak, Michal

2018-01-17

Since the seminal studies by Pauling in 1930s, planarity has become the defining characteristic of the amide bond. Planarity of amides has central implications for the reactivity and chemical properties of amides of relevance to a range of chemical disciplines. While the vast majority of amides are planar, nonplanarity has a profound effect on the properties of the amide bond, with the most common method to restrict the amide bond relying on the incorporation of the amide function into a rigid cyclic ring system. In a major departure from this concept, here, we report the first class of acyclic twisted amides that can be prepared, reversibly, from common primary amides in a single, operationally trivial step. Di-tert-butoxycarbonylation of the amide nitrogen atom yields twisted amides in which the amide bond exhibits nearly perpendicular twist. Full structural characterization of a range of electronically diverse compounds from this new class of twisted amides is reported. Through reactivity studies we demonstrate unusual properties of the amide bond, wherein selective cleavage of the amide bond can be achieved by a judicious choice of the reaction conditions. Through computational studies we evaluate structural and energetic details pertaining to the amide bond deformation. The ability to selectively twist common primary amides, in a reversible manner, has important implications for the design and application of the amide bond nonplanarity in structural chemistry, biochemistry and organic synthesis.

Knocking on wood: base metal complexes as catalysts for selective oxidation of lignin models and extracts.

PubMed

Hanson, Susan K; Baker, R Tom

2015-07-21

This work began as part of a biomass conversion catalysis project with UC Santa Barbara funded by the first NSF Chemical Bonding Center, CATSB. Recognizing that catalytic aerobic oxidation of diol C-C bonds could potentially be used to break down lignocellulose, we began to synthesize oxovanadium complexes and explore their fundamental reactivity. Of course there were theories regarding the oxidation mechanism, but our mechanistic studies soon revealed a number of surprises of the type that keep all chemists coming back to the bench! We realized that these reactions were also exciting in that they actually used the oxygen-on-every-carbon property of biomass-derived molecules to control the selectivity of the oxidation. When we found that these oxovanadium complexes tended to convert sugars predominantly to formic acid and carbon dioxide, we replaced one of the OH groups with an ether and entered the dark world of lignin chemistry. In this Account, we summarize results from our collaboration and from our individual labs. In particular, we show that oxidation selectivity (C-C vs C-O bond cleavage) of lignin models using air and vanadium complexes depends on the ancillary ligands, the reaction solvent, and the substrate structure (i.e., phenolic vs non-phenolic). Selected vanadium complexes in the presence of added base serve as effective alcohol oxidation catalysts via a novel base-assisted dehydrogenation pathway. In contrast, copper catalysts effect direct C-C bond cleavage of these lignin models, presumably through a radical pathway. The most active vanadium catalyst exhibits unique activity for the depolymerization of organosolv lignin. After Weckhuysen's excellent 2010 review on lignin valorization, the number of catalysis studies and approaches on both lignin models and extracts has expanded rapidly. Today we are seeing new start-ups and lignin production facilities sprouting up across the globe as we all work to prove wrong the old pulp and paper chemist's adage: you can make anything from lignin except money!

Unimolecular dissociation of protonated trans-1,4-diphenyl-2-butene-1,4-dione in the gas phase: rearrangement versus simple cleavage.

PubMed

Wu, Lianming; Liu, David Q; Vogt, Frederick G

2006-01-01

Fragmentation mechanisms of trans-1,4-diphenyl-2-butene-1,4-dione were studied using a variety of mass spectrometric techniques. The major fragmentation pathways occur by various rearrangements by loss of H(2)O, CO, H(2)O and CO, and CO(2). The other fragmentation pathways via simple alpha cleavages were also observed but accounted for the minor dissociation channels in both a two-dimensional (2-D) linear ion trap and a quadrupole time-of-flight (Q-TOF) mass spectrometer. The elimination of CO(2) (rather than CH(3)CHO or C(3)H(8)), which was confirmed by an exact mass measurement using the Q-TOF instrument, represented a major fragmentation pathway in the 2-D linear ion trap mass spectrometer. However, the elimination of H(2)O and CO becomes more competitive in the beam-type Q-TOF instrument. The loss of CO is observed in both the MS(2) experiment of m/z 237 and the MS(3) experiment of m/z 219 but via the different transition states. The data suggest that the olefinic double bond in protonated trans-1,4-diphenyl-2-butene-1,4-dione plays a key role in stabilizing the rearrangement transition states and increasing the bond dissociation (cleavage) energy to give favorable rearrangement fragmentation pathways. Copyright (c) 2006 John Wiley & Sons, Ltd.

A new and efficient synthetic method for 15N3-labeled cytosine nucleosides: Dimroth rearrangement of cytidine N3-oxides.

PubMed

Sako, Magoichi; Kawada, Hiroyoshi

2004-11-12

The treatment of (15)N(4)-labeled cytidine N(3)-oxide and (15)N(4)-labeled 2'-deoxycytidine N(3)-oxide, prepared from the appropriate unprotected uridines in three reaction steps, with benzyl bromide in the presence of excess lithium methoxide allowed the smooth occurrence of their Dimroth rearrangement even under mild conditions leading to the corresponding (15)N(3)-labeled uridine 4-O-benzyloximes which can easily undergo the reductive N-O bond cleavage to give the desirable (15)N(3)-labeled cytosine nucleosides in high total yields.

Crystal structure of rubidium methyl-diazo-tate.

PubMed

Grassl, Tobias; Korber, Nikolaus

2017-02-01

The title compound, Rb + ·H 3 CN 2 O - , has been crystallized in liquid ammonia as a reaction product of the reductive ammonolysis of the natural compound streptozocin. Elemental rubidium was used as reduction agent as it is soluble in liquid ammonia, forming a blue solution. Reductive bond cleavage in biogenic materials under kinetically controlled conditions offers a new approach to gain access to sustainably produced raw materials. The anion is nearly planar [dihedral angle O-N-N-C = -0.4 (2)°]. The Rb + cation has a coordination number of seven, and coordinates to five anions. One anion is bound via both its N atoms, one by both O and N, two anions are bound by only their O atoms, and the last is bound via the N atom adjacent to the methyl group. The diazo-tate anions are bridged by cations and do not exhibit any direct contacts with each other. The cations form corrugated layers that propagate in the (-101) plane.

Role of the Active Site Guanine in the glmS Ribozyme Self-Cleavage Mechanism: Quantum Mechanical/Molecular Mechanical Free Energy Simulations

PubMed Central

2015-01-01

The glmS ribozyme catalyzes a self-cleavage reaction at the phosphodiester bond between residues A-1 and G1. This reaction is thought to occur by an acid–base mechanism involving the glucosamine-6-phosphate cofactor and G40 residue. Herein quantum mechanical/molecular mechanical free energy simulations and pKa calculations, as well as experimental measurements of the rate constant for self-cleavage, are utilized to elucidate the mechanism, particularly the role of G40. Our calculations suggest that an external base deprotonates either G40(N1) or possibly A-1(O2′), which would be followed by proton transfer from G40(N1) to A-1(O2′). After this initial deprotonation, A-1(O2′) starts attacking the phosphate as a hydroxyl group, which is hydrogen-bonded to deprotonated G40, concurrent with G40(N1) moving closer to the hydroxyl group and directing the in-line attack. Proton transfer from A-1(O2′) to G40 is concomitant with attack of the scissile phosphate, followed by the remainder of the cleavage reaction. A mechanism in which an external base does not participate, but rather the proton transfers from A-1(O2′) to a nonbridging oxygen during nucleophilic attack, was also considered but deemed to be less likely due to its higher effective free energy barrier. The calculated rate constant for the favored mechanism is in agreement with the experimental rate constant measured at biological Mg2+ ion concentration. According to these calculations, catalysis is optimal when G40 has an elevated pKa rather than a pKa shifted toward neutrality, although a balance among the pKa’s of A-1, G40, and the nonbridging oxygen is essential. These results have general implications, as the hammerhead, hairpin, and twister ribozymes have guanines at a similar position as G40. PMID:25526516

Acetonitrile covalent adduct chemical ionization mass spectrometry for double bond localization in non-methylene-interrupted polyene fatty acid methyl esters.

PubMed

Lawrence, Peter; Brenna, J Thomas

2006-02-15

Covalent adduct chemical ionization (CACI) using a product of acetonitrile self-reaction, (1-methyleneimino)-1-ethenylium (MIE; CH2=C=N+=CH2), has been investigated as a method for localizing double bonds in a series of 16 non-methylene-interrupted fatty acid methyl esters (NMI-FAME) of polyenes with three and more double bonds. As with polyunsaturated homoallylic (methylene-interrupted) FAME and conjugated dienes, MIE (m/z 54) reacts across double bonds to yield molecular ions 54 mass units above the parent analyte. [M + 54]+ ions of several 20- and 22-carbon FAME that include one double bond in the C2-C3 position separated by two to five methylene units from a three, four, or five C homoallylic system dissociated according to rules for the homoallylic system, with an additional fragment corresponding to cleavage between the lone double bond and the carboxyl group and defining the position of the lone double bond. Triene FAME with both methylene and ethylene interruption yielded characteristic fragments distinguishable from homoallylic trienes. Fragmentation of fully conjugated trienes in the MS-1 spectra yields ratios of [M + 54]+/[M + 54 - 32]+ (loss of methanol) near unity, which distinguishes them from homoallylic FAME having a ratio of 8 or more; collisionally activated dissociation of [M + 54]+ yields a series of ions, including some rearrangement products, indicative of double bond position. Unlike conjugated dienes, fully conjugated triene diagnostic ion signal ratios did not follow any pattern based on double bond geometry. Partially conjugated trienes behave similarly to monoenes and conjugated dienes, yielding [M + 54]+/[M + 54 - 32]+ of 2-3 and, permitting them to be assigned as partially conjugated FAME using the MS-1 spectrum. They yield unique MS/MS spectra with weaker but assignable fragment ions, along with a diagnostic fragment that locates the lone double bond and permits 6,10,12-octatrienoate to be distinguished from 6,8,12-octatrienoate. The presence of a triple bond did not affect fragment formation in a methylene-interrupted yne-ene but did change fragments in a conjugated yne-ene. These data extend the principle of double bond localization by acetonitrile CACI-MS/MS to double bond structure in complex FAME found in nature.

Mechanistic Analysis of Oxidative C–H Cleavages Using Inter- and Intramolecular Kinetic Isotope Effects

PubMed Central

Jung, Hyung Hoon; Floreancig, Paul E.

2009-01-01

A series of monodeuterated benzylic and allylic ethers were subjected to oxidative carbon–hydrogen bond cleavage to determine the impact of structural variation on intramolecular kinetic isotope effects in DDQ-mediated cyclization reactions. These values are compared to the corresponding intermolecular kinetic isotope effects that were accessed through subjecting mixtures of non-deuterated and dideuterated substrates to the reaction conditions. The results indicate that carbon–hydrogen bond cleavage is rate determining and that a radical cation is most likely a key intermediate in the reaction mechanism. PMID:20640173

Selective collision-induced fragmentation of ortho-hydroxybenzyl-aminated lysyl-containing tryptic peptides.

PubMed

Simon, E S; Papoulias, P G; Andrews, P C

2013-07-30

In protein studies that employ tandem mass spectrometry the manipulation of protonated peptide fragmentation through exclusive dissociation pathways may be preferred in some applications over the comprehensive amide backbone fragmentation that is typically observed. In this study, we characterized the selective cleavage of the side-chain Cζ-Nε bond of peptides with ortho-hydroxybenzyl-aminated lysine residues. Internal lysyl residues of representative peptides were derivatized via reductive amination with ortho-hydroxybenzaldehyde. The modified peptides were analyzed using collision-induced dissociation (CID) on an Orbitrap tandem mass spectrometer. Theoretical calculations using computational methods (density functional theory) were performed to investigate the potential dissociation mechanisms for the Cζ-Nε bond of the derivatized lysyl residue resulting in the formation of the observed product ions. Tandem mass spectra of the derivatized peptide ions exhibit product peaks corresponding to selective cleavage of the side-chain Cζ-Nε bond that links the derivative to lysine. The ortho-hydroxybenzyl derivative is released either as a neutral moiety [C7H6O1] or as a carbocation [C7H7O1](+) through competing pathways (retro-Michael versus Carbocation Elimination (CCE), respectively). The calculated transition state activation barriers indicate that the retro-Michael pathway is kinetically favored over CCE and both are favored over amide cleavage. The application of ortho-hydroxybenzyl amination is a promising peptide derivatization scheme for promoting selective dissociation pathways in the tandem mass spectrometry of protonated peptides. This can be implemented in the rational development of peptide reactive reagents for applications that may benefit from selective fragmentation paths (including crosslinking or MRM reagents). Copyright © 2013 John Wiley & Sons, Ltd.

Sulfoximine-mediated syntheses of optically active alcohols. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Stark, C. J., Jr.

1978-01-01

Several routes are described for the production of optically active secondary and tertiary alcohols. In all cases, the asymmetry emanates from the use of (+)-(S)-N,S-dimethyl-S-phenyl-sulfoximine (1) at some point in the variation of the diastereomers. One route relies upon the separation of the diastereomers produced from the condensation of (+)-(S)-(N-methylphenyl-sulfonimidoyl) methyllithium with prochiral aldehydes and ketones. Subsequent carbon-sulfur bond cleavage of the separated diastereomeric beta-hydroxysulfoximines yields optically active alcohols. Alternatively, beta-hydroxysulfoximines were produced from the reduction of chiral beta-ketosulfoximines. The reductions were most successfully achieved with diborane generated externally and bubbled into a toluene solution of the ketone at -78 C. Optically active alcohols were also produced from prochiral ketones by reduction with diborane or lithium aluminum hydride complexes of resolved diastereomers of beta-hydroxysulfoximines.

Intracellular Chemistry: Integrating Molecular Inorganic Catalysts with Living Systems.

PubMed

Ngo, Anh H; Bose, Sohini; Do, Loi H

2018-03-23

This concept article focuses on the rapid growth of intracellular chemistry dedicated to the integration of small-molecule metal catalysts with living cells and organisms. Although biological systems contain a plethora of biomolecules that can deactivate inorganic species, researchers have shown that small-molecule metal catalysts could be engineered to operate in heterogeneous aqueous environments. Synthetic intracellular reactions have recently been reported for olefin hydrogenation, hydrolysis/oxidative cleavage, azide-alkyne cycloaddition, allylcarbamate cleavage, C-C bond cross coupling, and transfer hydrogenation. Other promising targets for new biocompatible reaction discovery will also be discussed, with a special emphasis on how such innovations could lead to the development of novel technologies and chemical tools. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Copper-Catalyzed Intermolecular Amidation and Imidation of Unactivated Alkanes

PubMed Central

2015-01-01

We report a set of rare copper-catalyzed reactions of alkanes with simple amides, sulfonamides, and imides (i.e., benzamides, tosylamides, carbamates, and phthalimide) to form the corresponding N-alkyl products. The reactions lead to functionalization at secondary C–H bonds over tertiary C–H bonds and even occur at primary C–H bonds. [(phen)Cu(phth)] (1-phth) and [(phen)Cu(phth)2] (1-phth2), which are potential intermediates in the reaction, have been isolated and fully characterized. The stoichiometric reactions of 1-phth and 1-phth2 with alkanes, alkyl radicals, and radical probes were investigated to elucidate the mechanism of the amidation. The catalytic and stoichiometric reactions require both copper and tBuOOtBu for the generation of N-alkyl product. Neither 1-phth nor 1-phth2 reacted with excess cyclohexane at 100 °C without tBuOOtBu. However, the reactions of 1-phth and 1-phth2 with tBuOOtBu afforded N-cyclohexylphthalimide (Cy-phth), N-methylphthalimide, and tert-butoxycyclohexane (Cy-OtBu) in approximate ratios of 70:20:30, respectively. Reactions with radical traps support the intermediacy of a tert-butoxy radical, which forms an alkyl radical intermediate. The intermediacy of an alkyl radical was evidenced by the catalytic reaction of cyclohexane with benzamide in the presence of CBr4, which formed exclusively bromocyclohexane. Furthermore, stoichiometric reactions of [(phen)Cu(phth)2] with tBuOOtBu and (Ph(Me)2CO)2 at 100 °C without cyclohexane afforded N-methylphthalimide (Me-phth) from β-Me scission of the alkoxy radicals to form a methyl radical. Separate reactions of cyclohexane and d12-cyclohexane with benzamide showed that the turnover-limiting step in the catalytic reaction is the C–H cleavage of cyclohexane by a tert-butoxy radical. These mechanistic data imply that the tert-butoxy radical reacts with the C–H bonds of alkanes, and the subsequent alkyl radical combines with 1-phth2 to form the corresponding N-alkyl imide product. PMID:24405209

Oxidation mechanism of formic acid on the bismuth adatom-modified Pt(111) surface.

PubMed

Perales-Rondón, Juan Victor; Ferre-Vilaplana, Adolfo; Feliu, Juan M; Herrero, Enrique

2014-09-24

In order to improve catalytic processes, elucidation of reaction mechanisms is essential. Here, supported by a combination of experimental and computational results, the oxidation mechanism of formic acid on Pt(111) electrodes modified by the incorporation of bismuth adatoms is revealed. In the proposed model, formic acid is first physisorbed on bismuth and then deprotonated and chemisorbed in formate form, also on bismuth, from which configuration the C-H bond is cleaved, on a neighbor Pt site, yielding CO2. It was found computationally that the activation energy for the C-H bond cleavage step is negligible, which was also verified experimentally.

Detection of OH on photolysis of styrene oxide at 193 nm in gas phase

NASA Astrophysics Data System (ADS)

Kumar, Awadhesh; SenGupta, Sumana; Pushpa, K. K.; Naik, P. D.; Bajaj, P. N.

2006-10-01

Photodissociation of styrene oxide at 193 nm in gas phase generates OH, as detected by laser-induced fluorescence technique. Under similar conditions, OH was not observed from ethylene and propylene oxides, primarily because of their low absorption cross-sections at 193 nm. Mechanism of OH formation involves first opening of the three-membered ring from the ground electronic state via cleavage of either of two C sbnd O bonds, followed by isomerization to enolic forms of phenylacetaldehyde and acetophenone, and finally scission of the C sbnd OH bond of enols. Ab initio molecular orbital calculations support the proposed mechanism.

Characterization of Disulfide-Linked Peptides Using Tandem Mass Spectrometry Coupled with Automated Data Analysis Software

NASA Astrophysics Data System (ADS)

Liang, Zhidan; McGuinness, Kenneth N.; Crespo, Alejandro; Zhong, Wendy

2018-05-01

Disulfide bond formation is critical for maintaining structure stability and function of many peptides and proteins. Mass spectrometry has become an important tool for the elucidation of molecular connectivity. However, the interpretation of the tandem mass spectral data of disulfide-linked peptides has been a major challenge due to the lack of appropriate tools. Developing proper data analysis software is essential to quickly characterize disulfide-linked peptides. A thorough and in-depth understanding of how disulfide-linked peptides fragment in mass spectrometer is a key in developing software to interpret the tandem mass spectra of these peptides. Two model peptides with inter- and intra-chain disulfide linkages were used to study fragmentation behavior in both collisional-activated dissociation (CAD) and electron-based dissociation (ExD) experiments. Fragments generated from CAD and ExD can be categorized into three major types, which result from different S-S and C-S bond cleavage patterns. DiSulFinder is a computer algorithm that was newly developed based on the fragmentation observed in these peptides. The software is vendor neutral and capable of quickly and accurately identifying a variety of fragments generated from disulfide-linked peptides. DiSulFinder identifies peptide backbone fragments with S-S and C-S bond cleavages and, more importantly, can also identify fragments with the S-S bond still intact to aid disulfide linkage determination. With the assistance of this software, more comprehensive disulfide connectivity characterization can be achieved. [Figure not available: see fulltext.

Characterization of Disulfide-Linked Peptides Using Tandem Mass Spectrometry Coupled with Automated Data Analysis Software

NASA Astrophysics Data System (ADS)

Liang, Zhidan; McGuinness, Kenneth N.; Crespo, Alejandro; Zhong, Wendy

2018-01-01

Disulfide bond formation is critical for maintaining structure stability and function of many peptides and proteins. Mass spectrometry has become an important tool for the elucidation of molecular connectivity. However, the interpretation of the tandem mass spectral data of disulfide-linked peptides has been a major challenge due to the lack of appropriate tools. Developing proper data analysis software is essential to quickly characterize disulfide-linked peptides. A thorough and in-depth understanding of how disulfide-linked peptides fragment in mass spectrometer is a key in developing software to interpret the tandem mass spectra of these peptides. Two model peptides with inter- and intra-chain disulfide linkages were used to study fragmentation behavior in both collisional-activated dissociation (CAD) and electron-based dissociation (ExD) experiments. Fragments generated from CAD and ExD can be categorized into three major types, which result from different S-S and C-S bond cleavage patterns. DiSulFinder is a computer algorithm that was newly developed based on the fragmentation observed in these peptides. The software is vendor neutral and capable of quickly and accurately identifying a variety of fragments generated from disulfide-linked peptides. DiSulFinder identifies peptide backbone fragments with S-S and C-S bond cleavages and, more importantly, can also identify fragments with the S-S bond still intact to aid disulfide linkage determination. With the assistance of this software, more comprehensive disulfide connectivity characterization can be achieved. [Figure not available: see fulltext.

SEA domain autoproteolysis accelerated by conformational strain: energetic aspects.

PubMed

Sandberg, Anders; Johansson, Denny G A; Macao, Bertil; Härd, Torleif

2008-04-04

A subclass of proteins with the SEA (sea urchin sperm protein, enterokinase, and agrin) domain fold exists as heterodimers generated by autoproteolytic cleavage within a characteristic G(-1)S+1VVV sequence. Autoproteolysis occurs by a nucleophilic attack of the serine hydroxyl on the vicinal glycine carbonyl followed by an N-->O acyl shift and hydrolysis of the resulting ester. The reaction has been suggested to be accelerated by the straining of the scissile peptide bond upon protein folding. In an accompanying article, we report the mechanism; in this article, we provide further key evidence and account for the energetics of coupled protein folding and autoproteolysis. Cleavage of the GPR116 domain and that of the MUC1 SEA domain occur with half-life (t((1/2))) values of 12 and 18 min, respectively, with lowering of the free energy of the activation barrier by approximately 10 kcal mol(-1) compared with uncatalyzed hydrolysis. The free energies of unfolding of the GPR116 and MUC1 SEA domains were measured to approximately 11 and approximately 15 kcal mol(-1), respectively, but approximately 7 kcal mol(-1) of conformational energy is partitioned as strain over the scissile peptide bond in the precursor to catalyze autoproteolysis by substrate destabilization. A straining energy of approximately 7 kcal mol(-1) was measured by using both a pre-equilibrium model to analyze stability and cleavage kinetics data obtained with the GPR116 SEA domain destabilized by core mutations or urea addition, as well as the difference in thermodynamic stabilities of the MUC1 SEA precursor mutant S1098A (with a G(-1)A+1VVV motif) and the wild-type protein. The results imply that cleavage by N-->O acyl shift alone would proceed with a t((1/2)) of approximately 2.3 years, which is too slow to be biochemically effective. A subsequent review of structural data on other self-cleaving proteins suggests that conformational strain of the scissile peptide bond may be a common mechanism of autoproteolysis.

Bio-inspired MOF-based Catalysts for Lignin Valorization.

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

Allendorf, Mark D.; Stavila, Vitalie; Ramakrishnan, Parthasarathi

2014-09-01

Lignin is a potentially plentiful source of renewable organics, with %7E50Mtons/yr produced by the pulp/paper industry and 200-300 Mtons/yr projected production by a US biofuels industry. This industry must process approximately 1 billion tons of biomass to meet the US Renewable Fuel goals. However, there are currently no efficient processes for converting lignin to value-added chemicals and drop-in fuels. Lignin is therefore an opportunity for production of valuable renewable chemicals, but presents staggering technical and economic challenges due to the quantities of material involved and the strong chemical bonds comprising this polymer. Aggressive chemistries and high temperatures are required tomore » degrade lignin without catalysts. Moreover, chemical non-uniformity among lignins leads to complex product mixtures that tend to repolymerize. Conventional petrochemical approaches (pyrolysis, catalytic cracking, gasification) are energy intensive (400-800 degC), require complicated separations, and remove valuable chemical functionality. Low-temperature (25-200 degC) alternatives are clearly desirable, but enzymes are thermally fragile and incompatible with liquid organic compounds, making them impractical for large-scale biorefining. Alternatively, homogeneous catalysts, such as recently developed vanadium complexes, must be separated from product mixtures, while many heterogenous catalysts involve costly noble metals. The objective of this project is to demonstrate proof of concept that an entirely new class of biomimetic, efficient, and industrially robust synthetic catalysts based on nanoporous Metal- Organic Frameworks (MOFs) can be developed. Although catalytic MOFs are known, catalysis of bond cleavage reactions needed for lignin degradation is completely unexplored. Thus, fundamental research is required that industry and most sponsoring agencies are currently unwilling to undertake. We introduce MOFs infiltrated with titanium and nickel species as catalysts for the C-O bond hydrogenolysis in model compounds, which mimic the b-O-4, a-O-4, and 4-O-5 linkages of natural lignin. The versatile IRMOF-74(n) series is proposed as a platform for creating efficient hydrogenolysis catalysts as it not only displays tunable pore sizes, but also has the required thermal and chemical stability. The catalytic C-O bond cleavage occurs at 10 bar hydrogen pressure and temperatures as low as 120 degC. The conversion efficiency of the aromatic ether substrates into the corresponding hydrocarbons and phenols varies as PhCH 2 CH 2 OPh > PhCH 2 OPh > PhOPh (Ph = phenyl), while the catalytic activity generally follows the following trend Ni@IRMOF-74>Ti@IRMOF-74>IRMOF-74. Conversions as high as 80%, coupled with good selectivity for hydrogenolysis vs. hydrogenation, highlight the potential of MOF-based catalysts for the selective cleavage of recalcitrant aryl-ether bonds found in lignin and other biopolymers. This project supports the DOE Integrated Biorefinery Program goals, the objective of which is to convert biomass to fuels and high-value chemicals, by addressing an important technology gap: the lack of low-temperature catalysts suitable for industrial lignin degradation. Biomass, which is %7E30 wt% lignin, constitutes a potentially major source of platform chemicals that could improve overall profitability and productivity of all energy-related products, thereby benefiting consumers and reducing national dependence on imported oil. Additionally, DoD has a strong interest in low-cost drop-in fuels (Navy Biofuel Initiative) and has signed a Memorandum of Understanding with DOE and USDA to develop a sustainable biofuels industry.« less

Efficient synthesis of isochromanones and isoquinolines via Yb(OTf)3-catalyzed tandem oxirane/aziridine ring opening/Friedel-Crafts cyclization.

PubMed

Wei, Lai; Zhang, Junliang

2012-03-07

The first example of Yb(OTf)(3)-catalyzed tandem ring opening/Friedel-Crafts cyclization of oxiranyl and aziridinyl ketones via selective C-C bond cleavage under mild conditions was developed. Isochromanones and isoquinolines are formed in reasonable yields, which often serve as building blocks for complex chemical synthesis. This journal is © The Royal Society of Chemistry 2012

Geometrical flexibility of platinum nanoclusters: impacts on catalytic decomposition of ethylene glycol.

PubMed

Mahmoodinia, Mehdi; Trinh, Thuat T; Åstrand, Per-Olof; Tran, Khanh-Quang

2017-11-01

Catalytic decomposition of ethylene glycol on the Pt 13 cluster was studied as a model system for hydrogen production from a lignocellulosic material. Ethylene glycol was chosen as a starting material because of two reasons, it is the smallest oxygenate with a 1 : 1 carbon to oxygen ratio and it contains the C-H, O-H, C-C, and C-O bonds also present in biomass. Density functional theory calculations were employed for predictions of reaction pathways for C-H, O-H, C-C and C-O cleavages, and Brønsted-Evans-Polanyi relationships were established between the final state and the transition state for all mechanisms. The results show that Pt 13 catalyzes the cleavage reactions of ethylene glycol more favourably than a Pt surface. The flexibility of Pt 13 clusters during the reactions is the key factor in reducing the activation barrier. Overall, the results demonstrate that ethylene glycol and thus biomass can be efficiently converted into hydrogen using platinum nanoclusters as catalysts.

Crystal structure of the fluorescent protein from Dendronephthya sp. in both green and photoconverted red forms

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

Pletneva, Nadya V.; Pletnev, Sergei; Pakhomov, Alexey A.

The fluorescent protein fromDendronephthyasp. (DendFP) is a member of the Kaede-like group of photoconvertible fluorescent proteins with a His62-Tyr63-Gly64 chromophore-forming sequence. Upon irradiation with UV and blue light, the fluorescence of DendFP irreversibly changes from green (506 nm) to red (578 nm). The photoconversion is accompanied by cleavage of the peptide backbone at the C α—N bond of His62 and the formation of a terminal carboxamide group at the preceding Leu61. The resulting double C α=C βbond in His62 extends the conjugation of the chromophore π system to include imidazole, providing the red fluorescence. Here, the three-dimensional structures of nativemore » green and photoconverted red forms of DendFP determined at 1.81 and 2.14 Å resolution, respectively, are reported. This is the first structure of photoconverted red DendFP to be reported to date. The structure-based mutagenesis of DendFP revealed an important role of positions 142 and 193: replacement of the original Ser142 and His193 caused a moderate red shift in the fluorescence and a considerable increase in the photoconversion rate. It was demonstrated that hydrogen bonding of the chromophore to the Gln116 and Ser105 cluster is crucial for variation of the photoconversion rate. The single replacement Gln116Asn disrupts the hydrogen bonding of Gln116 to the chromophore, resulting in a 30-fold decrease in the photoconversion rate, which was partially restored by a further Ser105Asn replacement.« less

The GlcN6P cofactor serves multiple catalytic roles in the glmS ribozyme

PubMed Central

Bingaman, Jamie L.; Zhang, Sixue; Stevens, David R.; Yennawar, Neela H.; Hammes-Schiffer, Sharon; Bevilacqua, Philip C.

