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Sample records for nucleophilic intermediate complex

  1. Highly nucleophilic acetylide, vinyl, and vinylidene complexes. Progress report

    SciTech Connect

    Not Available

    1992-06-15

    The research was divided into the following: studies of nucleophilic and chiral acetylide complex [Cp(CO)(PPh{sub 3})Mn-C{triple_bond}CR]{sup {minus}}; nucleophilic addition of carbene anions to organic ligands on electrophilic complexes; halide-promoted carbonylation of imido ligands; binuclear Fe{sub 2} complexes with bridging organonitrogen ligands; addition and cycloaddition reactions of carbyne complex [Cp(CO){sub 2}Re{triple_bond}CTol]{sup +}; addition and cycloaddition reactions of methylcarbyne complexes [Cp(CO){sub 2}M{triple_bond}CCH{sub 3}]{sup +} and vinylidene complexes Cp(CO){sub 2}M{double_bond}C{double_bond}CH{sub 2} (M=Mn, Re); studies of generation and reactivity of vinylcarbene complexes formed from reaction of manganese carbene anions and aldehydes; and addition of oxo ligands of nucleophilic oxo complexes to organic ligands on electrophilic metal centers.

  2. Characterization of Anionic Cluster Nucleophilic Substitution Reaction Intermediates

    NASA Astrophysics Data System (ADS)

    Cyr, Donna Marie

    Recent theoretical and experimental developments in the arena of the gas phase S_{rm N}2 reaction (X^- + RY to RX + Y^-) has rekindled interest in this classic chemical reaction. Consideration of the gas phase S_{rm N} 2 double minima potential surface from a valence bond perspective, advocated by Shaik et. al., predicts the presence of a low lying excited electronic state corresponding to electron transfer. In this work we take advantage of long range ion-molecule induced forces to stabilize the S_{rm N}2 reactants in a complex, X^-cdot RY, allowing us to search for this charge transfer excited state from the well defined location on the potential energy surface. Photoelectron spectroscopy of X^ - cdot RY confirms the identification of the species as essentially charge-localized. Vibrational fine structure observed in the case of I^- cdot CH_3I is found to be consistent with small distortions of the CH_3I neutral upon complexation to form a stable intermediate in the S_{rm N}2 identity reaction. A narrow photofragmentation band lies just below the vertical electron detachment energy and is assigned to the X^- cdot RY to X cdotcdot (RY) ^- charge transfer excited state. More detailed study of the photofragmentation band reveals the photoexcitation mechanism is not direct charge transfer but is mediated by a weakly bound negative ion state. The excited state photochemistry of the X ^- cdot RY reaction intermediates is characterized by the formation of the endothermic halide abstraction product XY^-. Trends in the formation of the dihalide product are strongly dependent of the nature of the R group and these results are consistent with a preferential ion binding site in the complex. Search for the XY^- dihalide product in the bimolecular ground state reaction at supra-thermal collision energies revealed halide abstraction as a competitive product channel to the well known Walden inversion mechanism. All of these results are integrated in the development a picture of

  3. Utilizing the σ-complex stability for quantifying reactivity in nucleophilic substitution of aromatic fluorides

    PubMed Central

    Rein, Tobias; Svensson, Mats

    2013-01-01

    Summary A computational approach using density functional theory to compute the energies of the possible σ-complex reaction intermediates, the “σ-complex approach”, has been shown to be very useful in predicting regioselectivity, in electrophilic as well as nucleophilic aromatic substitution. In this article we give a short overview of the background for these investigations and the general requirements for predictive reactivity models for the pharmaceutical industry. We also present new results regarding the reaction rates and regioselectivities in nucleophilic substitution of fluorinated aromatics. They were rationalized by investigating linear correlations between experimental rate constants (k) from the literature with a theoretical quantity, which we call the sigma stability (SS). The SS is the energy change associated with formation of the intermediate σ-complex by attachment of the nucleophile to the aromatic ring. The correlations, which include both neutral (NH3) and anionic (MeO−) nucleophiles are quite satisfactory (r = 0.93 to r = 0.99), and SS is thus useful for quantifying both global (substrate) and local (positional) reactivity in SNAr reactions of fluorinated aromatic substrates. A mechanistic analysis shows that the geometric structure of the σ-complex resembles the rate-limiting transition state and that this provides a rationale for the observed correlations between the SS and the reaction rate. PMID:23766792

  4. Utilizing the σ-complex stability for quantifying reactivity in nucleophilic substitution of aromatic fluorides.

    PubMed

    Liljenberg, Magnus; Brinck, Tore; Rein, Tobias; Svensson, Mats

    2013-01-01

    A computational approach using density functional theory to compute the energies of the possible σ-complex reaction intermediates, the "σ-complex approach", has been shown to be very useful in predicting regioselectivity, in electrophilic as well as nucleophilic aromatic substitution. In this article we give a short overview of the background for these investigations and the general requirements for predictive reactivity models for the pharmaceutical industry. We also present new results regarding the reaction rates and regioselectivities in nucleophilic substitution of fluorinated aromatics. They were rationalized by investigating linear correlations between experimental rate constants (k) from the literature with a theoretical quantity, which we call the sigma stability (SS). The SS is the energy change associated with formation of the intermediate σ-complex by attachment of the nucleophile to the aromatic ring. The correlations, which include both neutral (NH3) and anionic (MeO(-)) nucleophiles are quite satisfactory (r = 0.93 to r = 0.99), and SS is thus useful for quantifying both global (substrate) and local (positional) reactivity in SNAr reactions of fluorinated aromatic substrates. A mechanistic analysis shows that the geometric structure of the σ-complex resembles the rate-limiting transition state and that this provides a rationale for the observed correlations between the SS and the reaction rate.

  5. Highly nucleophilic acetylide, vinyl, and vinylidene complexes

    SciTech Connect

    Not Available

    1991-08-01

    In the past year we have completed our studies of the halide-promoted carbonylation of imido ligands, extended our explorations of Cp(CO)(L)Mn-X complexes which possess highly reactive acetylide, vinylidene, carbyne, and vinylcarbyne ligands, and have briefly investigated the formation of bimetallic complexes using anionic carbene complexes. 5 figs.

  6. Nucleophilic addition/double cyclization cascade processes between enynyl Fischer carbene complexes and alkynyl malonates.

    PubMed

    Álvarez-Fernández, Ana; Suárez-Rodríguez, Tatiana; Suárez-Sobrino, Ángel L

    2014-07-18

    Two new selective cascade processes for enynyl Fischer carbene complexes 1 are described in their reaction with alkynyl malonates. When carbene complexes 1 react with the sodium enolate of homopropargyl malonates 3 a consecutive Michael-type addition/cyclopentannulation/6-exo cyclization takes place leading, in a regio- and stereoselective way, to n/5/6 angular tricyclic compounds 5. Furthermore, when propargylic malonates are used, a delayed protonation of the reaction mixture allows intermediate 1,4-addition adduct Ia to evolve through a 5-exo cyclization, consisting of an intramolecular nucleophilic attack from the central carbon of the allenylmetallate over the triple C-C bond. Further spontaneous cyclopentannulation of the resulting metallatriene gives rise to bicyclic and linear polycyclic compounds 6 and 7, some of them bearing a polyquinane framework.

  7. Highly nucleophilic acetylide, vinyl, and vinylidene complexes. Progress report

    SciTech Connect

    Not Available

    1991-08-01

    In the past year we have completed our studies of the halide-promoted carbonylation of imido ligands, extended our explorations of Cp(CO)(L)Mn-X complexes which possess highly reactive acetylide, vinylidene, carbyne, and vinylcarbyne ligands, and have briefly investigated the formation of bimetallic complexes using anionic carbene complexes. 5 figs.

  8. Structure, bonding, and reactivity of reactant complexes and key intermediates.

    PubMed

    Soriano, Elena; Marco-Contelles, José

    2011-01-01

    Complexes of Pt and Au (gold(III) and cationic gold(I)) have shown an exceptional ability to promote a variety of organic transformations of unsaturated precursors due to their peculiar Lewis acid properties: the alkynophilic character of these soft metals and the π-acid activation of unsaturated groups promotes the intra- or intermolecular attack of a nucleophile. In this chapter we summarize the computational data reported on the structure, bonding, and reactivity of the reactant π-complexes and also on the key intermediate species.

  9. Nucleophilic reactivity and electrocatalytic reduction of halogenated organic compounds by nickel o-phenylenedioxamidate complexes.

    PubMed

    Das, Siva Prasad; Ganguly, Rakesh; Li, Yongxin; Soo, Han Sen

    2016-09-14

    A growing number of halogenated organic compounds have been identified as hazardous pollutants. Although numerous advanced oxidative processes have been developed to degrade organohalide compounds, reductive and nucleophilic molecular approaches to dehalogenate organic compounds have rarely been reported. In this manuscript, we employ nickel(ii)-ate complexes bearing the o-phenylenebis(N-methyloxamide) (Me2opba) tetraanionic ligand as nucleophilic reagents that can react with alkyl halides (methyl up to the bulky isobutyl) by O-alkylation to give their respective imidate products. Four new nickel(ii) complexes have been characterized by X-ray crystallography, and the salient structural parameters and FT-IR vibrational bands (∼1655 cm(-1)) concur with their assignment as the imidate tautomeric form. To the best of our knowledge, this is the first report on the nucleophilic reactivity of Ni(II)(Me2opba) with halogenated organic compounds. The parent nickel(ii) Me2opba complex exhibits reversible electrochemical oxidation and reduction behavior. As a proof of concept, Ni(II)(Me2opba) and its alkylated congeners were utilized for the electrocatalytic reduction of chloroform, as a representative, simple polyhalogenated organic molecule that could arise from the oxidative treatment of organic compounds by chlorination. Modest turnover numbers of up to 6 were recorded, with dichloromethane identified as one of the possible products. Future efforts are directed towards bulkier -ate complexes that possess metal-centered instead of ligand-centered nucleophilic activity to create more effective electrocatalysts for the reduction of halogenated organic compounds.

  10. Predicting regioselectivity in nucleophilic aromatic substitution.

    PubMed

    Liljenberg, Magnus; Brinck, Tore; Herschend, Björn; Rein, Tobias; Tomasi, Simone; Svensson, Mats

    2012-04-06

    We have investigated practical and computationally efficient methods for the quantitative prediction of regioisomer distribution in kinetically controlled nucleophilic aromatic substitution reactions. One of the methods is based on calculating the relative stabilities of the isomeric σ-complex intermediates using DFT. We show that predictions from this method can be used quantitatively both for anionic nucleophiles with F(-) as leaving group, as well as for neutral nucleophiles with HF as leaving group. The σ-complex approach failed when the leaving group was Cl/HCl or Br/HBr, both for anionic and neutral nucleophiles, because of difficulties in finding relevant σ-complex structures. An approach where we assumed a concerted substitution step and used such transition state structures gave quantitatively useful results. Our results are consistent with other theoretical works, where a stable σ-complex has been identified in some cases, whereas others have been indicated to proceed via a concerted substitution step.

  11. Enantioconvergent Nucleophilic Substitution Reaction of Racemic Alkyne-Dicobalt Complex (Nicholas Reaction) Catalyzed by Chiral Brønsted Acid.

    PubMed

    Terada, Masahiro; Ota, Yusuke; Li, Feng; Toda, Yasunori; Kondoh, Azusa

    2016-08-31

    Catalytic enantioselective syntheses enable a practical approach to enantioenriched molecules. While most of these syntheses have been accomplished by reaction at the prochiral sp(2)-hybridized carbon atom, little attention has been paid to enantioselective nucleophilic substitution at the sp(3)-hybridized carbon atom. In particular, substitution at the chiral sp(3)-hybridized carbon atom of racemic electrophiles has been rarely exploited. To establish an unprecedented enantioselective substitution reaction of racemic electrophiles, enantioconvergent Nicholas reaction of an alkyne-dicobalt complex derived from racemic propargylic alcohol was developed using a chiral phosphoric acid catalyst. In the present enantioconvergent process, both enantiomers of the racemic alcohol were transformed efficiently to a variety of thioethers with high enantioselectivity. The key to achieving success is dynamic kinetic asymmetric transformation (DYKAT) of enantiomeric cationic intermediates generated via dehydroxylation of the starting racemic alcohol under the influence of the chiral phosphoric acid catalyst. The present fascinating DYKAT involves the efficient racemization of these enantiomeric intermediates and effective resolution of these enantiomers through utilization of the chiral conjugate base of the phosphoric acid.

  12. Mechanism of phenol oxidation by heterodinuclear Ni Cu bis(μ-oxo) complexes involving nucleophilic oxo groups

    PubMed Central

    Kundu, Subrata; Miceli, Enrico; Farquhar, Erik R.

    2014-01-01

    Oxidation of phenols by heterodinuclear CuIII(μ-O)2NiIII complexes containing nucleophilic oxo groups occurs by both proton coupled electron transfer (PCET) and hydrogen atom transfer (HAT) mechanisms; the exact mechanism depends on the nature of the phenol as well as the substitution pattern of the ligand bound to Cu. PMID:24362244

  13. Catalytic Nucleophilic Fluorination of Secondary and Tertiary Propargylic Electrophiles with a Copper–N-Heterocyclic Carbene Complex

    PubMed Central

    Cheng, Li-Jie; Cordier, Christopher J

    2015-01-01

    A catalytic method for the nucleophilic fluorination of propargylic electrophiles is described. Our protocol involves the use of a Cu(NHC) complex as the catalyst and is suitable for the preparation of secondary and tertiary propargylic fluorides without the formation of isomeric fluoroallenes. Preliminary mechanistic investigations suggest that fluorination proceeds via copper acetylides and that cationic species are involved. PMID:26403935

  14. Long-lived glycosyl-enzyme intermediate mimic produced by formate re-activation of a mutant endoglucanase lacking its catalytic nucleophile.