2017-01-01

RNA enzymes have remarkably diverse biological roles despite having limited chemical diversity. Protein enzymes enhance their reactivity through recruitment of cofactors. The naturally occurring glmS ribozyme uses the glucosamine-6-phosphate (GlcN6P) organic cofactor for phosphodiester bond cleavage. Prior structural and biochemical studies implicated GlcN6P as the general acid. Here we describe new catalytic roles for GlcN6P through experiments and calculations. Large stereospecific normal thio effects and lack of metal ion rescue in the holoribozyme show that nucleobases and the cofactor play direct chemical roles and align the active site for self-cleavage. Large stereospecific inverse thio effects in the aporibozyme suggest that the GlcN6P cofactor disrupts an inhibitory interaction of the nucleophile. Strong metal ion rescue in the aporibozyme reveals this cofactor also provides electrostatic stabilization. Ribozyme organic cofactors thus perform myriad catalytic roles, allowing RNA to compensate for its limited functional diversity. PMID:28192411

A DNA enzyme with N-glycosylase activity

NASA Technical Reports Server (NTRS)

Sheppard, T. L.; Ordoukhanian, P.; Joyce, G. F.

2000-01-01

In vitro evolution was used to develop a DNA enzyme that catalyzes the site-specific depurination of DNA with a catalytic rate enhancement of about 10(6)-fold. The reaction involves hydrolysis of the N-glycosidic bond of a particular deoxyguanosine residue, leading to DNA strand scission at the apurinic site. The DNA enzyme contains 93 nucleotides and is structurally complex. It has an absolute requirement for a divalent metal cation and exhibits optimal activity at about pH 5. The mechanism of the reaction was confirmed by analysis of the cleavage products by using HPLC and mass spectrometry. The isolation and characterization of an N-glycosylase DNA enzyme demonstrates that single-stranded DNA, like RNA and proteins, can form a complex tertiary structure and catalyze a difficult biochemical transformation. This DNA enzyme provides a new approach for the site-specific cleavage of DNA molecules.

Diastereoselective sp2-sp3 coupling of sugar enol ethers with unactivated cycloalkenes: new entries to C-branched sugars.

PubMed

Hussain, Nazar; Tatina, Madhu Babu; Rasool, Faheem; Mukherjee, Debaraj

2016-10-25

Sugar enol ethers undergo efficient coupling at C-2 with unactivated cycloalkenes under a low Pd loading affording allylic substitution products. High diastereoselectivity was observed at the allylic centre with sterically hindered substrates. Generation of a π-allyl complex by the Pd(ii) catalyst via cleavage of the allylic C-H bond of the cycloalkene may be responsible for the formation of sp 2 -sp 3 coupling products.

Formation and Characterization of Silver Nanoparticle Composite with Poly(p-Br/F-phenylsilane).

PubMed

Roh, Sung-Hee; Noh, Ji Eun; Woo, Hee-Gweon; Cho, Myong-Shik; Sohn, Honglae

2015-02-01

The one-pot production and structural characterization of composites of silver nanoparticles with poly(p-Br/F-phenylsilane), Br/F-PPS, have been performed. The conversion of Ag+ ions to stable Ag0 nanoparticles is mediated by the copolymer Br/F-PPS having both possibly reactive Si-H bonds in the polymer backbone and C-Br bonds in the substituents along with relatively inert C-F bonds. Transmission electron microscopy and field emission scanning electron microscopy analyses show the formation of the composites where silver nanoparticles (less than 30 nm of size) are well dispersed over the Br/F-PPS matrix. X-ray diffraction patterns are consistent with that for face-centered-cubic typed silver. The polymer solubility in toluene implys that the cleavage of C-Br bond and the Si-F dative bonding may not be occurred appreciably at ambient temperature. Nonetheless, thermogravimetric analysis data suggest that some sort of cross-linking could take place at high temperature. Most of the silver particles undergo macroscopic aggregation without Br/F-PPS, which indicates that the polysilane is necessary for stabilizing the silver nanoparticles.

The covalently bound diazo group as an infrared probe for hydrogen bonding environments.

PubMed

You, Min; Liu, Liyuan; Zhang, Wenkai

2017-07-26

Covalently bound diazo groups are frequently found in biomolecular substrates. The C[double bond, length as m-dash]N[double bond, length as m-dash]N asymmetric stretching vibration (ν as ) of the diazo group has a large extinction coefficient and appears in an uncongested spectral region. To evaluate the solvatochromism of the C[double bond, length as m-dash]N[double bond, length as m-dash]N ν as band for studying biomolecules, we recorded the infrared (IR) spectra of a diazo model compound, 2-diazo-3-oxo-butyric acid ethyl ester, in different solvents. The width of the C[double bond, length as m-dash]N[double bond, length as m-dash]N ν as band was linearly dependent on the Kamlet-Taft solvent parameter, which reflects the polarizability and hydrogen bond accepting ability of the solvent. Therefore, the width of the C[double bond, length as m-dash]N[double bond, length as m-dash]N ν as band could be used to probe these properties for a solvent. We found that the position of the C[double bond, length as m-dash]N[double bond, length as m-dash]N ν as band was linearly correlated with the density of hydrogen bond donor groups in the solvent. We studied the relaxation dynamics and spectral diffusion of the C[double bond, length as m-dash]N[double bond, length as m-dash]N ν as band of a natural amino acid, 6-diazo-5-oxo-l-norleucine, in water using nonlinear IR spectroscopy. The relaxation and spectral diffusion time constants of the C[double bond, length as m-dash]N[double bond, length as m-dash]N ν as band were similar to those of the N[double bond, length as m-dash]N[double bond, length as m-dash]N ν as band. We concluded that the position and width of the C[double bond, length as m-dash]N[double bond, length as m-dash]N ν as band of the diazo group could be used to probe the hydrogen bond donating and accepting ability of a solvent, respectively. These results suggest that the diazo group could be used as a site-specific IR probe for the local hydration environments.

Charge stabilization and entropy reduction of central lysine residues in fructose-bisphosphate aldolase.

PubMed

St-Jean, Miguel; Blonski, Casimir; Sygusch, Jurgen

2009-06-02

Fructose-1,6-bisphosphate muscle aldolase is an essential glycolytic enzyme that catalyzes reversible carbon-carbon bond formation by cleaving fructose 1,6-bisphosphate to yield dihydroxyacetone phosphate (DHAP) and d-glyceraldehyde phosphate. To elucidate the mechanistic role of conserved amino acid Asp-33, Asn-33 and Ser-33 mutants were examined by kinetic and structural analyses. The mutations significantly compromised enzymatic activity and carbanion oxidation in presence of DHAP. Detailed structural analysis demonstrated that, like native crystals, Asp-33 mutant crystals, soaked in DHAP solutions, trapped Schiff base-derived intermediates covalently attached to Lys-229. The mutant structures, however, exhibited an abridged conformational change with the helical region (34-65) flanking the active site as well as pK(a) reductions and increased side chain disorder by central lysine residues, Lys-107 and Lys-146. These changes directly affect their interaction with the C-terminal Tyr-363, consistent with the absence of active site binding by the C-terminal region in the presence of phosphate. Lys-146 pK(a) reduction and side chain disorder would further compromise charge stabilization during C-C bond cleavage and proton transfer during enamine formation. These mechanistic impediments explain diminished catalytic activity and a reduced level of carbanion oxidation and are consistent with rate-determining proton transfer observed in the Asn-33 mutant. Asp-33 reduces the entropic cost and augments the enthalpic gain during catalysis by rigidifying Lys-107 and Lys-146, stabilizing their protonated forms, and promoting a conformational change triggered by substrate or obligate product binding, which lower kinetic barriers in C-C bond cleavage and Schiff base-enamine interconversion.

Structural and Enzymatic Analysis of MshA from Corynebacterium glutamicum

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

Vetting,M.; Frantom, P.; Blanchard, J.

2008-01-01

The glycosyltransferase termed MshA catalyzes the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine to 1-l-myo-inositol-1-phosphate in the first committed step of mycothiol biosynthesis. The structure of MshA from Corynebacterium glutamicum was determined both in the absence of substrates and in a complex with UDP and 1-l-myo-inositol-1-phosphate. MshA belongs to the GT-B structural family whose members have a two-domain structure with both domains exhibiting a Rossman-type fold. Binding of the donor sugar to the C-terminal domain produces a 97 rotational reorientation of the N-terminal domain relative to the C-terminal domain, clamping down on UDP and generating the binding site for 1-l-myo-inositol-1-phosphate. The structuremore » highlights the residues important in binding of UDP-N-acetylglucosamine and 1-l-myo-inositol-1-phosphate. Molecular models of the ternary complex suggest a mechanism in which the {beta}-phosphate of the substrate, UDP-N-acetylglucosamine, promotes the nucleophilic attack of the 3-hydroxyl group of 1-l-myo-inositol-1-phosphate while at the same time promoting the cleavage of the sugar nucleotide bond.« less

Mechanical forces regulate the reactivity of a thioester bond in a bacterial adhesin

PubMed Central

Echelman, Daniel J.; Lee, Alex Q.; Fernández, Julio M.

2017-01-01

Bacteria must withstand large mechanical shear forces when adhering to and colonizing hosts. Recent structural studies on a class of Gram-positive bacterial adhesins have revealed an intramolecular Cys-Gln thioester bond that can react with surface-associated ligands to covalently anchor to host surfaces. Two other examples of such internal thioester bonds occur in certain anti-proteases and in the immune complement system, both of which react with the ligand only after the thioester bond is exposed by a proteolytic cleavage. We hypothesized that mechanical forces in bacterial adhesion could regulate thioester reactivity to ligand analogously to such proteolytic gating. Studying the pilus tip adhesin Spy0125 of Streptococcus pyogenes, we developed a single molecule assay to unambiguously resolve the state of the thioester bond. We found that when Spy0125 was in a folded state, its thioester bond could be cleaved with the small-molecule nucleophiles methylamine and histamine, but when Spy0125 was mechanically unfolded and subjected to forces of 50–350 piconewtons, thioester cleavage was no longer observed. For folded Spy0125 without mechanical force exposure, thioester cleavage was in equilibrium with spontaneous thioester reformation, which occurred with a half-life of several minutes. Functionally, this equilibrium reactivity allows thioester-containing adhesins to sample potential substrates without irreversible cleavage and inactivation. We propose that such reversible thioester reactivity would circumvent potential soluble inhibitors, such as histamine released at sites of inflammation, and allow the bacterial adhesin to selectively associate with surface-bound ligands. PMID:28348083

DNA-Catalyzed DNA Cleavage by a Radical Pathway with Well-Defined Products.

PubMed

Lee, Yujeong; Klauser, Paul C; Brandsen, Benjamin M; Zhou, Cong; Li, Xinyi; Silverman, Scott K

2017-01-11

We describe an unprecedented DNA-catalyzed DNA cleavage process in which a radical-based reaction pathway cleanly results in excision of most atoms of a specific guanosine nucleoside. Two new deoxyribozymes (DNA enzymes) were identified by in vitro selection from N 40 or N 100 random pools initially seeking amide bond hydrolysis, although they both cleave simple single-stranded DNA oligonucleotides. Each deoxyribozyme generates both superoxide (O 2 -• or HOO • ) and hydrogen peroxide (H 2 O 2 ) and leads to the same set of products (3'-phosphoglycolate, 5'-phosphate, and base propenal) as formed by the natural product bleomycin, with product assignments by mass spectrometry and colorimetric assay. We infer the same mechanistic pathway, involving formation of the C4' radical of the guanosine nucleoside that is subsequently excised. Consistent with a radical pathway, glutathione fully suppresses catalysis. Conversely, adding either superoxide or H 2 O 2 from the outset strongly enhances catalysis. The mechanism of generation and involvement of superoxide and H 2 O 2 by the deoxyribozymes is not yet defined. The deoxyribozymes do not require redox-active metal ions and function with a combination of Zn 2+ and Mg 2+ , although including Mn 2+ increases the activity, and Mn 2+ alone also supports catalysis. In contrast to all of these observations, unrelated DNA-catalyzed radical DNA cleavage reactions require redox-active metals and lead to mixtures of products. This study reports an intriguing example of a well-defined, DNA-catalyzed, radical reaction process that cleaves single-stranded DNA and requires only redox-inactive metal ions.

Development and application of bond cleavage reactions in bioorthogonal chemistry.

PubMed

Li, Jie; Chen, Peng R

2016-03-01

Bioorthogonal chemical reactions are a thriving area of chemical research in recent years as an unprecedented technique to dissect native biological processes through chemistry-enabled strategies. However, current concepts of bioorthogonal chemistry have largely centered on 'bond formation' reactions between two mutually reactive bioorthogonal handles. Recently, in a reverse strategy, a collection of 'bond cleavage' reactions has emerged with excellent biocompatibility. These reactions have expanded our bioorthogonal chemistry repertoire, enabling an array of exciting new biological applications that range from the chemically controlled spatial and temporal activation of intracellular proteins and small-molecule drugs to the direct manipulation of intact cells under physiological conditions. Here we highlight the development and applications of these bioorthogonal cleavage reactions. Furthermore, we lay out challenges and propose future directions along this appealing avenue of research.

Combined Experimental and Computational Study on the Unimolecular Decomposition of JP-8 Jet Fuel Surrogates. II: n-Dodecane (n-C12H26).

PubMed

Zhao, Long; Yang, Tao; Kaiser, Ralf I; Troy, Tyler P; Ahmed, Musahid; Ribeiro, Joao Marcelo; Belisario-Lara, Daniel; Mebel, Alexander M

2017-02-16

We investigated temperature-dependent products in the pyrolysis of helium-seeded n-dodecane, which represents a surrogate of the n-alkane fraction of Jet Propellant-8 (JP-8) aviation fuel. The experiments were performed in a high temperature chemical reactor over a temperature range of 1200 K to 1600 K at a pressure of 600 Torr, with in situ identification of the nascent products in a supersonic molecular beam using single photon vacuum ultraviolet (VUV) photoionization coupled with the analysis of the ions in a reflectron time-of-flight mass spectrometer (ReTOF). For the first time, the initial decomposition products of n-dodecane-including radicals and thermally labile closed-shell species-were probed in experiments, which effectively exclude mass growth processes. A total of 15 different products were identified, such as molecular hydrogen (H 2 ), C2 to C7 1-alkenes [ethylene (C 2 H 4 ) to 1-heptene (C 7 H 14 )], C1-C3 radicals [methyl (CH 3 ), ethyl (C 2 H 5 ), allyl (C 3 H 5 )], small C1-C3 hydrocarbons [acetylene (C 2 H 2 ), allene (C 3 H 4 ), methylacetylene (C 3 H 4 )], as well as the reaction products [1,3-butadiene (C 4 H 6 ), 2-butene (C 4 H 8 )] attributed to higher-order processes. Electronic structure calculations carried out at the G3(CCSD,MP2)//B3LYP/6-311G(d,p) level of theory combined with RRKM/master equation of rate constants for relevant reaction steps showed that n-dodecane decomposes initially by a nonterminal C-C bond cleavage and producing a mixture of alkyl radicals from ethyl to decyl with approximately equal branching ratios. The alkyl radicals appear to be unstable under the experimental conditions and to rapidly dissociate either directly by C-C bond β-scission to produce ethylene (C 2 H 4 ) plus a smaller 1-alkyl radical with the number of carbon atoms diminished by two or via 1,5-, 1,6-, or 1,7- 1,4-, 1,9-, or 1,8-H shifts followed by C-C β-scission producing alkenes from propene to 1-nonene together with smaller 1-alkyl radicals. The stability and hence the branching ratios of higher alkenes decrease as temperature increases. The C-C β-scission continues all the way to the propyl radical (C 3 H 7 ), which dissociates to methyl (CH 3 ) plus ethylene (C 2 H 4 ). In addition, at higher temperatures, another mechanism can contribute, in which hydrogen atoms abstract hydrogen from C 12 H 26 producing various n-dodecyl radicals and these radicals then decompose by C-C bond β-scission to C3 to C11 alkenes.

A density functional theory study of the role of functionalized graphene particles as effective additives in power cable insulation.

PubMed

Song, Shuwei; Zhao, Hong; Zheng, Xiaonan; Zhang, Hui; Liu, Yang; Wang, Ying; Han, Baozhong

2018-02-01

The role of a series of functionalized graphene additives in power cable insulation in suppressing the growth of electrical treeing and preventing the degradation of the polymer matrix has been investigated by density functional theory calculations. Bader charge analysis indicates that pristine, doped or defect graphene could effectively capture hot electrons to block their attack on cross-linked polyethylene (XLPE) because of the π-π conjugated unsaturated structures. Further exploration of the electronic properties in the interfacial region between the additives and XLPE shows that N-doped single-vacancy graphene, graphene oxide and B-, N-, Si- or P-doped graphene oxide have relatively strong physical interaction with XLPE to restrict its mobility and rather weak chemical activity to prevent the cleavage of the C-H or C-C bond, suggesting that they are all potential candidates as effective additives. The understanding of the features of functionalized graphene additives in trapping electrons and interfacial interaction will assist in the screening of promising additives as voltage stabilizers in power cables.

Molecularly Tuning the Radicaloid N-H···O═C Hydrogen Bond.

PubMed

Lu, Norman; Chung, Wei-Cheng; Ley, Rebecca M; Lin, Kwan-Yu; Francisco, Joseph S; Negishi, Ei-Ichi

2016-03-03

Substituent effects on the open shell N-H···O═C hydrogen-bond has never been reported. This study examines how 12 functional groups composed of electron donating groups (EDG), halogen atoms and electron withdrawing groups (EWG) affect the N-H···O═C hydrogen-bond properties in a six-membered cyclic model system of O═C(Y)-CH═C(X)N-H. It is found that group effects on this open shell H-bonding system are significant and have predictive trends when X = H and Y is varied. When Y is an EDG, the N-H···O═C hydrogen-bond is strengthened; and when Y is an EWG, the bond is weakened; whereas the variation in electronic properties of X group do not exhibit a significant impact upon the hydrogen bond strength. The structural impact of the stronger N-H···O═C hydrogen-bond are (1) shorter H and O distance, r(H···O) and (2) a longer N-H bond length, r(NH). The stronger N-H···O═C hydrogen-bond also acts to pull the H and O in toward one another which has an effect on the bond angles. Our findings show that there is a linear relationship between hydrogen-bond angle and N-H···O═C hydrogen-bond energy in this unusual H-bonding system. In addition, there is a linear correlation of the r(H···O) and the hydrogen bond energy. A short r(H···O) distance corresponds to a large hydrogen bond energy when Y is varied. The observed trends and findings have been validated using three different methods (UB3LYP, M06-2X, and UMP2) with two different basis sets.

Microporosity and CO2 Capture Properties of Amorphous Silicon Oxynitride Derived from Novel Polyalkoxysilsesquiazanes

PubMed Central

Iwase, Yoshiaki; Horie, Yoji; Honda, Sawao; Daiko, Yusuke

2018-01-01

Polyalkoxysilsesquiazanes ([ROSi(NH)1.5]n, ROSZ, R = Et, nPr, iPr, nBu, sBu, nHex, sHex, cHex, decahydronaphthyl (DHNp)) were synthesized by ammonolysis at −78 °C of alkoxytrichlorosilane (ROSiCl3), which was isolated by distillation as a reaction product of SiCl4 and ROH. The simultaneous thermogravimetric and mass spectrometry analyses of the ROSZs under helium revealed a common decomposition reaction, the cleavage of the oxygen–carbon bond of the RO group to evolve alkene as a main gaseous species formed in-situ, leading to the formation of microporous amorphous Si–O–N at 550 °C to 800 °C. The microporosity in terms of the peak of the pore size distribution curve located within the micropore size range (<2 nm) and the total micropore volume, as well as the specific surface area (SSA) of the Si–O–N, increased consistently with the molecular size estimated for the alkene formed in-situ during the pyrolysis. The CO2 capture capacity at 0 °C of the Si–O–N material increased consistently with its SSA, and an excellent CO2 capture capacity of 3.9 mmol·g−1 at 0 °C and CO2 1 atm was achieved for the Si–O–N derived from DHNpOSZ having an SSA of 750 m2·g−1. The CO2 capture properties were further discussed based on their temperature dependency, and a surface functional group of the Si–O–N formed in-situ during the polymer/ceramics thermal conversion. PMID:29534056

Bromine isotopic signature facilitates de novo sequencing of peptides in free-radical-initiated peptide sequencing (FRIPS) mass spectrometry.

PubMed

Nam, Jungjoo; Kwon, Hyuksu; Jang, Inae; Jeon, Aeran; Moon, Jingyu; Lee, Sun Young; Kang, Dukjin; Han, Sang Yun; Moon, Bongjin; Oh, Han Bin

2015-02-01

We recently showed that free-radical-initiated peptide sequencing mass spectrometry (FRIPS MS) assisted by the remarkable thermochemical stability of (2,2,6,6-tetramethyl-piperidin-1-yl)oxyl (TEMPO) is another attractive radical-driven peptide fragmentation MS tool. Facile homolytic cleavage of the bond between the benzylic carbon and the oxygen of the TEMPO moiety in o-TEMPO-Bz-C(O)-peptide and the high reactivity of the benzylic radical species generated in •Bz-C(O)-peptide are key elements leading to extensive radical-driven peptide backbone fragmentation. In the present study, we demonstrate that the incorporation of bromine into the benzene ring, i.e. o-TEMPO-Bz(Br)-C(O)-peptide, allows unambiguous distinction of the N-terminal peptide fragments from the C-terminal fragments through the unique bromine doublet isotopic signature. Furthermore, bromine substitution does not alter the overall radical-driven peptide backbone dissociation pathways of o-TEMPO-Bz-C(O)-peptide. From a practical perspective, the presence of the bromine isotopic signature in the N-terminal peptide fragments in TEMPO-assisted FRIPS MS represents a useful and cost-effective opportunity for de novo peptide sequencing. Copyright © 2015 John Wiley & Sons, Ltd.

Competitive fragmentation pathways of acetic acid dimer explored by synchrotron VUV photoionization mass spectrometry and electronic structure calculations

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

Guan Jiwen; Hu Yongjun; Zou Hao

2012-09-28

In present study, photoionization and dissociation of acetic acid dimers have been studied with the synchrotron vacuum ultraviolet photoionization mass spectrometry and theoretical calculations. Besides the intense signal corresponding to protonated cluster ions (CH{sub 3}COOH){sub n}{center_dot}H{sup +}, the feature related to the fragment ions (CH{sub 3}COOH)H{sup +}{center_dot}COO (105 amu) via {beta}-carbon-carbon bond cleavage is observed. By scanning photoionization efficiency spectra, appearance energies of the fragments (CH{sub 3}COOH){center_dot}H{sup +} and (CH{sub 3}COOH)H{sup +}{center_dot}COO are obtained. With the aid of theoretical calculations, seven fragmentation channels of acetic acid dimer cations were discussed, where five cation isomers of acetic acid dimer are involved.more » While four of them are found to generate the protonated species, only one of them can dissociate into a C-C bond cleavage product (CH{sub 3}COOH)H{sup +}{center_dot}COO. After surmounting the methyl hydrogen-transfer barrier 10.84 {+-} 0.05 eV, the opening of dissociative channel to produce ions (CH{sub 3}COOH){sup +} becomes the most competitive path. When photon energy increases to 12.4 eV, we also found dimer cations can be fragmented and generate new cations (CH{sub 3}COOH){center_dot}CH{sub 3}CO{sup +}. Kinetics, thermodynamics, and entropy factors for these competitive dissociation pathways are discussed. The present report provides a clear picture of the photoionization and dissociation processes of the acetic acid dimer in the range of the photon energy 9-15 eV.« less

Elaboration of Copper-Oxygen Mediated C–H Activation Chemistry in Consideration of Future Fuel and Feedstock Generation

PubMed Central

Lee, Jung Yoon; Karlin, Kenneth D

2015-01-01

To contribute solutions for current energy concerns, improvements in the efficiency of C-H bond cleavage chemistry, e.g., 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, 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

Peroxidase-type reactions suggest a heterolytic/nucleophilic O–O joining mechanism in the heme-dependent chlorite dismutase†

PubMed Central

Mayfield, Jeffrey A.; Blanc, Béatrice; Rodgers, Kenton R.; Lukat-Rodgers, Gudrun S.; DuBois, Jennifer L.

2015-01-01

Heme-containing chlorite dismutases (Clds) catalyze a highly unusual O–O bond forming reaction. The O–O cleaving reactions of hydrogen peroxide and peracetic acid (PAA) with the Cld from Dechloromonas aromatica (DaCld) were studied to better understand the Cl–O cleavage of the natural substrate and subsequent O–O bond formation. While reactions with H2O2 resulted in slow destruction of the heme, at acidic pH, heterolytic cleavage of the O–O bond of PAA cleanly yielded the ferryl porphyrin cation radical (Compound I). At alkaline pH, the reaction proceeds more rapidly and the first observed intermediate is a ferryl heme. Freezequench EPR confirmed that the latter has an uncoupled protein-based radical, indicating that Compound I is the first intermediate formed at all pH values and that radical migration is faster at alkaline pH. These results suggest by analogy that two-electron Cl–O bond cleavage to yield a ferryl-porphyrin cation radical is the most likely initial step in O–O bond formation from chlorite. PMID:24001266

Base substitutions at scissile bond sites are sufficient to alter RNA-binding and cleavage activity of RNase III.

PubMed

Kim, Kyungsub; Sim, Se-Hoon; Jeon, Che Ok; Lee, Younghoon; Lee, Kangseok

2011-02-01

RNase III, a double-stranded RNA-specific endoribonuclease, degrades bdm mRNA via cleavage at specific sites. To better understand the mechanism of cleavage site selection by RNase III, we performed a genetic screen for sequences containing mutations at the bdm RNA cleavage sites that resulted in altered mRNA stability using a transcriptional bdm'-'cat fusion construct. While most of the isolated mutants showed the increased bdm'-'cat mRNA stability that resulted from the inability of RNase III to cleave the mutated sequences, one mutant sequence (wt-L) displayed in vivo RNA stability similar to that of the wild-type sequence. In vivo and in vitro analyses of the wt-L RNA substrate showed that it was cut only once on the RNA strand to the 5'-terminus by RNase III, while the binding constant of RNase III to this mutant substrate was moderately increased. A base substitution at the uncleaved RNase III cleavage site in wt-L mutant RNA found in another mutant lowered the RNA-binding affinity by 11-fold and abolished the hydrolysis of scissile bonds by RNase III. Our results show that base substitutions at sites forming the scissile bonds are sufficient to alter RNA cleavage as well as the binding activity of RNase III. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Far-UV photochemical bond cleavage of n-amyl nitrite: bypassing a repulsive surface.

PubMed

Minitti, Michael P; Zhang, Yao; Rosenberg, Martin; Brogaard, Rasmus Y; Deb, Sanghamitra; Sølling, Theis I; Weber, Peter M

2012-01-19

We have investigated the deep-UV photoinduced, homolytic bond cleavage of amyl nitrite to form NO and pentoxy radicals. One-color multiphoton ionization with ultrashort laser pulses through the S(2) state resonance gives rise to photoelectron spectra that reflect ionization from the S(1) state. Time-resolved pump-probe photoionization measurements show that upon excitation at 207 nm, the generation of NO in the v = 2 state is delayed, with a rise time of 283 (16) fs. The time-resolved mass spectrum shows the NO to be expelled with a kinetic energy of 1.0 eV, which is consistent with dissociation on the S(1) state potential energy surface. Combined, these observations show that the first step of the dissociation reaction involves an internal conversion from the S(2) to the S(1) state, which is followed by the ejection of the NO radical on the predissociative S(1) state potential energy surface.

Effects of Single Amino Acid Substitution on the Collision-Induced Dissociation of Intact Protein Ions: Turkey Ovomucoid Third Domain

PubMed Central

Newton, Kelly A.; Pitteri, Sharon J.; Laskowski, Michael; McLuckey, Scott A.

2005-01-01

Expanded understanding of the factors that direct polypeptide ion fragmentation can lead to improved specificity in the use of tandem mass spectrometry for the identification and characterization of proteins. Like the fragmentation of peptide cations, the dissociation of whole protein cations shows several preferred cleavages, the likelihood for which is parent ion charge dependent. While such cleavages are often observed, they are far from universally observed, despite the presence of the residues known to promote them. Furthermore, cleavages at residues not noted to be common in a variety of proteins can be dominant for a particular protein or protein ion charge state. Motivated by the ability to study a small protein, turkey ovomucoid third domain, for which a variety of single amino acid variants are available, the effects of changing the identity of one amino acid in the protein sequence on its dissociation behavior were examined. In particular, changes in amino acids associated with C-terminal aspartic acid cleavage and N-terminal proline cleavage were emphasized. Consistent with previous studies, the product ion spectra were found to be dependent upon the parent ion charge state. Furthermore, the fraction of possible C-terminal aspartic acid cleavages observed to occur for this protein was significantly larger than the fraction of possible N-terminal proline cleavages. In fact, very little N-terminal proline cleavage was noted for the wild-type protein despite the presence of three proline residues in the protein. The addition/removal of proline and aspartic acids was studied along with changes in selected residues adjacent to proline residues. Evidence for inhibition of proline cleavage by the presence of nearby basic residues was noted, particularly if the basic residue was likely to be protonated. PMID:15473693

From a remarkable manifestation of polar effects in a radical fragmentation to the convergent synthesis of highly functionalized ketones.

PubMed

Debien, Laurent; Zard, Samir Z

2013-03-13

A new radical addition/C-C bond fragmentation process is reported. Vinyl carbinols derived from 2-methyl-2-phenylpropanal react with radicals generated from xanthates to give the corresponding ketones. The radical cleavage reaction proceeds under mild conditions, in good to high yield, and in the presence of the unprotected carbinol. Highly functionalized 1,5-diketones and pyridines are readily available using this approach.

Research on ribosome-inactivating proteins from angiospermae to gymnospermae and cryptogamia

PubMed Central

Liu, Wang-Yi

2017-01-01

Ribosome-inactivating Proteins (RIPs) are a group of cytotoxin proteins that usually contain a RNA N-glycosidase domain, which irreversibly inactivates ribosome, thus inhibiting protein synthesis. During the past 14 years (1990-2004), the studies conducted in our laboratory had been focusing on the structure and enzymatic mechanism of several PIPs. Herein, we briefly described a summary of the studies conducted mainly in our laboratory on RIPs from angiospermae to gymnospermae and cryptogamia as follows. (1) Cinnamomin is a novel type II RIP isolated from mature seeds of camphor tree. Like ricin, it specifically removes the adenine at A4324 in rat liver 28S rRNA. We systematically studied this low-toxic RIP in term of its enzymatic mechanism, the primary and crystal structure and the nucleotide sequence of its gene, the genetic expression, and its physiological role in the seed cell and the toxicity to human cancer cells and insect larvae. The cleavage of supercoiled double-stranded DNA was its intrinsic property of cinnamomin A-chain, its N- and C-terminal regions were found to be required for deadenylation of rRNA and also necessary for deadenylation of supercoiled double-stranded circular DNA. These results strongly excluded the possibility that cleavage of supercoiled DNA was due to nuclease contamination. (2) Trichosanthin, an abortifacient protein, was purified from the Chinese medicinal herb, Tian-hua-fen, obtained from root tubers of Chinese trichosanthes plant. We proved that trichosanthin was a RNA N-glycosidase, inactivating eukaryotic ribosome by hydrolyzing the N-C glycosidic bond of the adenose at site 4324 in rat 28S rRNA, and inhibited protein synthesis in vitro. (3) A unique Biota orientalis RNase (RNase Bo) was extracted from the mature seeds of the cypress cypress tree (Oriental arborvita), which was gymnospermae plant. It cleaved only a specific phosphodiester bond between C4453 and A4454 of 28S RNA in rat ribosomes, producing a small RNA-fragment (S-fragment), thus inhibiting protein synthesis and belonging to RNase-like RIP, similar to α-sarcin, a special RIP. (4) Lamjapin, the first RIP purified from kelp, the marine cryptogamia algal plant, was shown to be the first single-chained RNA N-glycosidase from marine plant to date. It hydrolyzed rat ribosomal 28S RNA to produce meanly a rather smaller RNA, shorter than the diagnostic R-fragment under the restricted condition. The significance of existence of type I RIP in the lower marine algal plant was briefly discussed. PMID:29312524

Oxidatively Generated Guanine(C8)-Thymine(N3) Intrastrand Cross-links in Double-stranded DNA Are Repaired by Base Excision Repair Pathways.

PubMed

Talhaoui, Ibtissam; Shafirovich, Vladimir; Liu, Zhi; Saint-Pierre, Christine; Akishev, Zhiger; Matkarimov, Bakhyt T; Gasparutto, Didier; Geacintov, Nicholas E; Saparbaev, Murat

2015-06-05

Oxidatively generated guanine radical cations in DNA can undergo various nucleophilic reactions including the formation of C8-guanine cross-links with adjacent or nearby N3-thymines in DNA in the presence of O2. The G*[C8-N3]T* lesions have been identified in the DNA of human cells exposed to oxidative stress, and are most likely genotoxic if not removed by cellular defense mechanisms. It has been shown that the G*[C8-N3]T* lesions are substrates of nucleotide excision repair in human cell extracts. Cleavage at the sites of the lesions was also observed but not further investigated (Ding et al. (2012) Nucleic Acids Res. 40, 2506-2517). Using a panel of eukaryotic and prokaryotic bifunctional DNA glycosylases/lyases (NEIL1, Nei, Fpg, Nth, and NTH1) and apurinic/apyrimidinic (AP) endonucleases (Apn1, APE1, and Nfo), the analysis of cleavage fragments by PAGE and MALDI-TOF/MS show that the G*[C8-N3]T* lesions in 17-mer duplexes are incised on either side of G*, that none of the recovered cleavage fragments contain G*, and that T* is converted to a normal T in the 3'-fragment cleavage products. The abilities of the DNA glycosylases to incise the DNA strand adjacent to G*, while this base is initially cross-linked with T*, is a surprising observation and an indication of the versatility of these base excision repair proteins. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Oxidatively Generated Guanine(C8)-Thymine(N3) Intrastrand Cross-links in Double-stranded DNA Are Repaired by Base Excision Repair Pathways*

PubMed Central

Talhaoui, Ibtissam; Shafirovich, Vladimir; Liu, Zhi; Saint-Pierre, Christine; Akishev, Zhiger; Matkarimov, Bakhyt T.; Gasparutto, Didier; Geacintov, Nicholas E.; Saparbaev, Murat

2015-01-01

Oxidatively generated guanine radical cations in DNA can undergo various nucleophilic reactions including the formation of C8-guanine cross-links with adjacent or nearby N3-thymines in DNA in the presence of O2. The G*[C8-N3]T* lesions have been identified in the DNA of human cells exposed to oxidative stress, and are most likely genotoxic if not removed by cellular defense mechanisms. It has been shown that the G*[C8-N3]T* lesions are substrates of nucleotide excision repair in human cell extracts. Cleavage at the sites of the lesions was also observed but not further investigated (Ding et al. (2012) Nucleic Acids Res. 40, 2506–2517). Using a panel of eukaryotic and prokaryotic bifunctional DNA glycosylases/lyases (NEIL1, Nei, Fpg, Nth, and NTH1) and apurinic/apyrimidinic (AP) endonucleases (Apn1, APE1, and Nfo), the analysis of cleavage fragments by PAGE and MALDI-TOF/MS show that the G*[C8-N3]T* lesions in 17-mer duplexes are incised on either side of G*, that none of the recovered cleavage fragments contain G*, and that T* is converted to a normal T in the 3′-fragment cleavage products. The abilities of the DNA glycosylases to incise the DNA strand adjacent to G*, while this base is initially cross-linked with T*, is a surprising observation and an indication of the versatility of these base excision repair proteins. PMID:25903131

The Oxygenase CAO-1 of Neurospora crassa Is a Resveratrol Cleavage Enzyme

PubMed Central

Díaz-Sánchez, Violeta; F. Estrada, Alejandro; Limón, M. Carmen; Al-Babili, Salim

2013-01-01

The genome of the ascomycete Neurospora crassa encodes CAO-1 and CAO-2, two members of the carotenoid cleavage oxygenase family that target double bonds in different substrates. Previous studies demonstrated the role of CAO-2 in cleaving the C40 carotene torulene, a key step in the synthesis of the C35 apocarotenoid pigment neurosporaxanthin. In this work, we investigated the activity of CAO-1, assuming that it may provide retinal, the chromophore of the NOP-1 rhodopsin, by cleaving β-carotene. For this purpose, we tested CAO-1 activity with carotenoid substrates that were, however, not converted. In contrast and consistent with its sequence similarity to family members that act on stilbenes, CAO-1 cleaved the interphenyl Cα-Cβ double bond of resveratrol and its derivative piceatannol. CAO-1 did not convert five other similar stilbenes, indicating a requirement for a minimal number of unmodified hydroxyl groups in the stilbene background. Confirming its biological function in converting stilbenes, adding resveratrol led to a pronounced increase in cao-1 mRNA levels, while light, a key regulator of carotenoid metabolism, did not alter them. Targeted Δcao-1 mutants were not impaired by the presence of resveratrol, a phytoalexin active against different fungi, which did not significantly affect the growth and development of wild-type Neurospora. However, under partial sorbose toxicity, the Δcao-1 colonies exhibited faster radial growth than control strains in the presence of resveratrol, suggesting a moderate toxic effect of resveratrol cleavage products. PMID:23893079

Abundance and reactivity of dibenzodioxocins in softwood lignin.

PubMed

Argyropoulos, Dimitris S; Jurasek, Lubo; Kristofová, Lívia; Xia, Zhicheng; Sun, Yujun; Palus, Ernest

2002-02-13

To define the abundance and comprehend the reactivity of dibenzodioxocins in lignin, model compound studies, specific degradation experiments on milled wood lignin, and molecular modeling calculations have been performed. Quantitative (31)P NMR measurements of the increase of biphenolic hydroxyl groups formed after a series of alkaline degradations in the presence of hydrosulfide anions (kraft conditions) showed the presence of 3.7 dibenzodioxocin rings/100 C9 units in milled wood lignin. The DFRC degradation protocol (Derivatization Followed by Reductive Cleavage) was chosen as an independent means to estimate their abundance. Initial experiments with a dibenzodioxocin model compound, trans-6,7-dihydro-7-(4-hydroxy-3-methoxyphenyl)-4,9-dimethoxy-2,11-dipropyldibenzo[e,g][1,4]dioxocin-6-ylmethanol, showed that it is not cleaved under DFRC conditions, but rather it isomerizes into a cyclic oxepine structure. Steric effects precluded this isomerization from occurring when DFRC was applied to milled wood lignin. Instead, monoacetylated biphenolic moieties were released and quantified by (31)P NMR, at 4.3 dibenzodioxocin rings/100 C9 units. The dibenzodioxocin content in residual lignins isolated from kraft pulps delignified to various degrees showed that during pulp delignification, the initial rate of dibenzodioxocin removal was considerably greater than the cleavage rate of arylglycerol-beta-aryl ether bonds. The activation energy for the degradation of dibenzodioxocins under kraft conditions in milled wood lignin was 96 +/- 9 kJ/mol, similar to that of arylglycerol-beta-aryl ether bond cleavage.

Amavadin and other vanadium complexes as remarkably efficient catalysts for one-pot conversion of ethane to propionic and acetic acids.

PubMed

Kirillova, Marina V; Kuznetsov, Maxim L; da Silva, José A L; Guedes da Silva, Maria Fátima C; Fraústo da Silva, João J R; Pombeiro, Armando J L

2008-01-01

Synthetic amavadin Ca[V{ON[CH(CH(3))COO](2)}(2)] and its models Ca[V{ON(CH(2)COO)(2)}(2)] and [VO{N(CH(2)CH(2)O)(3)}], in the presence of K(2)S(2)O(8) in trifluoroacetic acid (TFA), exhibit remarkable catalytic activity for the one-pot carboxylation of ethane to propionic and acetic acids with the former as the main product (overall yields up to 93 %, catalyst turnover numbers (TONs) up to 2.0 x 10(4)). The simpler V complexes [VO(CF(3)SO(3))(2)], [VO(acac)(2)] and VOSO(4) are less active. The effects of various factors, namely, C(2)H(6) and CO pressures, time, temperature, and amounts of catalyst, TFA and K(2)S(2)O(8), have been investigated, and this allowed optimisation of the process and control of selectivity. (13)C-labelling experiments indicated that the formation of acetic acid follows two pathways, the dominant one via oxidation of ethane with preservation of the C--C bond, and the other via rupture of this bond and carbonylation of the methyl group by CO; the C--C bond is retained in the formation of propionic acid upon carbonylation of ethane. The reactions proceed via both C- and O-centred radicals, as shown by experiments with radical traps. On the basis of detailed DFT calculations, plausible reaction mechanisms are discussed. The carboxylation of ethane in the presence of CO follows the sequential formation of C(2)H(5) (*), C(2)H(5)CO(*), C(2)H(5)COO(*) and C(2)H(5)COOH. The C(2)H(5)COO(*) radical is easily formed on reaction of C(2)H(5)CO(*) with a peroxo V catalyst via a V{eta(1)-OOC(O)C(2)H(5)} intermediate. In the absence of CO, carboxylation proceeds by reaction of C(2)H(5) (*) with TFA. For the oxidation of ethane to acetic acid, either with preservation or cleavage of the C-C bond, metal-assisted and purely organic pathways are also proposed and discussed.

Efficient oxidation of alcohols to carbonyl compounds with molecular oxygen catalyzed by N-hydroxyphthalimide combined with a Co species

PubMed

Iwahama; Yoshino; Keitoku; Sakaguchi; Ishii

2000-10-06

Highly efficient catalytic oxidation of alcohols with molecular oxygen by N-hydroxyphthalimide (NHPI) combined with a Co species was developed. The oxidation of 2-octanol in the presence of catalytic amounts of NHPI and Co(OAc)2 under atmospheric dioxygen in AcOEt at 70 degrees C gave 2-octanone in 93% yield. The oxidation was significantly enhanced by adding a small amount of benzoic acid to proceed smoothly even at room temperature. Primary alcohols were oxidized by NHPI in the absence of any metal catalyst to form the corresponding carboxylic acids in good yields. In the oxidation of terminal vic-diols such as 1,2-butanediol, carbon-carbon bond cleavage was induced to give one carbon less carboxylic acids such as propionic acid, while internal vic-diols were selectively oxidized to 1,2-diketones.

Lignin-derived oxygenate reforming on a bimetallic surface: The reaction of benzaldehyde on Zn/Pt(111)

NASA Astrophysics Data System (ADS)

Shi, Daming; Vohs, John M.

2016-08-01

Temperature programmed desorption (TPD) and high-resolution electron energy loss spectroscopy (HREELS) were used to characterize the adsorption and reaction of benzaldehyde (C6H5CHO) on hydrogen-covered Pt(111) and Zn-modified Pt(111) surfaces. Benzaldehyde was found to interact with Pt(111) via both the phenyl ring and carbonyl of the aldehyde group. This bonding configuration facilitates unselective decomposition of the benzaldehyde to produce CO, H2, and small hydrocarbon fragments at relatively low temperatures. On the other hand, benzaldehyde was found to bond to Zn-decorated Pt(111) surface exclusively via the carbonyl group in an η2(C, O) configuration, with the phenyl ring tilted away from the surface. This configuration weakens Csbnd O bond in the carbonyl facilitating its cleavage and helps prevent hydrogenation of the phenyl ring.

Nitrogen reduction and functionalization by a multimetallic uranium nitride complex

NASA Astrophysics Data System (ADS)

Falcone, Marta; Chatelain, Lucile; Scopelliti, Rosario; Živković, Ivica; Mazzanti, Marinella

2017-07-01

Molecular nitrogen (N2) is cheap and widely available, but its unreactive nature is a challenge when attempting to functionalize it under mild conditions with other widely available substrates (such as carbon monoxide, CO) to produce value-added compounds. Biological N2 fixation can do this, but the industrial Haber-Bosch process for ammonia production operates under harsh conditions (450 degrees Celsius and 300 bar), even though both processes are thought to involve multimetallic catalytic sites. And although molecular complexes capable of binding and even reducing N2 under mild conditions are known, with co-operativity between metal centres considered crucial for the N2 reduction step, the multimetallic species involved are usually not well defined, and further transformation of N2-binding complexes to achieve N-H or N-C bond formation is rare. Haber noted, before an iron-based catalyst was adopted for the industrial Haber-Bosch process, that uranium and uranium nitride materials are very effective heterogeneous catalysts for ammonia production from N2. However, few examples of uranium complexes binding N2 are known, and soluble uranium complexes capable of transforming N2 into ammonia or organonitrogen compounds have not yet been identified. Here we report the four-electron reduction of N2 under ambient conditions by a fully characterized complex with two UIII ions and three K+ centres held together by a nitride group and a flexible metalloligand framework. The addition of H2 and/or protons, or CO to the resulting complex results in the complete cleavage of N2 with concomitant N2 functionalization through N-H or N-C bond-forming reactions. These observations establish that a molecular uranium complex can promote the stoichiometric transformation of N2 into NH3 or cyanate, and that a flexible, electron-rich, multimetallic, nitride-bridged core unit is a promising starting point for the design of molecular complexes capable of cleaving and functionalizing N2 under mild conditions.

Electronegativity identification of novel superhard materials.

PubMed

Li, Keyan; Wang, Xingtao; Zhang, Fangfang; Xue, Dongfeng

2008-06-13

We show that electronegativity can be used to effectively identify the hardness of crystal materials on the basis of a new microscopic model for hardness. Bond electronegativity is proposed to characterize the electron-holding energy of a bond, which is the intrinsic origin of hardness. Applying this model to c-BC(2)N materials, we confirm the proper bond composition of the experimentally observed phase of c-BC(2)N, in which the bond ratio N(C-C):N(B-N):N(B-C):N(C-N) is 3:3:1:1. A number of bonds that can or cannot form a superhard material are qualitatively distinguished, which enables us to explore novel superhard materials by screening possible elemental combinations.

Topology of charge density of flucytosine and related molecules and characteristics of their bond charge distributions.

PubMed

Murgich, Juan; Franco, Héctor J; San-Blas, Gioconda

2006-08-24

The molecular charge distribution of flucytosine (4-amino-5-fluoro-2-pyrimidone), uracil, 5-fluorouracil, and thymine was studied by means of density functional theory calculations (DFT). The resulting distributions were analyzed by means of the atoms in molecules (AIM) theory. Bonds were characterized through vectors formed with the charge density value, its Laplacian, and the bond ellipticity calculated at the bond critical point (BCP). Within each set of C=O, C-H, and N-H bonds, these vectors showed little dispersion. C-C bonds formed three different subsets, one with a significant degree of double bonding, a second corresponding to single bonds with a finite ellipticity produced by hyperconjugation, and a third one formed by a pure single bond. In N-C bonds, a decrease in bond length (an increase in double bond character) was not reflected as an increase in their ellipticity, as in all C-C bonds studied. It was also found that substitution influenced the N-C, C-O, and C-C bond ellipticity much more than density and its Laplacian at the BCP. The Laplacian of charge density pointed to the existence of both bonding and nonbonding maxima in the valence shell charge concentration of N, O, and F, while only bonding ones were found for the C atoms. The nonbonding maxima related to the sites for electrophilic attack and H bonding in O and N, while sites of nucleophilic attack were suggested by the holes in the valence shell of the C atoms of the carbonyl groups.

Distinct oxidative cleavage and modification of bovine [Cu-Zn]-SOD by an ascorbic acid/Cu(II) system: Identification of novel copper binding site on SOD molecule

PubMed Central

Uehara, Hiroshi; Luo, Shen; Aryal, Baikuntha; Levine, Rodney L.; Rao, V. Ashutosh

2016-01-01

We investigated the combined effect of ascorbate and copper [Asc/Cu(II)] on the integrity of bovine [Cu-Zn]-superoxide dismutase (bSOD1) as a model system to study the metal catalyzed oxidation (MCO) and fragmentation of proteins. We found Asc/Cu(II) mediates specific cleavage of bSOD1 and generates 12.5 and 3.2 kDa fragments in addition to oxidation/carbonylation of the protein. The effect of other tested transition metals, a metal chelator, and hydrogen peroxide on the cleavage and oxidation indicated that binding of copper to a previously unknown site on SOD1 is responsible for the Asc/Cu(II) specific cleavage and oxidation. We utilized tandem mass spectrometry to identify the specific cleavage sites of Asc/Cu(II)-treated bSOD1. Analyses of tryptic- and AspN-peptides have demonstrated the cleavage to occur at Gly31 with peptide bond breakage with Thr30 and Ser32 through diamide and α-amidation pathways, respectively. The three-dimensional structure of bSOD1 reveals the imidazole ring of His19 localized within 5 Angstrom from the α-carbon of Gly31 providing a structural basis that copper ion, most likely coordinated by His19, catalyzes the specific cleavage reaction. PMID:26872685

Distinct oxidative cleavage and modification of bovine [Cu- Zn]-SOD by an ascorbic acid/Cu(II) system: Identification of novel copper binding site on SOD molecule.

PubMed

Uehara, Hiroshi; Luo, Shen; Aryal, Baikuntha; Levine, Rodney L; Rao, V Ashutosh

2016-05-01

We investigated the combined effect of ascorbate and copper [Asc/Cu(II)] on the integrity of bovine [Cu-Zn]-superoxide dismutase (bSOD1) as a model system to study the metal catalyzed oxidation (MCO) and fragmentation of proteins. We found Asc/Cu(II) mediates specific cleavage of bSOD1 and generates 12.5 and 3.2kDa fragments in addition to oxidation/carbonylation of the protein. The effect of other tested transition metals, a metal chelator, and hydrogen peroxide on the cleavage and oxidation indicated that binding of copper to a previously unknown site on SOD1 is responsible for the Asc/Cu(II) specific cleavage and oxidation. We utilized tandem mass spectrometry to identify the specific cleavage sites of Asc/Cu(II)-treated bSOD1. Analyses of tryptic- and AspN-peptides have demonstrated the cleavage to occur at Gly31 with peptide bond breakage with Thr30 and Ser32 through diamide and α-amidation pathways, respectively. The three-dimensional structure of bSOD1 reveals the imidazole ring of His19 localized within 5Å from the α-carbon of Gly31 providing a structural basis that copper ion, most likely coordinated by His19, catalyzes the specific cleavage reaction. Published by Elsevier Inc.

Development of a QSAR model for predicting aqueous reaction rate constants of organic chemicals with hydroxyl radicals.

PubMed

Luo, Xiang; Yang, Xianhai; Qiao, Xianliang; Wang, Ya; Chen, Jingwen; Wei, Xiaoxuan; Peijnenburg, Willie J G M

2017-03-22

Reaction with hydroxyl radicals (˙OH) is an important removal pathway for organic pollutants in the aquatic environment. The aqueous reaction rate constant (k OH ) is therefore an important parameter for fate assessment of aquatic pollutants. Since experimental determination fails to meet the requirement of being able to efficiently handle numerous organic chemicals at limited cost and within a relatively short period of time, in silico methods such as quantitative structure-activity relationship (QSAR) models are needed to predict k OH . In this study, a QSAR model with a larger and wider applicability domain as compared with existing models was developed. Following the guidelines for the development and validation of QSAR models proposed by the Organization for Economic Co-operation and Development (OECD), the model shows satisfactory performance. The applicability domain of the model has been extended and contained chemicals that have rarely been covered in most previous studies. The chemicals covered in the current model contain functional groups including [double bond splayed left]C[double bond, length as m-dash]C[double bond splayed right], -C[triple bond, length as m-dash]C-, -C 6 H 5 , -OH, -CHO, -O-, [double bond splayed left]C[double bond, length as m-dash]O, -C[double bond, length as m-dash]O(O)-, -COOH, -C[triple bond, length as m-dash]N, [double bond splayed left]N-, -NH 2 , -NH-C(O)-, -NO 2 , -N[double bond, length as m-dash]C-N[double bond splayed right], [double bond splayed left]N-N[double bond splayed right], -N[double bond, length as m-dash]N-, -S-, -S-S-, -SH, -SO 3 , -SO 4 , -PO 4 , and -X (F, Cl, Br, and I).

The dehydroalanine effect in the fragmentation of ions derived from polypeptides

PubMed Central

Pilo, Alice L.; Peng, Zhou; McLuckey, Scott A.

2016-01-01

The fragmentation of peptides and proteins upon collision-induced dissociation (CID) is highly dependent on sequence and ion type (e.g. protonated, deprotonated, sodiated, odd electron, etc.). Some amino acids, for example aspartic acid and proline, have been found to enhance certain cleavages along the backbone. Here, we show that peptides and proteins containing dehydroalanine, a non-proteinogenic amino acid with an unsaturated side-chain, undergo enhanced cleavage of the N—Cα bond of the dehydroalanine residue to generate c- and z-ions. Because these fragment ion types are not commonly observed upon activation of positively charged even-electron species, they can be used to identify dehydroalanine residues and localize them within the peptide or protein chain. While dehydroalanine can be generated in solution, it can also be generated in the gas phase upon CID of various species. Oxidized S-alkyl cysteine residues generate dehydroalanine upon activation via highly efficient loss of the alkyl sulfenic acid. Asymmetric cleavage of disulfide bonds upon collisional activation of systems with limited proton mobility also generates dehydroalanine. Furthermore, we show that gas-phase ion/ion reactions can be used to facilitate the generation of dehydroalanine residues via, for example, oxidation of S-alkyl cysteine residues and conversion of multiply-protonated peptides to radical cations. In the latter case, loss of radical side-chains to generate dehydroalanine from some amino acids gives rise to the possibility for residue-specific backbone cleavage of polypeptide ions. PMID:27484024

Rapid, reversible, solid–gas and solution-phase insertion of CO 2 into In–P bonds

DOE PAGES

Dickie, Diane A.; Barker, Madeline T.; Land, Michael A.; ...

2015-11-17

The P,P-chelated heteroleptic complex bis[bis(diisopropylphosphino)amido]indium chloride [(i-Pr 2P) 2N] 2InCl was prepared in high yield by treating InCl 3 with 2 equiv of (i-Pr 2P) 2NLi in Et 2O/tetrahydrofuran solution. Samples of [(i-Pr 2P) 2N] 2InCl in a pentane slurry, a CH 2Cl 2 solution, or in the solid state were exposed to CO 2, resulting in the insertion of CO 2 into two of the four M–P bonds to produce [O 2CP(i-Pr 2)NP(i-Pr 2)] 2InCl in each case. These compounds were characterized by multinuclear NMR and IR spectroscopy, as well as single-crystal X-ray diffraction. ReactIR solution studies show thatmore » the reaction is complete in less than 1 min at room temperature in solution and in less than 2 h in the solid–gas reaction. The CO 2 complex is stable up to at least 60 °C under vacuum, but the starting material is regenerated with concomitant loss of carbon dioxide upon heating above 75 °C. Furthermore, the compound [(i-Pr 2P) 2N] 2InCl also reacts with CS 2 to give a complicated mixture of products, one of which was identified as the CS 2 cleavage product [S=P(i-Pr 2)NP(i-Pr 2)] 2InCl] 2(μ-Cl)[μ-(i-Pr 2P) 2N)].« less

Cocrystals of 6-propyl-2-thiouracil: N-H···O versus N-H···S hydrogen bonds.

PubMed

Tutughamiarso, Maya; Egert, Ernst

2011-11-01

In order to investigate the relative stability of N-H···O and N-H···S hydrogen bonds, we cocrystallized the antithyroid drug 6-propyl-2-thiouracil with two complementary heterocycles. In the cocrystal pyrimidin-2-amine-6-propyl-2-thiouracil (1/2), C(4)H(5)N(3)·2C(7)H(10)N(2)OS, (I), the `base pair' is connected by one N-H···S and one N-H···N hydrogen bond. Homodimers of 6-propyl-2-thiouracil linked by two N-H···S hydrogen bonds are observed in the cocrystal N-(6-acetamidopyridin-2-yl)acetamide-6-propyl-2-thiouracil (1/2), C(9)H(11)N(3)O(2)·2C(7)H(10)N(2)OS, (II). The crystal structure of 6-propyl-2-thiouracil itself, C(7)H(10)N(2)OS, (III), is stabilized by pairwise N-H···O and N-H···S hydrogen bonds. In all three structures, N-H···S hydrogen bonds occur only within R(2)(2)(8) patterns, whereas N-H···O hydrogen bonds tend to connect the homo- and heterodimers into extended networks. In agreement with related structures, the hydrogen-bonding capability of C=O and C=S groups seems to be comparable.

Intramolecular Pauson-Khand reactions of methylenecyclopropane and bicyclopropylidene derivatives as an approach to spiro(cyclopropanebicyclo[n.3.0]alkenones).

PubMed

de Meijere, Armin; Becker, Heike; Stolle, Andreas; Kozhushkov, Sergei I; Bes, M Teresa; Salaün, Jacques; Noltemeyer, Mathias

2005-04-08

The trimethylsilyl-protected enynes 9a-c and 14a,b with alkynyl substituents on the three-membered ring or on the double bond of a methylenecyclopropane or a bicyclopropylidene moiety were prepared in two steps from the alcohols 6a-c and 12a,b, respectively, by conversion to the iodides and their coupling with lithium (trimethylsilyl)acetylide (8) in 38-73% overall yields. The bicyclopropylidene derivative 9d was synthesized in 49% yield directly from bicyclopropylidene (3) by lithiation followed by coupling with (5-iodopent-1-ynyl)trimethylsilane (11). Enynes 9b-d were protiodesilylated by treatment with K2CO3 in methanol to give the corresponding unprotected enynes 10b-d in 53, 74 and 94% yield, respectively. Enynes 17a-c with a carbonyl group adjacent to the acetylenic moiety were synthesized from oxo derivatives 15a-c by Wittig olefination followed by coupling with 8 in 47, 18 and 12% overall yield, respectively. Pauson-Khand reactions of the methylenecyclopropane derivatives with a substituent on the ring (9a,b and 10a) as well as on the double bond (14a,b and their in situ prepared protiodesilylated analogues) proceeded smoothly by stirring of the corresponding enyne with [Co2(CO)8] in dichloromethane at ambient temperature followed by treatment of the formed complexes with trimethylamine N-oxide under an oxygen atmosphere at -78 degrees C to give tricyclic or spirocyclopropanated bicyclic enones 18a,b, 19a, 20a,b, 21a,b in good yields. Alkynylbicyclopropylidene derivatives 9c,d and 10c,d formed the corresponding cobalt complexes at -78 to -20 degrees C. Treatment of the latter with N-methylmorpholine N-oxide under an argon atmosphere at -20 degrees C gave the spirocyclopropanated tricyclic enones 18c, 19c and 18d in 31-45% yields. The structure of 19c was proved by X-ray crystal structure analysis. The cyclization of enynones 17a-c in MeCN at 80 degrees C gave the spirocyclopropanated bicyclic diketones 22a-c in 38-65% yields. Intramolecular PKRs of the enynes 25a,d with a chiral auxiliary adjacent to the triple bond gave the corresponding products 26a,d in 70 and 79% yield, respectively, as 5:1 and 8:1 mixtures of diastereomers, respectively. Addition of lithium dimethylcuprate or higher order cuprates to the double bond of the former furnished bridgehead-substituted bicyclo[3.3.0]octanones 27a-c in 57-86% yields. Protiodesilylation of 27a followed by acetal cleavage gave the enantiomerically pure spirocyclopropanated bicyclo[3.3.0]octanedione (1R,5R)- 29a with [alpha]D(20)=-148 (c=1.0 in CHCl3) in 55% overall yield.