    PubMed Central

    Viladot, J L; Canals, F; Batllori, X; Planas, A

    2001-01-01

    The mutant E134A 1,3-1,4-beta-glucanase from Bacillus licheniformis, in which the catalytic nucleophilic residue has been removed by mutation to alanine, has its hydrolytic activity rescued by exogenous formate in a concentration-dependent manner. A long-lived alpha-glycosyl formate is detected and identified by (1)H-NMR and matrix-assisted laser desorption ionization-time-of-flight-MS. The intermediate is kinetically competent, since it is, at least partially, enzymically hydrolysed, and able to act as a glycosyl donor in transglycosylation reactions. This transient compound represents a true covalent glycosyl-enzyme intermediate mimic of the proposed covalent intermediate in the reaction mechanism of retaining glycosidases. PMID:11256951

  15. Nucleophilic aromatic substitution for heteroatoms: an oxidative electrochemical approach.

    PubMed

    Gallardo, Iluminada; Guirado, Gonzalo; Marquet, Jordi

    2002-04-19

    The nucleophilic aromatic substitution for heteroatom through electrochemical oxidation of the intermediate sigma-complexes (Meisenheimer complexes) in simple nitroaromatic compounds is reported for the first time (NASX process). The studies have been carried out with hydride, cyanide, fluoride, methoxy, and ethanethiolate anions and n-butylamine as a nucleophile, at the cyclic voltammetry (CV) and preparative electrolysis level. The cyclic voltammetry experiments allow for detection and characterization of the sigma-complexes and they have led us to a proposal for the mechanism of the oxidation step. Furthermore, the power of the CV technique in the analysis of the reaction mixture throughout the whole chemical and electrochemical process is described.

  16. Nucleoprotein complex intermediates in HIV-1 integration

    PubMed Central

    Li, Min; Craigie, Robert

    2012-01-01

    Integration of retroviral DNA into the host genome is an essential step in the viral replication cycle. The viral DNA, made by reverse transcription in the cytoplasm, forms part of a large nucleoprotein complex called the preintegration complex (PIC). The viral integrase protein is the enzyme within the PIC that is responsible for integrating the viral DNA into the host genome. Integrase is tightly associated with the viral DNA within the PIC as demonstrated by functional assays. Integrase protein catalyzes the key DNA cutting and joining steps of integration in vitro with DNA substrates that mimic the ends of the viral DNA. Under most in vitro assay conditions the stringency of the reaction is relaxed; most products result from “half-site” integration in which only one viral DNA end is integrated into one strand of target DNA rather than concerted integration of pairs of DNA as occurs with PICs and in vivo. Under these relaxed conditions catalysis appears to occur without formation of the highly stable nucleoprotein complexes that is characteristic of the association of integrase with viral DNA in the PIC. Here we describe methods for the assembly of nucleoprotein complex intermediates in HIV-1 DNA integration from purified HIV-1 integrase and substrates that mimic the viral DNA ends. PMID:19232539

  17. Highly nucleophilic acetylide, vinyl, and vinylidene complexes. Final progress report, 1 January 1991--31 March 1994

    SciTech Connect

    Geoffroy, G.L.

    1994-10-04

    In the course of this research the authors found that the anionic alkynyl complex [Cp{prime}(CO)(PPh{sub 3})Mn-C{triple_bond}C-CH{sub 3}]{sup {minus}} can be generated in situ by the addition of two equivalents of n-BuLi to a solution of the carbene complex Cp{prime}(CO)(PPh{sub 3})Mn{double_bond}C(OMe)CH{sub 2}CH{sub 3}. It was also found that the highly nucleophilic propynyl complex [Cp(CO)(PPh{sub 3})Mn-C{triple_bond}C-Me]{sup {minus}} reacts with a variety of aldehydes and ketones in the presence of BF{sub 3}{center_dot}Et{sub 2}O to give, after quenching with MeOH, a series of cationic vinylcarbyne complexes of the general form [Cp(CO)(PPh{sub 3})Mn{triple_bond}C-C(Me){double_bond}C(R)(R{prime})]BF{sub 4}. The cationic alkylidyne complexes [Cp(CO){sub 2}M{triple_bond}C-CH{sub 2}R]{sup +} [M = Re, R = H, M = Mn, R = H, Me, Ph] have been found to undergo facile deprotonation to give the corresponding neutral vinylidene complexes Cp(CO){sub 2}M{double_bond}C{double_bond}C(H)R. The authors have also investigated reactions relevant to the halide promoted Fe and Ru catalyzed carbonylation of nitroaromatics. The final part of this work has involved investigations of metal-oxo complexes.

  18. Nucleophilic arylation with tetraarylphosphonium salts

    PubMed Central

    Deng, Zuyong; Lin, Jin-Hong; Xiao, Ji-Chang

    2016-01-01

    Organic phosphonium salts have served as important intermediates in synthetic chemistry. But the use of a substituent on the positive phosphorus as a nucleophile to construct C–C bond remains a significant challenge. Here we report an efficient transition-metal-free protocol for the direct nucleophilic arylation of carbonyls and imines with tetraarylphosphonium salts in the presence of caesium carbonate. The aryl nucleophile generated from phosphonium salt shows low basicity and good nucleophilicity, as evidenced by the successful conversion of enolizable aldehydes and ketones. The reaction is not particularly sensitive to water, shows wide substrate scope, and is compatible with a variety of functional groups including cyano and ester groups. Compared with the arylmetallic reagents that are usually moisture sensitive, the phosphonium salts are shelf-stable and can be easily handled. PMID:26822205

  19. Concerted nucleophilic aromatic substitution with 19F- and 18F-

    NASA Astrophysics Data System (ADS)

    Neumann, Constanze N.; Hooker, Jacob M.; Ritter, Tobias

    2016-06-01

    Nucleophilic aromatic substitution (SNAr) is widely used by organic chemists to functionalize aromatic molecules, and it is the most commonly used method to generate arenes that contain 18F for use in positron-emission tomography (PET) imaging. A wide range of nucleophiles exhibit SNAr reactivity, and the operational simplicity of the reaction means that the transformation can be conducted reliably and on large scales. During SNAr, attack of a nucleophile at a carbon atom bearing a ‘leaving group’ leads to a negatively charged intermediate called a Meisenheimer complex. Only arenes with electron-withdrawing substituents can sufficiently stabilize the resulting build-up of negative charge during Meisenheimer complex formation, limiting the scope of SNAr reactions: the most common SNAr substrates contain strong π-acceptors in the ortho and/or para position(s). Here we present an unusual concerted nucleophilic aromatic substitution reaction (CSNAr) that is not limited to electron-poor arenes, because it does not proceed via a Meisenheimer intermediate. We show a phenol deoxyfluorination reaction for which CSNAr is favoured over a stepwise displacement. Mechanistic insights enabled us to develop a functional-group-tolerant 18F-deoxyfluorination reaction of phenols, which can be used to synthesize 18F-PET probes. Selective 18F introduction, without the need for the common, but cumbersome, azeotropic drying of 18F, can now be accomplished from phenols as starting materials, and provides access to 18F-labelled compounds not accessible through conventional chemistry.

  20. Concerted nucleophilic aromatic substitution with 19F− and 18F−

    PubMed Central

    Neumann, Constanze N.; Hooker, Jacob M.; Ritter, Tobias

    2016-01-01

    Nucleophilic aromatic substitution (SNAr) is widely used by organic chemists to functionalize aromatic molecules, and it is the most commonly used method to generate arenes that contain a 18F for use in PET imaging.1 A wide range of nucleophiles exhibit SNAr reactivity, and the operational simplicity of the reaction means that the transformation can be conducted reliably and on large scales.2 During SNAr, attack of a nucleophile at a carbon atom bearing a ‘leaving group’ leads to a negatively charged intermediate called a Meisenheimer complex. Only arenes with electron-withdrawing substituents can sufficiently stabilize the resulting build-up of negative charge during Meisenheimer complex formation, limiting the scope of SNAr reactions: the most common SNAr substrates contain strong π-acceptors in the ortho and/or para position(s).3 In this manuscript, we present an unusual concerted nucleophilic aromatic substitution reaction (CSNAr) that is not limited to electron-poor arenes, because it does not proceed via a Meisenheimer intermediate. We show a phenol deoxyfluorination reaction for which CSNAr is favored over a stepwise displacement. Mechanistic insights enabled us to develop a functional group–tolerant 18F-deoxyfluorination reaction of phenols, which can be used to synthesize 18F-PET probes. Selective 18F introduction, without the need for the common, but cumbersome, azeotropic drying of 18F, can now be accomplished from phenols as starting materials, and provides access to 18F-labeled compounds not accessible through conventional chemistry. PMID:27281221

  1. Fabricating Complex Culture Substrates Using Robotic Microcontact Printing (R-µCP) and Sequential Nucleophilic Substitution

    PubMed Central

    McNulty, Jason D.; Ashton, Randolph S.

    2014-01-01

    In tissue engineering, it is desirable to exhibit spatial control of tissue morphology and cell fate in culture on the micron scale. Culture substrates presenting grafted poly(ethylene glycol) (PEG) brushes can be used to achieve this task by creating microscale, non-fouling and cell adhesion resistant regions as well as regions where cells participate in biospecific interactions with covalently tethered ligands. To engineer complex tissues using such substrates, it will be necessary to sequentially pattern multiple PEG brushes functionalized to confer differential bioactivities and aligned in microscale orientations that mimic in vivo niches. Microcontact printing (μCP) is a versatile technique to pattern such grafted PEG brushes, but manual μCP cannot be performed with microscale precision. Thus, we combined advanced robotics with soft-lithography techniques and emerging surface chemistry reactions to develop a robotic microcontact printing (R-μCP)-assisted method for fabricating culture substrates with complex, microscale, and highly ordered patterns of PEG brushes presenting orthogonal ‘click’ chemistries. Here, we describe in detail the workflow to manufacture such substrates. PMID:25407245

  2. Fabricating complex culture substrates using robotic microcontact printing (R-µCP) and sequential nucleophilic substitution.

    PubMed

    Knight, Gavin T; Klann, Tyler; McNulty, Jason D; Ashton, Randolph S

    2014-10-31

    In tissue engineering, it is desirable to exhibit spatial control of tissue morphology and cell fate in culture on the micron scale. Culture substrates presenting grafted poly(ethylene glycol) (PEG) brushes can be used to achieve this task by creating microscale, non-fouling and cell adhesion resistant regions as well as regions where cells participate in biospecific interactions with covalently tethered ligands. To engineer complex tissues using such substrates, it will be necessary to sequentially pattern multiple PEG brushes functionalized to confer differential bioactivities and aligned in microscale orientations that mimic in vivo niches. Microcontact printing (μCP) is a versatile technique to pattern such grafted PEG brushes, but manual μCP cannot be performed with microscale precision. Thus, we combined advanced robotics with soft-lithography techniques and emerging surface chemistry reactions to develop a robotic microcontact printing (R-μCP)-assisted method for fabricating culture substrates with complex, microscale, and highly ordered patterns of PEG brushes presenting orthogonal 'click' chemistries. Here, we describe in detail the workflow to manufacture such substrates.

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

    SciTech Connect

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

    1992-11-01

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

  4. Nucleophilic ring opening of bridging thietanes in open triosmium cluster complexes

    SciTech Connect

    Adams, R.D.; Belinski, J.A.

    1992-07-01

    The complexes Os{sub 3}(CO){sub 9}({mu}{sub 3}-S)[{mu}-SCH{sub 2}CMe{sub 2}CMe{sub 2}CH{sub 2}] (1) and Os{sub 3}(CO){sub 9}({mu}{sub 3}-S)[{mu}-SCH{sub 2}CH{sub 2}CH{sub 2}] (2) were obtained from the reactions of Os{sub 3}(CO){sub 10}({mu}{sub 3}-S) with 3,3-dimethylthietane (DMT) and thietane, respectively, at -42 {degree}C in the presence of Me{sub 3}NO. Compound 1 was characterized by a single-crystal X-ray diffraction analysis and was found to contain a DMT group bridging two of the nonbonded metal atoms in the open cluster of three metal atoms by using both lone pairs of electrons on the sulfur atom. Compound 1 reacted with bis(triphenylphosphine)nitrogen(1+) chloride ([PPN]Cl) at 25 {degrees}C to yield the salt [PPN][Os{sub 3}-(CO){sub 9}({mu}-SCH{sub 2}CMe{sub 2}CH{sub 2}Cl)({mu}{sub 3}-S)] (3; 76%), in which the chloride ion was added to one of the methylene groups of the DMT ring in a process that caused the ring to open by cleavage of one of the carbon-sulfur bonds. A 4-chloro-3,3-dimethylpropanethiolate ligand bridges the open edge of the anionic triosmium cluster. Compound 3 was converted to the neutral complex Os{sub 3}(CO){sub 9}[{mu}-SCH{sub 2}CMe{sub 2}CMe{sub 2}CH{sub 2}Cl]({mu}{sub 3}-S)({mu}-H) (4) by reaction with HCl at 25 {degrees}C. Compound 4 is structurally similar to 3, except that is contains a hydride ligand bridging one of the two metal-metal bonds. Compounds 1 and 2 react with HCl in CH{sub 2}Cl{sub 2} solvent to yield the neutral compounds 4 and Os{sub 3}(CO){sub 9}[{mu}-SCH{sub 2}CH{sub 2}CH{sub 2}Cl]({mu}{sub 3}-S)({mu}-H) (5) in 89% and 90% yields, respectively, in one step. 11 refs., 3 figs., 10 tabs.

  5. Nucleophilic attack of hydroxide on a Mn(V) oxo complex: a model of the O-O bond formation in the oxygen evolving complex of photosystem II.

    PubMed

    Gao, Yan; Akermark, Torbjörn; Liu, Jianhui; Sun, Licheng; Akermark, Björn

    2009-07-01

    A manganese(III) corrole complex, 1, has been synthesized and used to study a potential mechanism for oxidation of water to molecular oxygen. Oxidation by t-BuOOH gave the Mn(V)=O complex 2. Addition of hydroxide led to release of oxygen via the Mn(IV) complex 4 and regeneration of complex 1. It could be shown that the oxygen from (18)O-labeled water was incorporated in both the formed molecular oxygen and the peroxy intermediate 4.

  6. PLASIM-GENIE: a new intermediate complexity AOGCM

    NASA Astrophysics Data System (ADS)

    Holden, P. B.; Edwards, N. R.; Fraedrich, K.; Kirk, E.; Lunkeit, F.; Zhu, X.

    2015-12-01

    We describe the development, tuning and climate of PLASIM-GENIE, a new intermediate complexity Atmosphere-Ocean Global Climate Model (AOGCM), built by coupling the Planet Simulator to the GENIE earth system model. PLASIM-GENIE supersedes "GENIE-2", a coupling of GENIE to the Reading IGCM. It has been developed to join the limited number of models that bridge the gap between EMICS with simplified atmospheric dynamics and state of the art AOGCMs. A 1000 year simulation with PLASIM-GENIE requires approximately two weeks on a single node of a 2.1 GHz AMD 6172 CPU. An important motivation for intermediate complexity models is the evaluation of uncertainty. We here demonstrate the tractability of PLASIM-GENIE ensembles by deriving a "subjective" tuning of the model with a 50 member ensemble of 1000 year simulations.

  7. Complexity of the Ibero-Magrhebian region: intermediate depth earthquakes

    NASA Astrophysics Data System (ADS)

    Buforn, Elisa; Cesca, Simone; Del Fresno, Carmen; Udias, Agustin

    2010-05-01

    Complexity of the Ibero-Magrhebian region: intermediate depth earthquakes Buforn E. (1), Cesca S.(2), del Fresno C.(3), Udías, A. (1) (1) Dpt. Geofísica y Meteorología. Universidad Complutense, Madrid (Spain (2) Institute of Geophysics, University of Hamburg, Germany (3) Instituto Geográfico Nacional, Madrid (Spain) The Ibero-Magrhebian region is located at the plate boundary between Eurasia and Africa and it is a tectonically complex region. A sign of the complexity, is the occurrence of intermediate depth earthquakes (40Intermediate depth shocks are mostly confined within a relatively narrow region (50 km width) located East of Gibraltar, extending NNE-SSW from the Malaga (Spain) area to a region offshore the Moroccan coast. The moderate magnitude of the intermediate depth events (less than 5.5), the heterogeneity of the crustal structure in the region, and the strong influence of microseismic noise on seismic data represent significant challenges for the inversion of focal mechanism based on waveform modelling. We have estimated the focal mechanisms of 9 intermediate depth earthquakes (Mw 3.3 to 4.5) occurred in the period 2002-2009 from moment tensor inversion of broad-band data at regional distances, using the recently developed Kiwi tools. Moment tensor inversion is carried out by fitting body waves amplitude spectra, solving for strike, dip, rake, scalar moment and improving the original hypocentral depth. For each earthquake, we carry out a set of inversions, comparing results using different station subsets, seismic phases and earth models. The new obtained results, together with other selected solutions estimated previously using different methods, show a change on the stress pattern: to the west of 4.5°W, focal mechanisms show vertical tension axis, while to the east

  8. Carbonylmetallates--A Special Family of Nucleophiles in Aromatic and Vinylic Substitution Reactions.

    PubMed

    Sazonov, Petr K; Beletskaya, Irina P

    2016-03-07

    Carbonylmetallates, [M(CO)(n)L](-), anionic transition-metal carbonyl complexes, represent a large family of metal-centered nucleophiles, and studying carbonylmetallates allows us to understand the differences in the behavior of the metal-centered complexes versus heteroatom-based nucleophiles. The mechanisms of carbonylmetallate reactions with aryl- and alkenyl halides have been examined by employing radical and, especially, carbanion trapping techniques. Carbonylmetallates show a marked preference for halogenophilic attack, and nucleophilic substitution with carbonylmetallates is often not a direct process, but proceeds through the initial attack at halogen with subsequent coupling of carbanion and HalM(CO)(n)L intermediates. Factors governing the competition between the halogenophilic and more common "carbophilic" reaction pathways, as well as the means of predicting the actual course of reaction are discussed. The review also considers other aspects of carbonylmetallate reactivity, including ion-pairing effects, radical-mediated nucleophilic substitution pathways, and the carbonylmetallate nucleophilicity scale in the reactions with π-electrophiles.

  9. Nucleophilic Aromatic Substitution.

    ERIC Educational Resources Information Center

    Avila, Walter B.; And Others

    1990-01-01

    Described is a microscale organic chemistry experiment which demonstrates one feasible route in preparing ortho-substituted benzoic acids and provides an example of nucleophilic aromatic substitution chemistry. Experimental procedures and instructor notes for this activity are provided. (CW)

  10. Lithium-stabilized nucleophilic addition of thiamin to a ketone provides an efficient route to mandelylthiamin, a critical pre-decarboxylation intermediate.

    PubMed

    Bielecki, Michael; Howe, Graeme W; Kluger, Ronald

    2015-10-01

    Mandelylthiamin (MTh) is an accurate model of the covalent intermediate derived from the condensation of thiamin diphosphate and benzoylformate in benzoylformate decarboxylase. The properties and catalytic susceptibilities of mandelylthiamin are the subjects of considerable interest. However, the existing synthesis gives only trace amounts of the precursor to MTh as it is conducted under reversible conditions. An improved approach derives from the unique ability of lithium ions to drive to completion the otherwise unfavorable condensation of the conjugate base of thiamin and methyl benzoylformate. The unique efficiency of the condensation reaction in the presence of lithium ions is established in contrast to the effects of other Lewis acids. Interpretation of the pattern of the results indicates that the condensation of the ketone and thiamin is thermodynamically controlled. It is proposed that the addition of lithium ions displaces the equilibrium toward the product through formation of a stable lithium-alkoxide.

  11. Oxygen-Atom Transfer Reactivity of Axially Ligated Mn(V)–Oxo Complexes: Evidence for Enhanced Electrophilic and Nucleophilic Pathways

    PubMed Central

    2015-01-01

    Addition of anionic donors to the manganese(V)–oxo corrolazine complex MnV(O)(TBP8Cz) has a dramatic influence on oxygen-atom transfer (OAT) reactivity with thioether substrates. The six-coordinate anionic [MnV(O)(TBP8Cz)(X)]− complexes (X = F–, N3–, OCN–) exhibit a ∼5 cm–1 downshift of the Mn–O vibrational mode relative to the parent MnV(O)(TBP8Cz) complex as seen by resonance Raman spectroscopy. Product analysis shows that the oxidation of thioether substrates gives sulfoxide product, consistent with single OAT. A wide range of OAT reactivity is seen for the different axial ligands, with the following trend determined from a comparison of their second-order rate constants for sulfoxidation: five-coordinate ≈ thiocyanate ≈ nitrate < cyanate < azide < fluoride ≪ cyanide. This trend correlates with DFT calculations on the binding of the axial donors to the parent MnV(O)(TBP8Cz) complex. A Hammett study was performed with p-X-C6H4SCH3 derivatives and [MnV(O)(TBP8Cz)(X)]− (X = CN– or F–) as the oxidant, and unusual “V-shaped” Hammett plots were obtained. These results are rationalized based upon a change in mechanism that hinges on the ability of the [MnV(O)(TBP8Cz)(X)]− complexes to function as either an electrophilic or weak nucleophilic oxidant depending upon the nature of the para-X substituents. For comparison, the one-electron-oxidized cationic MnV(O)(TBP8Cz•+) complex yielded a linear Hammett relationship for all substrates (ρ = −1.40), consistent with a straightforward electrophilic mechanism. This study provides new, fundamental insights regarding the influence of axial donors on high-valent MnV(O) porphyrinoid complexes. PMID:25238495

  12. Troposphere-lower-stratosphere connection in an intermediate complexity model.

    NASA Astrophysics Data System (ADS)

    Ruggieri, Paolo; King, Martin; Kucharski, Fred; Buizza, Roberto; Visconti, Guido

    2016-04-01

    The dynamical coupling between the troposphere and the lower stratosphere has been investigated using a low-top, intermediate complexity model provided by the Abdus Salam International Centre for Theoretical Physics (SPEEDY). The key question that we wanted to address is whether a simple model like SPEEDY can be used to understand troposphere-stratosphere interactions, e.g. forced by changes of sea-ice concentration in polar arctic regions. Three sets of experiments have been performed. Firstly, a potential vorticity perspective has been applied to understand the wave-like forcing of the troposphere on the stratosphere and to provide quantitative information on the sub seasonal variability of the coupling. Then, the zonally asymmetric, near-surface response to a lower-stratospheric forcing has been analysed in a set of forced experiments with an artificial heating imposed in the extra-tropical lower stratosphere. Finally, the lower-stratosphere response sensitivity to tropospheric initial conditions has been examined. Results indicate how SPEEDY captures the physics of the troposphere-stratosphere connection but also show the lack of stratospheric variability. Results also suggest that intermediate-complexity models such as SPEEDY could be used to investigate the effects that surface forcing (e.g. due to sea-ice concentration changes) have on the troposphere and the lower stratosphere.

  13. Characterizing global evolutions of complex systems via intermediate network representations

    NASA Astrophysics Data System (ADS)

    Iwayama, Koji; Hirata, Yoshito; Takahashi, Kohske; Watanabe, Katsumi; Aihara, Kazuyuki; Suzuki, Hideyuki

    2012-05-01

    Recent developments in measurement techniques have enabled us to observe the time series of many components simultaneously. Thus, it is important to understand not only the dynamics of individual time series but also their interactions. Although there are many methods for analysing the interaction between two or more time series, there are very few methods that describe global changes of the interactions over time. Here, we propose an approach to visualise time evolution for the global changes of the interactions in complex systems. This approach consists of two steps. In the first step, we construct a meta-time series of networks. In the second step, we analyse and visualise this meta-time series by using distance and recurrence plots. Our two-step approach involving intermediate network representations elucidates the half-a-day periodicity of foreign exchange markets and a singular functional network in the brain related to perceptual alternations.

  14. Theoretical exploration of the mechanism of riboflavin formation from 6,7-dimethyl-8-ribityllumazine: nucleophilic catalysis, hydride transfer, hydrogen atom transfer, or nucleophilic addition?

    PubMed

    Breugst, Martin; Eschenmoser, Albert; Houk, K N

    2013-05-01

    The cofactor riboflavin is biochemically synthesized by a constitutionally intricate process in which two molecules of 6,7-dimethyl-8-ribityllumazine react with each other to form one molecule of the cofactor and one molecule of 5-amino-6-(ribitylamino)uracil. Remarkably, this complex molecular transformation also proceeds non-enzymatically in boiling aqueous solution at pH 7.3. Four different mechanistic pathways for this transformation (nucleophilic catalysis, hydride transfer, hydrogen atom transfer, and a nucleophilic addition mechanism) have now been analyzed by density functional theory [M06-2X/def2-TZVPP/CPCM//M06-2X/6-31+G(d,p)/IEFPCM]. On the basis of these computational results, a so far unpublished nucleophilic addition mechanism is the lowest energy pathway yielding riboflavin. The previously proposed mechanism involving nucleophilic catalysis is higher in energy but is still a viable alternative for an enzyme-catalyzed process assisted by suitably positioned catalytic groups. Pathways involving the transfer of a hydride ion or of a hydrogen atom are predicted to proceed through higher energy transition states and intermediates.

  15. Intramolecular nucleophilic activation promoting efficient hydrolytic cleavage of DNA by (aqua)bis(dipyridoquinoxaline)copper(II) complex.

    PubMed

    Dhar, Shanta; Reddy, Pattubala A N; Chakravarty, Akhil R

    2004-03-07

    The axial aqua bound copper(II) complex [Cu(dpq)2(H2O)](ClO4)2, having a planar NN-donor heterocyclic base dipyridoquinoxaline (dpq) as the DNA minor groove binder, shows efficient hydrolytic cleavage of supercoiled DNA in the dark and in the absence of any external reagents, as evidenced from T4 ligase experiments, with a rate of 5.58 +/- 0.4 h(-1) and a rate enhancement of 1.55 x 10(8).

  16. Mechanism of Oxidative Amidation of Nitroalkanes with Oxygen and Amine Nucleophiles by Using Electrophilic Iodine.

    PubMed

    Li, Jing; Lear, Martin J; Kwon, Eunsang; Hayashi, Yujiro

    2016-04-11

    Recently, we developed a direct method to oxidatively convert primary nitroalkanes into amides that entailed mixing an iodonium source with an amine, base, and oxygen. Herein, we systematically investigated the mechanism and likely intermediates of such methods. We conclude that an amine-iodonium complex first forms through N-halogen bonding. This complex reacts with aci-nitronates to give both α-iodo- and α,α-diiodonitroalkanes, which can act as alternative sources of electrophilic iodine and also generate an extra equimolar amount of I(+) under O2. In particular, evidence supports α,α-diiodonitroalkane intermediates reacting with molecular oxygen to form a peroxy adduct; alternatively, these tetrahedral intermediates rearrange anaerobically to form a cleavable nitrite ester. In either case, activated esters are proposed to form that eventually reacts with nucleophilic amines in a traditional fashion.

  17. Purification of Restriction Fragments Containing Replication Intermediates from Complex Genomes

    PubMed Central

    Mesner, Larry D.; Dijkwel, Pieter A.; Hamlin, Joyce L.

    2010-01-01

    In order to perform 2-D gel analyses on restriction fragments from higher eukaryotic genomes, it is necessary to remove most of the linear, non-replicating, fragments from the starting DNA preparation. This is because the replication intermediates in a single-copy locus constitute such a minute fraction of all of the restriction fragments in a standard DNA preparation - whether isolated from synchronized or asynchronous cultures. Furthermore, the very long linear DNA strands that characterize higher eukaryotic genomes are inordinately subject to branch migration and shear. We have developed a method that results in significant enrichment of replicating fragments that largely maintain their branched intermediates. The method depends upon two important factors: 1) replicating fragments in higher eukaryotic nuclei appear to be attached to the nuclear matrix in a supercoiled fashion, and 2) partially single-stranded fragments (e.g., those containing replication forks) are selectively adsorbed to BND-cellulose in high salt concentrations. By combining matrix-enrichment and BND-cellulose chromatography, it is possible to obtain preparations that are enriched 200–300-fold over the starting genomic DNA, and are thus suitable for analysis on 2-D gels. PMID:19563104

  18. Nucleophilic Substitution by Benzodithioate Anions.

    ERIC Educational Resources Information Center

    Bonnans-Plaisance, Chantal; Gressier, Jean-Claude

    1988-01-01

    Describes a two-session experiment designed to provide a good illustration of, and to improve student knowledge of, the Grignard reaction and nucleophilic substitution. Discusses the procedure, experimental considerations, and conclusion of this experiment. (CW)

  19. Polybenzimidazoles Via Aromatic Nucleophilic Displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W.; Hergenrother, Paul M.; Smith, Joseph G.