Efficient Hydrogenation of Ketones and Aldehydes Catalyzed by Well-Defined Iron(II) PNP Pincer Complexes: Evidence for an Insertion Mechanism

PubMed Central

2014-01-01

We have prepared and structurally characterized a new class of Fe(II) PNP pincer hydride complexes [Fe(PNP-iPr)(H)(CO)(L)]n (L = Br–, CH3CN, pyridine, PMe3, SCN–, CO, BH4–; n = 0, +1) based on the 2,6-diaminopyridine scaffold where the PiPr2 moieties of the PNP ligand are connected to the pyridine ring via NH and/or NMe spacers. Complexes [Fe(PNP-iPr)(H)(CO)(L)]n with labile ligands (L = Br–, CH3CN, BH4–) and NH spacers are efficient catalysts for the hydrogenation of both ketones and aldehydes to alcohols under mild conditions, while those containing inert ligands (L = pyridine, PMe3, SCN–, CO) are catalytically inactive. Interestingly, complex [Fe(PNPMe-iPr)(H)(CO)(Br)], featuring NMe spacers, is an efficient catalyst for the chemoselective hydrogenation of aldehydes. The first type of complexes involves deprotonation of the PNP ligand as well as heterolytic dihydrogen cleavage via metal-alkoxide cooperation, but no reversible aromatization/deprotonation of the PNP ligand. In the case of the N-methylated complex the mechanism remains unclear, but obviously does not allow bifunctional activation of dihydrogen. The experimental results complemented by DFT calculations strongly support an insertion of the C=O bond of the carbonyl compound into the Fe–H bond. PMID:27642211

Ionic liquid [OMIm][OAc] directly inducing oxidation cleavage of the β-O-4 bond of lignin model compounds.

PubMed

Yang, Yingying; Fan, Honglei; Meng, Qinglei; Zhang, Zhaofu; Yang, Guanying; Han, Buxing

2017-08-03

We explored the oxidation reactions of lignin model compounds directly induced by ionic liquids under metal-free conditions. In this work, it was found that ionic liquid 1-octyl-3-methylimidazolium acetate as a solvent could promote the aerobic oxidation of lignin model compound 2-phenoxyacetophenone (1) and the yields of phenol and benzoic acid from 1 could be as high as 96% and 86%, respectively. A possible reaction pathway was proposed based on a series of control experiments. An acetate anion from the ionic liquid attacked the hydrogen from the β-carbon thereby inducing the cleavage of the C-O bond of the aromatic ether. Furthermore, it was found that 2-(2-methoxyphenoxy)-1-phenylethanone (4) with a methoxyl group could also be transformed into aromatic products in this simple reaction system and the yields of phenol and benzoic acid from 4 could be as high as 98% and 85%, respectively. This work provides a simple way for efficient transformation of lignin model compounds.

Metallo-deuteroporphyrin as a biomimetic catalyst for the catalytic oxidation of lignin to aromatics.

PubMed

Zhu, Chenjie; Ding, Weiwei; Shen, Tao; Tang, Chenglun; Sun, Chenguo; Xu, Shichao; Chen, Yong; Wu, Jinglan; Ying, Hanjie

2015-05-22

A series of metallo-deuteroporphyrins derived from hemin were prepared as models of the cytochrome P450 enzyme. With the aid of the highly active Co(II) deuteroporphyrin complex, the catalytic oxidation system was applied for the oxidation of several lignin model compounds, and high yields of monomeric products were obtained under mild reaction conditions. It was found that the modified cobalt deuteroporphyrin that has no substituents at the meso sites but does have the disulfide linkage in the propionate side chains at the β sites exhibited much higher activity and stability than the synthetic tetraphenylporphyrin. The changes in the propionate side chains can divert the reactivity of cobalt deuteroporphyrins from the typical CC bond cleavage to CO bond cleavage. Furthermore, this novel oxidative system can convert enzymolysis lignin into depolymerized products including a significant portion of well-defined aromatic monomers. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Two-Dimensional NMR Evidence for Cleavage of Lignin and Xylan Substituents in Wheat Straw Through Hydrothermal Pretreatment and Enzymatic Hydrolysis

Treesearch

Daniel J. Yelle; Prasad Kaparaju; Christopher G. Hunt; Kolby Hirth; Hoon Kim; John Ralph; Claus Felby

2012-01-01

Solution-state two-dimensional (2D) nuclear magnetic resonance (NMR) spectroscopy of plant cell walls is a powerful tool for characterizing changes in cell wall chemistry during the hydrothermal pretreatment process of wheat straw for second-generation bioethanol production. One-bond 13C-1H NMR correlation spectroscopy, via...

Condensed tannins. Base-catalysed reactions of polymeric procyanidins with phloroglucinol: Intramolecular rearrangements

Treesearch

Peter E. Laks; Richard W. Hemingway; Anthony H. Conner

1987-01-01

Reactions of polymeric procyanidins with phloroglucinol at pH 12.0 and temperatures of 23 or 50°C gave epicatechin-(4β)-phloroglucinol (7), by cleavage of the interflavanoid bond between procyanidin units with subsequent addition of phloroglucinol, and (+)-catechin from the terminal unit. The phloroglucinol adduct (7) rearranged to an enolic form of 8-(3,4-...

Methods to Increase the Metabolic Stability of (18)F-Radiotracers.

PubMed

Kuchar, Manuela; Mamat, Constantin

2015-09-03

The majority of pharmaceuticals and other organic compounds incorporating radiotracers that are considered foreign to the body undergo metabolic changes in vivo. Metabolic degradation of these drugs is commonly caused by a system of enzymes of low substrate specificity requirement, which is present mainly in the liver, but drug metabolism may also take place in the kidneys or other organs. Thus, radiotracers and all other pharmaceuticals are faced with enormous challenges to maintain their stability in vivo highlighting the importance of their structure. Often in practice, such biologically active molecules exhibit these properties in vitro, but fail during in vivo studies due to obtaining an increased metabolism within minutes. Many pharmacologically and biologically interesting compounds never see application due to their lack of stability. One of the most important issues of radiotracers development based on fluorine-18 is the stability in vitro and in vivo. Sometimes, the metabolism of (18)F-radiotracers goes along with the cleavage of the C-F bond and with the rejection of [(18)F]fluoride mostly combined with high background and accumulation in the skeleton. This review deals with the impact of radiodefluorination and with approaches to stabilize the C-F bond to avoid the cleavage between fluorine and carbon.

Both positional and chemical variables control in vitro proteolytic cleavage of a presenilin ortholog

PubMed Central

Naing, Swe-Htet; Kalyoncu, Sibel; Smalley, David M.; Kim, Hyojung; Tao, Xingjian; George, Josh B.; Jonke, Alex P.; Oliver, Ryan C.; Urban, Volker S.; Torres, Matthew P.; Lieberman, Raquel L.

2018-01-01

Mechanistic details of intramembrane aspartyl protease (IAP) chemistry, which is central to many biological and pathogenic processes, remain largely obscure. Here, we investigated the in vitro kinetics of a microbial intramembrane aspartyl protease (mIAP) fortuitously acting on the renin substrate angiotensinogen and the C-terminal transmembrane segment of amyloid precursor protein (C100), which is cleaved by the presenilin subunit of γ-secretase, an Alzheimer disease (AD)-associated IAP. mIAP variants with substitutions in active-site and putative substrate-gating residues generally exhibit impaired, but not abolished, activity toward angiotensinogen and retain the predominant cleavage site (His–Thr). The aromatic ring, but not the hydroxyl substituent, within Tyr of the catalytic Tyr–Asp (YD) motif plays a catalytic role, and the hydrolysis reaction incorporates bulk water as in soluble aspartyl proteases. mIAP hydrolyzes the transmembrane region of C100 at two major presenilin cleavage sites, one corresponding to the AD-associated Aβ42 peptide (Ala–Thr) and the other to the non-pathogenic Aβ48 (Thr–Leu). For the former site, we observed more favorable kinetics in lipid bilayer–mimicking bicelles than in detergent solution, indicating that substrate–lipid and substrate–enzyme interactions both contribute to catalytic rates. High-resolution MS analyses across four substrates support a preference for threonine at the scissile bond. However, results from threonine-scanning mutagenesis of angiotensinogen demonstrate a competing positional preference for cleavage. Our results indicate that IAP cleavage is controlled by both positional and chemical factors, opening up new avenues for selective IAP inhibition for therapeutic interventions. PMID:29382721

Final Technical Report for grant entitled "New Horizons in C-F Activation by Main Group Electrophiles"

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

Ozerov, Oleg V; Ozerov, Oleg V.

2014-01-16

We became interested in developing new methods for hydrodefluorination (HDF) and other types of C-F bond conversion in polyfluoroalkanes under mild conditions. We were attracted to an approach to C-F activation, where the key C-F cleavage proceeds by a Lewis acid abstraction of fluoride rather than a redox event. The efforts during the previous period were aimed at a) advancing the HDF reactivity with improvement in scope and catalyst longevity; b) extending C-F activation beyond HDF; c) generating insight about the elementary steps of the reaction and potential intermediates.

2,4-Dinitrophenylhydrazine, redetermined at 120 K: a three-dimensional framework built from N-H...O, N-H...(O)2, N-H...pi(arene) and C-H...O hydrogen bonds.

PubMed

Wardell, James L; Low, John N; Glidewell, Christopher

2006-06-01

In the title compound, C6H6N4O4, the bond distances indicate significant bond fixation, consistent with charge-separated polar forms. The molecules are almost planar and there is an intramolecular N-H...O hydrogen bond. The molecules are linked into a complex three-dimensional framework structure by a combination of N-H...O, N-H...(O)2, N-H...pi(arene) and C-H...O hydrogen bonds.

A P-H functionalized Al/P-based frustrated Lewis pair - hydrophosphination of nitriles, ring opening with cyclopropenones and evidence of P[double bond, length as m-dash]C double bond formation.

PubMed

Keweloh, Lukas; Aders, Niklas; Hepp, Alexander; Pleschka, Damian; Würthwein, Ernst-Ulrich; Uhl, Werner

2018-06-12

Hydroalumination of R-P(H)-C[triple bond, length as m-dash]C-tBu with bulky H-Al[CH(SiMe3)2]2 afforded the new P-H functionalized Al/P-based frustrated Lewis pair R-P(H)-C[[double bond, length as m-dash]C(H)-tBu]-AlR2 [R = CH(SiMe3)2; FLP 7]. A weak adduct of 7 with benzonitrile (8) was detected by NMR spectroscopy, but could not be isolated. tert-Butyl isocyanide afforded a similar, but isolable adduct (9), in which the isocyanide C atom was coordinated to aluminium. The unique reactivity of 7 became evident from its reactions with the heteroatom substituted nitriles PhO-C[triple bond, length as m-dash]N, PhCH2S-C[triple bond, length as m-dash]N and H8C4N-C[triple bond, length as m-dash]N. Hydrophosphination of the C[triple bond, length as m-dash]N triple bonds afforded imines at room temperature which were coordinated to the FLP by Al-N and P-C bonds to yield AlCPCN heterocycles (10 to 12). These processes depend on substrate activation by the FLP. Diphenylcyclopropenone and its sulphur derivative reacted with 7 by addition of the P-H bond to a C-C bond of the strained C3 ring and ring opening to afford the fragment (Z)-Ph-C(H)[double bond, length as m-dash]C(Ph)-C-X-Al (X = O, S). The C-O or C-S groups were coordinated to the FLP to yield AlCPCX heterocycles (13 and 14). The thiocarbonyl derived compound 14 contains an internally stabilized phosphenium cation with a localized P[double bond, length as m-dash]C bond, a trigonal planar coordinated P atom and a short P[double bond, length as m-dash]C distance (168.9 pm). Insight into formation mechanisms, the structural and energetic properties of FLP 7 and compounds 13 and 14 was gained by quantum chemical DFT calculations.

The localization of a vitamin K-induced modification in an N-terminal fragment of human prothrombin

PubMed Central

Skotland, Tore; Holm, Turid; Østerud, Bjarne; Flengsrud, Ragnar; Prydz, Hans

1974-01-01

1. The N-terminal fragment (PF-I) split off from prothrombin during coagulation was purified to homogeneity from human serum. 2. The apparent molecular weight is 27000±2000 in sodium dodecyl sulphate–polyacrylamide-gel electrophoresis, whereas a value of about 19600 is obtained by calculation based on amino acid and carbohydrate analyses. The N-terminal sequence is an Ala-Asx bond. The fragment contains about 16% carbohydrate, binds phospholipids in the presence of Ca2+ and is adsorbed to BaSO4. The pKa of its BaSO4-binding group(s) is 3.1–3.5. 3. By CNBr cleavage of fragment PF-I two peptides (C-1 and C-2) were obtained with molecular weights of about 5900 (C-2) and 12400 (C-1) on the basis of amino acid and carbohydrate analyses. Only the smaller (N-terminal) peptide is adsorbed to BaSO4 and, since the ability of the whole protein to bind to BaSO4 is known to be absent in samples obtained from patients treated with vitamin K antagonists, this peptide probably contains the site of a modification to the structure of the protein which occurs during biosynthesis and depends on vitamin K. This peptide does not contain hexosamine or sialic acid. ImagesFig. 2. PMID:4219283

Direct Structural and Chemical Characterization of the Photolytic Intermediates of Methylcobalamin Using Time-Resolved X-ray Absorption Spectroscopy

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

Subramanian, Ganesh; Zhang, Xiaoyi; Kodis, Gerdenis

Cobalt-carbon bond cleavage is crucial to most natural and synthetic applications of the cobalamin class of compounds, and here we present the first direct electronic and geometric structural characteristics of intermediates formed following photoexcitation of methylcobalamin (MeCbl) using time-resolved X-ray absorption spectroscopy (XAS). We catch transients corresponding to two intermediates, in the hundreds of picoseconds and a few microseconds. Highlights of the picosecond intermediate, which is reduced in comparison to the ground state, are elongation of the upper axial Co-C bond and relaxation of the corrin ring. This is not so with the recombining photocleaved products captured at a fewmore » microseconds, where the Co-C bond almost (yet not entirely) reverts to its ground state configuration and a substantially elongated lower axial Co-NIm bond is observed. The reduced cobalt site here confirms formation of methyl radical as the photoproduct.« less

Reactions in 1,1,1-trifluoroacetone triggered by low energy electrons (0-10 eV): from simple bond cleavages to complex unimolecular reactions.

PubMed

Illenberger, Eugen; Meinke, Martina C

2014-08-21

The impact of low energy electrons (0-10 eV) to 1,1,1-trifluoroacetone yields a variety of fragment anions which are formed via dissociative electron attachment (DEA) through three pronounced resonances located at 0.8 eV, near 4 eV, and in the energy range 8-9 eV. The fragment ions arise from different reactions ranging from the direct cleavage of one single or double bond (formation of F(-), CF3(-), O(-), (M-H)(-), and M-F)(-)) to remarkably complex unimolecular reactions associated with substantial geometric and electronic rearrangement in the transitory intermediate (formation of OH(-), FHF(-), (M-HF)(-), CCH(-), and HCCO(-). The ion CCH(-), for example, is formed by an excision of unit from the target molecule through the concerted cleavage of four bonds and recombination to H2O within the neutral component of the reaction.

Synthesis, characterization and DNA-binding studies of mono and heterobimetallic complexes Cu sbnd Sn 2/Zn sbnd Sn 2 and their DNA cleavage activity

NASA Astrophysics Data System (ADS)

Arjmand, Farukh; Sayeed, Fatima

2010-02-01

Heterobimetallic complexes C 6H 24N 4O 6CuSn 2Cl 63, C 6H 24N 4O 6ZnSn 2Cl 64 have been synthesized from their monometallic analogs C 6H 16N 4O 2CuCl 21, C 6H 16N 4O 2ZnCl 22, and were characterized by various spectroscopic and analytical methods. The complexes 1-4 reveal an octahedral geometry for both central metal ions Cu/Zn as well as for Sn metal ion. The interaction of complexes 1-4 with CT-DNA, were investigated by using absorption, emission, cyclic voltammetry, viscometry and DNA cleavage studies. The emission quenching of 3 and 4 by [Fe(CN) 6] 4- depressed greatly when bound to CT-DNA. The results of spectroscopic, viscometric and cyclic voltammetry of complexes 3 and 4 revealed electrostatic mode of binding of the complexes with CT-DNA. These results revealed that 4 bind more avidly in comparison to 3 with CT-DNA. Gel electrophoresis of DNA with complexes 3 and 4 demonstrated that the complexes exhibit excellent cleavage activity under physiological conditions.

Familial Alzheimer’s mutations within APPTM increase Aβ42 production by enhancing accessibility of ɛ-cleavage site

NASA Astrophysics Data System (ADS)

Chen, Wen; Gamache, Eric; Rosenman, David J.; Xie, Jian; Lopez, Maria M.; Li, Yue-Ming; Wang, Chunyu

2014-01-01

The high Aβ42/Aβ40 production ratio is a hallmark of familial Alzheimer’s disease, which can be caused by mutations in the amyloid precursor protein (APP). The C-terminus of Aβ is generated by γ-secretase cleavage within the transmembrane domain of APP (APPTM), a process that is primed by an initial ɛ-cleavage at either T48 or L49, resulting in subsequent production of Aβ42 or Aβ40, respectively. Here we solve the dimer structures of wild-type APPTM (AAPTM WT) and mutant APPTM (FAD mutants V44M) with solution NMR. The right-handed APPTM helical dimer is mediated by GXXXA motif. From the NMR structural and dynamic data, we show that the V44M and V44A mutations can selectively expose the T48 site by weakening helical hydrogen bonds and increasing hydrogen-deuterium exchange rate (kex). We propose a structural model in which FAD mutations (V44M and V44A) can open the T48 site γ-secretase for the initial ɛ-cleavage, and consequently shift cleavage preference towards Aβ42.

Structural characterization and identification of biflavones in Selaginella tamariscina by liquid chromatography-diode-array detection/electrospray ionization tandem mass spectrometry.

PubMed

Zhang, Yi-Xuan; Li, Qiu-Yue; Yan, Li-Li; Shi, Yue

2011-08-15

Biflavonoids, a special class of flavonoids, are widely distributed in gymnosperm plants and have various biological activities. They are also major bioactive ingredients in Selaginella tamariscina. In this work, we report the use of high-performance liquid chromatography with a diode-array detector (HPLC-DAD) and electrospray ionization multi-stage tandem mass spectrometry (ESI-MS(n)) to study the fragmentation behavior of three main types of biflavonoids using seven biflavonoid reference compounds and analyze the biflavonoids in Selaginella tamariscina. The most useful fragmentations in terms of structural identification are those involving the C-ring cleavage of biflavonoids. For amentoflavone-type biflavonoids (containing flavonoid parts I and II), fragmentation on the flavonoid part II at positions 1/3 and 0/4 are the primary pathways, whereas the chances are greater for C-ring cleavage fragmentation occurring on flavonoid part I at positions 1/3 and 1/4 for robustaflavone-type biflavonoids. However, the predominant diagnostic ions of the specific C-O-C-connected hinokiflavone-type biflavonoids are a series of ions resulting from the rupture of the connective C-O bond. Based on the fragmentation patterns of these reference compounds, 17 biflavonoids were identified in an extract of Selaginella tamariscina, three of which have not been previously reported as constituents of this plant. This study provides a powerful approach for the online structural elucidation and identification of different types of biflavonoids and positional isomers from Selaginella tamariscina and other biflavonoids distributed in related plants and prescriptions. Copyright © 2011 John Wiley & Sons, Ltd.

Low-energy collision induced dissociation (low-energy CID), collision induced dissociation (CID) and higher-energy collision dissociation (HCD) mass spectrometry for structural elucidation of saccharides and clarification of their dissolution mechanism in DMAc/LiCl.

PubMed

Bayat, Parisa; Lesage, Denis; Cole, Richard B

2018-05-29

The dissolution mechanism of oligosaccharides in N,N-dimethylacetamide/lithium chloride (DMAc/LiCl), a solvent used for cellulose dissolution, and the capabilities of low-energy collision induced dissociation (low-energy CID), collision induced dissociation (CID) and higher-energy collision dissociation (HCD) for structural analysis of carbohydrates were investigated. Comparing the spectra obtained using three techniques shows that, generally, when working with mono-lithiated sugars, CID spectra provide more structurally informative fragments, and glycosidic bond cleavage is the main pathway. However, when working with di-lithiated sugars, HCD spectra can be more informative providing predominately cross-ring cleavage fragments. This is because HCD is a non-resonant activation technique and it allows a higher amount of energy to be deposited in a short time, giving access to more endothermic decomposition pathways as well as consecutive fragmentations. The difference in preferred dissociation pathways of mono-lithiated and di-lithiated sugars indicates that the presence of the second lithium strongly influences the relative rate constants for cross-ring cleavages (rearrangement) vs. direct glycosidic bond cleavages, and disfavors the latter. Regarding the dissolution mechanism of sugars in DMAc/LiCl, CID and HCD experiments on di-lithiated and tri-lithiated sugars reveal that intensities of product ions containing two Li + or three Li + , respectively, are higher than those bearing only one Li + . In addition, comparing the fragmentation spectra (both HCD and CID) of LiCl adducted lithiated sugar and NaCl adducted sodiated sugar shows that while, in the latter case, loss of NaCl is dominant, in the former case, loss of HCl occurs preferentially. The compiled evidence implies that there is a strong and direct interaction between lithium and the saccharide during the dissolution process in the DMAc/LiCl solvent system. This article is protected by copyright. All rights reserved.

Characterization of an extensin-modifying metalloprotease: N-terminal processing and substrate cleavage pattern of Pectobacterium carotovorum Prt1.

PubMed

Feng, Tao; Nyffenegger, Christian; Højrup, Peter; Vidal-Melgosa, Silvia; Yan, Kok-Phen; Fangel, Jonatan Ulrik; Meyer, Anne S; Kirpekar, Finn; Willats, William G; Mikkelsen, Jørn D

2014-12-01

Compared to other plant cell wall-degrading enzymes, proteases are less well understood. In this study, the extracellular metalloprotease Prt1 from Pectobacterium carotovorum (formerly Erwinia carotovora) was expressed in Escherichia coli and characterized with respect to N-terminal processing, thermal stability, substrate targets, and cleavage patterns. Prt1 is an autoprocessing protease with an N-terminal signal pre-peptide and a pro-peptide which has to be removed in order to activate the protease. The sequential cleavage of the N-terminus was confirmed by mass spectrometry (MS) fingerprinting and N-terminus analysis. The optimal reaction conditions for the activity of Prt1 on azocasein were at pH 6.0, 50 °C. At these reaction conditions, K M was 1.81 mg/mL and k cat was 1.82 × 10(7) U M(-1). The enzyme was relatively stable at 50 °C with a half-life of 20 min. Ethylenediaminetetraacetic acid (EDTA) treatment abolished activity; Zn(2+) addition caused regain of the activity, but Zn(2+)addition decreased the thermal stability of the Prt1 enzyme presumably as a result of increased proteolytic autolysis. In addition to casein, the enzyme catalyzed degradation of collagen, potato lectin, and plant extensin. Analysis of the cleavage pattern of different substrates after treatment with Prt1 indicated that the protease had a substrate cleavage preference for proline in substrate residue position P1 followed by a hydrophobic residue in residue position P1' at the cleavage point. The activity of Prt1 against plant cell wall structural proteins suggests that this enzyme might become an important new addition to the toolbox of cell-wall-degrading enzymes for biomass processing.

Direct bonding of gallium nitride to silicon carbide: Physical, and electrical characterization

NASA Astrophysics Data System (ADS)

Lee, Jaeseob

The direct bonding method is applied to the GaN/SiC system, and the processing conditions for successful direct bonding are clarified. Direct bonding of GaN/SiC is achieved at 900°C. The direct bonding of GaN to Si-face SiC is very dependent on the choice of chemical treatments, but the bonding of GaN to C-face SiC is less dependent on surface preparation. If a native oxide is present when the bonded interface is prepared, the current through the interface is decreased, which is attributed to an energy barrier due to the presence of charged interface states. TEM images indicate 10nm spaced dislocations at the interface for the GaN/SiC (Si-face), and ˜6nm for the GaN/SiC (C-face), which form to accommodate the lattice mismatch (3.4%) and twist (1˜2°) and tilt misfit (0.2° for Si-face SiC and 3° for C-face SiC). In some regions (˜30%) an amorphous oxide layer forms at the interface, which is attributed to inadequate surface preparation prior to bonding. The strain of the GaN film with a Ga/C interface was ˜0.1%, tensile strain, and that of GaN with a Ga/Si interface was ˜0.2%, tensile strain. Our analysis indicates that the GaN/SiC thermal misfit dominates the strain of the GaN after bonding. The electrical characteristics of n-p GaN/SiC heterojunctions display diode ideality factors, saturation currents, energy barrier heights, and band offsets of 1.5 +/- 0.1, 10-13 A/cm 2, 0.75 +/- 0.10 eV, and DeltaEC = 0.87 +/- 0.10 eV for the Ga/Si interface and 1.2 +/- 0.1, 10 -16 A/cm2, 0.56 +/- 0.10 eV, and Delta EC = 0.46 +/- 0.10 eV for the Ga/C interface.

Tandem mass spectrometric analysis of cyclophosphamide, ifosfamide and their metabolites.

PubMed

Liu, Zhongfa; Chan, Kenneth K; Wang, Jeffrey J

2005-01-01

A detailed multi-stage (MSn) fragmentation study of cyclophosphamide (CP), ifosfamide (IF) and their major metabolites, using an ion-trap mass spectrometer and a Q-TOF mass spectrometer, was performed with the aid of specifically deuterium-labeled analogs. The analytes showed good responses in positive-ion electrospray mass spectrometry as [MH]+ ions. Tandem mass spectra revealed a wealth of structurally specific ions, allowing characterization of the fragmentation pathways of these analytes. The major fragmentation pathways of the protonated CP and IF are elimination of ethylene from C5 and C6 of 1,3,2-oxazaphosphorine-2-oxide via a McLafferty rearrangement, and cleavage of the P-N bond. However, their activated 4-OOH and 4-OH metabolites primarily underwent hydrogen peroxide elimination and dehydration, respectively, followed by fragmentation pathways similar to those of CP and IF. These results should prove useful in structural elucidation of future analogs of CP and IF, and/or of their metabolites. Copyright (c) 2005 John Wiley & Sons, Ltd.

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. Copyright © 2015 Elsevier Ltd. All rights reserved.

Kinetic and structural characterization of amyloid-β peptide hydrolysis by human angiotensin-1-converting enzyme.

PubMed

Larmuth, Kate M; Masuyer, Geoffrey; Douglas, Ross G; Schwager, Sylva L; Acharya, K Ravi; Sturrock, Edward D

2016-03-01

Angiotensin-1-converting enzyme (ACE), a zinc metallopeptidase, consists of two homologous catalytic domains (N and C) with different substrate specificities. Here we report kinetic parameters of five different forms of human ACE with various amyloid beta (Aβ) substrates together with high resolution crystal structures of the N-domain in complex with Aβ fragments. For the physiological Aβ(1-16) peptide, a novel ACE cleavage site was found at His14-Gln15. Furthermore, Aβ(1-16) was preferentially cleaved by the individual N-domain; however, the presence of an inactive C-domain in full-length somatic ACE (sACE) greatly reduced enzyme activity and affected apparent selectivity. Two fluorogenic substrates, Aβ(4-10)Q and Aβ(4-10)Y, underwent endoproteolytic cleavage at the Asp7-Ser8 bond with all ACE constructs showing greater catalytic efficiency for Aβ(4-10)Y. Surprisingly, in contrast to Aβ(1-16) and Aβ(4-10)Q, sACE showed positive domain cooperativity and the double C-domain (CC-sACE) construct no cooperativity towards Aβ(4-10)Y. The structures of the Aβ peptide-ACE complexes revealed a common mode of peptide binding for both domains which principally targets the C-terminal P2' position to the S2' pocket and recognizes the main chain of the P1' peptide. It is likely that N-domain selectivity for the amyloid peptide is conferred through the N-domain specific S2' residue Thr358. Additionally, the N-domain can accommodate larger substrates through movement of the N-terminal helices, as suggested by the disorder of the hinge region in the crystal structures. Our findings are important for the design of domain selective inhibitors as the differences in domain selectivity are more pronounced with the truncated domains compared to the more physiological full-length forms. The atomic coordinates and structure factors for N-domain ACE with Aβ peptides 4-10 (5AM8), 10-16 (5AM9), 1-16 (5AMA), 35-42 (5AMB) and (4-10)Y (5AMC) complexes have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ, USA (http://www.rcsb.org/). © 2016 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Facet-dependent solar ammonia synthesis of BiOCl nanosheets via a proton-assisted electron transfer pathway

NASA Astrophysics Data System (ADS)

Li, Hao; Shang, Jian; Shi, Jingu; Zhao, Kun; Zhang, Lizhi

2016-01-01

Under the pressure of a fossil fuels shortage and global climate change, solar ammonia synthesis and the need to develop N2 fixation under mild conditions is becoming more urgent need; however, their intrinsic mechanisms still remain unclear. Herein, we demonstrate that the kinetic inertia of N2 can be overcome using oxygen vacancies (OVs) of BiOCl as the catalytic centers to create lower energy molecular steps, which are amendable for the solar light driven N-N triple bond cleavage via a proton-assisted electron transfer pathway. Moreover, the distinct structures of OVs on different BiOCl facets strongly determine the N2 fixation pathways by influencing both the adsorption structure and the activation level of N2. The fixation of terminal end-on bound N2 on the OVs of BiOCl {001} facets follows an asymmetric distal mode by selectively generating NH3, while the reduction of side-on bridging N2 on the OVs of BiOCl {010} facets is more energetically favorable in a symmetric alternating mode to produce N2H4 as the main intermediate.Under the pressure of a fossil fuels shortage and global climate change, solar ammonia synthesis and the need to develop N2 fixation under mild conditions is becoming more urgent need; however, their intrinsic mechanisms still remain unclear. Herein, we demonstrate that the kinetic inertia of N2 can be overcome using oxygen vacancies (OVs) of BiOCl as the catalytic centers to create lower energy molecular steps, which are amendable for the solar light driven N-N triple bond cleavage via a proton-assisted electron transfer pathway. Moreover, the distinct structures of OVs on different BiOCl facets strongly determine the N2 fixation pathways by influencing both the adsorption structure and the activation level of N2. The fixation of terminal end-on bound N2 on the OVs of BiOCl {001} facets follows an asymmetric distal mode by selectively generating NH3, while the reduction of side-on bridging N2 on the OVs of BiOCl {010} facets is more energetically favorable in a symmetric alternating mode to produce N2H4 as the main intermediate. Electronic supplementary information (ESI) available: Other experimental details, additional SEM and TEM images, X-ray diffraction patterns (XRD), UV-Vis diffuse reflectance spectra (DRS), and additional data. See DOI: 10.1039/c5nr07380d

Degradation pattern of photosystem II reaction center protein D1 in intact leaves. The major photoinhibition-induced cleavage site in D1 polypeptide is located amino terminally of the DE loop.