    1994-01-01

    Soluble polybenzimidazoles (PBI's) synthesized by nucleophilic displacement reaction of di(hydroxyphenyl)-benzimidazole monomers with activated aromatic difluoride compounds in presence of anhydrous potassium carbonate. These polymers exhibit good thermal, thermo-oxidative, and chemical stability, and high mechanical properties. Using benzimidazole monomers, more economical, and new PBI's processed more easily than commercial PBI, without loss of desirable physical properties.

  20. Chiral phosphines in nucleophilic organocatalysis

    PubMed Central

    Xiao, Yumei; Sun, Zhanhu

    2014-01-01

    Summary This review discusses the tertiary phosphines possessing various chiral skeletons that have been used in asymmetric nucleophilic organocatalytic reactions, including annulations of allenes, alkynes, and Morita–Baylis–Hillman (MBH) acetates, carbonates, and ketenes with activated alkenes and imines, allylic substitutions of MBH acetates and carbonates, Michael additions, γ-umpolung additions, and acylations of alcohols. PMID:25246969

  1. Nucleophilic Aromatic Substitution Between Halogenated Benzene Dopants and Nucleophiles in Atmospheric Pressure Photoionization.

    PubMed

    Kauppila, Tiina J; Haack, Alexander; Kroll, Kai; Kersten, Hendrik; Benter, Thorsten

    2016-03-01

    In a preceding work with dopant assisted-atmospheric pressure photoionization (DA-APPI), an abundant ion at [M + 77](+) was observed in the spectra of pyridine and quinoline with chlorobenzene dopant. This contribution aims to reveal the identity and route of formation of this species, and to systematically investigate structurally related analytes and dopants. Compounds containing N-, O-, and S-lone pairs were investigated with APPI in the presence of fluoro-, chloro-, bromo-, and iodobenzene dopants. Computational calculations on a density functional theory (DFT) level were carried out to study the reaction mechanism for pyridine and the different halobenzenes. The experimental and computational results indicated that the [M + 77](+) ion was formed by nucleophilic aromatic ipso-substitution between the halobenzene radical cation and nucleophilic analytes. The reaction was most efficient for N-heteroaromatic compounds, and it was weakened by sterical effects and enhanced by resonance stabilization. The reaction was most efficient with chloro-, bromo-, and iodobenzenes, whereas with fluorobenzene the reaction was scarcely observed. The calculated Gibbs free energies for the reaction between pyridine and the halobenzenes were shown to increase in the order I < Br < Cl < F. The reaction was found endergonic for fluorobenzene due to the strong C-F bonding, and exergonic for the other halobenzenes. For fluoro- and chlorobenzenes the reaction was shown to proceed through an intermediate state corresponding to [M + dopant](+), which was highly stable for fluorobenzene. For the bulkier bromine and iodine, this intermediate did not exist, but the halogens were shown to detach already during the approach by the nucleophile.

  2. A Substrate-Assisted Mechanism of Nucleophile Activation in a Ser-His-Asp Containing C-C Bond Hydrolase

    SciTech Connect

    Ruzzini, Antonio C.; Bhowmik, Shiva; Ghosh, Subhangi; Yam, Katherine C.; Bolin, Jeffrey T.; Eltis, Lindsay D.

    2013-11-12

    The meta-cleavage product (MCP) hydrolases utilize a Ser–His–Asp triad to hydrolyze a carbon–carbon bond. Hydrolysis of the MCP substrate has been proposed to proceed via an enol-to-keto tautomerization followed by a nucleophilic mechanism of catalysis. Ketonization involves an intermediate, ESred, which possesses a remarkable bathochromically shifted absorption spectrum. We investigated the catalytic mechanism of the MCP hydrolases using DxnB2 from Sphingomonas wittichii RW1. Pre-steady-state kinetic and LC ESI/MS evaluation of the DxnB2-mediated hydrolysis of 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoic acid to 2-hydroxy-2,4-pentadienoic acid and benzoate support a nucleophilic mechanism catalysis. In DxnB2, the rate of ESred decay and product formation showed a solvent kinetic isotope effect of 2.5, indicating that a proton transfer reaction, assigned here to substrate ketonization, limits the rate of acylation. For a series of substituted MCPs, this rate was linearly dependent on MCP pKa2nuc ~ 1). Structural characterization of DxnB2 S105A:MCP complexes revealed that the catalytic histidine is displaced upon substrate-binding. The results provide evidence for enzyme-catalyzed ketonization in which the catalytic His–Asp pair does not play an essential role. The data further suggest that ESred represents a dianionic intermediate that acts as a general base to activate the serine nucleophile. This substrate-assisted mechanism of nucleophilic catalysis distinguishes MCP hydrolases from other serine hydrolases.

  3. Nucleophilic fluorination of aromatic compounds

    SciTech Connect

    Satyamurthy, Nagichettiar; Barrio, Jorge R

    2014-03-18

    Iodylbenzene derivatives substituted with electron donating as well as electron withdrawing groups on the aromatic ring are used as precursors in aromatic nucleophilic substitution reactions. The iodyl group (IO.sub.2) is regiospecifically substituted by nucleophilic fluoride to provide the corresponding fluoroaryl derivatives. No-carrier-added [F-18]fluoride ion derived from anhydrous [F-18](F/Kryptofix, [F-18]CsF or a quaternary ammonium fluoride (e.g., Me.sub.4NF, Et.sub.4NF, n-Bu.sub.4NF, (PhCH.sub.2).sub.4NF) exclusively substitutes the iodyl moiety in these derivatives and provides high specific activity F-18 labeled fluoroaryl analogs. Iodyl derivatives of a benzothiazole analog and 6-iodyl-L-dopa derivatives have been synthesized as precursors and have been used in the preparation of no-carrier-added [F-18]fluorobenzothiazole as well as 6-[F-18]fluoro-L-dopa.

  4. Polybenzimidazole via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Joseph G. (Inventor)

    1994-01-01

    Di(hydroxyphenyl)benzimidazole monomers were prepared from phenyl-4-hydroxybenzoate and aromatic bis(o-diamine)s. These monomers were used in the synthesis of soluble polybenzimidazoles. The reaction involved the aromatic nucleophilic displacement of various di(hydroxyphenyl)benzimidazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds in the presence of an alkali metal base. These polymers exhibited lower glass transition temperatures, improved solubility, and better compression moldability over their commercial counterparts.

  5. Polyphenylquinoxalines via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M. (Inventor); Connell, John W. (Inventor)

    1990-01-01

    Polyphenylquinoxalines are prepared by the nucleophilic displacement reaction of di(hydroxyphenyl)quinoxaline monomers with activated aromatic dihalides or dinitro compounds. The reactions are carried out in polar aprotic solvents using alkali metal bases at elevated temperatures under nitrogen. The di(hydroxyphenyl)quinoxaline monomers are prepared either by reacting stoichiometric quantities of aromatic bis(o-diamines) with a hydroxybenzil or by reacting o-phenylenediamine with a dihydroxybenzil or bis(hydroxyphenylglyoxylyl)benzene.

  6. Polyphenylquinoxalines via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M. (Inventor); Connell, John W. (Inventor)

    1991-01-01

    Polyphenylquinoxalines are prepared by the nucleophilic displacement reaction of di(hydroxyphenyl)quinoxaline monomers with activated aromatic dihalides or dinitro compounds. The reactions are carried out in polar aprotic solvents during alkali metal bases at elevated temperatures under nitrogen. The di(hydroxyphenyl)quinoxaline monomers are prepared either by reacting stoichiometric quantities of aromatic bis(o-diamines) with a hydroxybenzil or by reacting o-phenylenediamine with a dihydroxybenzil or bis(hydroxyphenylglyoxylyl)benzene.

  7. Palladium and platinum complexes of tellurium-containing imidodiphosphinate ligands: nucleophilic attack of Li[(P(i)Pr2)(TeP(i)Pr2)N] on coordinated 1,5-cyclooctadiene.

    PubMed

    Robertson, Stuart D; Ritch, Jamie S; Chivers, Tristram

    2009-10-28

    Homoleptic group 10 complexes of ditellurido PNP (PNP = imidodiphosphinate), heterodichalcogenido PNP and monotellurido PNP ligands, M[(TeP(i)Pr2)2N]2 (1: M = Pd; 2: M = Pt), M[(EP(i)Pr2)(TeP(i)Pr2)N]2 (3: M = Pd, E = Se; 4: M = Pt, E = Se; 5: M = Pd, E = S; 6: M = Pt, E = S) and M[(P(i)Pr2)(TeP(i)Pr2)N]2 (7: M = Pd; 8: M = Pt), respectively, were prepared by metathesis between alkali-metal derivatives of the appropriate ligand and MCl2(COD) in THF. Complexes 1-8 were characterised in solution by multinuclear (31P, 77Se, 125Te and 195Pt) NMR spectroscopy and, in the case of 1, 2, trans-7, cis-7 and trans-8, in the solid state by X-ray crystallography. The square-planar complexes 3-6 are formed as a mixture of cis- and trans-isomers on the basis of NMR data. The cis and trans isomers of 7 were separated by crystallisation from different solvents. In addition to trans-8, the reaction of Li[(P(i)Pr2)(TeP(i)Pr2)N] with MCl2(COD) produced the heteroleptic complex Pt[(P(i)Pr2)(TeP(i)Pr2)N][sigma:eta2-C8H12(P(i)Pr2NP(i)Pr2Te)] (9) resulting from nucleophilic attack on coordinated 1,5-cyclooctadiene. Complex 9 was identified by multinuclear (13C, 31P, 125Te and 195Pt) NMR spectroscopy, which revealed a mixture of geometric isomers, and by X-ray crystallography.

  8. The active site sulfenic acid ligand in nitrile hydratases can function as a nucleophile.

    PubMed

    Martinez, Salette; Wu, Rui; Sanishvili, Ruslan; Liu, Dali; Holz, Richard

    2014-01-29

    Nitrile hydratase (NHase) catalyzes the hydration of nitriles to their corresponding commercially valuable amides at ambient temperatures and physiological pH. Several reaction mechanisms have been proposed for NHase enzymes; however, the source of the nucleophile remains a mystery. Boronic acids have been shown to be potent inhibitors of numerous hydrolytic enzymes due to the open shell of boron, which allows it to expand from a trigonal planar (sp(2)) form to a tetrahedral form (sp(3)). Therefore, we examined the inhibition of the Co-type NHase from Pseudonocardia thermophila JCM 3095 (PtNHase) by boronic acids via kinetics and X-ray crystallography. Both 1-butaneboronic acid (BuBA) and phenylboronic acid (PBA) function as potent competitive inhibitors of PtNHase. X-ray crystal structures for BuBA and PBA complexed to PtNHase were solved and refined at 1.5, 1.6, and 1.2 Å resolution. The resulting PtNHase-boronic acid complexes represent a "snapshot" of reaction intermediates and implicate the cysteine-sulfenic acid ligand as the catalytic nucleophile, a heretofore unknown role for the αCys(113)-OH sulfenic acid ligand. Based on these data, a new mechanism of action for the hydration of nitriles by NHase is presented.

  9. A cloud feedback emulator (CFE, version 1.0) for an intermediate complexity model

    NASA Astrophysics Data System (ADS)

    Ullman, David J.; Schmittner, Andreas

    2017-02-01

    The dominant source of inter-model differences in comprehensive global climate models (GCMs) are cloud radiative effects on Earth's energy budget. Intermediate complexity models, while able to run more efficiently, often lack cloud feedbacks. Here, we describe and evaluate a method for applying GCM-derived shortwave and longwave cloud feedbacks from 4 × CO2 and Last Glacial Maximum experiments to the University of Victoria Earth System Climate Model. The method generally captures the spread in top-of-the-atmosphere radiative feedbacks between the original GCMs, which impacts the magnitude and spatial distribution of surface temperature changes and climate sensitivity. These results suggest that the method is suitable to incorporate multi-model cloud feedback uncertainties in ensemble simulations with a single intermediate complexity model.

  10. Crystal Structures of EF-G-Ribosome Complexes Trapped in Intermediate States of Translocation

    SciTech Connect

    Zhou, Jie; Lancaster, Laura; Donohue, John Paul; Noller, Harry F.

    2013-11-12

    Translocation of messenger and transfer RNA (mRNA and tRNA) through the ribosome is a crucial step in protein synthesis, whose mechanism is not yet understood. The crystal structures of three Thermus ribosome-tRNA-mRNA–EF-G complexes trapped with β,γ-imidoguanosine 5'-triphosphate (GDPNP) or fusidic acid reveal conformational changes occurring during intermediate states of translocation, including large-scale rotation of the 30S subunit head and body. In all complexes, the tRNA acceptor ends occupy the 50S subunit E site, while their anticodon stem loops move with the head of the 30S subunit to positions between the P and E sites, forming chimeric intermediate states. Two universally conserved bases of 16S ribosomal RNA that intercalate between bases of the mRNA may act as “pawls” of a translocational ratchet. These findings provide new insights into the molecular mechanism of ribosomal translocation.

  11. Intermediate-Valence Tautomerism in Decamethylytterbocene Complexes of Methyl-Substituted Bipyridines

    SciTech Connect

    Booth, Corwin H.; Kazhdan, Daniel; Werkema, Evan L.; Walter, Marc D.; Lukens, Wayne W.; Bauer, Eric D.; Hu, Yung-Jin; Maron, Laurent; Eisenstein, Odile; Head-Gordon, Martin; Andersen, Richard A.

    2011-01-25

    Multiconfigurational, intermediate valent ground states are established in several methyl-substituted bipyridine complexes of bispentamethylcyclopentadienylytterbium, Cp*{sub 2} Yb(Me{sub x}-bipy). In contrast to Cp*{sub 2} Yb(bipy) and other substituted-bipy complexes, the nature of both the ground state and the first excited state are altered by changing the position of the methyl or dimethyl substitutions on the bipyridine rings. In particular, certain substitutions result in multiconfigurational, intermediate valent open-shell singlet states in both the ground state and the first excited state. These conclusions are reached after consideration of single-crystal x-ray diffraction (XRD), the temperature dependence of x-ray absorption near-edge structure (XANES), extended x-ray absorption fine-structure (EXAFS), and magnetic susceptibility data, and are supported by CASSCF-MP2 calculations. These results place the various Cp*{sub 2}Yb(bipy) complexes in a new tautomeric class, that is, intermediate-valence tautomers.

  12. Spectroscopic characterization of the complex between water and the simplest Criegee intermediate CH2OO.

    PubMed

    Nakajima, Masakazu; Endo, Yasuki

    2014-04-07

    The hydrogen-bonded complex between water and the simplest Criegee intermediate CH2OO was detected by Fourier-transform microwave spectroscopy under a jet-cooled condition. Both a-type and b-type rotational transitions were observed for H2O-CH2OO and D2O-CH2OO. The determined rotational constants enable us to conclude that the complex has an almost planar ring structure with the terminal oxygen atom of CH2OO being a strong proton acceptor.

  13. Spectroscopic characterization of the complex between water and the simplest Criegee intermediate CH2OO

    NASA Astrophysics Data System (ADS)

    Nakajima, Masakazu; Endo, Yasuki

    2014-04-01

    The hydrogen-bonded complex between water and the simplest Criegee intermediate CH2OO was detected by Fourier-transform microwave spectroscopy under a jet-cooled condition. Both a-type and b-type rotational transitions were observed for H2O-CH2OO and D2O-CH2OO. The determined rotational constants enable us to conclude that the complex has an almost planar ring structure with the terminal oxygen atom of CH2OO being a strong proton acceptor.

  14. Unprecedented Carbonato Intermediates in Cyclic Carbonate Synthesis Catalysed by Bimetallic Aluminium(Salen) Complexes.

    PubMed

    Castro-Osma, José A; North, Michael; Offermans, Willem K; Leitner, Walter; Müller, Thomas E

    2016-04-21

    The mechanism by which [Al(salen)]2 O complexes catalyse the synthesis of cyclic carbonates from epoxides and carbon dioxide in the absence of a halide cocatalyst has been investigated. Density functional theory (DFT) studies, mass spectrometry and (1) H NMR, (13) C NMR and infrared spectroscopies provide evidence for the formation of an unprecedented carbonato bridged bimetallic aluminium complex which is shown to be a key intermediate for the halide-free synthesis of cyclic carbonates from epoxides and carbon dioxide. Deuterated and enantiomerically-pure epoxides were used to study the reaction pathway. Based on the experimental and theoretical results, a catalytic cycle is proposed.

  15. Regioselective nucleophilic addition of triphenylphosphine to the nitrosylruthenium alkynyl complexes having a hydrotris(pyrazol-1-yl)borate: formation of phosphonio-alkenyl, alkynyl, and allenyl species.

    PubMed

    Nishimura, Yoshimasa; Arikawa, Yasuhiro; Inoue, Takanori; Onishi, Masayoshi

    2005-03-07

    A nitrosylruthenium alkynyl complex of TpRuCl(C[triple bond]CPh)(NO)(1a) was reacted with PPh3 in the presence of HBF4.Et2O at room temperature to give a beta-phosphonio-alkenyl complex (E)-[TpRuCl{CH=C(PPh3)Ph}(NO)]BF4(2.BF4). On the other hand, for gamma-hydroxyalkynyl complexes TpRuCl{C[triple bond]CC(R)2OH}(NO)(R = Me (1b), Ph (1c), H (1d)), similar treatments with PPh3 were found to give gamma-phosphonio-alkynyl [TpRuCl{C[triple bond]CC(Me)2PPh3}(NO)]BF4(3.BF4),alpha-phosphonio-allenyl [TpRuCl{C(PPh3)=C=CPh2}(NO)]BF4(4.BF4), and a novel product of gamma-hydroxy-beta-phosphonio-alkenyl (E)-[TpRuCl{CH=C(PPh3)CH2OH}(NO)]BF4(5.BF4), respectively. Dominant factors for the selectivity in affording 3-5 were associated with the steric congestion and electronic properties at the gamma-carbons, along with those around the metal fragment. From the bis(alkynyl) complex TpRu(C[triple bond]CPh)2(NO)6, a bis(beta-phosphonio-alkenyl)(E,E)-[TpRu{CH=C(PPh3)Ph}2(NO)](BF4)2{7.(BF4)2} was produced at room temperature. However, similar reactions at 0 degrees C gave an alkynyl beta-phosphonio-alkenyl complex (E)-[TpRu(C[triple bondCPh){CH=C(PPh3)Ph}(NO)]BF4(8.BF4) as a sole product, of which additional hydration in the presence of HBF4.Et2O afforded a [small beta]-phosphonio-alkenyl ketonyl (E)-[TpRu{CH2C(O)Ph}{CH=C(PPh3)Ph}(NO)]BF(.9BF4). Five complexes, 2-5 and 7 were crystallographically characterized.

  16. Polyphenylquinoxalines via Aromatic Nucleophilic Displacement

    NASA Technical Reports Server (NTRS)

    Hergenrother, Paul M.; Connell, John W.

    1988-01-01

    Polyphenylquinoxalines are produced by an aromatic nucleophilic displacement reaction involving an activated aromatic dihalide with an appropriate quinoxaline monomer. Polyphenylquinoxalines are high temperature thermoplastics used as adhesives, coatings, films and composite matrices. The novelty of this invention is threefold: (1) some of the quinoxaline monomers are new compositions of matter; (2) the phenylquinoxaline polymers which are the end products of the invention are new compositions of matter; and (3) the method of forming the polymers is novel, replacing a more costly prior art process, which is also limited in the kinds of products prepared therefrom.

  17. Controlling the ambiphilic nature of σ-arylpalladium intermediates in intramolecular cyclization reactions.

    PubMed

    Solé, Daniel; Fernández, Israel

    2014-01-21

    The reactivity of main group organometallics, such as organolithium compounds (RLi) and Grignard reagents (RMgX), is quite straightforward. In these species the R group usually exhibits nucleophilic reactivity without any possibility of inducing electrophilic character. In contrast, in organopalladium complexes, researchers can switch the reactivity from electrophilic to nucleophilic relatively simply. Although σ-aryl and σ-vinylpalladium complexes are commonly used as electrophiles in C-C bond-forming reactions, recent research has demonstrated that they can also react with carbon-heteroatom multiple bonds in a nucleophilic manner. Nevertheless, researchers have completely ignored the issue of controlling the ambiphilic nature of such species. This Account describes our efforts toward selectively promoting the same starting materials toward either electrophilic α-arylation or nucleophilic addition reactions to different carbonyl groups. We could tune the properties of the σ-arylpalladium intermediates derived from amino-tethered aryl halides and carbonyl compounds to achieve chemoselective transformations. Therefore, chemists can control the ambiphilic nature of such intermediates and, consequently, the competition between the alternative reaction pathways by the adequate selection of the reaction conditions and additives (base, presence/absence of phenol, bidentate phosphines). The nature of the carbonyl group (aldehydes, ketones, esters, and amides) and the length of the tether connecting it to the aniline moiety also play an important role in the outcome of these processes. Our joint computational and experimental efforts to elucidate the reaction mechanism of these palladium-catalyzed transformations suggest that beyond the formation of the four-membered azapalladacycle, two major factors help to control the dual character of the palladium(II) intermediates derived from 2-haloanilines. First, their high nucleophilicity strongly modifies the interaction of

  18. Developing mononuclear copper-active-oxygen complexes relevant to reactive intermediates of biological oxidation reactions.

    PubMed

    Itoh, Shinobu

    2015-07-21

    Active-oxygen species generated on a copper complex play vital roles in several biological and chemical oxidation reactions. Recent attention has been focused on the reactive intermediates generated at the mononuclear copper active sites of copper monooxygenases such as dopamine β-monooxygenase (DβM), tyramine β-monooxygenase (TβM), peptidylglycine-α-hydroxylating monooxygenase (PHM), and polysaccharide monooxygenases (PMO). In a simple model system, reaction of O2 and a reduced copper(I) complex affords a mononuclear copper(II)-superoxide complex or a copper(III)-peroxide complex, and subsequent H(•) or e(-)/H(+) transfer, which gives a copper(II)-hydroperoxide complex. A more reactive species such as a copper(II)-oxyl radical type species could be generated via O-O bond cleavage of the peroxide complex. However, little had been explored about the chemical properties and reactivity of the mononuclear copper-active-oxygen complexes due to the lack of appropriate model compounds. Thus, a great deal of effort has recently been made to develop efficient ligands that can stabilize such reactive active-oxygen complexes in synthetic modeling studies. In this Account, I describe our recent achievements of the development of a mononuclear copper(II)-(end-on)superoxide complex using a simple tridentate ligand consisting of an eight-membered cyclic diamine with a pyridylethyl donor group. The superoxide complex exhibits a similar structure (four-coordinate tetrahedral geometry) and reactivity (aliphatic hydroxylation) to those of a proposed reactive intermediate of copper monooxygenases. Systematic studies based on the crystal structures of copper(I) and copper(II) complexes of the related tridentate supporting ligands have indicated that the rigid eight-membered cyclic diamine framework is crucial for controlling the geometry and the redox potential, which are prerequisites for the generation of such a unique mononuclear copper(II)-(end-on)superoxide complex

  19. MHC class II complexes sample intermediate states along the peptide exchange pathway

    PubMed Central

    Wieczorek, Marek; Sticht, Jana; Stolzenberg, Sebastian; Günther, Sebastian; Wehmeyer, Christoph; El Habre, Zeina; Álvaro-Benito, Miguel; Noé, Frank; Freund, Christian

    2016-01-01

    The presentation of peptide-MHCII complexes (pMHCIIs) for surveillance by T cells is a well-known immunological concept in vertebrates, yet the conformational dynamics of antigen exchange remain elusive. By combining NMR-detected H/D exchange with Markov modelling analysis of an aggregate of 275 microseconds molecular dynamics simulations, we reveal that a stable pMHCII spontaneously samples intermediate conformations relevant for peptide exchange. More specifically, we observe two major peptide exchange pathways: the kinetic stability of a pMHCII's ground state defines its propensity for intrinsic peptide exchange, while the population of a rare, intermediate conformation correlates with the propensity of the HLA-DM-catalysed pathway. Helix-destabilizing mutants designed based on our model shift the exchange behaviour towards the HLA-DM-catalysed pathway and further allow us to conceptualize how allelic variation can shape an individual's MHC restricted immune response. PMID:27827392

  20. Nucleophilic substitution at silicon (SN2@Si) via a central reaction barrier.

    PubMed

    Bento, A Patrícia; Bickelhaupt, F Matthias

    2007-03-16

    It is textbook knowledge that nucleophilic substitution at carbon (SN2@C) proceeds via a central reaction barrier which disappears in the corresponding nucleophilic substitution reaction at silicon (SN2@Si). Here, we address the question why the central barrier disappears from SN2@C to SN2@Si despite the fact that these processes are isostructural and isoelectronic. To this end, we have explored and analyzed the potential energy surfaces (PES) of various Cl-+CR3Cl (R=H, CH3) and Cl-+SiR3Cl model reactions (R=H, CH3, C2H5, and OCH3). Our results show that the nature of the SN2 reaction barrier is in essence steric, but that it can be modulated by electronic factors. Thus, simply by increasing the steric demand of the substituents R around the silicon atom, the SN2@Si mechanism changes from its regular single-well PES (with a stable intermediate transition complex, TC), via a triple-well PES (with a pre- and a post-TS before and after the central TC), to a double-well PES (with a TS; R=OCH3), which is normally encountered for SN2@C reactions.

  1. The syn/anti-Dichotomy in the Palladium-Catalyzed Addition of Nucleophiles to Alkenes

    PubMed Central

    Kočovský, Pavel; Bäckvall, Jan-E

    2015-01-01

    In this review the stereochemistry of palladium-catalyzed addition of nucleophiles to alkenes is discussed, and examples of these reactions in organic synthesis are given. Most of the reactions discussed involve oxygen and nitrogen nucleophiles; the Wacker oxidation of ethylene has been reviewed in detail. An anti-hydroxypalladation in the Wacker oxidation has strong support from both experimental and computational studies. From the reviewed material it is clear that anti-addition of oxygen and nitrogen nucleophiles is strongly favored in intermolecular addition to olefin–palladium complexes even if the nucleophile is coordinated to the metal. On the other hand, syn-addition is common in the case of intramolecular oxy- and amidopalladation as a result of the initial coordination of the internal nucleophile to the metal. PMID:25378278

  2. Highly Enantioselective Nucleophilic Dearomatization of Pyridines by Anion-Binding Catalysis.

    PubMed

    García Mancheño, Olga; Asmus, Sören; Zurro, Mercedes; Fischer, Theresa

    2015-07-20

    The asymmetric dearomatization of N-heterocycles is an important synthetic method to gain bioactive and synthetically valuable chiral heterocycles. However, the catalytic enantio- and regioselective dearomatization of the simplest six-membered-ring N-heteroarenes, the pyridines, is still very challenging. The first anion-binding-catalyzed, highly enantioselective nucleophilic dearomatization of pyridines with triazole-based H-bond donor catalysts is presented. Contrary to other more common NH-based H-bond donors, this type of organocatalyst shows a prominent higher C2-regioselectivity and is able to promote high enantioinductions via formation of a close chiral anion-pair complex with a preformed N-acyl pyridinium ionic intermediate. This method offers a straightforward and useful synthetic approach to chiral N-heterocycles from abundant and readily available pyridines.