PubMed

Kettunen, R; Tyystjärvi, E; Aro, E M

1996-08-01

Photoinhibition-induced degradation of the D1 protein of the photosystem II reaction center was studied in intact pumpkin (Cucurbita pepo L.) leaves. Photoinhibition was observed to cause the cleavage of the D1 protein at two distinct sites. The main cleavage generated an 18-kD N-terminal and a 20-kD C-terminal degradation fragment of the D1 protein. this cleavage site was mapped to be located clearly N terminally of the DE loop. The other, less-frequent cleavage occurred at the DE loop and produced the well-documented 23-kD, N-terminal D1 degradation product. Furthermore, the 23-kD, N-terminal D1 fragment appears to be phosphorylated and can be detected only under severe photoinhibition in vivo. Comparison of the D1 degradation pattern after in vivo photoinhibition to that after in vitro acceptor-side and donor-side photoinhibition, performed with isolated photosystem II core particles, gives indirect evidence in support of donor-side photoinhibition in intact leaves.

Synthesis of a Novel Polyethoxysilsesquiazane and Thermal Conversion into Ternary Silicon Oxynitride Ceramics with Enhanced Thermal Stability.

PubMed

Iwase, Yoshiaki; Horie, Yoji; Daiko, Yusuke; Honda, Sawao; Iwamoto, Yuji

2017-12-05

A novel polyethoxysilsesquiazane ([EtOSi(NH) 1.5 ] n , EtOSZ) was synthesized by ammonolysis at -78 °C of ethoxytrichlorosilane (EtOSiCl₃), which was isolated by distillation as a reaction product of SiCl₄ and EtOH. Attenuated total reflection-infra red (ATR-IR), 13 C-, and 29 Si-nuclear magnetic resonance (NMR) spectroscopic analyses of the ammonolysis product resulted in the detection of Si-NH-Si linkage and EtO group. The simultaneous thermogravimetric and mass spectrometry analyses of the EtOSZ under helium revealed cleavage of oxygen-carbon bond of the EtO group to evolve ethylene as a main gaseous species formed in-situ, which lead to the formation at 800 °C of quaternary amorphous Si-C-N with an extremely low carbon content (1.1 wt %) when compared to the theoretical EtOSZ (25.1 wt %). Subsequent heat treatment up to 1400 °C in N₂ lead to the formation of X-ray amorphous ternary Si-O-N. Further heating to 1600 °C in N₂ promoted crystallization and phase partitioning to afford Si₂N₂O nanocrystallites identified by the XRD and TEM analyses. The thermal stability up to 1400 °C of the amorphous state achieved for the ternary Si-O-N was further studied by chemical composition analysis, as well as X-ray photoelectron spectroscopy (XPS) and 29 Si-NMR spectroscopic analyses, and the results were discussed aiming to develop a novel polymeric precursor for ternary amorphous Si-O-N ceramics with an enhanced thermal stability.

[Mass spectrum and uniformity of decomposition of certain 2-substituted 9-(o-chlorbenzyl)-8-azahypoxanthines].

PubMed

Kuleshov, K V; Adamov, A V; Belokon', A I; Rodin, O G; Perevalov, V P; El'man, A R

2004-01-01

The regularities of mass spectrometric fragmentation under electron impact of new 9-(o-chlorobenzyl)-8-azahypoxantines with (N-aryl)amidocarbonylmethylthiomethyl substituents in position 2 were studied. The main fragmentation pathways are the elimination of Ar-NH+ and o-chlorobenzyl ions and cleavage of C-S bonds, characteristic of organic sulfides. During the fragmentations, some rearrangements occur, consisting in the transfer of labile hydrogen atoms from the alpha-positions to ions being eliminated. Fragmentation of 8-azapurine parts of the molecules does not prevail. Peaks of molecular ions are clearly visible in the mass spectra of all the substances studied. The English version of the paper: Russian Journal of Bioorganic Chemistry, 2004, vol. 30, no. 1; see also http://www.maik.ru.

Theoretical studies on the unimolecular decomposition of ethylene glycol.

PubMed

Ye, Lili; Zhao, Long; Zhang, Lidong; Qi, Fei

2012-01-12

The unimolecular decomposition processes of ethylene glycol have been investigated with the QCISD(T) method with geometries optimized at the B3LYP/6-311++G(d,p) level. Among the decomposition channels identified, the H(2)O-elimination channels have the lowest barriers, and the C-C bond dissociation is the lowest-energy dissociation channel among the barrierless reactions (the direct bond cleavage reactions). The temperature and pressure dependent rate constant calculations show that the H(2)O-elimination reactions are predominant at low temperature, whereas at high temperature, the direct C-C bond dissociation reaction is dominant. At 1 atm, in the temperature range 500-2000 K, the calculated rate constant is expressed to be 7.63 × 10(47)T(-10.38) exp(-42262/T) for the channel CH(2)OHCH(2)OH → CH(2)CHOH + H(2)O, and 2.48 × 10(51)T(-11.58) exp(-43593/T) for the channel CH(2)OHCH(2)OH → CH(3)CHO + H(2)O, whereas for the direct bond dissociation reaction CH(2)OHCH(2)OH → CH(2)OH + CH(2)OH the rate constant expression is 1.04 × 10(71)T(-16.16) exp(-52414/T).

Activation energies for dissociation of double strand oligonucleotide anions: evidence for watson-crick base pairing in vacuo.

PubMed

Schnier, P D; Klassen, J S; Strittmatter, E F; Williams, E R

1998-09-23

The dissociation kinetics of a series of complementary and noncomplementary DNA duplexes, (TGCA)(2) (3-), (CCGG)(2) (3-), (AATTAAT)(2) (3-), (CCGGCCG)(2) (3-), A(7)*T(7) (3-), A(7)*A(7) (3-), T(7)*T(7) (3-), and A(7)*C(7) (3-) were investigated using blackbody infrared radiative dissociation in a Fourier transform mass spectrometer. From the temperature dependence of the unimolecular dissociation rate constants, Arrhenius activation parameters in the zero-pressure limit are obtained. Activation energies range from 1.2 to 1.7 eV, and preexponential factors range from 10(13) to 10(19) s(-1). Dissociation of the duplexes results in cleavage of the noncovalent bonds and/or cleavage of covalent bonds leading to loss of a neutral nucleobase followed by backbone cleavage producing sequence-specific (a - base) and w ions. Four pieces of evidence are presented which indicate that Watson-Crick (WC) base pairing is preserved in complementary DNA duplexes in the gas phase: i. the activation energy for dissociation of the complementary dimer, A(7)*T(7) (3-), to the single strands is significantly higher than that for the related noncomplementary A(7)*A(7) (3-) and T(7)*T(7) (3-) dimers, indicating a stronger interaction between strands with a specific base sequence, ii. extensive loss of neutral adenine occurs for A(7)*A(7) (3-) and A(7)*C(7) (3-) but not for A(7)*T(7) (3-) consistent with this process being shut down by WC hydrogen bonding, iii. a correlation is observed between the measured activation energy for dissociation to single strands and the dimerization enthalpy (-DeltaH(d)) in solution, and iv. molecular dynamics carried out at 300 and 400 K indicate that WC base pairing is preserved for A(7)*T(7) (3-) duplex, although the helical structure is essentially lost. In combination, these results provide strong evidence that WC base pairing can exist in the complete absence of solvent.

Isolation, crystallization and preliminary crystallographic analysis of Salmonella typhimurium uridine phosphorylase crystallized with 2,2′-anhydrouridine

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

Timofeev, Vladimir I.; Lashkov, Alexander A.; Gabdoulkhakov, Azat G.

2007-10-01

S. typhimurium uridine phosphorylase has been isolated and crystallized in the presence of ligand. Uridine phosphorylase (UPh; EC 2.4.2.3) is a member of the pyrimidine nucleoside phosphorylase family of enzymes which catalyzes the phosphorolytic cleavage of the C—N glycoside bond of uridine, with the formation of ribose 1-phosphate and uracil. This enzyme has been shown to be important in the activation and catabolism of fluoropyrimidines. Modulation of its enzymatic activity may affect the therapeutic efficacy of chemotherapeutic agents. The structural investigation of the bacterial uridine phosphorylases, both unliganded and complexed with substrate/product analogues and inhibitors, may help in understanding themore » catalytic mechanism of the phosphorolytic cleavage of uridine. Salmonella typhimurium uridine phosphorylase has been crystallized with 2,2′-anhydrouridine. X-ray diffraction data were collected to 2.15 Å. Preliminary analysis of the diffraction data indicates that the crystal belongs to space group P2{sub 1}2{sub 1}2{sub 1}, with unit-cell parameters a = 88.52, b = 123.98, c = 133.52 Å. The solvent content is 45.51%, assuming the presence of one hexamer molecule per asymmetric unit.« less

Enzymatic reduction of azo and indigoid compounds.

PubMed

Pricelius, S; Held, C; Murkovic, M; Bozic, M; Kokol, V; Cavaco-Paulo, A; Guebitz, G M

2007-11-01

A customer- and environment-friendly method for the decolorization azo dyes was developed. Azoreductases could be used both to bleach hair dyed with azo dyes and to reduce dyes in vat dyeing of textiles. A new reduced nicotinamide adenine dinucleotide-dependent azoreductase of Bacillus cereus, which showed high potential for reduction of these dyes, was purified using a combination of ammonium sulfate precipitation and chromatography and had a molecular mass of 21.5 kDa. The optimum pH of the azoreductase depended on the substrate and was within the range of pH 6 to 7, while the maximum temperature was reached at 40 degrees C. Oxygen was shown to be an alternative electron acceptor to azo compounds and must therefore be excluded during enzymatic dye reduction. Biotransformation of the azo dyes Flame Orange and Ruby Red was studied in more detail using UV-visible spectroscopy, high-performance liquid chromatography, and mass spectrometry (MS). Reduction of the azo bonds leads to cleavage of the dyes resulting in the cleavage product 2-amino-1,3 dimethylimidazolium and N approximately 1 approximately ,N approximately 1 approximately -dimethyl-1,4-benzenediamine for Ruby Red, while only the first was detected for Flame Orange because of MS instability of the expected 1,4-benzenediamine. The azoreductase was also found to reduce vat dyes like Indigo Carmine (C.I. Acid Blue 74). Hydrogen peroxide (H(2)O(2)) as an oxidizing agent was used to reoxidize the dye into the initial form. The reduction and oxidation mechanism of Indigo Carmine was studied using UV-visible spectroscopy.

Theoretical Study of the Mechanism of Oxoiron(IV) Formation from H2O2 and a Nonheme Iron(II) Complex: O–O Cleavage Involving Proton-Coupled Electron Transfer

PubMed Central

Hirao, Hajime; Li, Feifei; Que, Lawrence; Morokuma, Keiji

2011-01-01

It has recently been shown that the nonheme oxoiron(IV) species supported by the 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane ligand (TMC) can be generated in near-quantitative yield by reacting [FeII(TMC)(OTf)2] with a stoichiometric amount of H2O2 in CH3CN in the presence of 2,6-lutidine (Li, F.; England, J.; Que L., Jr. J. Am. Chem. Soc. 2010, 132, 2134–2135). This finding has major implications for O–O bond cleavage events in both Fenton chemistry and nonheme iron enzymes. To understand the mechanism of this process, especially the intimate details of the O–O bond cleavage step, a series of density functional theory (DFT) calculations and analyses have been carried out. Two distinct reaction paths (A and B) were identified. Path A consists of two principal steps: (1) coordination of H2O2 to Fe(II) and (2) a combination of partial homolytic O–O bond cleavage and proton-coupled electron transfer (PCET). The latter combination renders the rate-limiting O–O cleavage effectively a heterolytic process. Path B proceeds via a simultaneous homolytic O–O bond cleavage of H2O2 and Fe–O bond formation. This is followed by H-abstraction from the resultant Fe(III)–OH species by an •OH radical. Calculations suggest that path B is plausible in the absence of base. However, once 2,6-lutidine is added to the reacting system, the reaction barrier is lowered and more importantly the mechanistic path switches to path A, where 2,6-lutidine plays an essential role as an acid-base catalyst in a manner similar to how the distal histidine or glutamate residue assists in Compound I formation in heme peroxidases. The reaction was found to proceed predominantly on the quintet spin state surface, and a transition to the triplet state, the experimentally known ground state for the TMC-oxoiron(IV) species, occurs in the last stage of the oxoiron(IV) formation process. PMID:21678930

Reactions of the linear tetranuclear complex Ru sub 4 (CO) sub 10 (CH sub 3 C double bond C(H)C(H) double bond N-i-Pr) sub 2 with oxidizing reagents. Syntheses of halide-bridged (Ru(CO) sub 2 X(CH sub 3 C double bond C(H)C(H) double bond N-i-Pr)) sub 2 and fac-Ru(CO) sub 3 X(CH sub 3 C double bond C(H)C(H) double bond N-i-Pr)

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

Mul, W.P.; Elsevier, C.J.; van Leijen, M.

1991-01-01

The linear tetranuclear complex Ru{sub 4}(CO){sub 10}(CH{sub 3}C{double bond}C(H)C(H){double bond}N-i-Pr){sub 2} (1), containing two {eta}{sup 5}-azaruthenacyclopentadienyl systems, reacts with oxidizing reagents (I{sub 2}, Br{sub 2}, NBS, CCl{sub 4}) at elevated temperatures (40-90C) in heptane or benzene to give the new dimeric halide-bridged organoruthenium(II) complexes (Ru(CO){sub 2}X(CH{sub 3}C{double bond}C(H)C(H){double bond}N-i-Pr)){sub 2} (X = I (3a), X = Br (3b), Cl (3c); yield 30-80%) together with (Ru(CO){sub 3}X{sub 2}){sub 2}. The reactions of 1 with CX{sub 4} (X = I, Br, Cl) are accelerated by CO, probably because Ru{sub 4}(CO){sub 12}(CH{sub 3}C{double bond}C(H)C(H){double bond}N-i-Pr){sub 2} (5), which contains two unbridged metal-metal bonds,more » is formed prior to oxidation. The halide-bridged dimers 3a-c are obtained as mixtures of four isomers, the configurations of which are discussed. Splitting of the halide bridges takes place when a solution of 3a-c is saturated with CO, whereby mononuclear fac-Ru(CO){sub 3}X(CH{sub 3}C{double bond}C(H)C(H){double bond}N-i-Pr) (4a-c) is obtained. This process is reversible; ie., passing a stream of nitrogen through a solution of 4a-c or removal of the solvent under vacuum causes the reverse reaction with reformation of 3a-c. Compounds 3a-c and 4a-c have been characterized by IR (3, 4), FD mass (3), {sup 1}H (3, 4), and {sup 13}C{l brace}H{r brace} NMR (4) spectroscopy and satisfactory elemental analyses have been obtained for 3a-c. Compounds 3 and 4 are suitable precursors for the preparation of new homo- and heteronuclear transition-metal complexes.« less

Processing of the precursor of protamine P2 in mouse. Peptide mapping and N-terminal sequence analysis of intermediates.

PubMed Central

Carré-Eusèbe, D; Lederer, F; Lê, K H; Elsevier, S M

1991-01-01

Protamine P2, the major basic chromosomal protein of mouse spermatozoa, is synthesized as a precursor almost twice as long as the mature protein, its extra length arising from an N-terminal extension of 44 amino acid residues. This precursor is integrated into chromatin of spermatids, and the extension is processed during chromatin condensation in the haploid cells. We have studied processing in the mouse and have identified two intermediates generated by proteolytic cleavage of the precursor. H.p.l.c. separated protamine P2 from four other spermatid proteins, including the precursor and three proteins known to possess physiological characteristics expected of processing intermediates. Peptide mapping indicated that all of these proteins were structurally similar. Two major proteins were further purified by PAGE, transferred to poly(vinylidene difluoride) membranes and submitted to automated N-terminal sequence analysis. Both sequences were found within the deduced sequence of the precursor extension. The N-terminus of the larger intermediate, PP2C, was Gly-12, whereas the N-terminus of the smaller, PP2D, was His-21. Both processing sites involved a peptide bond in which the carbonyl function was contributed by an acidic amino acid. Images Fig. 1. Fig. 3. Fig. 4. PMID:1854346

Double bonds? Studies on the barrier to rotation about the cumulenic C=C bonds of tetraaryl[n]cumulenes (n = 3, 5, 7, 9).

PubMed

Buehringer, Martina U; Padberg, Kevin; Phleps, Martin; Maid, Harald; Placht, Christian; Neiss, Christian; Ferguson, Michael; Goerling, Andreas; Tykwinski, Rik R

2018-03-31

Bonding is the fundamental aspect of organic chemistry, yet the magnitude of C=C bonding in [n]cumulenes as a function of increasing chain length has yet to be experimentally verified for derivatives longer than n = 5. The synthesis of a series of apolar and unsymmetrically substituted tetraaryl[n]cumulenes (n = 3, 5, 7, 9) has been developed and rotational barriers for Z-/E-isomerization have been measured using dynamic VT-NMR spectroscopy. Both experiment and theory confirm a dramatic reduction of the rotational barrier (through estimation of G≠rot for the isomerization) from >24 to 19 to 15 to 11 kcal-1 in [n]cumulenes with n = 3, 5, 7, 9, respectively. Thus, the reduction of cumulenic bonding in longer cumulenes affords bond rotational barriers that are more characteristic of a sterically hindered single bond than that of a double bond. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nucleophilic modification of human complement protein C3: correlation of conformational changes with acquisition of C3b-like functional properties.

PubMed

Isenman, D E; Kells, D I; Cooper, N R; Müller-Eberhard, H J; Pangburn, M K

1981-07-21

Inactivation of C3 by enzymatic cleavage, nucleophilic addition, or slow freezing and thawing resulted in the acquisition of similar end-state conformations as judged by near-UV circular dichroism. Although inactivation by the two nonenzymatic processes involves no peptide bond scission, the inactivated C3 resembled C3b in that it possessed a free sulfhydryl group not present in the native protein and an increased surface hydrophobicity as evidenced by enhanced binding of the fluorophore 8-anilino-1-naphthalensulfonate (ANS). The C3b-like functional properties of modified C3 [Pangburn, M. K., & Müller-Eberhard, H. J. (1980) J. Exp. Med. 152, 1102-1114] may thus be understood in terms of the similarity of its conformation to that of C3b. The rate of the conformational change following proteolytic cleavage was fast and appeared to be limited by the rate of the enzymatic reaction. In contrast, the rate of conformational change following addition of methylamine was slow and rate limited by the conformational rearrangement itself, not by the chemical modification. A kinetic analysis of the changes in circular dichroism and ANS fluorescence enhancement suggested that the nucleophilic addition was spectroscopically undetectable and was followed by a minimally biphasic, spectroscopically demonstrable conformational rearrangement. The appearance of C3b-like functional activity in nucleophile-modified C3 largely parallels the time course of the spectroscopically detectable conformational change but is distinctly slower than the rate at which hemolytic activity is lost. While fully transconformed methylamine-inactivated C3 can bind factor B and is susceptible to cleavage by C3b inactivator and its cofactor beta 1H, this cleavage occurs at a substantially slower rate than the equivalent process in C3b. The implications of these findings in terms of the mechanism through which the alterative pathway of complement is initiated are discussed.

Heterobimetallic Complexes Comprised of Nb and Fe: Isolation of a Coordinatively Unsaturated NbIII/Fe0 Bimetallic Complex Featuring a Nb≡Fe Triple Bond.

PubMed

Culcu, Gursu; Iovan, Diana A; Krogman, Jeremy P; Wilding, Matthew J T; Bezpalko, Mark W; Foxman, Bruce M; Thomas, Christine M

2017-07-19

Heterometallic multiple bonds between niobium and other transition metals have not been reported to date, likely owing to the highly reactive nature of low-valent niobium centers. Herein, a C 3 -symmetric tris(phosphinoamide) ligand framework is used to construct a Nb/Fe heterobimetallic complex Cl-Nb( i PrNPPh 2 ) 3 Fe-Br (2), which features a Fe→Nb dative bond with a metal-metal distance of 2.4269(4) Å. Reduction of 2 in the presence of PMe 3 affords Nb( i PrNPPh 2 ) 3 Fe-PMe 3 (6), a compound with an unusual trigonal pyramidal geometry at a Nb III center, a Nb≡Fe triple bond, and the shortest bond distance (2.1446(8) Å) ever reported between Nb and any other transition metal. Complex 6 is thermally unstable and degrades via P-N bond cleavage to form a Nb V ═NR imide complex, i PrN═Nb( i PrNPPh 2 ) 3 Fe-PMe 3 (9). The heterobimetallic complexes i PrN═Nb( i PrNPPh 2 ) 3 Fe-Br (8) and 9 are independently synthesized, revealing that the strongly π-bonding imido functionality prevents significant metal-metal interactions. The 57 Fe Mössbauer spectra of 2, 6, 8, and 9 show a clear trend in isomer shift (δ), with a decrease in δ as metal-metal interactions become stronger and the Fe center is reduced. The electronic structure and metal-metal bonding of 2, 6, 8, and 9 are explored through computational studies, and cyclic voltammetry is used to better understand the effect of metal-metal interaction in early/late heterobimetallic complexes on the redox properties of the two metals involved.

Synthesis of a Novel Polyethoxysilsesquiazane and Thermal Conversion into Ternary Silicon Oxynitride Ceramics with Enhanced Thermal Stability

PubMed Central

Iwase, Yoshiaki; Horie, Yoji; Daiko, Yusuke; Honda, Sawao

2017-01-01

A novel polyethoxysilsesquiazane ([EtOSi(NH)1.5]n, EtOSZ) was synthesized by ammonolysis at −78 °C of ethoxytrichlorosilane (EtOSiCl3), which was isolated by distillation as a reaction product of SiCl4 and EtOH. Attenuated total reflection-infra red (ATR-IR), 13C-, and 29Si-nuclear magnetic resonance (NMR) spectroscopic analyses of the ammonolysis product resulted in the detection of Si–NH–Si linkage and EtO group. The simultaneous thermogravimetric and mass spectrometry analyses of the EtOSZ under helium revealed cleavage of oxygen-carbon bond of the EtO group to evolve ethylene as a main gaseous species formed in-situ, which lead to the formation at 800 °C of quaternary amorphous Si–C–N with an extremely low carbon content (1.1 wt %) when compared to the theoretical EtOSZ (25.1 wt %). Subsequent heat treatment up to 1400 °C in N2 lead to the formation of X-ray amorphous ternary Si–O–N. Further heating to 1600 °C in N2 promoted crystallization and phase partitioning to afford Si2N2O nanocrystallites identified by the XRD and TEM analyses. The thermal stability up to 1400 °C of the amorphous state achieved for the ternary Si-O-N was further studied by chemical composition analysis, as well as X-ray photoelectron spectroscopy (XPS) and 29Si-NMR spectroscopic analyses, and the results were discussed aiming to develop a novel polymeric precursor for ternary amorphous Si–O–N ceramics with an enhanced thermal stability. PMID:29206217

Boundary conditions for the Swain-Schaad relationship as a criterion for hydrogen tunneling.

PubMed

Kohen, Amnon; Jensen, Jan H

2002-04-17

Hydrogen quantum mechanical tunneling has been suggested to play a role in a wide variety of hydrogen-transfer reactions in chemistry and enzymology. An important experimental criterion for tunneling is based on the breakdown of the semiclassical prediction for the relationship among the rates of the three isotopes of hydrogen (hydrogen -H, deuterium -D, and tritium -T). This is denoted the Swain-Schaad relationship. This study examines the breakdown of the Swain-Schaad relationship as criterion for tunneling. The semiclassical (no tunneling) limit used hereto (e.g., 3.34, for H/T to D/T kinetic isotope effects), was based on simple theoretical considerations of a diatomic cleavage of a stable covalent bond, for example, a C-H bond. Yet, most experimental evidence for a tunneling contribution has come from breakdown of those relationship for a secondary hydrogen, that is, not the hydrogen whose bond is being cleaved but its geminal neighbor. Furthermore, many of the reported experiments have been mixed-labeling experiments, in which a secondary H/T kinetic isotope effect was measured for C-H cleavage, while the D/T secondary effect accompanied C-D cleavage. In experiments of this type, the breakdown of the Swain-Schaad relationship indicates both tunneling and the degree of coupled motion between the primary and secondary hydrogens. We found a new semiclassical limit (e.g., 4.8 for H/T to D/T kinetic isotope effects), whose breakdown can serve as a more reliable experimental evidence for tunneling in this common mixed-labeling experiment. We study the tunneling contribution to C-H bond activation, for which many relevant experimental and theoretical data are available. However, these studies can be applied to any hydrogen-transfer reaction. First, an extension of the original approach was applied, and then vibrational analysis studies were carried out for a model system (the enzyme alcohol dehydrogenase). Finally, the effect of complex kinetics on the observed Swain-Schaad relationship was examined. All three methods yield a new semiclassical limit (4.8), above which tunneling must be considered. Yet, it was found that for many cases the original, localized limit (3.34), holds fairly well. For experimental results that are between the original and new limits (within statistical errors), several methods are suggested that can support or exclude tunneling. These new and clearer criteria provide a basis for future applications of the Swain-Schaad relationship to demonstrate tunneling in complex systems.

Key binding and susceptibility of NS3/4A serine protease inhibitors against hepatitis C virus.

PubMed

Meeprasert, Arthitaya; Hannongbua, Supot; Rungrotmongkol, Thanyada

2014-04-28

Hepatitis C virus (HCV) causes an infectious disease that manifests itself as liver inflammation, cirrhosis, and can lead to the development of liver cancer. Its NS3/4A serine protease is a potent target for drug design and development since it is responsible for cleavage of the scissile peptide bonds in the polyprotein important for the HCV life cycle. Herein, the ligand-target interactions and the binding free energy of the four current NS3/4A inhibitors (boceprevir, telaprevir, danoprevir, and BI201335) were investigated by all-atom molecular dynamics simulations with three different initial atomic velocities. The per-residue free energy decomposition suggests that the key residues involved in inhibitor binding were residues 41-43, 57, 81, 136-139, 155-159, and 168 in the NS3 domain. The van der Waals interactions yielded the main driving force for inhibitor binding at the protease active site for the cleavage reaction. In addition, the highest number of hydrogen bonds was formed at the reactive P1 site of the four studied inhibitors. Although the hydrogen bond patterns of these inhibitors were different, their P3 site was most likely to be recognized by the A157 backbone. Both molecular mechanic (MM)/Poisson-Boltzmann surface area and MM/generalized Born surface area approaches predicted the relative binding affinities of the four inhibitors in a somewhat similar trend to their experimentally derived biological activities.

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

PubMed

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

2008-11-28

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

Cloning a Chymotrypsin-Like 1 (CTRL-1) Protease cDNA from the Jellyfish Nemopilema nomurai

PubMed Central

Heo, Yunwi; Kwon, Young Chul; Bae, Seong Kyeong; Hwang, Duhyeon; Yang, Hye Ryeon; Choudhary, Indu; Lee, Hyunkyoung; Yum, Seungshic; Shin, Kyoungsoon; Yoon, Won Duk; Kang, Changkeun; Kim, Euikyung

2016-01-01

An enzyme in a nematocyst extract of the Nemopilema nomurai jellyfish, caught off the coast of the Republic of Korea, catalyzed the cleavage of chymotrypsin substrate in an amidolytic kinetic assay, and this activity was inhibited by the serine protease inhibitor, phenylmethanesulfonyl fluoride. We isolated the full-length cDNA sequence of this enzyme, which contains 850 nucleotides, with an open reading frame of 801 encoding 266 amino acids. A blast analysis of the deduced amino acid sequence showed 41% identity with human chymotrypsin-like (CTRL) and the CTRL-1 precursor. Therefore, we designated this enzyme N. nomurai CTRL-1. The primary structure of N. nomurai CTRL-1 includes a leader peptide and a highly conserved catalytic triad of His69, Asp117, and Ser216. The disulfide bonds of chymotrypsin and the substrate-binding sites are highly conserved compared with the CTRLs of other species, including mammalian species. Nemopilema nomurai CTRL-1 is evolutionarily more closely related to Actinopterygii than to Scyphozoan (Aurelia aurita) or Hydrozoan (Hydra vulgaris). The N. nomurai CTRL1 was amplified from the genomic DNA with PCR using specific primers designed based on the full-length cDNA, and then sequenced. The N. nomurai CTRL1 gene contains 2434 nucleotides and four distinct exons. The 5′ donor splice (GT) and 3′ acceptor splice sequences (AG) are wholly conserved. This is the first report of the CTRL1 gene and cDNA structures in the jellyfish N. nomurai. PMID:27399771

Cloning a Chymotrypsin-Like 1 (CTRL-1) Protease cDNA from the Jellyfish Nemopilema nomurai.

PubMed

Heo, Yunwi; Kwon, Young Chul; Bae, Seong Kyeong; Hwang, Duhyeon; Yang, Hye Ryeon; Choudhary, Indu; Lee, Hyunkyoung; Yum, Seungshic; Shin, Kyoungsoon; Yoon, Won Duk; Kang, Changkeun; Kim, Euikyung

2016-07-05

An enzyme in a nematocyst extract of the Nemopilema nomurai jellyfish, caught off the coast of the Republic of Korea, catalyzed the cleavage of chymotrypsin substrate in an amidolytic kinetic assay, and this activity was inhibited by the serine protease inhibitor, phenylmethanesulfonyl fluoride. We isolated the full-length cDNA sequence of this enzyme, which contains 850 nucleotides, with an open reading frame of 801 encoding 266 amino acids. A blast analysis of the deduced amino acid sequence showed 41% identity with human chymotrypsin-like (CTRL) and the CTRL-1 precursor. Therefore, we designated this enzyme N. nomurai CTRL-1. The primary structure of N. nomurai CTRL-1 includes a leader peptide and a highly conserved catalytic triad of His(69), Asp(117), and Ser(216). The disulfide bonds of chymotrypsin and the substrate-binding sites are highly conserved compared with the CTRLs of other species, including mammalian species. Nemopilema nomurai CTRL-1 is evolutionarily more closely related to Actinopterygii than to Scyphozoan (Aurelia aurita) or Hydrozoan (Hydra vulgaris). The N. nomurai CTRL1 was amplified from the genomic DNA with PCR using specific primers designed based on the full-length cDNA, and then sequenced. The N. nomurai CTRL1 gene contains 2434 nucleotides and four distinct exons. The 5' donor splice (GT) and 3' acceptor splice sequences (AG) are wholly conserved. This is the first report of the CTRL1 gene and cDNA structures in the jellyfish N. nomurai.