  3. Semiquinone Intermediates are involved in the Energy Coupling Mechanism of E. coli Complex I

    PubMed Central

    Narayanan, Madhavan; Leung, Steven A.; Inaba, Yuta; Elguindy, Mahmoud M.; Nakamaru-Ogiso, Eiko

    2015-01-01

    Complex I (NADH:quinone oxidoreductase) is central to cellular aerobic energy metabolism, and its deficiency is involved in many human mitochondrial diseases. Complex I translocates protons across the membrane using electron transfer energy. Semiquinone (SQ) intermediates appearing during catalysis are suggested to be key for the coupling mechanism in complex I. However, the existence of SQ has remained controversial due to the extreme difficulty in detecting unstable and low intensity SQ signals. Here, for the first time with E. coli complex I reconstituted in proteoliposomes, we successfully resolved and characterized three distinct SQ species by EPR. These species include: fast-relaxing SQ (SQNf) with P1/2 (half-saturation power level) > 50 mW and a wider linewidth (12.8 G); slow-relaxing SQ (SQNs) with P1/2 = 2–3 mW and a 10 G linewidth; and very slow-relaxing SQ (SQNvs) with P1/2 = ~ 0.1 mW and a 7.5 G linewidth. The SQNf signals completely disappeared in the presence of the uncoupler gramicidin D or squamotacin, a potent E. coli complex I inhibitor. The pH dependency of the SQNf signals correlated with the proton-pumping activities of complex I. The SQNs signals were insensitive to gramicidin D, but sensitive to squamotacin. The SQNvs signals were insensitive to both gramicidin D and squamotacin. Our deuterium exchange experiments suggested that SQNf is neutral, while SQNs and SQNvs are anion radicals. The SQNs signals were lost in the ΔNuoL mutant missing transporter module subunits NuoL and NuoM. The roles and relationships of the SQ intermediates in the coupling mechanism are discussed. PMID:25868873

  4. Mechanism of hydrogenolysis of an iridium-methyl bond: evidence for a methane complex intermediate.

    PubMed

    Campos, Jesús; Kundu, Sabuj; Pahls, Dale R; Brookhart, Maurice; Carmona, Ernesto; Cundari, Thomas R

    2013-01-30

    Evidence for key σ-complex intermediates in the hydrogenolysis of the iridium-methyl bond of (PONOP)Ir(H)(Me)(+) (1) [PONOP = 2,6-bis(di-tert-butylphosphinito)pyridine] has been obtained. The initially formed η(2)-H(2) complex, 2, was directly observed upon treatment of 1 with H(2), and evidence for reversible formation of a σ-methane complex, 5, was obtained through deuterium scrambling from η(2)-D(2) in 2-d(2) into the methyl group of 2 prior to methane loss. This sequence of reactions was modeled by density functional theory calculations. The transition state for formation of 5 from 2 showed significant shortening of the Ir-H bond for the hydrogen being transferred; no true Ir(V) trihydride intermediate could be located. Barriers to methane loss from 2 were compared to those of 1 and the six-coordinate species (PONOP)Ir(H)(Me)(CO)(+) and (PONOP)Ir(H)(Me)(Cl).

  5. Detection of Electrophilic and Nucleophilic Chemical Agents

    SciTech Connect

    McElhanon, James R.; Shepodd, Timothy J.

    2008-11-11

    A "real time" method for detecting electrophilic and nucleophilic species generally by employing tunable, precursor sensor materials that mimic the physiological interaction of these agents to form highly florescent berberine-type alkaloids that can be easily and rapidly detected. These novel precursor sensor materials can be tuned for reaction with both electrophilic (chemical species, toxins) and nucleophilic (proteins and other biological molecules) species.

  6. Polyimidazoles via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor)

    1991-01-01

    Polyimidazoles (Pl) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl)imidazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The reactions are carried out in polar aprotic solvents such as N,N-dimethylacetamide, sulfolane, N-methylpyrroldinone, dimethylsulfoxide, or diphenylsulfone using alkali metal bases such as potassium carbonate at elevated temperature under nitrogen. The di(hydroxyphenyl)imidazole monomers are prepared by reacting an aromatic aldehyde with a dimethoxybenzil or by reacting an aromatic dialdehyde with a methoxybenzil in the presence of ammonium acetate. The di(methoxyphenyl)imidazole is subsequently treated with aqueous hydrobromic acid to give the di(hydroxyphenyl)imidazole monomer. This synthetic route has provided high molecular weight Pl of new chemical structure, is economically and synthetically more favorable than other routes, and allows for facile chemical structure variation due to the availability of a large variety of activated aromatic dihalides and dinitro compounds.

  7. Polyimidazoles via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor)

    1992-01-01

    Polyimidazoles (PI) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl) imidazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The reactions are carried out in polar aprotic solvents such as N,N-dimethyl acetamide, sulfolane, N-methylpyrrolidinone, dimethylsulfoxide, or diphenylsulfone using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl) imidazole monomers are prepared by reacting an aromatic aldehyde with a dimethoxybenzil or by reacting an aromatic dialdehyde with a methoxybenzil in the presence of ammonium acetate. The di(methoxyphenyl) imidazole is subsequently treated with aqueous hydrobromic acid to give the di(hydroxphenyl) imidazole monomer. This synthetic route has provided high molecular weight PI of new chemical structure, is economically and synthetically more favorable than other routes, and allows for facile chemical structure variation due to the availability of a large variety of activated aromatic dihalides and dinitro compounds.

  8. Polybenzimidazoles via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Joseph G., Jr. (Inventor)

    1995-01-01

    Novel molecular weight controlled and endcapped polybenzimidazoles (PBI) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl benzimidazole) monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The PBI are endcapped with mono(hydroxyphenyl) benzimidazoles. The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. Mono(hydroxyphenyl) benzimidazoles are synthesizedby reacting phenyl-4-hydroxybenzoate with aromatic (o-diamine)s in diphenylsulfone. Molecular weight controlled and endcapped PBI of new chemical structures are prepared that exhibit a favorable combination of physical and mechanical properties.

  9. Polybenzimidazoles Via Aromatic Nucleophilic Displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergerrother, Paul M. (Inventor); Smith, Joseph G., Jr. (Inventor)

    1997-01-01

    Novel molecular weight controlled and endcapped polybenzimidazoles (PBI) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenylbenzimidazole) monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The PBI are endcapped with mono(hydroxyphenyl)benzimidazoles. The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. Mono(hydroxyphenyl)benzimidazoles are synthesized by reacting phenyl-4-hydroxybenzoate with aromatic (o-diamine)s in diphenylsulfone. Molecular weight controlled and endcapped PBI of new chemical structures are prepared that exhibit a favorable combination of physical and mechanical properties.

  10. Structure of GroEL in Complex with an Early Folding Intermediate of Alanine Glyoxylate Aminotransferase*

    PubMed Central

    Albert, Armando; Yunta, Cristina; Arranz, Rocío; Peña, Álvaro; Salido, Eduardo; Valpuesta, José María; Martín-Benito, Jaime

    2010-01-01

    Primary hyperoxaluria type 1 is a rare autosomal recessive disease caused by mutations in the alanine glyoxylate aminotransferase gene (AGXT). We have previously shown that P11L and I340M polymorphisms together with I244T mutation (AGXT-LTM) represent a conformational disease that could be amenable to pharmacological intervention. Thus, the study of the folding mechanism of AGXT is crucial to understand the molecular basis of the disease. Here, we provide biochemical and structural data showing that AGXT-LTM is able to form non-native folding intermediates. The three-dimensional structure of a complex between the bacterial chaperonin GroEL and a folding intermediate of AGXT-LTM mutant has been solved by cryoelectron microscopy. The electron density map shows the protein substrate in a non-native extended conformation that crosses the GroEL central cavity. Addition of ATP to the complex induces conformational changes on the chaperonin and the internalization of the protein substrate into the folding cavity. The structure provides a three-dimensional picture of an in vivo early ATP-dependent step of the folding reaction cycle of the chaperonin and supports a GroEL functional model in which the chaperonin promotes folding of the AGXT-LTM mutant protein through forced unfolding mechanism. PMID:20056599

  11. Combining intermediate complexity models and seasonal palaeo records: how to deal with model and climate variability?

    NASA Astrophysics Data System (ADS)

    de Boer, H. J.; Dekker, S. C.; Wassen, M. J.

    2009-04-01

    Earth System Models of Intermediate Complexity (EMICs) are popular tools for palaeo climate simulations. Recent studies applied these models in comparison to terrestrial proxy records and aimed to reconstruct changes in seasonal climate forced by altered ocean circulation patterns. To strengthen this powerful methodology, we argue that the magnitude of the simulated atmospheric changes should be considered in relation to the internal variability of both the climate system and the intermediate complexity model. To attribute a shift in modelled climate to reality, this ‘signal' should be detectable above the ‘noise' related to the internal variability of the climate system and the internal variability of the model. Both noise and climate signals vary over the globe and change with the seasons. We therefore argue that spatial explicit fields of noise should be considered in relation to the strengths of the simulated signals at a seasonal timescale. We approximated total noise on terrestrial temperature and precipitation from a 29 member simulation with the EMIC PUMA-2 and global temperature and precipitation datasets. To illustrate this approach, we calculate Signal-to-Noise-Ratios (SNRs) in terrestrial temperature and precipitation on simulations of an El Niño warm event, a phase change in Atlantic Meridional Oscillation (AMO) and a Heinrich cooling event. The results of the El Niño and AMO simulations indicate that the chance to accurately detect a climate signal increases with increasing SNRs. Considering the regions and seasons with highest SNRs, the simulated El Niño anomalies show good agreement with observations (r² = 0.8 and 0.6 for temperature and precipitation at SNRs > 4). The AMO signals rarely surpass the noise levels and remain mostly undetected. The simulation of a Heinrich event predicts highest SNRs for temperature (up to 10) over Arabia and Russia during Boreal winter and spring. Highest SNRs for precipitation (up to 12) are predicted over

  12. Directional DNA methylation changes and complex intermediate states accompany lineage specificity in the adult hematopoietic compartment.

    PubMed

    Hodges, Emily; Molaro, Antoine; Dos Santos, Camila O; Thekkat, Pramod; Song, Qiang; Uren, Philip J; Park, Jin; Butler, Jason; Rafii, Shahin; McCombie, W Richard; Smith, Andrew D; Hannon, Gregory J

    2011-10-07

    DNA methylation has been implicated as an epigenetic component of mechanisms that stabilize cell-fate decisions. Here, we have characterized the methylomes of human female hematopoietic stem/progenitor cells (HSPCs) and mature cells from the myeloid and lymphoid lineages. Hypomethylated regions (HMRs) associated with lineage-specific genes were often methylated in the opposing lineage. In HSPCs, these sites tended to show intermediate, complex patterns that resolve to uniformity upon differentiation, by increased or decreased methylation. Promoter HMRs shared across diverse cell types typically display a constitutive core that expands and contracts in a lineage-specific manner to fine-tune the expression of associated genes. Many newly identified intergenic HMRs, both constitutive and lineage specific, were enriched for factor binding sites with an implied role in genome organization and regulation of gene expression, respectively. Overall, our studies represent an important reference data set and provide insights into directional changes in DNA methylation as cells adopt terminal fates.

  13. Synthesis of a Fluorescent Acridone Using a Grignard Addition, Oxidation, and Nucleophilic Aromatic Substitution Reaction Sequence

    ERIC Educational Resources Information Center

    Goodrich, Samuel; Patel, Miloni; Woydziak, Zachary R.

    2015-01-01

    A three-pot synthesis oriented for an undergraduate organic chemistry laboratory was developed to construct a fluorescent acridone molecule. This laboratory experiment utilizes Grignard addition to an aldehyde, alcohol oxidation, and iterative nucleophilic aromatic substitution steps to produce the final product. Each of the intermediates and the…

  14. Reaction of a copper(II)-nitrosyl complex with hydrogen peroxide: putative formation of a copper(I)-peroxynitrite intermediate.

    PubMed

    Kalita, Apurba; Kumar, Pankaj; Mondal, Biplab

    2012-05-14

    The reaction of a Cu(II)-nitrosyl complex (1) with hydrogen peroxide at -20 °C in acetonitrile results in the formation of the corresponding Cu(I)-peroxynitrite intermediate. The reduction of the Cu(II) center was monitored by UV-visible spectroscopic studies. Formation of the peroxynitrite intermediate has been confirmed by its characteristic phenol ring nitration reaction as well as isolation of corresponding Cu(I)-nitrate (2). On air oxidation, 2 resulted in the corresponding Cu(II)-nitrate (3). Thus, these results demonstrate a possible decomposition pathway for H(2)O(2) and NO through the formation of a peroxynitrite intermediate in biological systems.

  15. Intermediates in assembly by photoactivation after thermally accelerated disassembly of the manganese complex of photosynthetic water oxidation.

    PubMed

    Barra, Marcos; Haumann, Michael; Loja, Paola; Krivanek, Roland; Grundmeier, Alexander; Dau, Holger

    2006-12-05

    The Mn4Ca complex bound to photosystem II (PSII) is the active site of photosynthetic water oxidation. Its assembly involves binding and light-driven oxidation of manganese, a process denoted as photoactivation. The disassembly of the Mn complex is a thermally activated process involving distinct intermediates. Starting from intermediate states of the disassembly, which was initiated by a temperature jump to 47 degrees C, we photoactivated PSII membrane particles and monitored the activity recovery by O2 polarography and delayed chlorophyll fluorescence measurements. Oxidation state and structural features of the formed intermediates of the Mn complex were assayed by X-ray absorption spectroscopy at the Mn K-edge. The photoactivation time courses, which exhibit a lag phase characteristic of intermediate formation only when starting with the apo-PSII, suggest that within approximately 5 min of photoactivation of apo-PSII, a binuclear Mn complex is formed. It is proposed that a MnIII2(di-mu-oxo) complex is a key intermediate both in the disassembly and in the assembly reaction paths.

  16. Reactive transport modelling of organic complexing agents in cement stabilized low and intermediate level waste

    NASA Astrophysics Data System (ADS)

    von Schenck, Henrik; Källström, Klas

    The Swedish final repository for short-lived radioactive waste (SFR 1) is located at Forsmark in Sweden. It holds low and intermediate-level operational waste from the Swedish nuclear power plants, as well as industrial, research-related, and medical waste. A variety of low molecular weight organic compounds are present in the waste or in its matrix. Such compounds can also be formed by chemical degradation of organic macromolecules. These organics can ligate to metal atoms forming stable complexes and also adsorb to the surface of cement, thereby influencing the net release of radionuclides from the repository. This motivates the study of the concentration distribution of complexing agents in the repository as a function of time. The following paper reports the results of mass transport modelling, describing the transport of complexing agents through the cementitous matrix in the rock vault for intermediate-level waste in the SFR 1 repository. Nitrilotriacetate (NTA) and isosaccharinate (ISA) have been investigated, where the former is considered to be non-sorbing and non-reacting, while the latter is produced from cellulose degradation and adsorbs strongly to cement. The 3D model considers advection, diffusion, and sorption of solvated species in cement pore water over a time period of 20,000 years. The model accounts for the spatial distribution of the flow field in the repository structure and also considers changing groundwater flow during the investigated time period. It is found that 99% of the NTA is removed after approximately 4000 years, while 90% of the ISA is retained in the rock vault after 20,000 years. The maximum pore water concentration of ISA is found to be 8.6 mol/m3 after approximately 2300 years, based on the degradation of the deposited amounts of cellulose. Over the investigated time scale, the ligands retained in the repository can redistribute across several waste compartments where the organic compounds were not originally deposited. In

  17. Active-site models for complexes of quinolinate synthase with substrates and intermediates

    SciTech Connect

    Soriano, Erika V.; Zhang, Yang; Colabroy, Keri L.; Sanders, Jennie M.; Settembre, Ethan C.; Dorrestein, Pieter C.; Begley, Tadhg P.; Ealick, Steven E.

    2013-09-01

    Structural studies of quinolinate synthase suggest a model for the enzyme–substrate complex and an enzyme–intermediate complex with a [4Fe–4S] cluster. Quinolinate synthase (QS) catalyzes the condensation of iminoaspartate and dihydroxyacetone phosphate to form quinolinate, the universal precursor for the de novo biosynthesis of nicotinamide adenine dinucleotide. QS has been difficult to characterize owing either to instability or lack of activity when it is overexpressed and purified. Here, the structure of QS from Pyrococcus furiosus has been determined at 2.8 Å resolution. The structure is a homodimer consisting of three domains per protomer. Each domain shows the same topology with a four-stranded parallel β-sheet flanked by four α-helices, suggesting that the domains are the result of gene triplication. Biochemical studies of QS indicate that the enzyme requires a [4Fe–4S] cluster, which is lacking in this crystal structure, for full activity. The organization of domains in the protomer is distinctly different from that of a monomeric structure of QS from P. horikoshii [Sakuraba et al. (2005 ▶), J. Biol. Chem.280, 26645–26648]. The domain arrangement in P. furiosus QS may be related to protection of cysteine side chains, which are required to chelate the [4Fe–4S] cluster, prior to cluster assembly.

  18. Intermediately complex models for the hydrological interactions in the atmosphere-vegetation-soil system

    NASA Astrophysics Data System (ADS)

    Zeng, X. D.; Wang, A. H.; Zeng, Q. C.; Dickinson, R. E.; Zeng, X. B.; Shen, S. S. P.

    2006-01-01

    This paper investigates the hydrological interactions in the atmosphere-evegetation-soil system by using the bucket model and several new simplified intermediately complex models. The results of mathematical analysis and numerical simulations show that these models, despite their simplicity, can very clearly reveal the essential features of the rather complex hydrological system of atmosphere-ecosystem-soil. For given atmospheric variables, these models clearly demonstrate multiple timescales, the "red shift" of response spectra, multi-equilibria and limit cycles, bifurcation, abrupt change, self-organization, recovery, "desertification", and chaos. Most of these agree with observations. Especially, the weakening of "shading effect" of living canopy and the wilted biomass might be a major mechanism leading to the desertification in a relatively short period due to overgrazing, and the desertification in a relatively long period or in climate of change might be due to both Charney's mechanism and the shading effect. These ideas could be validated with further numerical simulations. In the paper, some methods for improving the estimation of timescales in the soil water evolution responding to the forcing are also proposed.

  19. Electrophilic and nucleophilic enzymatic cascade reactions in biosynthesis.

    PubMed

    Ueberbacher, Barbara T; Hall, Mélanie; Faber, Kurt

    2012-03-01

    The biosynthesis of cyclic terpenoids and polyethers involves enzyme-initiated cascade reactions for ring formation. While the former are obtained by electrophilic cascades through carbenium ions as intermediates, cyclic polyethers are formed by nucleophilic cascade reactions of (poly)epoxide precursors. These mechanistically complementary pathways follow common principles via (i) triggering of the cascade by forming a reactive intermediate ('initiation'), (ii) sequential 'proliferation' of the cyclization and finally (iii) 'termination' of the cascade. As analyzed in this concept paper, the multiplicity of precursors, combined with various initiation and termination routes and kinetically favored or disfavored cyclization modes accounts for the enormous diversity in cyclic terpenoid and polyether scaffolds. Although the essential role of enzymes in the triggering of these cascades is reasonably well understood, remarkably little is known about their influence in proliferation reactions, especially those implying kinetically disfavored (anti-Markovnikov and anti-Baldwin) routes. Mechanistic analysis of enzymatic cascade reactions provides biomimetic strategies for natural product synthesis.

  20. PLASIM-GENIE v1.0: a new intermediate complexity AOGCM

    NASA Astrophysics Data System (ADS)

    Holden, Philip B.; Edwards, Neil R.; Fraedrich, Klaus; Kirk, Edilbert; Lunkeit, Frank; Zhu, Xiuhua

    2016-09-01

    We describe the development, tuning and climate of Planet Simulator (PLASIM)-Grid-ENabled Integrated Earth system model (GENIE), a new intermediate complexity Atmosphere-Ocean General Circulation Model (AOGCM), built by coupling the Planet Simulator to the ocean, sea-ice and land-surface components of the GENIE Earth system model. PLASIM-GENIE supersedes GENIE-2, a coupling of GENIE to the Reading Intermediate General Circulation Model (IGCM). The primitive-equation atmosphere includes chaotic, three-dimensional (3-D) motion and interactive radiation and clouds, and dominates the computational load compared to the relatively simpler frictional-geostrophic ocean, which neglects momentum advection. The model is most appropriate for long-timescale or large ensemble studies where numerical efficiency is prioritised, but lack of data necessitates an internally consistent, coupled calculation of both oceanic and atmospheric fields. A 1000-year simulation with PLASIM-GENIE requires approximately 2 weeks on a single node of a 2.1 GHz AMD 6172 CPU. We demonstrate the tractability of PLASIM-GENIE ensembles by deriving a subjective tuning of the model with a 50-member ensemble of 1000-year simulations. The simulated climate is presented considering (i) global fields of seasonal surface air temperature, precipitation, wind, solar and thermal radiation, with comparisons to reanalysis data; (ii) vegetation carbon, soil moisture and aridity index; and (iii) sea surface temperature, salinity and ocean circulation. Considering its resolution, PLASIM-GENIE reproduces the main features of the climate system well and demonstrates usefulness for a wide range of applications.

  1. Advances in Nucleophilic Phosphine Catalysis of Alkenes, Allenes, Alkynes, and MBHADs

    PubMed Central

    Fan, Yi Chiao

    2014-01-01

    In nucleophilic phosphine catalysis, tertiary phosphines undergo conjugate additions to activated carbon–carbon multiple bonds to form β-phosphonium enolates, β-phosphonium dienolates, β-phosphonium enoates, and vinyl phosphonium ylides as intermediates. When these reactive zwitterionic species react with nucleophiles and electrophiles, they may generate carbo- and heterocycles with multifarious molecular architectures. This Article describes the reactivities of these phosphonium zwitterions, the applications of phosphine catalysis in the syntheses of biologically active compounds and natural products, and recent developments in the enantioselective phosphine catalysis. PMID:24196409

  2. General allylic C-H alkylation with tertiary nucleophiles.

    PubMed

    Howell, Jennifer M; Liu, Wei; Young, Andrew J; White, M Christina

    2014-04-16

    A general method for intermolecular allylic C-H alkylation of terminal olefins with tertiary nucleophiles has been accomplished employing palladium(II)/bis(sulfoxide) catalysis. Allylic C-H alkylation furnishes products in good yields (avg. 64%) with excellent regio- and stereoselectivity (>20:1 linear:branched, >20:1 E:Z). For the first time, the olefin scope encompasses unactivated aliphatic olefins as well as activated aromatic/heteroaromatic olefins and 1,4-dienes. The ease of appending allyl moieties onto complex scaffolds is leveraged to enable this mild and selective allylic C-H alkylation to rapidly diversify phenolic natural products. The tertiary nucleophile scope is broad and includes latent functionality for further elaboration (e.g., aliphatic alcohols, α,β-unsaturated esters). The opportunities to effect synthetic streamlining with such general C-H reactivity are illustrated in an allylic C-H alkylation/Diels-Alder reaction cascade: a reactive diene is generated via intermolecular allylic C-H alkylation and approximated to a dienophile contained within the tertiary nucleophile to furnish a common tricyclic core found in the class I galbulimima alkaloids.

  3. Uranium transport experiments at the intermediate scale: Do more heterogeneous systems create more complex behaviors?

    NASA Astrophysics Data System (ADS)

    Miller, A. W.; Rodriguez, D.; Honeyman, B.

    2010-12-01

    With respect to complexity, two things occur as experimental scale increases. The first is that as total system size increases, the heterogeneities at smaller scales are explicitly included while simultaneously allowing for a general increase in total complexity. The second is that model constraining measurements become more difficult to make. Bench scale systems limit total complexity; field scale systems are limited in the amount of characterization that can be completed. Intermediate scale systems can bridge this gap, allowing for increased complexity relative to the bench scale and better characterization ability relative to the field scale. We have completed three intermediate scale experiments with a uranium contaminated sediment from a former uranium mill site near Naturita in southwestern Colorado, USA. Three tanks were packed with various particle size distributions of this sediment. The first two tanks were 2-D in nature and had dimensions of 2.44m x 1.22m x 7.62cm (tank #1, LxHxW), and 2.44m x 0.61m x 7.62cm (tank #2, LxHxW). Tank #3 was 3-D in nature with dimensions of 2.44m x 0.61m x 0.61m (LxHxW). Tank #1 was packed in a homogenous manner with only the <2mm size fraction of sediment. For tank #2 the <2mm fraction was split into <0.250mm and >0.250mm fractions, and these two fractions allowed for a physically heterogeneous packing. Using all three of the previously mentioned size fractions as well as a 0.125-0.250mm and a 4-12mm fraction, tank #3 was also packed in a heterogeneous fashion. The masses of sediment used in the three tanks are: tank #1 ~280kg, tank #2 - 163kg, and tank #3 - 1160kg. Flow through all three systems was comparable, and controlled by constant head boundaries. Three different artificial ground waters (AGW) were used with ionic compositions similar to that found at the field site. The major distinctions are that AGW #1 was in equilibrium with atmospheric CO2 and had no Si; AGW#2 was in equilibrium with 2%CO2 and had no Si; AGW#3

  4. MEDUSA: a new intermediate complexity plankton ecosystem model for the global domain

    NASA Astrophysics Data System (ADS)

    Yool, A.; Popova, E. E.; Anderson, T. R.

    2010-10-01

    The ongoing, anthropogenically-driven changes to the global ocean are expected to have significant consequences for plankton ecosystems in the future. Because of the role that plankton play in the ocean's "biological pump", changes in abundance, distribution and productivity will likely have additional consequences for the wider carbon cycle. Just as in the terrestrial biosphere, marine ecosystems exhibit marked diversity in species and functional types of organisms. Predicting potential change in plankton ecosystems therefore requires the use of models that are suited to this diversity, but whose parameterisation also permits robust and realistic functional behaviour. In the past decade, advances in model sophistication have attempted to address diversity, but have been criticised for doing so inaccurately or ahead of a requisite understanding of underlying processes. Here we introduce MEDUSA (Model of Ecosystem Dynamics, nutrient Utilisation, Sequestration and Acidification), a new "intermediate complexity" plankton ecosystem model that expands on traditional nutrient-phytoplankton-zooplankton-detritus (NPZD) models, and remains amenable to global-scale evaluation. MEDUSA includes the biogeochemical cycles of nitrogen, silicon and iron, broadly structured into "small" and "large" plankton size classes, of which the "large" phytoplankton class is representative of a key phytoplankton group, the diatoms. A full description of MEDUSA's state variables, differential equations, functional forms and parameter values is included, with particular attention focused on the submodel describing the export of organic carbon from the surface to the deep ocean. MEDUSA is used here in a multi-decadal hindcast simulation, and its biogeochemical performance evaluated at the global scale.

  5. Light-particle-complex-fragment coincidence cross sections from intermediate energy nucleus-nucleus collisions

    SciTech Connect

    Hasselquist, B.E.; Crawley, G.M.; Jacak, B.V.; Koenig, Z.M.; Westfall, G.D.; Yurkon, J.E.; Tickle, R.S.; Dufour, J.P.; Symons, T.J.M.

    1985-07-01

    Light-particle (Zintermediate rapidity fragments (3complex-fragment-triggered coincidence cross sections is observed, indicating that all the fragments have a common source.

  6. Gold(I)-catalyzed asymmetric induction of planar chirality by intramolecular nucleophilic addition to chromium-complexed alkynylarenes: asymmetric synthesis of planar chiral (1H-isochromene and 1,2-dihydroisoquinoline)chromium complexes.