Carbon elimination from silicon kerf: Thermogravimetric analysis and mechanistic considerations

NASA Astrophysics Data System (ADS)

Vazquez-Pufleau, Miguel; Chadha, Tandeep S.; Yablonsky, Gregory; Biswas, Pratim

2017-01-01

40% of ultrapure silicon is lost as kerf during slicing to produce wafers. Kerf is currently not being recycled due to engineering challenges and costs associated with removing its abundant impurities. Carbon left behind from the lubricant remains as one of the most difficult contaminants to remove in kerf without significant silicon oxidation. The present work enables to better understand the mechanism of carbon elimination in kerf which can aid the design of better processes for kef recycling and low cost photovoltaics. In this paper, we studied the kinetics of carbon elimination from silicon kerf in two atmospheres: air and N2, under a regime of no-diffusion-limitation. We report the apparent activation energy in both atmospheres using three methods: Kissinger, and two isoconversional approaches. In both atmospheres, a bimodal apparent activation energy is observed, suggesting a two stage process. A reaction mechanism is proposed in which (a) C-C and C-O bond cleavage reactions occur in parallel with polymer formation; (b) at higher temperatures, this polymer fully degrades in air but leaves a tarry residue in N2 that accounts for about 12% of the initial total carbon.

Carbon elimination from silicon kerf: Thermogravimetric analysis and mechanistic considerations

PubMed Central

Vazquez-Pufleau, Miguel; Chadha, Tandeep S.; Yablonsky, Gregory; Biswas, Pratim

2017-01-01

40% of ultrapure silicon is lost as kerf during slicing to produce wafers. Kerf is currently not being recycled due to engineering challenges and costs associated with removing its abundant impurities. Carbon left behind from the lubricant remains as one of the most difficult contaminants to remove in kerf without significant silicon oxidation. The present work enables to better understand the mechanism of carbon elimination in kerf which can aid the design of better processes for kef recycling and low cost photovoltaics. In this paper, we studied the kinetics of carbon elimination from silicon kerf in two atmospheres: air and N2, under a regime of no-diffusion-limitation. We report the apparent activation energy in both atmospheres using three methods: Kissinger, and two isoconversional approaches. In both atmospheres, a bimodal apparent activation energy is observed, suggesting a two stage process. A reaction mechanism is proposed in which (a) C-C and C-O bond cleavage reactions occur in parallel with polymer formation; (b) at higher temperatures, this polymer fully degrades in air but leaves a tarry residue in N2 that accounts for about 12% of the initial total carbon. PMID:28098187

Molecular Basis for the Recognition and Cleavages of IGF-II, TGF-[alpha], and Amylin by Human Insulin-Degrading Enzyme

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

Guo, Qing; Manolopoulou, Marika; Bian, Yao

2010-02-11

Insulin-degrading enzyme (IDE) is involved in the clearance of many bioactive peptide substrates, including insulin and amyloid-{beta}, peptides vital to the development of diabetes and Alzheimer's disease, respectively. IDE can also rapidly degrade hormones that are held together by intramolecular disulfide bond(s) without their reduction. Furthermore, IDE exhibits a remarkable ability to preferentially degrade structurally similar peptides such as the selective degradation of insulin-like growth factor (IGF)-II and transforming growth factor-{alpha} (TGF-{alpha}) over IGF-I and epidermal growth factor, respectively. Here, we used high-accuracy mass spectrometry to identify the cleavage sites of human IGF-II, TGF-{alpha}, amylin, reduced amylin, and amyloid-{beta} bymore » human IDE. We also determined the structures of human IDE-IGF-II and IDE-TGF-{alpha} at 2.3 {angstrom} and IDE-amylin at 2.9 {angstrom}. We found that IDE cleaves its substrates at multiple sites in a biased stochastic manner. Furthermore, the presence of a disulfide bond in amylin allows IDE to cut at an additional site in the middle of the peptide (amino acids 18-19). Our amylin-bound IDE structure offers insight into how the structural constraint from a disulfide bond in amylin can alter IDE cleavage sites. Together with NMR structures of amylin and the IGF and epidermal growth factor families, our work also reveals the structural basis of how the high dipole moment of substrates complements the charge distribution of the IDE catalytic chamber for the substrate selectivity. In addition, we show how the ability of substrates to properly anchor their N-terminus to the exosite of IDE and undergo a conformational switch upon binding to the catalytic chamber of IDE can also contribute to the selective degradation of structurally related growth factors.« less

Weak coordination as a powerful means for developing broadly useful C-H functionalization reactions.

PubMed

Engle, Keary M; Mei, Tian-Sheng; Wasa, Masayuki; Yu, Jin-Quan

2012-06-19

Reactions that convert carbon-hydrogen (C-H) bonds into carbon-carbon (C-C) or carbon-heteroatom (C-Y) bonds are attractive tools for organic chemists, potentially expediting the synthesis of target molecules through new disconnections in retrosynthetic analysis. Despite extensive inorganic and organometallic study of the insertion of homogeneous metal species into unactivated C-H bonds, practical applications of this technology in organic chemistry are still rare. Only in the past decade have metal-catalyzed C-H functionalization reactions become more widely utilized in organic synthesis. Research in the area of homogeneous transition metal-catalyzed C-H functionalization can be broadly grouped into two subfields. They reflect different approaches and goals and thus have different challenges and opportunities. One approach involves reactions of completely unfunctionalized aromatic and aliphatic hydrocarbons, which we refer to as "first functionalization". Here the substrates are nonpolar and hydrophobic and thus interact very weakly with polar metal species. To overcome this weak affinity and drive metal-mediated C-H cleavage, chemists often use hydrocarbon substrates in large excess (for example, as solvent). Because highly reactive metal species are needed in first functionalization, controlling the chemoselectivity to avoid overfunctionalization is often difficult. Additionally, because both substrates and products are comparatively low-value chemicals, developing cost-effective catalysts with exceptionally high turnover numbers that are competitive with alternatives (including heterogeneous catalysts) is challenging. Although an exciting field, first functionalization is beyond the scope of this Account. The second subfield of C-H functionalization involves substrates containing one or more pre-existing functional groups, termed "further functionalization". One advantage of this approach is that the existing functional group (or groups) can be used to chelate the metal catalyst and position it for selective C-H cleavage. Precoordination can overcome the paraffin nature of C-H bonds by increasing the effective concentration of the substrate so that it need not be used as solvent. From a synthetic perspective, it is desirable to use a functional group that is an intrinsic part of the substrate so that extra steps for installation and removal of an external directing group can be avoided. In this way, dramatic increases in molecular complexity can be accomplished in a single stroke through stereo- and site-selective introduction of a new functional group. Although reactivity is a major challenge (as with first functionalization), the philosophy in further functionalization differs; the major challenge is developing reactions that work with predictable selectivity in intricately functionalized contexts on commonly occurring structural motifs. In this Account, we focus on an emergent theme within the further functionalization literature: the use of commonly occurring functional groups to direct C-H cleavage through weak coordination. We discuss our motivation for studying Pd-catalyzed C-H functionalization assisted by weakly coordinating functional groups and chronicle our endeavors to bring reactions of this type to fruition. Through this approach, we have developed reactions with a diverse range of substrates and coupling partners, with the broad scope likely stemming from the high reactivity of the cyclopalladated intermediates, which are held together through weak interactions.

Near-UV Photodissociation of Tryptic Peptide Cation Radicals. Scope and Effects of Amino Acid Residues and Radical Sites

NASA Astrophysics Data System (ADS)

Nguyen, Huong T. H.; Tureček, František

2017-07-01

Peptide cation-radical fragment ions of the z-type, [●AXAR+], [●AXAK+], and [●XAR+], where X = A, C, D, E, F, G, H, K, L, M, N, P, Y, and W, were generated by electron transfer dissociation of peptide dications and investigated by MS3-near-ultraviolet photodissociation (UVPD) at 355 nm. Laser-pulse dependence measurements indicated that the ion populations were homogeneous for most X residues except phenylalanine. UVPD resulted in dissociations of backbone CO-NH bonds that were accompanied by hydrogen atom transfer, producing fragment ions of the [yn]+ type. Compared with collision-induced dissociation, UVPD yielded less side-chain dissociations even for residues that are sensitive to radical-induced side-chain bond cleavages. The backbone dissociations are triggered by transitions to second ( B) excited electronic states in the peptide ion R-CH●-CONH- chromophores that are resonant with the 355-nm photon energy. Electron promotion increases the polarity of the B excited states, R-CH+-C●(O-)NH-, and steers the reaction to proceed by transfer of protons from proximate acidic Cα and amide nitrogen positions.

Ternary iron(II) complex with an emissive imidazopyridine arm from Schiff base cyclizations and its oxidative DNA cleavage activity.

PubMed

Mukherjee, Arindam; Dhar, Shanta; Nethaji, Munirathinam; Chakravarty, Akhil R

2005-01-21

The ternary iron(II) complex [Fe(L')(L")](PF6)3(1) as a synthetic model for the bleomycins, where L' and L" are formed from metal-mediated cyclizations of N,N'-(2-hydroxypropane-1,3-diyl)bis(pyridine-2-aldimine)(L), is synthesized and structurally characterized by X-ray crystallography. In the six-coordinate iron(ii) complex, ligands L' and L" show tetradentate and bidentate chelating modes of bonding. Ligand L' is formed from an intramolecular attack of the alcoholic OH group of L to one imine moiety leading to the formation of a stereochemically constrained five-membered ring. Ligand L" which is formed from an intermolecular reaction involving one imine moiety of L and pyridine-2-carbaldehyde has an emissive cationic imidazopyridine pendant arm. The complex binds to double-stranded DNA in the minor groove giving a Kapp value of 4.1 x 10(5) M(-1) and displays oxidative cleavage of supercoiled DNA in the presence of H2O2 following a hydroxyl radical pathway. The complex also shows photo-induced DNA cleavage activity on UV light exposure involving formation of singlet oxygen as the reactive species.

Degradation and mineralization of atrazine by a soil bacterial isolate.

PubMed Central

Radosevich, M; Traina, S J; Hao, Y L; Tuovinen, O H

1995-01-01

An atrazine-degrading bacterial culture was isolated from an agricultural soil previously impacted by herbicide spills. The organism was capable of using atrazine under aerobic conditions as the sole source of C and N. Cyanuric acid could replace atrazine as the sole source of N, indicating that the organism was capable of ring cleavage. Ring cleavage was confirmed in 14CO2 evolution experiments with [U-14C-ring]atrazine. Between 40 and 50% of ring-14C was mineralized to 14CO2. [14C]biuret and [14C]urea were detected in spent culture media. Cellular assimilation of 14C was negligible, in keeping with the fully oxidized valence of the ring carbon. Chloride release was stoichiometric. The formation of ammonium during atrazine degradation was below the stoichiometric amount, suggesting a deficit due to cellular assimilation and metabolite-N accumulation. With excess glucose and with atrazine as the sole N source, free ammonium was not detected, suggesting assimilation into biomass. The organism degraded atrazine anaerobically in media which contained (i) atrazine only, (ii) atrazine and glucose, and (iii) atrazine, glucose, and nitrate. To date, this is the first report of a pure bacterial isolate with the ability to cleave the s-triazine ring structure of atrazine. It was also concluded that this bacterium was capable of dealkylation, dechlorination, and deamination in addition to ring cleavage. PMID:7887609

Low-Temperature Bonding of Bi0.5Sb1.5Te3 Thermoelectric Material with Cu Electrodes Using a Thin-Film In Interlayer

NASA Astrophysics Data System (ADS)

Lin, Yan-Cheng; Yang, Chung-Lin; Huang, Jing-Yi; Jain, Chao-Chi; Hwang, Jen-Dong; Chu, Hsu-Shen; Chen, Sheng-Chi; Chuang, Tung-Han

2016-09-01

A Bi0.5Sb1.5Te3 thermoelectric material electroplated with a Ni barrier layer and a Ag reaction layer was bonded with a Ag-coated Cu electrode at low temperatures of 448 K (175 °C) to 523 K (250 °C) using a 4- μm-thick In interlayer under an external pressure of 3 MPa. During the bonding process, the In thin film reacted with the Ag layer to form a double layer of Ag3In and Ag2In intermetallic compounds. No reaction occurred at the Bi0.5Sb1.5Te3/Ni interface, which resulted in low bonding strengths of about 3.2 MPa. The adhesion of the Bi0.5Sb1.5Te3/Ni interface was improved by precoating a 1- μm Sn film on the surface of the thermoelectric element and preheating it at 523 K (250 °C) for 3 minutes. In this case, the bonding strengths increased to a range of 9.1 to 11.5 MPa after bonding at 473 K (200 °C) for 5 to 60 minutes, and the shear-tested specimens fractured with cleavage characteristics in the interior of the thermoelectric material. The bonding at 448 K (175 °C) led to shear strengths ranging from 7.1 to 8.5 MPa for various bonding times between 5 and 60 minutes, which were further increased to the values of 10.4 to 11.7 MPa by increasing the bonding pressure to 9.8 MPa. The shear strengths of Bi0.5Sb1.5Te3/Cu joints bonded with the optimized conditions of the modified solid-liquid interdiffusion bonding process changed only slightly after long-term exposure at 473 K (200 °C) for 1000 hours.

Selective Ether/Ester C–O Cleavage of an Acetylated Lignin Model via Tandem Catalysis

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

Lohr, Tracy L.; Li, Zhi; Marks, Tobin J.

2015-11-06

Lignin, a heterogeneous phenolic polymer which constitutes roughly 15 to 20 wt % of lignocellulosic biomass (cellulose, hemicellose, and lignin), represents one of the few renewable sources of aromatic monomers.(1) Current lignin depolymerization methodologies, including base-catalyzed,(2) acid-catalyzed,(3) metal-catalyzed,(4) ionic liquid (IL)-assisted,(5) and supercritical-fluid-assisted(2b, 6) approaches, typically afford low yields (~10–20% or less) of low molecular weight aromatics under relatively harsh reaction conditions (>300 °C).(7) Recent advances include using oxidized lignin and lignin models,(8) where oxidation of the Cα alcohol facilitates depolymerizaton, with aromatic monomer yields reaching up to 52% for aspen “hardwood” lignin.(9) The most common structural lignin motifs containmore » a β-O-4 aryl-ether linkage,(10) a primary alcohol in the γ skeletal position, and a secondary alcohol in the α position (Scheme 1). Our laboratory has previously demonstrated an effective strategy for thermodynamically leveraged etheric and esteric C–O bond hydrogenolysis using a tandem metal triflate + supported palladium catalytic system.(11) A homogeneous M(OTf)n catalyst mediates endothermic ether or near thermoneutral ester C–O bond scission (the reverse of hydroelementation), which is coupled to exothermic Pd-catalyzed hydrogenation of the resulting C=C unsaturation, driving the overall process downhill. We next asked whether this tandem system might be applicable to cleaving the β-O-4 aryl-ether bond in lignin and lignin models. The promising results of that investigation are communicated here.« less

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.

Late metal carbene complexes generated by multiple C-H activations: examining the continuum of M=C bond reactivity.

PubMed

Whited, Matthew T; Grubbs, Robert H

2009-10-20

Unactivated C(sp(3))-H bonds are ubiquitous in organic chemicals and hydrocarbon feedstocks. However, these resources remain largely untapped, and the development of efficient homogeneous methods for hydrocarbon functionalization by C-H activation is an attractive and unresolved challenge for synthetic chemists. Transition-metal catalysis offers an attractive possible means for achieving selective, catalytic C-H functionalization given the thermodynamically favorable nature of many desirable partial oxidation schemes and the propensity of transition-metal complexes to cleave C-H bonds. Selective C-H activation, typically by a single cleavage event to produce M-C(sp(3)) products, is possible through myriad reported transition-metal species. In contrast, several recent reports have shown that late transition metals may react with certain substrates to perform multiple C-H activations, generating M=C(sp(2)) complexes for further elaboration. In light of the rich reactivity of metal-bound carbenes, such a route could open a new manifold of reactivity for catalytic C-H functionalization, and we have targeted this strategy in our studies. In this Account, we highlight several early examples of late transition-metal complexes that have been shown to generate metal-bound carbenes by multiple C-H activations and briefly examine factors leading to the selective generation of metal carbenes through this route. Using these reports as a backdrop, we focus on the double C-H activation of ethers and amines at iridium complexes supported by Ozerov's amidophosphine PNP ligand (PNP = [N(2-P(i)Pr(2)-4-Me-C(6)H(3))(2)](-)), allowing isolation of unusual square-planar iridium(I) carbenes. These species exhibit reactivity that is distinct from the archetypal Fischer and Schrock designations. We present experimental and theoretical studies showing that, like the classical square-planar iridium(I) organometallics, these complexes are best described as nucleophilic at iridium. We discuss the classification of this reactivity in the context of a scheme originally delineated by Roper. These "Roper-type" carbenes perform a number of multiple-bond metatheses leading to atom and group transfer from electrophilic heterocumulene (e.g., CO(2), CS(2), PhNCS) and diazo (e.g., N(2)O, AdN(3)) reagents. In one instance, we have extended this methodology to a process for catalytic C-H functionalization by a double C-H activation-group transfer process. Although the scope of these reactions is currently limited, these new pathways may find broader utility as the reactivity of late-metal carbenes continues to be explored. Examination of alternative transition metals and supporting ligand sets will certainly be important. Nonetheless, our findings show that carbene generation by double C-H activation is a viable strategy for C-H functionalization, leading to products not accessible through traditional C(sp(3))-H activation pathways.

Constitutive production of catalytic antibodies to a Staphylococcus aureus virulence factor and effect of infection.

PubMed

Brown, Eric L; Nishiyama, Yasuhiro; Dunkle, Jesse W; Aggarwal, Shreya; Planque, Stephanie; Watanabe, Kenji; Csencsits-Smith, Keri; Bowden, M Gabriela; Kaplan, Sheldon L; Paul, Sudhir

2012-03-23

Antibodies that recognize microbial B lymphocyte superantigenic epitopes are produced constitutively with no requirement for adaptive immune maturation. We report cleavage of the Staphylococcus aureus virulence factor extracellular fibrinogen-binding protein (Efb) by catalytic antibodies produced with no exposure to the bacterium and reduction of the catalytic antibody activity following infection. IgG catalytic antibodies that specifically hydrolyzed Efb via a nucleophilic catalytic mechanism were found in the blood of healthy humans and aseptic mice free of S. aureus infection. IgG hydrolyzed peptide bonds on the C-terminal side of basic amino acids, including a bond located within the C3b-binding domain of Efb. Efb digested with the IgG lost its ability to bind C3b and inhibit complement-dependent antibody-mediated red blood cell lysis. In addition to catalysis, the IgG expressed saturable Efb binding activity. IgG from S. aureus-infected mice displayed reduced Efb cleaving activity and increased Efb binding activity compared with uninfected controls, suggesting differing effects of the infection on the antibody subsets responsible for the two activities. IgG from children hospitalized for S. aureus infection also displayed reduced Efb cleavage compared with healthy children. These data suggest a potential defense function for constitutively produced catalytic antibodies to a putative superantigenic site of Efb, but an adaptive catalytic response appears to be proscribed.

Two Antagonistic MALT1 Auto-Cleavage Mechanisms Reveal a Role for TRAF6 to Unleash MALT1 Activation

PubMed Central

Renner, Florian; Lam, Stephen; Freuler, Felix; Gerrits, Bertran; Voshol, Johannes; Calzascia, Thomas; Régnier, Catherine H.; Renatus, Martin; Nikolay, Rainer; Israël, Laura; Bornancin, Frédéric

2017-01-01

The paracaspase MALT1 has arginine-directed proteolytic activity triggered by engagement of immune receptors. Recruitment of MALT1 into activation complexes is required for MALT1 proteolytic function. Here, co-expression of MALT1 in HEK293 cells, either with activated CARD11 and BCL10 or with TRAF6, was used to explore the mechanism of MALT1 activation at the molecular level. This work identified a prominent self-cleavage site of MALT1 isoform A (MALT1A) at R781 (R770 in MALT1B) and revealed that TRAF6 can activate MALT1 independently of the CBM. Intramolecular cleavage at R781/R770 removes a C-terminal TRAF6-binding site in both MALT1 isoforms, leaving MALT1B devoid of the two key interaction sites with TRAF6. A previously identified auto-proteolysis site of MALT1 at R149 leads to deletion of the death-domain, thereby abolishing interaction with BCL10. By using MALT1 isoforms and cleaved fragments thereof, as well as TRAF6 WT and mutant forms, this work shows that TRAF6 induces N-terminal auto-proteolytic cleavage of MALT1 at R149 and accelerates MALT1 protein turnover. The MALT1 fragment generated by N-terminal self-cleavage at R149 was labile and displayed enhanced signaling properties that required an intact K644 residue, previously shown to be a site for mono-ubiquitination of MALT1. Conversely, C-terminal self-cleavage at R781/R770 hampered the ability for self-cleavage at R149 and stabilized MALT1 by hindering interaction with TRAF6. C-terminal self-cleavage had limited impact on MALT1A but severely reduced MALT1B proteolytic and signaling functions. It also abrogated NF-κB activation by N-terminally cleaved MALT1A. Altogether, this study provides further insights into mechanisms that regulate the scaffolding and activation cycle of MALT1. It also emphasizes the reduced functional capacity of MALT1B as compared to MALT1A. PMID:28052131

Neurotensin and neuromedin N undergo distinct catabolic processes in murine astrocytes and primary cultured neurons.

PubMed

Vincent, B; Vincent, J P; Checler, F

1994-04-01

We examined the occurrence of various endopeptidases and exopeptidases and their subcellular partition within soluble and membrane-associated compartments of 15-day-old astrocytes and 4-day-old primary cultured neurons. Peptidases were monitored with chromogenic or fluorimetric substrates and identified by means of specific inhibitors. We assessed the contribution of these peptidases in the catabolism of two related neuropeptides, neurotensin and neuromedin N. Metabolites were separated by HPLC and the identity of the proteolytic activities involved in their formation was established using specific inhibitors. Neuromedin N and neurotensin undergo both quantitative and qualitative differential proteolysis. Initial maximal rates of neuromedin N degradation were higher than those of neurotensin in both cell types. Furthermore, the two peptides were inactivated much more rapidly by the soluble than by the membrane-associated fractions prepared from both cell cultures. Neuromedin N was rapidly broken down by an aminopeptidase M/leucine aminopeptidase attack, leading to the functionally silent Des-Lys1-neuromedin N metabolite. In the astrocytic membrane-associated fraction, neuromedin N underwent an additional minor endoproteolytic cleavage at the Pro3-Tyr4 bond elicited by endopeptidase 24.11, as suggested by the protective effect of its blocking agent phosphoramidon. Unlike neuromedin N, neurotensin totally resisted hydrolysis by aminopeptidases. Primary inactivating cleavages detected in both cell types appeared mainly located at the Arg8-Arg9 and Pro10-Tyr11 bonds, leading to the formations of neurotensin-(1-8) and neurotensin-(1-10) as the major biologically inactive neurotensin catabolites. Endopeptidase 24.15 appeared mainly responsible for neurotensin-(1-8) formation by the soluble fraction of neurons and astrocytes. In contrast, endopeptidase 24.16 was involved in neurotensin-(1-10) formation by both soluble and membrane-associated fractions of the two cell types. An additional cleavage leading to neurotensin-(1-11) formation and ascribed to endopeptidase 24.11 was detected mainly in the membrane-associated fraction from astrocytes. Finally, the secondary processing of neurotensin degradation products indicated that: (a) neurotensin-(1-11) was converted into neurotensin-(1-8) in the membrane fraction prepared from astrocytes; (b) neurotensin-(1-10) was transformed into neurotensin-(1-8) by an unidentified peptidase belonging to the class of metalloenzymes. The significance of distinct quantitative and qualitative catabolic fates of neuromedin N and neurotensin in cultured astrocytes and neurons is discussed.

Microsolvated Model for the Kinetics and Thermodynamics of Glycosidic Bond Dissociative Cleavage of Nucleoside D4G.

PubMed

Jiang, Yang; Xue, Ying; Zeng, Yi

2018-02-15

Using the microsolvated model that involves explicit water molecules and implicit solvent in the optimization, two proposed dissociative hydrolysis mechanisms of 2',3'-didehydro-2',3'-dideoxyguanosine (d4G) have been first investigated by means of M06-2X(CPCM, water)/6-31++G(d,p) method. The glycosidic bond dissociation for the generation of the oxacarbenium ion intermediate is the rate-determining step (RDS). The subsequent nucleophilic water attack from different side of the oxacarbenium ion intermediate gives either the α-product [(2S,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-ol] or β-product [(2R,5S)-5-(hydroxymethyl)-2,5-dihydrofuran-2-ol] and is thus referred to as α-path (inversion) and β-path (retention). Two to five explicit water molecules (n = 2-5) are considered in the microsolvated model, and n = 3 or 4 is the smallest model capable of minimizing the activation energy for α-path and β-path, respectively. Our theoretical results suggest that α-path (n = 3) is more kinetically favorable with lower free energy barrier (RDS) of 27.7 kcal mol -1 , in contrast to that of 30.7 kcal mol -1 for the β-path (n = 4). The kinetic preference of the α-path is rationalized by NBO analysis. Whereas thte β-path is more thermodynamically favorable over the α-path, where the formation of β-product and α-product are exergonic and endergonic, respectively, providing theoretical support for the experimental observation that the β-cleavage product was the major one after sufficient reaction time. Comparisons of d4G with analogous cyclo-d4G and dG from kinetic free energy barriers and thermodynamic heterolytic dissociation energies were also carried out. Our kinetic and thermodynamic results manifest that the order of glycosidic bond stability should be d4G < cyclo-d4G < dG, which agrees well with the reported experimental stability order of d4G compounds and analogues and gives further understanding on the influence of 6-cyclopropylamino and unsaturated ribose to the glycosidic bond instability of d4G.

Site-specific O-Glycosylation on the MUC2 Mucin Protein Inhibits Cleavage by the Porphyromonas gingivalis Secreted Cysteine Protease (RgpB)*

PubMed Central

van der Post, Sjoerd; Subramani, Durai B.; Bäckström, Malin; Johansson, Malin E. V.; Vester-Christensen, Malene B.; Mandel, Ulla; Bennett, Eric P.; Clausen, Henrik; Dahlén, Gunnar; Sroka, Aneta; Potempa, Jan; Hansson, Gunnar C.

2013-01-01

The colonic epithelial surface is protected by an inner mucus layer that the commensal microflora cannot penetrate. We previously demonstrated that Entamoeba histolytica secretes a protease capable of dissolving this layer that is required for parasite penetration. Here, we asked whether there are bacteria that can secrete similar proteases. We screened bacterial culture supernatants for such activity using recombinant fragments of the MUC2 mucin, the major structural component, and the only gel-forming mucin in the colonic mucus. MUC2 has two central heavily O-glycosylated mucin domains that are protease-resistant and has cysteine-rich N and C termini responsible for polymerization. Culture supernatants of Porphyromonas gingivalis, a bacterium that secretes proteases responsible for periodontitis, cleaved the MUC2 C-terminal region, whereas the N-terminal region was unaffected. The active enzyme was isolated and identified as Arg-gingipain B (RgpB). Two cleavage sites were localized to IR↓TT and NR↓QA. IR↓TT cleavage will disrupt the MUC2 polymers. Because this site has two potential O-glycosylation sites, we tested whether recombinant GalNAc-transferases (GalNAc-Ts) could glycosylate a synthetic peptide covering the IRTT sequence. Only GalNAc-T3 was able to glycosylate the second Thr in IRTT, rendering the sequence resistant to cleavage by RgpB. Furthermore, when GalNAc-T3 was expressed in CHO cells expressing the MUC2 C terminus, the second threonine was glycosylated, and the protein became resistant to RgpB cleavage. These findings suggest that bacteria can produce proteases capable of dissolving the inner protective mucus layer by specific cleavages in the MUC2 mucin and that this cleavage can be modulated by site-specific O-glycosylation. PMID:23546879

Facile CO Cleavage by a Multimetallic CsU2 Nitride Complex.

PubMed

Falcone, Marta; Kefalidis, Christos E; Scopelliti, Rosario; Maron, Laurent; Mazzanti, Marinella

2016-09-26

Uranium nitrides are important materials with potential for application as fuels for nuclear power generation, and as highly active catalysts. Molecular nitride compounds could provide important insight into the nature of the uranium-nitride bond, but currently little is known about their reactivity. In this study, we found that a complex containing a nitride bridging two uranium centers and a cesium cation readily cleaved the C≡O bond (one of the strongest bonds in nature) under ambient conditions. The product formed has a [CsU2 (μ-CN)(μ-O)] core, thus indicating that the three cations cooperate to cleave CO. Moreover, the addition of MeOTf to the nitride complex led to an exceptional valence disproportionation of the CsU(IV) -N-U(IV) core to yield CsU(III) (OTf) and [MeN=U(V) ] fragments. The important role of multimetallic cooperativity in both reactions is illustrated by the computed reaction mechanisms. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Efficient Cleavage of Ribosome-Associated Poly(A)-Binding Protein by Enterovirus 3C Protease

PubMed Central

Kuyumcu-Martinez, N. Muge; Joachims, Michelle; Lloyd, Richard E.

2002-01-01

Poliovirus (PV) causes a rapid and drastic inhibition of host cell cap-dependent protein synthesis during infection while preferentially allowing cap-independent translation of its own genomic RNA via an internal ribosome entry site element. Inhibition of cap-dependent translation is partly mediated by cleavage of an essential translation initiation factor, eIF4GI, during PV infection. In addition to cleavage of eIF4GI, cleavage of eIF4GII and poly(A)-binding protein (PABP) has been recently proposed to contribute to complete host translation shutoff; however, the relative importance of eIF4GII and PABP cleavage has not been determined. At times when cap-dependent translation is first blocked during infection, only 25 to 35% of the total cellular PABP is cleaved; therefore, we hypothesized that the pool of PABP associated with polysomes may be preferentially targeted by viral proteases. We have investigated what cleavage products of PABP are produced in vivo and the substrate determinants for cleavage of PABP by 2A protease (2Apro) or 3C protease (3Cpro). Our results show that PABP in ribosome-enriched fractions is preferentially cleaved in vitro and in vivo compared to PABP in other fractions. Furthermore, we have identified four N-terminal PABP cleavage products produced during PV infection and have shown that viral 3C protease generates three of the four cleavage products. Also, 3Cpro is more efficient in cleaving PABP in ribosome-enriched fractions than 2Apro in vitro. In addition, binding of PABP to poly(A) RNA stimulates 3Cpro-mediated cleavage and inhibits 2Apro-mediated cleavage. These results suggest that 3Cpro plays a major role in processing PABP during virus infection and that the interaction of PABP with translation initiation factors, ribosomes, or poly(A) RNA may promote its cleavage by viral 2A and 3C proteases. PMID:11836384

Dynamics and mechanism of UV-damaged DNA repair in indole-thymine dimer adduct: molecular origin of low repair quantum efficiency.

PubMed

Guo, Xunmin; Liu, Zheyun; Song, Qinhua; Wang, Lijuan; Zhong, Dongping

2015-02-26

Many biomimetic chemical systems for repair of UV-damaged DNA showed very low repair efficiency, and the molecular origin is still unknown. Here, we report our systematic characterization of the repair dynamics of a model compound of indole-thymine dimer adduct in three solvents with different polarity. By resolving all elementary steps including three electron-transfer processes and two bond-breaking and bond-formation dynamics with femtosecond resolution, we observed the slow electron injection in 580 ps in water, 4 ns in acetonitrile, and 1.38 ns in dioxane, the fast back electron transfer without repair in 120, 150, and 180 ps, and the slow bond splitting in 550 ps, 1.9 ns, and 4.5 ns, respectively. The dimer bond cleavage is clearly accelerated by the solvent polarity. By comparing with the biological repair machine photolyase with a slow back electron transfer (2.4 ns) and a fast bond cleavage (90 ps), the low repair efficiency in the biomimetic system is mainly determined by the fast back electron transfer and slow bond breakage. We also found that the model system exists in a dynamic heterogeneous C-clamped conformation, leading to a stretched dynamic behavior. In water, we even identified another stacked form with ultrafast cyclic electron transfer, significantly reducing the repair efficiency. Thus, the comparison of the repair efficiency in different solvents is complicated and should be cautious, and only the dynamics by resolving all elementary steps can finally determine the total repair efficiency. Finally, we use the Marcus electron-transfer theory to analyze all electron-transfer reactions and rationalize all observed electron-transfer dynamics.

Probing the structural evolution and bonding properties of PtnC2-/0 (n = 1-7) clusters by density functional calculations

NASA Astrophysics Data System (ADS)

Lu, Sheng-Jie

2018-05-01

We present a theoretical investigation on the structural evolution and bonding properties of PtnC2-/0 (n = 1-7) clusters using density functional theoretical calculations. The results showed that both anionic and neutral PtnC2 (n = 1-7) clusters primarily adopt 2D planar chain-shaped or ring-based structures. The two C atoms directly interact with each other to form a Csbnd C bond for n = 1-3, while the two C atoms are separated by the Pt atoms for n = 4-7, except for neutral Pt5C2. Pt4C2- anion and Pt4C2 neutral both show σ plus π double delocalized bonding patterns.

Characterization of a backbone cleavage product of BMS-196854 (Oncostatin M), a recombinant anti-inflammatory cytokine.

PubMed

Zhao, F; Stein, D J; Paborji, M; Cash, P W; Root, B J; Wei, Z; Knupp, C J

2001-01-01

BMS-196843 (Oncostatin M) is a therapeutic recombinant protein in development. Scale-up process changes led to unexpected instability of the bulk drug substance solution during storage. A product with an apparent higher MW than the parent protein was observed by the size-exclusion chromatography (SEC). This study was aimed to fully characterize the product and to identify a solution to stabilize the protein. SEC, SDS-PAGE, tryptic mapping, and N-terminal sequencing were performed to characterize the unknown product. The effect of pH, temperature, bulk concentration, and immobilized trypsin inhibitor on the degradation rate was studied to elucidate the mechanism and to identify stabilization strategies. Despite the apparent high MW indicated initially by SEC, the unknown was characterized to be a degradation product resulted from a backbone cleavage between residues Arg145-Gly146. The resulting fragments from the backbone cleavage were, however, still linked through an intramolecular disulfide bond. Thus, the final product had a more open structure with an increased hydrodynamic radius compared to the parent protein, which explains the initial SEC results. The site-specific backbone cleavage was suspected to be catalyzed by trypsin-like protease impurities in the bulk solution. The bulk drug substance solution was subsequently treated with immobilized soybean trypsin inhibitor, and the degradation rate was significantly reduced. Furthermore, increasing the solution pH from 5 to 8 led to an increase in the degradation rate, which was consistent with the expected pH dependency of trypsin activity. In addition, the effect of bulk concentration also supported the involvement of protease impurities rather than a spontaneous peptide bond hydrolysis reaction. Trace trypsin-like protease impurities led to an unusual site-specific backbone cleavage of BMS-196854. The proteolytic degradation can be minimized by treating the bulk solution with immobilized soybean trypsin inhibitor and/or controlling the solution pH and storage temperature.

Failure mechanisms in wood joints bonded with urea-formaldehyde adhesives

Treesearch

B.H. River; R.O. Ebewele; G.E. Myers

1994-01-01

Wood joints bonded with urea-formaldehyde (UF) are weakened by cyclic swelling and shrinking. To study the failure mechanisms in UF-bonded joints, specimens were bonded with unmodified, modified (amine), or phenol formaldehyde adhesive and subjected to accelerated aging. Modification of the adhesive properties increased the cleavage fracture toughness and shear...

Structural Basis for Flip-Flop Action of Thiamin Pyrophosphate-Dependent Enzymes Revealed by Human Pyruvate Dehydrogenase

NASA Technical Reports Server (NTRS)

Dominiak, Paulina; Ciszak, Ewa M.; Korotchkina, Lioubov; Sidhu, Sukhdeep; Patel, Mulchand

2003-01-01

Thiamin pyrophosphate (TPP), the biologically active form of vitamin BI, is a cofactor of enzymes catalyzing reactions involving the cleavage of a carbon-carbon bond adjacent to an oxo group. TPP-dependent enzymes show a common mechanism of TPP activation by: (1) forming the ionic N-H...O(sup -) hydrogen bonding between the N1' atom of the aminopirymidine ring of the coenzyme and intrinsic gamma-carboxylate group of glutamate and (2) imposing an "active" V-conformation that brings the N4' atom of the aminopirymidine to the distance required for the intramolecular C-H.. .N hydrogen bonding with the thiazolium C2 atom. Within these two hydrogen bonds that rapidly exchange protons, protonation of the N1' atom is strictly coordinated with the deprotonation of the 4' -amino group and eventually abstraction of the proton from C2. The human pyruvate dehydrogenase Elp, component of human pyruvate dehydrogenase complex, catalyzes the irreversible decarboxylation of the pyruvate followed by the reductive acetylation of the lipoyl group of dihydrolipoyl acyltransferase. Elp is alpha(sub 2)beta(sub2)-heterotetrameric with a molecular mass of I54 kDa, which has two catalytic sites, each providing TPP and magnesium ion as cofactors and each formed on the interface between the PP and PYR domains. The dynamic nonequivalence of two otherwise chemically equivalent catalytic sites has been observed and the flip-flop mechanism was suggested, according to which two active sites affect each other and in which different steps of the catalytic reaction are performed in each of the sites at any given moment. Based on specific futures of human pyruvate dehydrogenase including rigid and flexible connections between domains that bind the cofactor we propose a mechanistic model for the flip-flop action of this enzyme. We postulate that the dynamic protein environment drives the exchange of tautomers in the 4' -aminopyrimidine ring of the cofactor through a concerted shuttl-like motion of tightly connected domains. The dynamic exchange of those tautomers, in turns, is required during the reactions of pyruvate decarboxylation and reductive acetylation of lipoamide. Thus the shuttle-like motion of the domains is coordinated with the reactions of decarboxylation and acetylation, which are carried out in each of the cofactor sites resulting in a flip-flop action of the enzyme. The structure-derived mechanism of action of human pyruvate dehydrogenase may be likely common for other TPP-dependent enzymes.

Switching "on" and "off" the adhesion in stimuli-responsive elastomers.

PubMed

Kaiser, S; Radl, S V; Manhart, J; Ayalur-Karunakaran, S; Griesser, T; Moser, A; Ganser, C; Teichert, C; Kern, W; Schlögl, S

2018-03-28

The present work aims at the preparation of dry adhesives with switchable bonding properties by using the reversible nature of the [4πs+4πs] cycloaddition of anthracenes. Photo-responsive hydrogenated carboxylated nitrile butadiene rubber with photo-responsive pendant anthracene groups is prepared by one-pot synthesis. The formation of 3D networks relies on the photodimerization of the anthracene moieties upon UV exposure (λ > 300 nm). Controlled cleavage of the crosslink sites is achieved by either deep UV exposure (λ = 254 nm) or thermal dissociation at 70 °C. The kinetics of the optical and thermal cleavage routes are compared in thin films using UV-vis spectroscopy and their influence on the reversibility of the network is detailed. Going from thin films to free standing samples the modulation of the network structure and thermo-mechanical properties over repeated crosslinking and cleavage cycles are characterized by low-field NMR spectroscopy and dynamic mechanical analysis. The applicability of the stimuli-responsive networks as adhesives with reversible bonding properties is demonstrated. The results evidence that the reversibility of the crosslinking reaction enables a controlled switching "on" and "off" of adhesion properties. The recovery of the adhesion force amounts to 75 and 80% for photo- and thermal dissociation, respectively. Spatial control of adhesion properties is evidenced by adhesion force mapping experiments of photo-patterned films.

Electrochemistry-Assisted Top-Down Characterization of Disulfide-Containing Proteins

PubMed Central

Zhang, Yun; Cui, Weidong; Zhang, Hao; Dewald, Howard D.; Chen, Hao

2013-01-01

Covalent disulfide bond linkage in a protein represents an important challenge for mass spectrometry (MS)-based top-down protein structure analysis as it reduces the backbone cleavage efficiency for MS/MS dissociation. This study presents a strategy for solving this critical issue via integrating electrochemistry (EC) online with top-down MS approach. In this approach, proteins undergo electrolytic reduction in an electrochemical cell to break disulfide bonds and then online ionized into gaseous ions for analysis by electron-capture dissociation (ECD) and collision-induced dissociation (CID). The electrochemical reduction of proteins allows to remove disulfide bond constraints and also leads to increased charge numbers of the resulting protein ions. As a result, sequence coverage was significantly enhanced, as exemplified by β-lactoglobulin A (24 vs. 73 backbone cleavages before and after electrolytic reduction, respectively) and lysozyme (5 vs. 66 backbone cleavages before and after electrolytic reduction, respectively). This methodology is fast and does not need chemical reductants, which would have an important impact in high-throughput proteomics research. PMID:22448817

Electrochemistry-assisted top-down characterization of disulfide-containing proteins.

PubMed

Zhang, Yun; Cui, Weidong; Zhang, Hao; Dewald, Howard D; Chen, Hao

2012-04-17

Covalent disulfide bond linkage in a protein represents an important challenge for mass spectrometry (MS)-based top-down protein structure analysis as it reduces the backbone cleavage efficiency for MS/MS dissociation. This study presents a strategy for solving this critical issue via integrating electrochemistry (EC) online with a top-down MS approach. In this approach, proteins undergo electrolytic reduction in an electrochemical cell to break disulfide bonds and then undergo online ionization into gaseous ions for analysis by electron-capture dissociation (ECD) and collision-induced dissociation (CID). The electrochemical reduction of proteins allows one to remove disulfide bond constraints and also leads to increased charge numbers of the resulting protein ions. As a result, sequence coverage was significantly enhanced, as exemplified by β-lactoglobulin A (24 vs 75 backbone cleavages before and after electrolytic reduction, respectively) and lysozyme (5 vs 66 backbone cleavages before and after electrolytic reduction, respectively). This methodology is fast and does not need chemical reductants, which would have an important impact in high-throughput proteomics research.

Effect of the Phosphine Steric and Electronic Profile on the Rh-Promoted Dehydrocoupling of Phosphine–Boranes

PubMed Central

2014-01-01

The electronic and steric effects in the stoichiometric dehydrocoupling of secondary and primary phosphine–boranes H3B·PR2H [R = 3,5-(CF3)2C6H3; p-(CF3)C6H4; p-(OMe)C6H4; adamantyl, Ad] and H3B·PCyH2 to form the metal-bound linear diboraphosphines H3B·PR2BH2·PR2H and H3B·PRHBH2·PRH2, respectively, are reported. Reaction of [Rh(L)(η6-FC6H5)][BArF4] [L = Ph2P(CH2)3PPh2, ArF = 3,5-(CF3)2C6H3] with 2 equiv of H3B·PR2H affords [Rh(L)(H)(σ,η-PR2BH3)(η1-H3B·PR2H)][BArF4]. These complexes undergo dehydrocoupling to give the diboraphosphine complexes [Rh(L)(H)(σ,η2-PR2·BH2PR2·BH3)][BArF4]. With electron-withdrawing groups on the phosphine–borane there is the parallel formation of the products of B–P cleavage, [Rh(L)(PR2H)2][BArF4], while with electron-donating groups no parallel product is formed. For the bulky, electron rich, H3B·P(Ad)2H no dehydrocoupling is observed, but an intermediate Rh(I) σ phosphine–borane complex is formed, [Rh(L){η2-H3B·P(Ad)2H}][BArF4], that undergoes B–P bond cleavage to give [Rh(L){η1-H3B·P(Ad)2H}{P(Ad)2H}][BArF4]. The relative rates of dehydrocoupling of H3B·PR2H (R = aryl) show that increasingly electron-withdrawing substituents result in faster dehydrocoupling, but also suffer from the formation of the parallel product resulting from P–B bond cleavage. H3B·PCyH2 undergoes a similar dehydrocoupling process, and gives a mixture of stereoisomers of the resulting metal-bound diboraphosphine that arise from activation of the prochiral P–H bonds, with one stereoisomer favored. This diastereomeric mixture may also be biased by use of a chiral phosphine ligand. The selectivity and efficiencies of resulting catalytic dehydrocoupling processes are also briefly discussed. PMID:24617924

Roles of the redox-active disulfide and histidine residues forming a catalytic dyad in reactions catalyzed by 2-ketopropyl coenzyme M oxidoreductase/carboxylase.

PubMed

Kofoed, Melissa A; Wampler, David A; Pandey, Arti S; Peters, John W; Ensign, Scott A

2011-09-01

NADPH:2-ketopropyl-coenzyme M oxidoreductase/carboxylase (2-KPCC), an atypical member of the disulfide oxidoreductase (DSOR) family of enzymes, catalyzes the reductive cleavage and carboxylation of 2-ketopropyl-coenzyme M [2-(2-ketopropylthio)ethanesulfonate; 2-KPC] to form acetoacetate and coenzyme M (CoM) in the bacterial pathway of propylene metabolism. Structural studies of 2-KPCC from Xanthobacter autotrophicus strain Py2 have revealed a distinctive active-site architecture that includes a putative catalytic triad consisting of two histidine residues that are hydrogen bonded to an ordered water molecule proposed to stabilize enolacetone formed from dithiol-mediated 2-KPC thioether bond cleavage. Site-directed mutants of 2-KPCC were constructed to test the tenets of the mechanism proposed from studies of the native enzyme. Mutagenesis of the interchange thiol of 2-KPCC (C82A) abolished all redox-dependent reactions of 2-KPCC (2-KPC carboxylation or protonation). The air-oxidized C82A mutant, as well as wild-type 2-KPCC, exhibited the characteristic charge transfer absorbance seen in site-directed variants of other DSOR enzymes but with a pK(a) value for C87 (8.8) four units higher (i.e., four orders of magnitude less acidic) than that for the flavin thiol of canonical DSOR enzymes. The same higher pK(a) value was observed in native 2-KPCC when the interchange thiol was alkylated by the CoM analog 2-bromoethanesulfonate. Mutagenesis of the flavin thiol (C87A) also resulted in an inactive enzyme for steady-state redox-dependent reactions, but this variant catalyzed a single-turnover reaction producing a 0.8:1 ratio of product to enzyme. Mutagenesis of the histidine proximal to the ordered water (H137A) led to nearly complete loss of redox-dependent 2-KPCC reactions, while mutagenesis of the distal histidine (H84A) reduced these activities by 58 to 76%. A redox-independent reaction of 2-KPCC (acetoacetate decarboxylation) was not decreased for any of the aforementioned site-directed mutants. We interpreted and rationalized these results in terms of a mechanism of catalysis for 2-KPCC employing a unique hydrophobic active-site architecture promoting thioether bond cleavage and enolacetone formation not seen for other DSOR enzymes. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

Effects of defects on thermal decomposition of HMX via ReaxFF molecular dynamics simulations.

PubMed

Zhou, Ting-Ting; Huang, Feng-Lei

2011-01-20

Effects of molecular vacancies on the decomposition mechanisms and reaction dynamics of condensed-phase β-HMX at various temperatures were studied using ReaxFF molecular dynamics simulations. Results show that three primary initial decomposition mechanisms, namely, N-NO(2) bond dissociation, HONO elimination, and concerted ring fission, exist at both high and lower temperatures. The contribution of the three mechanisms to the initial decomposition of HMX is influenced by molecular vacancies, and the effects vary with temperature. At high temperature (2500 K), molecular vacancies remarkably promote N-N bond cleavage and concerted ring breaking but hinder HONO formation. N-N bond dissociation and HONO elimination are two primary competing reaction mechanisms, and the former is dominant in the initial decomposition. Concerted ring breaking of condensed-phase HMX is not favored at high temperature. At lower temperature (1500 K), the most preferential initial decomposition pathway is N-N bond dissociation followed by the formation of NO(3) (O migration), although all three mechanisms are promoted by molecular vacancies. The promotion effect on concerted ring breaking is considerable at lower temperature. Products resulting from concerted ring breaking appear in the defective system but not in the perfect crystal. The mechanism of HONO elimination is less important at lower temperature. We also estimated the reaction rate constant and activation barriers of initial decomposition with different vacancy concentrations. Molecular vacancies accelerate the decomposition of condensed-phase HMX by increasing the reaction rate constant and reducing activation barriers.

The crystal structures of the tri-functional Chloroflexus aurantiacus and bi-functional Rhodobacter sphaeroides malyl-CoA lyases and comparison with CitE-like superfamily enzymes and malate synthases.

PubMed

Zarzycki, Jan; Kerfeld, Cheryl A

2013-11-09

Malyl-CoA lyase (MCL) is a promiscuous carbon-carbon bond lyase that catalyzes the reversible cleavage of structurally related Coenzyme A (CoA) thioesters. This enzyme plays a crucial, multifunctional role in the 3-hydroxypropionate bi-cycle for autotrophic CO2 fixation in Chloroflexus aurantiacus. A second, phylogenetically distinct MCL from Rhodobacter sphaeroides is involved in the ethylmalonyl-CoA pathway for acetate assimilation. Both MCLs belong to the large superfamily of CitE-like enzymes, which includes the name-giving β-subunit of citrate lyase (CitE), malyl-CoA thioesterases and other enzymes of unknown physiological function. The CitE-like enzyme superfamily also bears sequence and structural resemblance to the malate synthases. All of these different enzymes share highly conserved catalytic residues, although they catalyze distinctly different reactions: C-C bond formation and cleavage, thioester hydrolysis, or both (the malate synthases). Here we report the first crystal structures of MCLs from two different phylogenetic subgroups in apo- and substrate-bound forms. Both the C. aurantiacus and the R. sphaeroides MCL contain elaborations on the canonical β8/α8 TIM barrel fold and form hexameric assemblies. Upon ligand binding, changes in the C-terminal domains of the MCLs result in closing of the active site, with the C-terminal domain of one monomer forming a lid over and contributing side chains to the active site of the adjacent monomer. The distinctive features of the two MCL subgroups were compared to known structures of other CitE-like superfamily enzymes and to malate synthases, providing insight into the structural subtleties that underlie the functional versatility of these enzymes. Although the C. aurantiacus and the R. sphaeroides MCLs have divergent primary structures (~37% identical), their tertiary and quaternary structures are very similar. It can be assumed that the C-C bond formation catalyzed by the MCLs occurs as proposed for malate synthases. However, a comparison of the two MCL structures with known malate synthases raised the question why the MCLs are not also able to hydrolyze CoA thioester bonds. Our results suggest the previously proposed reaction mechanism for malate synthases may be incomplete or not entirely correct. Further studies involving site-directed mutagenesis based on these structures may be required to solve this puzzling question.

Molecular Signatures of Methanogens in Cultures and Environmental Samples

NASA Astrophysics Data System (ADS)

Summons, R. E.; Embaye, T.; Jahnke, L. L.; Baumgartner, M.

2002-12-01

The core lipids of methanogens comprise C20 and C40 isoprenoid chains, linked through ether bonds to glycerol. Additional structural diversity is encoded into the polar head groups that are attached to the glycerol ether cores. These compounds are potentially very useful as taxonomic markers in microbial mats and other environmental samples while the nature of the hydrocarbon chains provide a means to identify methanogenic inputs to ancient sediments. The structural diversity of methanogen polar lipids is most valuable when it can be directly correlated to 16S rRNA phylogeny. On the other hand, this diversity can also leads to analytical challenges because there is no single approach that works for all structural types. While some intact methanogen lipids have been identified using mass spectrometry and NMR spectroscopy, the most common means of analysing the lipid cores involves cleavage of the ether bonds using HI and subsequent reduction of the alkyl iodides to hydrocarbons with LiAlH4. One class of methanogenic lipids, the 3?-hydroxyarchaeols, escaped detection for some years because strong acid treatments in the analysis protocols destroyed hydroxyl-containing isoprenoid chains. We have been systematically re-examining the lipids of methanogens, using milder procedures involving weak acid hydrolysis of polar head groups, derivatisation to form trimethylsilyl ethers and analysis by GC-MS. As well as archaeol, sn-2- and sn-3-hydroxyarchaeol, we have tentatively identified a dihydroxyarchaeol in several Methanococcus sp. For Methanococcus thermolithotrophicus an analysis of the total lipid extracts using BBr3 as an ether cleavage reagent followed by LiBEt3H, reduction revealed a very complex mixture consisting of phytane, phytenes, biphytane, biphytenes and a suite of related alcohols. The latter compounds were analysed by GC-MS as their trimethylsilyl ethers and found to comprise a mixture tentatively identified as phytan-N-ol and biphytan-N-ol where N= 3 or 7 or 11 or 15. Apart from phytan-3-ol, these compounds appear to have been overlooked in previous analyses of methanogen lipids. Methanopyrus kandleri, a hyperthermophile that is distinguished from other methanogens by some unusual biochemical features, is also differentiated by having biphytanyl chains with cyclopentane rings. This is a structural feature more commonly found in the Crenarchaeota. We are applying this biomarker methodology to environmental samples in studies of the spatial distribution of methanogenesis relative to other physiologies.

A photochemical strategy for lignin degradation at room temperature.

PubMed

Nguyen, John D; Matsuura, Bryan S; Stephenson, Corey R J

2014-01-29

The development of a room-temperature lignin degradation strategy consisting of a chemoselective benzylic oxidation with a recyclable oxidant ([4-AcNH-TEMPO]BF4) and a catalytic reductive C-O bond cleavage utilizing the photocatalyst [Ir(ppy)2(dtbbpy)]PF6 is described. This system was tested on relevant lignin model substrates containing β-O-4 linkages to generate fragmentation products in good to excellent yields.

Hydrogen production by aqueous phase reforming of light oxygenated hydrocarbons

NASA Astrophysics Data System (ADS)

Shabaker, John William

Aqueous phase reforming (APR) of renewable oxygenated hydrocarbons (e.g., methanol, ethylene glycol, glycerol, sorbitol, glucose) is a promising new technology for the catalytic production of high-purity hydrogen for fuel cells and chemical processing. Supported Pt catalysts are effective catalysts for stable and rapid H2 production at temperatures near 500 K (H 2 turnover frequencies near 10 min-1). Inexpensive Raney Ni-based catalysts have been developed using a combination of fundamental and high-throughput studies that have similar catalytic properties as Pt-based materials. Promotion of Raney Ni with Sn by controlled surface reaction of organometallic tin compounds is necessary to control formation of thermodynamically-favorable alkane byproducts. Detailed characterization by Mossbauer spectroscopy, electron microscopy, adsorption studies, and x-ray photoelectron spectroscopy (XPS/ESCA) has shown that NiSn alloys are formed during heat treatment, and may be responsible for enhanced stability and selectivity for hydrogen production. Detailed kinetic studies led to the development of a kinetic mechanism for the APR reaction on Pt and NiSn catalysts, in which the oxygenate decomposes through C--H and O--H cleavage, followed by C--C cleavage and water gas shift of the CO intermediate. The rate limiting step on Pt surfaces is the initial dehydrogenation, while C--C cleavage appears rate limiting over NiSn catalysts. Tin promotion of Raney Ni catalysts suppresses C--O bond scission reactions that lead to alkane formation without inhibiting fast C--C and C--H cleavage steps that are necessary for high rates of reforming. A window of operating temperature, pressure, and reactor residence time has been identified for use of the inexpensive NiSn catalysts as a Pt substitute. Concentrated feed stocks and aggressive pretreatments have been found to counteract catalyst deactivation by sintering in the hydrothermal APR environment and allow stable, long-term production of H2 over Raney-NiSn materials.

An ab initio molecular dynamics study of thermal decomposition of 3,6-di(azido)-1,2,4,5-tetrazine.

PubMed

Wu, Qiong; Zhu, Weihua; Xiao, Heming

2014-10-21

Ab initio molecular dynamics simulations were performed to study the thermal decomposition of isolated and crystal 3,6-di(azido)-1,2,4,5-tetrazine (DiAT). During unimolecular decomposition, the three different initiation mechanisms were observed to be N-N2 cleavage, ring opening, and isomerization, respectively. The preferential initial decomposition step is the homolysis of the N-N2 bond in the azido group. The release mechanisms of nitrogen gas are found to be very different in the early and later decomposition stages of crystal DiAT. In the early decomposition, DiAT decomposes very fast and drastically without forming any stable long-chains or heterocyclic clusters, and most of the nitrogen gases are released through rapid rupture of nitrogen-nitrogen and carbon-nitrogen bonds. But in the later decomposition stage, the release of nitrogen gas is inhibited due to low mobility, long distance from each other, and strong carbon-nitrogen bonds. To overcome the obstacles, the nitrogen gases are released through slow formation and disintegration of polycyclic networks. Our simulations suggest a new decomposition mechanism for the organic polyazido initial explosive at the atomistic level.

Reactivity of nitrido complexes of ruthenium(VI), osmium(VI), and manganese(V) bearing Schiff base and simple anionic ligands.

PubMed

Man, Wai-Lun; Lam, William W Y; Lau, Tai-Chu

2014-02-18

Nitrido complexes (M≡N) may be key intermediates in chemical and biological nitrogen fixation and serve as useful reagents for nitrogenation of organic compounds. Osmium(VI) nitrido complexes bearing 2,2':6',2″-terpyridine (terpy), 2,2'-bipyridine (bpy), or hydrotris(1-pyrazolyl)borate anion (Tp) ligands are highly electrophilic: they can react with a variety of nucleophiles to generate novel osmium(IV)/(V) complexes. This Account describes our recent results studying the reactivity of nitridocomplexes of ruthenium(VI), osmium(VI), and manganese(V) that bear Schiff bases and other simple anionic ligands. We demonstrate that these nitrido complexes exhibit rich chemical reactivity. They react with various nucleophiles, activate C-H bonds, undergo N···N coupling, catalyze the oxidation of organic compounds, and show anticancer activities. Ruthenium(VI) nitrido complexes bearing Schiff base ligands, such as [Ru(VI)(N)(salchda)(CH3OH)](+) (salchda = N,N'-bis(salicylidene)o-cyclohexyldiamine dianion), are highly electrophilic. This complex reacts readily at ambient conditions with a variety of nucleophiles at rates that are much faster than similar reactions using Os(VI)≡N. This complex also carries out unique reactions, including the direct aziridination of alkenes, C-H bond activation of alkanes and C-N bond cleavage of anilines. The addition of ligands such as pyridine can enhance the reactivity of [Ru(VI)(N)(salchda)(CH3OH)](+). Therefore researchers can tune the reactivity of Ru≡N by adding a ligand L trans to nitride: L-Ru≡N. Moreover, the addition of various nucleophiles (Nu) to Ru(VI)≡N initially generate the ruthenium(IV) imido species Ru(IV)-N(Nu), a new class of hydrogen-atom transfer (HAT) reagents. Nucleophiles also readily add to coordinated Schiff base ligands in Os(VI)≡N and Ru(VI)≡N complexes. These additions are often stereospecific, suggesting that the nitrido ligand has a directing effect on the incoming nucleophile. M≡N is also a potential platform for the design of new oxidation catalysts. For example, [Os(VI)(N)Cl4](-) catalyzes the oxidation of alkanes by a variety of oxidants, and the addition of Lewis acids greatly accelerates these reactions. [Mn(V)(N)(CN)4]2(-) is another highly efficient oxidation catalyst, which facilitates the epoxidation of alkenes and the oxidation of alcohols to carbonyl compounds using H2O2. Finally, M≡N can potentially bind to and exert various effects on biomolecules. For example, a number of Os(VI)≡N complexes exhibit novel anticancer properties, which may be related to their ability to bind to DNA or other biomolecules.

Decarbonylative Cross-Couplings: Nickel Catalyzed Functional Group Interconversion Strategies for the Construction of Complex Organic Molecules.

PubMed

Guo, Lin; Rueping, Magnus

2018-05-15

The utilization of carboxylic acid esters as electrophiles in metal-catalyzed cross-coupling reactions is increasingly popular, as environmentally friendly and readily available ester derivatives can be powerful alternatives to the commonly used organohalides. However, key challenges associated with the use of these chemicals remain to be addressed, including the stability of ester substrates and the high energy barrier associated with their oxidative addition to low-valent metal species. Due to recent developments in nickel catalysis that make it easier to perform oxidative additions, chemists have become interested in applying less reactive electrophiles as coupling counterparts in nickel-catalyzed transformations. Hence, our group and others have independently investigated various ester group substitutions and functionalizations enabled by nickel catalysis. Such methods are of great interest as they enable the exchange of ester groups, which can be used as directing groups in metal-catalyzed C-H functionalizations prior to their replacement. Here, we summarize our recent efforts toward the development of nickel-catalyzed decarbonylative cross-coupling reactions of carboxylic esters. Achievements accomplished by other groups in this area are also included. To this day, a number of new transformations have been successfully developed, including decarbonylative arylations, alkylations, cyanations, silylations, borylations, aminations, thioetherifications, stannylations, and hydrogenolysis reactions. These transformations proceed via a nickel-catalyzed decarbonylative pathway and have shown a high degree of reactivity and chemoselectivity, as well as several other unique advantages in terms of substrate availability, due to the use of esters as coupling partners. Although the mechanisms of these reactions have not yet been fully understood, chemists have already provided some important insights. For example, Yamamoto explored the stoichiometric nickel-mediated decarbonylation process of esters and proposed a reaction mechanism involving a C(acyl)-O bond cleavage and a CO extrusion. Key nickel intermediates were isolated and characterized by Shi and co-workers, supporting the assumption of a nickel/ N-heterocyclic carbene-promoted C(acyl)-O bond activation and functionalization. Our combined experimental and computational study of a ligand-controlled chemoselective nickel-catalyzed cross-coupling of aromatic esters with alkylboron reagents provided further insight into the reaction mechanism. We demonstrated that nickel complexes with bidentate ligands favor the C(aryl)-C bond cleavage in the oxidative addition step, resulting in decarbonylative alkylations, while nickel complexes with monodentate phosphorus ligands promote the activation of the C(acyl)-O bond, leading to the production of ketone products. Although more detailed mechanistic investigations need to be undertaken, the successful development of decarbonylative cross-coupling reactions can serve as a solid foundation for future studies. We believe that this type of decarbonylative cross-coupling reactions will be of significant value, in particularly in combination with the retrosynthetic analysis and synthesis of natural products and biologically active molecules. Thus, the presented ester substitution methods will pave the way for successful applications in the construction of complex frameworks by late-stage modification and functionalization of carboxylic acid derivatives.

Time-dependent infrared emission following photodissociation of nitromethane and chloropicrin.

PubMed

Wade, Elisabeth A; Reak, Kristina E; Li, Sissi L; Clegg, Samuel M; Zou, Peng; Osborn, David L

2006-04-06

Nitromethane (CH(3)NO(2)) and its chlorinated analogue, chloropicrin (CCl(3)NO(2)), were photolyzed at 193, 248, and 266 nm, and the products were observed by time-dependent Fourier transform infrared emission spectroscopy. At 193 and 248 nm, the primary photodissociation pathway for nitromethane was cleavage of the C-N bond to produce CH(3) + NO(2)(A (2)B(2)). At 266 nm, weak emission was observed following photodissociation of nitromethane, but an infrared spectrum could not be obtained. The photodissociation of chloropicrin at 193 nm produced the analogous product channel CCl(3) + NO(2)(A (2)B(2)) in addition to several other product channels. At 248 and 266 nm, only CCl(3) + NO(2)(A (2)B(2)) was observed. The production of phosgene (CCl(2)O) from chloropicrin photodissociation was not observed in this study.

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

Nganga, John K.; Samanamu, Christian R.; Tanski, Joseph M.

In a series of rhenium tricarbonyl complexes coordinated by asymmetric diimine ligands containing a pyridine moiety bound to an oxazoline ring were synthesized, structurally and electrochemically characterized, and screened for CO 2 reduction ability. We reported complexes are of the type Re(N-N)(CO) 3Cl, with N-N = 2-(pyridin-2-yl)-4,5-dihydrooxazole (1), 5-methyl-2-(pyridin-2-yl)-4,5-dihydrooxazole (2), and 5-phenyl-2-(pyridin-2-yl)-4,5-dihydrooxazole (3). The electrocatalytic reduction of CO 2 by these complexes was observed in a variety of solvents and proceeds more quickly in acetonitrile than in dimethylformamide (DMF) and dimethyl sulfoxide (DMSO). The analysis of the catalytic cycle for electrochemical CO 2 reduction by 1 in acetonitrile using densitymore » functional theory (DFT) supports the C–O bond cleavage step being the rate-determining step (RDS) (ΔG ‡ = 27.2 kcal mol –1). Furthermore, the dependency of the turnover frequencies (TOFs) on the donor number (DN) of the solvent also supports that C–O bond cleavage is the rate-determining step. Moreover, the calculations using explicit solvent molecules indicate that the solvent dependence likely arises from a protonation-first mechanism. Unlike other complexes derived from fac-Re(bpy)(CO) 3Cl (I; bpy = 2,2'-bipyridine), in which one of the pyridyl moieties in the bpy ligand is replaced by another imine, no catalytic enhancement occurs during the first reduction potential. Remarkably, catalysts 1 and 2 display relative turnover frequencies, (i cat/i p) 2, up to 7 times larger than that of I.« less

Spontaneous Isomerization of Peptide Cation Radicals Following Electron Transfer Dissociation Revealed by UV-Vis Photodissociation Action Spectroscopy.

PubMed

Imaoka, Naruaki; Houferak, Camille; Murphy, Megan P; Nguyen, Huong T H; Dang, Andy; Tureček, František

2018-01-16

Peptide cation radicals of the z-type were produced by electron transfer dissociation (ETD) of peptide dications and studied by UV-Vis photodissociation (UVPD) action spectroscopy. Cation radicals containing the Asp (D), Asn (N), Glu (E), and Gln (Q) residues were found to spontaneously isomerize by hydrogen atom migrations upon ETD. Canonical N-terminal [z 4 + H] +● fragment ion-radicals of the R-C ● H-CONH- type, initially formed by N-C α bond cleavage, were found to be minor components of the stable ion fraction. Vibronically broadened UV-Vis absorption spectra were calculated by time-dependent density functional theory for several [ ● DAAR + H] + isomers and used to assign structures to the action spectra. The potential energy surface of [ ● DAAR + H] + isomers was mapped by ab initio and density functional theory calculations that revealed multiple isomerization pathways by hydrogen atom migrations. The transition-state energies for the isomerizations were found to be lower than the dissociation thresholds, accounting for the isomerization in non-dissociating ions. The facile isomerization in [ ● XAAR + H] + ions (X = D, N, E, and Q) was attributed to low-energy intermediates having the radical defect in the side chain that can promote hydrogen migration along backbone C α positions. A similar side-chain mediated mechanism is suggested for the facile intermolecular hydrogen migration between the c- and [z + H] ● -ETD fragments containing Asp, Asn, Glu, and Gln residues. Graphical Abstract ᅟ.

Addition of aluminium, zinc and magnesium hydrides to rhodium(iii)† †Electronic supplementary information (ESI) available. CCDC 1047853–1047855 1056989. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c5sc01309g Click here for additional data file. Click here for additional data file.

PubMed Central

Ekkert, Olga; White, Andrew J. P.; Toms, Harold

2015-01-01

We report the addition of M–H bonds (M = Al, Zn, Mg) to a Rh(iii) intermediate generated from the reductive elimination of triethylsilane from [Cp*Rh(H)2(SiEt3)2]. A series of new heterobimetallic complexes possessing Rh–M bonds have been isolated and characterised by a number of spectroscopic (1H, 29Si, 13C, 103Rh NMR, infrared, and X-ray diffraction) and computational techniques (NBO and QTAIM analysis). Experimental and computational data are consistent with cleavage of the M–H bond upon addition to rhodium with formation of new Rh–M and Rh–H bonds. Upon photolysis the Al analogue of this series undergoes a further elimination reaction producing triethylsilane and a highly unusual Rh2Al2H4 containing cluster proposed to contain an Al(i) bridging ligand. PMID:28757949

Synthesis of 3-iodoindoles by the Pd/Cu-catalyzed coupling of N,N-dialkyl-2-iodoanilines and terminal acetylenes, followed by electrophilic cyclization.

PubMed

Yue, Dawei; Yao, Tuanli; Larock, Richard C

2006-01-06

[reaction: see text] 3-Iodoindoles have been prepared in excellent yields by coupling terminal acetylenes with N,N-dialkyl-o-iodoanilines in the presence of a Pd/Cu catalyst, followed by an electrophilic cyclization of the resulting N,N-dialkyl-o-(1-alkynyl)anilines using I2 in CH2Cl2. Aryl-, vinylic-, alkyl-, and silyl-substituted terminal acetylenes undergo this process to produce excellent yields of 3-iodoindoles. The reactivity of the carbon-nitrogen bond cleavage during cyclization follows the following order: Me > n-Bu, Me > Ph, and cyclohexyl > Me. Subsequent palladium-catalyzed Sonogashira, Suzuki, and Heck reactions of the resulting 3-iodoindoles proceed smoothly in good yields.

Hydrolytic cleavage of pyroglutamyl-peptide bond. V. selective removal of pyroglutamic acid from biologically active pyroglutamylpeptides in high concentrations of aqueous methanesulfonic acid.

PubMed

Kobayashi, Junko; Ohki, Kazuhiro; Okimura, Keiko; Hashimoto, Tadashi; Sakura, Naoki

2006-06-01

Application of aqueous methanesulfonic acid (MSA) for selective chemical removal of pyroglutamic acid (pGlu) residue from five biologically active pyroglutamyl-peptides (pGlu-X-peptides, X=amino acid residue at position 2) was examined. Gonadotropin releasing hormone (Gn-RH), dog neuromedin U-8 (d-NMU-8), physalaemin (PH), a bradykinin potentiating peptide (BPP-5a) and neurotensin (NT) as pGlu-X-peptides were incubated in either 70% or 90% aqueous MSA at 25 degrees C. HPLC analysis of the incubation solutions showed that the main decomposition product was H-X-peptide derived from each pGlu-X-peptide by the removal of pGlu. The results revealed that the pGlu-X peptide bond had higher susceptibility than various internal amide bonds in the five peptides examined, including the Trp-Ser bond in Gn-RH, the C-terminal Asn-NH(2) in d-NMU-8, and the Asp-Pro bond in PH, whose acid susceptibility is well known. Thus, mild hydrolysis with high concentrations of aqueous MSA may be applicable to chemically selective removal of pGlu from pGlu-X-peptides for structural examinations.

Highly Efficient Release of Glycopeptides from Hydrazide Beads by Hydroxylamine Assisted PNGase F Deglycosylation for N-Glycoproteome Analysis.

PubMed

Huang, Junfeng; Wan, Hao; Yao, Yating; Li, Jinan; Cheng, Kai; Mao, Jiawei; Chen, Jin; Wang, Yan; Qin, Hongqiang; Zhang, Weibing; Ye, Mingliang; Zou, Hanfa

2015-10-20

Selective enrichment of glycopeptides from complex sample followed by cleavage of N-glycans by PNGase F to expose an easily detectable mark on the former glycosylation sites has become the popular protocol for comprehensive glycoproteome analysis. On account of the high enrichment specificity, hydrazide chemistry based solid-phase extraction of N-linked glycopeptides technique has sparked numerous interests. However, the enzymatic release of glycopeptides captured by hydrazide beads through direct incubation of the beads with PNGase F is not efficient due to the inherent steric hindrance effect. In this study, we developed a hydroxylamine assisted PNGase F deglycosylation (HAPD) method using the hydroxylamine to release glycopeptides captured on the hydrazide beads through the cleavage of hydrazone bonds by transamination followed with the PNGase F deglycosylation of the released glycopeptides in the free solution. Because of the homogeneous condition for the deglycosylation, the recovery of deglycosylated peptides (deglycopeptides) was improved significantly. It was found that 27% more N-glycosylation sites were identified by the HAPD strategy compared with the conventional method. Moreover, the ratio of identified N-terminal glycosylated peptides was improved over 5-fold.

4-Bromo-N-(di-n-propyl-carbamothioyl)-benzamide.

PubMed

Binzet, Gün; Flörke, Ulrich; Külcü, Nevzat; Arslan, Hakan

2009-02-04

The synthesis of the title compound, C(14)H(19)BrN(2)OS, involves the reaction of 4-bromo-benzoyl chloride with potassium thio-cyanate in acetone followed by condensation of the resulting 4-bromo-benzoyl isothio-cyanate with di-n-propyl-amine. Typical thio-urea carbonyl and thio-carbonyl double bonds, as well as shortened C-N bonds, are observed in the title compound. The short C-N bond lengths in the centre of the mol-ecule reveal the effects of resonance in this part of the mol-ecule. The asymmetric unit of the title compound contains two crystallographically independent mol-ecules, A and B. There is very little difference between the bond lengths and angles of these mol-ecules. In mol-ecule B, one di-n-propyl group is twisted in a -anti-periplanar conformation with C-C-C-H = -179.1 (3)° and the other adopts a -synclinal conformation with C-C-C-H = -56.7 (4)°; in mol-ecule A the two di-n-propyl groups are twisted in + and -anti-periplanar conformations, with C-C-C-H = -179.9 (3) and 178.2 (3)°, respectively. In the crystal, the mol-ecules are linked into dimeric pairs via pairs of N-H⋯S hydrogen bonds.

Hydrogen-bonded supramolecular structures of three related 4-(5-nitro-2-furyl)-1,4-dihydropyridines.

PubMed

Quesada, Antonio; Argüello, Jacqueline; Squella, Juan A; Wardell, James L; Low, John N; Glidewell, Christopher

2006-01-01

In ethyl 5-cyano-2,6-dimethyl-4-(5-nitro-2-furyl)-1,4-dihydropyridine-3-carboxylate, C15H15N3O5, the molecules are linked into chains by a single N-H...O hydrogen bond. The molecules in diethyl 2,6-dimethyl-4-(5-nitro-2-furyl)-1,4-dihydropyridine-3,5-dicarboxylate, C17H20N2O7, are linked by a combination of one N-H...O hydrogen bond and two C-H...O hydrogen bonds into sheets built from equal numbers of R(2)(2)(17) and R(4)(4)(18) rings. In 2,6-dimethyl-4-(5-nitro-2-furyl)-1,4-dihydropyridine-3,5-dicarbonitrile, C13H10N4O3, the molecules are linked by a combination of a three-centre N-H...(O)2 hydrogen bond and two independent two-centre C-H...O hydrogen bonds into complex sheets containing four types of ring.

Atypical behavior in the electron capture induced dissociation of biologically relevant transition metal ion complexes of the peptide hormone oxytocin

NASA Astrophysics Data System (ADS)

Kleinnijenhuis, Anne J.; Mihalca, Romulus; Heeren, Ron M. A.; Heck, Albert J. R.

2006-07-01

Doubly protonated ions of the disulfide bond containing nonapeptide hormone oxytocin and oxytocin complexes with different transition metal ions, that have biological relevance under physiological conditions, were subjected to electron capture dissociation (ECD) to probe their structural features in the gas phase. Although, all the ECD spectra were strikingly different, typical ECD behavior was observed for complexes of the nonapeptide hormone oxytocin with Ni2+, Co2+ and Zn2+, i.e., abundant c/z' and a'/y backbone cleavages and ECD characteristic S-S and S-C bond cleavages were observed. We propose that, although in the oxytocin-transition metal ion complexes the metal ions serve as the main initial capture site, the captured electron is transferred to other sites in the complex to form a hydrogen radical, which drives the subsequent typical ECD fragmentations. The complex of oxytocin with Cu2+ displayed noticeably different ECD behavior. The fragment ions were similar to fragment ions typically observed with low-energy collision induced dissociation (CID). We propose that the electrons captured by the oxytocin-Cu2+ complex might be favorably involved in reducing the Cu2+ metal ion to Cu+. Subsequent energy redistribution would explain the observed low-energy CID-type fragmentations. Electron capture resulted also in quite different specific cleavage sites for the complexes of oxytocin with Ni2+, Co2+ and Zn2+. This is an indication for structural differences in these complexes possibly linked to their significantly different biological effects on oxytocin-receptor binding, and suggests that ECD may be used to study subtle structural differences in transition metal ion-peptide complexes.

The selective activation of a C-F bond with an auxiliary strong Lewis acid: a method to change the activation preference of C-F and C-H bonds.

PubMed

Wang, Lin; Sun, Hongjian; Li, Xiaoyan; Fuhr, Olaf; Fenske, Dieter

2016-11-15

The selective activation of the C-F bonds in substituted (2,6-difluorophenyl)phenylimines (2,6-F 2 H 3 C 6 -(C[double bond, length as m-dash]NH)-n'-R-C 6 H 4 (n' = 2, R = H (1); n' = 2, R = Me (2); n' = 4, R = tBu (3))) by Fe(PMe 3 ) 4 with an auxiliary strong Lewis acid (LiBr, LiI, or ZnCl 2 ) was explored. As a result, iron(ii) halides ((H 5 C 6 -(C[double bond, length as m-dash]NH)-2-FH 3 C 6 )FeX(PMe 3 ) 3 (X = Br (8); Cl (9)) and (n-RH 4 C 6 -(C[double bond, length as m-dash]NH)-2'-FH 3 C 6 )FeX(PMe 3 ) 3 (n = 2, R = Me, X = Br (11); n = 4, R = tBu, X = I (12))) were obtained. Under similar reaction conditions, using LiBF 4 instead of LiBr or ZnCl 2 , the reaction of (2,6-difluorophenyl)phenylimine with Fe(PMe 3 ) 4 afforded an ionic complex [(2,6-F 2 H 3 C 6 -(C[double bond, length as m-dash]NH)-H 4 C 6 )Fe(PMe 3 ) 4 ](BF 4 ) (10) via the activation of a C-H bond. The method of C-F bond activation with an auxiliary strong Lewis acid is appropriate for monofluoroarylmethanimines. Without the Lewis acid, iron(ii) hydrides ((2-RH 4 C 6 -(C[double bond, length as m-dash]NH)-2'-FH 3 C 6 )FeH(PMe 3 ) 3 (R = H (13); Me (14))) were generated from the reactions of Fe(PMe 3 ) 4 with the monofluoroarylmethanimines (2-FH 4 C 6 -(C[double bond, length as m-dash]NH)-2'-RC 6 H 4 (R = H (4); Me (5))); however, in the presence of ZnCl 2 or LiBr, iron(ii) halides ((2-RH 4 C 6 -(C[double bond, length as m-dash]NH)-H 4 C 6 )FeX(PMe 3 ) 3 (R = H, X = Cl (15); R = Me, X = Br (16))) could be obtained through the activation of a C-F bond. Furthermore, a C-F bond activation with good regioselectivity in (pentafluorophenyl)arylmethanimines (F 5 C 6 -(C[double bond, length as m-dash]NH)-2,6-Y 2 C 6 H 3 (Y = F (6); H (7))) could be realized in the presence of ZnCl 2 to produce iron(ii) chlorides ((2,6-Y 2 H 3 C 6 -(C[double bond, length as m-dash]NH)-F 4 C 6 )FeCl(PMe 3 ) 3 (Y = F (17); H (18))). This series of iron(ii) halides could be used to catalyze the hydrosilylation reaction of aldehydes. Due to the stability of iron(ii) halides to high temperature, the reaction mixture was allowed to be heated to 100 °C and the reaction could finish within 0.5 h.

Mn-Catalyzed Highly Efficient Aerobic Oxidative Hydroxyazidation of Olefins: A Direct Approach to β-Azido Alcohols.

PubMed

Sun, Xiang; Li, Xinyao; Song, Song; Zhu, Yuchao; Liang, Yu-Feng; Jiao, Ning

2015-05-13

An efficient Mn-catalyzed aerobic oxidative hydroxyazidation of olefins for synthesis of β-azido alcohols has been developed. The aerobic oxidative generation of azido radical employing air as the terminal oxidant is disclosed as the key process for this transformation. The reaction is appreciated by its broad substrate scope, inexpensive Mn-catalyst, high efficiency, easy operation under air, and mild conditions at room temperature. This chemistry provides a novel approach to high value-added β-azido alcohols, which are useful precursors of aziridines, β-amino alcohols, and other important N- and O-containing heterocyclic compounds. This chemistry also provides an unexpected approach to azido substituted cyclic peroxy alcohol esters. A DFT calculation indicates that Mn catalyst plays key dual roles as an efficient catalyst for the generation of azido radical and a stabilizer for peroxyl radical intermediate. Further calculation reasonably explains the proposed mechanism for the control of C-C bond cleavage or for the formation of β-azido alcohols.

Reactivity of hydropersulfides toward the hydroxyl radical unraveled: disulfide bond cleavage, hydrogen atom transfer, and proton-coupled electron transfer.

PubMed

Anglada, Josep M; Crehuet, Ramon; Adhikari, Sarju; Francisco, Joseph S; Xia, Yu

2018-02-14

Hydropersulfides (RSSH) are highly reactive as nucleophiles and hydrogen atom transfer reagents. These chemical properties are believed to be key for them to act as antioxidants in cells. The reaction involving the radical species and the disulfide bond (S-S) in RSSH, a known redox-active group, however, has been scarcely studied, resulting in an incomplete understanding of the chemical nature of RSSH. We have performed a high-level theoretical investigation on the reactions of the hydroxyl radical (˙OH) toward a set of RSSH (R = -H, -CH 3 , -NH 2 , -C(O)OH, -CN, and -NO 2 ). The results show that S-S cleavage and H-atom abstraction are the two competing channels. The electron inductive effect of R induces selective ˙OH substitution at one sulfur atom upon S-S cleavage, forming RSOH and ˙SH for the electron donating groups (EDGs), whereas producing HSOH and ˙SR for the electron withdrawing groups (EWGs). The H-Atom abstraction by ˙OH follows a classical hydrogen atom transfer (hat) mechanism, producing RSS˙ and H 2 O. Surprisingly, a proton-coupled electron transfer (pcet) process also occurs for R being an EDG. Although for RSSH having EWGs hat is the leading channel, S-S cleavage can be competitive or even dominant for the EDGs. The overall reactivity of RSSH toward ˙OH attack is greatly enhanced with the presence of an EDG, with CH 3 SSH being the most reactive species found in this study (overall rate constant: 4.55 × 10 12 M -1 s -1 ). Our results highlight the complexity in RSSH reaction chemistry, the extent of which is closely modulated by the inductive effect of the substituents in the case of the oxidation by hydroxyl radicals.

Ni(ClO4)(2)-catalysed regio- and diastereoselective [3+2] cycloaddition of indoles and aryl oxiranyl-dicarboxylates/diketones: a facile access to furo[3,4-b]indoles.

PubMed

Zhang, Jieming; Chen, Zuliang; Wu, Hai-Hong; Zhang, Junliang

2012-02-07

Ni(ClO(4))(2)·6H(2)O-catalysed regioselective and diastereoselective [3+2]-annulations of aryl oxiranyl-dicarboxylates and indoles via selective C-C bond cleavage of oxirane were revealed. The cycloadditions proceed smoothly with high regio- and diastereoselectivity under mild conditions leading to 1H-furo[3,4-b]indoles in good to excellent yields. This journal is © The Royal Society of Chemistry 2012

Experimental and theoretical study on activation of the C-H bond in pyridine by [M(m)]- (M = Cu, Ag, Au, m = 1-3).

PubMed

Liu, Xiao-Jing; Hamilton, I P; Han, Ke-Li; Tang, Zi-Chao

2010-09-21

Activation of the C-H bond of pyridine by [M(m)](-) (M = Cu, Ag, Au, m = 1-3) is investigated by experiment and theory. Complexes of coinage metal clusters and the pyridyl group, [M(m)-C(5)H(4)N](-), are produced from reactions between metal clusters formed by laser ablation of coinage metal samples and pyridine molecules seeded in argon carrier gas. We examine the structure and formation mechanism of these pyridyl-coinage metal complexes. Our study shows that C(5)H(4)N bonds to the metal clusters through a M-C sigma bond and [M(m)-C(5)H(4)N](-) is produced via a stepwise mechanism. The first step is a direct insertion reaction between [M(m)](-) and C(5)H(5)N with activation of the C-H bond to yield the intermediate [HM(m)-C(5)H(4)N](-). The second step is H atom abstraction by a neutral metal atom to yield [M(m)-C(5)H(4)N](-).

Investigation of the fracture mechanics of boride composites

NASA Technical Reports Server (NTRS)

Kaufman, L.; Clougherty, E. V.; Nesor, H.

1971-01-01

Fracture energies of WC-6Co, Boride 5 (ZrB2+SiC), Boride 8(ZrB2+SiC+C) and Boride 8-M2(ZrB2+SiC+C) were measured by slow bend and impact tests of notched charpy bars. Cobalt bonded tungsten carbide exhibited impact energies of 0.76 ft-lb or 73.9 in-lb/square inch. Boride 5 and the Boride 8 exhibit impact energies one third and one quarter of that observed for WC-6Co comparing favorably with measurements for SiC and Si3N4. Slow bend-notched bar-fracture energies for WC-6Co were near 2.6 in-lb/square inch or 1/20 the impact energies. Slow bend energies for Boride 8-M2, Boride 8 and Boride 5 were 58%, 42% and 25% of the value observed for WC-6Co. Fractograph showed differences for WC-6Co where slow bend testing resulted in smooth transgranular cleavage while samples broken by impact exhibited intergranular failures. By contrast the boride fractures showed no distinction based on testing method. Fabrication studies were conducted to effect alteration of the boride composites by alloying and introduction of graphite cloth.

Isothermal Fourier transform infrared microspectrosopic studies on the stability kinetics of solid-state intramolecular cyclization of aspartame sweetener.

PubMed

Cheng, Y D; Lin, S Y

2000-03-01

A novel Fourier transform infrared (FT-IR) microspectrophotometer equipped with differential scanning calorimetry (DSC) was used to investigate the kinetics of intramolecular cyclization of aspartame (APM) sweetener in the solid state under isothermal conditions. The thermal-dependent changes in the peak intensity of IR spectra at 1543, 1283, and 1259 cm(-1) were examined to explore the reaction. The results support that the intramolecular cyclization process in APM proceeded in three steps: the methoxyl group of ester was first thermolyzed to release methanol, then an acyl cation was attacked by the lone pair of electrons available on nitrogen by an S(N)1 pathway, and finally ring-closure occurred. The intramolecular cyclization of APM determined by this microscopic FT-IR/DSC system was found to follow zero-order kinetics after a brief induction period. The bond cleavage energy (259.38 kJ/mol) of thermolysis for the leaving group of -OCH(3), the bond conversion energy (328.88 kJ/mol) for the amide II NH band to DKP NH band, and the CN bond formation energy (326.93 kJ/mol) of cyclization for the DKP in the APM molecule were also calculated from the Arrhenius equation. The total activation energy of the DKP formation via intramolecular cyclization was 261.33 kJ/mol, calculated by the above summation of the bond energy of cleavage, conversion, and formation, which was near to the value determined by the DSC or TGA method. This indicates that the microscopic FT-IR/DSC system is useful as a potential tool not only to investigate the degradation mechanism of drugs in the solid state but also to directly predict the bond energy of the reaction.

Interaction of benzene thiol and thiolate with small gold clusters.

PubMed

Letardi, Sara; Cleri, Fabrizio

2004-06-01

We studied the interaction between benzene thiol and thiolate molecules, and gold clusters made of 1 to 3 atoms, by means of ab initio density functional theory in the local density approximation. We find that the thiolate is energetically more stable than the thiol, however the process of detachment of H from the thiol appears to be possibly mediated by the intermediate step of H chemisorption on Au. Cleavage of the S-H bond is accompanied by a 90 degrees rotation of the molecule around the S-Au bond, showing a strong steric specificity. Such a rotation is induced by the relative energy shift of the S atom p orbitals with respect to the benzene pi ring and the Au d orbitals. By analyzing the correlation of the bond energy, bond lengths, and HOMO-LUMO gap with the number of S-Au bonds, we find that the thiolate S atom appears to prefer a low-coordination condition on Au clusters. (c) 2004 American Institute of Physics.

Chymase Cleavage of Stem Cell Factor Yields a Bioactive, Soluble Product

NASA Astrophysics Data System (ADS)

Longley, B. Jack; Tyrrell, Lynda; Ma, Yongsheng; Williams, David A.; Halaban, Ruth; Langley, Keith; Lu, Hsieng S.; Schechter, Norman M.

1997-08-01

Stem cell factor (SCF) is produced by stromal cells as a membrane-bound molecule, which may be proteolytically cleaved at a site close to the membrane to produce a soluble bioactive form. The proteases producing this cleavage are unknown. In this study, we demonstrate that human mast cell chymase, a chymotrypsin-like protease, cleaves SCF at a novel site. Cleavage is at the peptide bond between Phe-158 and Met-159, which are encoded by exon 6 of the SCF gene. This cleavage results in a soluble bioactive product that is 7 amino acids shorter at the C terminus than previously identified soluble SCF. This research shows the identification of a physiologically relevant enzyme that specifically cleaves SCF. Because mast cells express the KIT protein, the receptor for SCF, and respond to SCF by proliferation and degranulation, this observation identifies a possible feedback loop in which chymase released from mast cell secretory granules may solubilize SCF bound to the membrane of surrounding stromal cells. The liberated soluble SCF may in turn stimulate mast cell proliferation and differentiated functions; this loop could contribute to abnormal accumulations of mast cells in the skin and hyperpigmentation at sites of chronic cutaneous inflammation.