    PubMed

    Murai, Masato; Sota, Yumi; Onohara, Yuki; Uenishi, Jun'ichi; Uemura, Motokazu

    2013-11-01

    Gold(I)-catalyzed asymmetric intramolecular cyclization of prochiral 1,3-dihydroxymethyl-2-alkynylbenzene or 1,3-bis(carbamate)-2-alkynylbenzene tricarbonylchromium complexes with axially chiral diphosphine ligand gave planar chiral tricarbonylchromium complexes of 1H-isochromene or 1,2-dihydroisoquinoline with high enantioselectivity. An enantiomeric excess of the planar chiral arene chromium complexes was largely affected by a combination of axially chiral diphosphine(AuCl)2 precatalysts and silver salts. In the case of 1,3-dihydroxymethyl-2-alkynylbenzene chromium complexes, a system of segphos(AuCl)2 with AgBF4 resulted in the formation of the corresponding antipode.

  7. The role of intramolecular hydrogen bonds in nucleophilic addition reactions of ketenaminals

    NASA Astrophysics Data System (ADS)

    Isaev, A. N.

    2012-08-01

    Quantum-chemical calculations of the geometries and electronic structures of molecules of ketenaminals 3-(diaminomethylene)-2,4-pentanedione and dimethyl-2-(diaminomethylene)-malonate and calculations of the structures of intermediates in the reaction of the nucleophilic addition of the ketenaminals to the acetonitrile molecule are performed by B3LYP/6-31+G** method. Two possible scenarios of the process are shown, depending on the mutual orientation of reacting molecules. The nucleophilic addition proceeds in two stages. It is found that the rate-limiting stage of the process is the transfer of the proton of the intramolecular hydrogen bond in a ketenaminal molecule. The experimentally observed faster reaction of pyrimidine formation for the 3-(diaminomethylene)-2,4-pentanedione molecule relative to that for dimethyl-2-(diaminomethylene)-malonate is explained by the hydrogen bond being stronger and the barrier of proton transfer from the aminogroup to the ketogroup oxygen falling upon nucleophilic attack in the former molecule.

  8. The interchange of immunophilins leads to parallel pathways and different intermediates in the assembly of Hsp90 glucocorticoid receptor complexes

    PubMed Central

    Ebong, Ima-obong; Beilsten-Edmands, Victoria; Patel, Nisha A; Morgner, Nina; Robinson, Carol V

    2016-01-01

    Hormone receptors require participation of the chaperones Hsp40/Hsp70 to form client-transfer complexes with Hsp90/Hop. Interaction with the co-chaperone p23 releases Hop and Hsp70, and the immunophilin FKBP52 mediates transfer of the Hsp90-receptor complex to the nucleus. Inhibition of glucocorticoid receptor (GR) transport by FKBP51, but not by FKBP52, has been observed at the cellular level, but the subunit composition of the intermediates involved has not been deduced. Here we use mass spectrometry to show that FKBP51/52 form analogous complexes with GR/Hsp90/Hop/Hsp70/ATP, but differences emerge upon addition of p23 to client-transfer complexes. When FKBP51 is present, a stable intermediate is formed (FKBP51)1(GR)1(Hsp90)2(p23)2 by expulsion of Hsp70 and Hop. By contrast, in the presence of FKBP52, ejection of p23 also takes place to form the nuclear transfer complex (FKBP52)1(GR)1(Hsp90)2. Our results are therefore consistent with pathways in which FKBP51/52 are interchangeable during the early assembly reactions. Following interaction with p23, however, the pathways diverge with FKBP51 sequestering GR in a stable intermediate complex with p23. By contrast, binding of FKBP52 occurs almost concomitantly with release of p23 to form a highly dynamic transfer complex, primed for interaction with the dynactin transport machinery. PMID:27462449

  9. An unexpected transmetalation intermediate: isolation and structural characterization of a solely CH3 bridged di-copper(i) complex.

    PubMed

    Molteni, Roberto; Bertermann, Rüdiger; Edkins, Katharina; Steffen, Andreas

    2016-04-11

    Structural characterization of unsupported, two metal centres bridging methyl groups is rare. They have been proposed as transmetalation intermediates in cuprate chemistry, but as yet no structural evidence has been presented. We have isolated a di-copper(i) complex with solely a methyl ligand bridging two Cu(i) atoms, representing a new bonding mode of CH3.

  10. Non-stabilized nucleophiles in Cu-catalysed dynamic kinetic asymmetric allylic alkylation

    NASA Astrophysics Data System (ADS)

    You, Hengzhi; Rideau, Emeline; Sidera, Mireia; Fletcher, Stephen P.

    2015-01-01

    The development of new reactions forming asymmetric carbon-carbon bonds has enabled chemists to synthesize a broad range of important carbon-containing molecules, including pharmaceutical agents, fragrances and polymers. Most strategies to obtain enantiomerically enriched molecules rely on either generating new stereogenic centres from prochiral substrates or resolving racemic mixtures of enantiomers. An alternative strategy--dynamic kinetic asymmetric transformation--involves the transformation of a racemic starting material into a single enantiomer product, with greater than 50 per cent maximum yield. The use of stabilized nucleophiles (pKa < 25, where Ka is the acid dissociation constant) in palladium-catalysed asymmetric allylic alkylation reactions has proved to be extremely versatile in these processes. Conversely, the use of non-stabilized nucleophiles in such reactions is difficult and remains a key challenge. Here we report a copper-catalysed dynamic kinetic asymmetric transformation using racemic substrates and alkyl nucleophiles. These nucleophiles have a pKa of >=50, more than 25 orders of magnitude more basic than the nucleophiles that are typically used in such transformations. Organometallic reagents are generated in situ from alkenes by hydrometallation and give highly enantioenriched products under mild reaction conditions. The method is used to synthesize natural products that possess activity against tuberculosis and leprosy, and an inhibitor of para-aminobenzoate biosynthesis. Mechanistic studies indicate that the reaction proceeds through a rapidly isomerizing intermediate. We anticipate that this approach will be a valuable complement to existing asymmetric catalytic methods.

  11. Frustrated Lewis pair-like reactions of nucleophilic palladium carbenes with B(C6F5)3.

    PubMed

    Cui, Peng; Comanescu, Cezar C; Iluc, Vlad M

    2015-04-11

    The reactions of two nucleophilic palladium carbene complexes with the strong Lewis acid B(C6F5)3 afforded two zwitterionic products. One of them features a remote nucleophilic attack at the para-carbon of the supporting ligand, while the other indicates C-F activation of B(C6F5)3. Both behaviours are reminiscent of the reactivity of frustrated Lewis pairs due to the steric inaccessibility of the nucleophilic carbon center, but are unprecedented for transition metal carbene complexes. Furthermore, when those reactions are carried out in the presence of H2, products resulting from H2 splitting are observed.

  12. Detection of electrophilic and nucleophilic chemical agents

    DOEpatents

    McElhanon, James R.; Shepodd, Timothy J.

    2014-08-12

    A "real time" method for detecting chemical agents generally and particularly electrophilic and nucleophilic species by employing tunable, precursor sensor materials that mimic the physiological interaction of these agents to form highly florescent berberine-type alkaloids that can be easily and rapidly detected. These novel precursor sensor materials can be tuned for reaction with both electrophilic (chemical species, toxins) and nucleophilic (proteins and other biological molecules) species. By bonding or otherwise attaching these precursor molecules to a surface or substrate they can be used in numerous applications.

  13. Arylsulfonate-Based Nucleophile Assisting Leaving Groups

    PubMed Central

    Lepore, Salvatore D.; Bhunia, Anjan K.; Cohn, Pamela

    2013-01-01

    The synthesis and unique reactivity of a series of arylsulfonate-based nucleophile assisting leaving groups (NALG) containing oligomeric ether units (including crown ethers) attached to the arylsulfonyl ring in the ortho orientation are described. The reactions of a variety of these ether-containing alkyl sulfonates with metal halides proceeded at substantially greater rates than electronically similar sulfonates. These ether-containing leaving groups also displayed marked selectivity for lithium halides relative to the corresponding sodium and potassium salts in nucleophilic displacement reactions. PMID:16277337

  14. Medusa-1.0: a new intermediate complexity plankton ecosystem model for the global domain

    NASA Astrophysics Data System (ADS)

    Yool, A.; Popova, E. E.; Anderson, T. R.

    2011-05-01

    The ongoing, anthropogenically-driven changes to the global ocean are expected to have significant consequences for plankton ecosystems in the future. Because of the role that plankton play in the ocean's "biological pump", changes in abundance, distribution and productivity will likely have additional consequences for the wider carbon cycle. Just as in the terrestrial biosphere, marine ecosystems exhibit marked diversity in species and functional types of organisms. Predicting potential change in plankton ecosystems therefore requires the use of models that are suited to this diversity, but whose parameterisation also permits robust and realistic functional behaviour. In the past decade, advances in model sophistication have attempted to address diversity, but have been criticised for doing so inaccurately or ahead of a requisite understanding of underlying processes. Here we introduce MEDUSA-1.0 (Model of Ecosystem Dynamics, nutrient Utilisation, Sequestration and Acidification), a new "intermediate complexity" plankton ecosystem model that expands on traditional nutrient-phytoplankton-zooplankton-detritus (NPZD) models, and remains amenable to global-scale evaluation. MEDUSA-1.0 includes the biogeochemical cycles of nitrogen, silicon and iron, broadly structured into "small" and "large" plankton size classes, of which the "large" phytoplankton class is representative of a key phytoplankton group, the diatoms. A full description of MEDUSA-1.0's state variables, differential equations, functional forms and parameter values is included, with particular attention focused on the submodel describing the export of organic carbon from the surface to the deep ocean. MEDUSA-1.0 is used here in a multi-decadal hindcast simulation, and its biogeochemical performance evaluated at the global scale.

  15. Snapshot of a Reaction Intermediate: Analysis of Benzoylformate Decarboxylase in Complex with a Benzoylphosphonate Inhibitor

    SciTech Connect

    Brandt, Gabriel S.; Kneen, Malea M.; Chakraborty, Sumit; Baykal, Ahmet T.; Nemeria, Natalia; Yep, Alejandra; Ruby, David I.; Petsko, Gregory A.; Kenyon, George L.; McLeish, Michael J.; Jordan, Frank; Ringe, Dagmar

    2009-04-22

    Benzoylformate decarboxylase (BFDC) is a thiamin diphosphate- (ThDP-) dependent enzyme acting on aromatic substrates. In addition to its metabolic role in the mandelate pathway, BFDC shows broad substrate specificity coupled with tight stereo control in the carbon-carbon bond-forming reverse reaction, making it a useful biocatalyst for the production of chiral-hydroxy ketones. The reaction of methyl benzoylphosphonate (MBP), an analogue of the natural substrate benzoylformate, with BFDC results in the formation of a stable analogue (C2{alpha}-phosphonomandelyl-ThDP) of the covalent ThDP-substrate adduct C2{alpha}-mandelyl-ThDP. Formation of the stable adduct is confirmed both by formation of a circular dichroism band characteristic of the 1',4'-iminopyrimidine tautomeric form of ThDP (commonly observed when ThDP forms tetrahedral complexes with its substrates) and by high-resolution mass spectrometry of the reaction mixture. In addition, the structure of BFDC with the MBP inhibitor was solved by X-ray crystallography to a spatial resolution of 1.37 {angstrom} (PDB ID 3FSJ). The electron density clearly shows formation of a tetrahedral adduct between the C2 atom of ThDP and the carbonyl carbon atom of the MBP. This adduct resembles the intermediate from the penultimate step of the carboligation reaction between benzaldehyde and acetaldehyde. The combination of real-time kinetic information via stopped-flow circular dichroism with steady-state data from equilibrium circular dichroism measurements and X-ray crystallography reveals details of the first step of the reaction catalyzed by BFDC. The MBP-ThDP adduct on BFDC is compared to the recently solved structure of the same adduct on benzaldehyde lyase, another ThDP-dependent enzyme capable of catalyzing aldehyde condensation with high stereospecificity.

  16. Response of the intermediate complexity Mars Climate Simulator to different obliquity angles

    NASA Astrophysics Data System (ADS)

    Segschneider, J.; Grieger, B.; Keller, H. U.; Lunkeit, F.; Kirk, E.; Fraedrich, K.; Rodin, A.; Greve, R.

    2005-05-01

    A climate model of intermediate complexity, named the Mars Climate Simulator, has been developed based on the Portable University Model of the Atmosphere (PUMA). The main goal of this new development is to simulate the climate variations on Mars resulting from the changes in orbital parameters and their impact on the layered polar terrains (also known as permanent polar ice caps). As a first step towards transient simulations over several obliquity cycles, the model is applied to simulate the dynamical and thermodynamical response of the Martian climate system to different but fixed obliquity angles. The model is forced by the annual and daily cycle of solar insolation. Experiments have been performed for obliquities of φ=15∘ (minimum), φ=25.2∘ (present), and φ=35∘ (maximum). The resulting changes in solar insolation mainly in the polar regions impact strongly on the cross-equatorial circulation which is driven by the meridional temperature gradient and steered by the Martian topography. At high obliquity, the cross-equatorial near surface flow from the winter to the summer hemisphere is strongly enhanced compared to low obliquity periods. The summer ground temperature ranges from 200 K (φ=15∘) to 250 K (φ=35∘) at 80∘N in northern summer, and from 220 K (φ=15∘) to 270 K (φ=35∘) at 80∘S in southern summer. In the atmosphere at 1 km above ground, the respective range is 195-225 K in northern summer, and 210-250 K in southern summer.

  17. Protein-Protein Interactions between Intermediate Chains and the Docking Complex of Chlamydomonas Flagellar Outer Arm Dynein

    PubMed Central

    Ide, Takahiro; Owa, Mikito; King, Stephen M.; Kamiya, Ritsu; Wakabayashi, Ken-ichi

    2013-01-01

    Outer arm dynein (OAD) is bound to specific loci on outer-doublet-microtubules by interactions at two sites: via intermediate chain 1 (IC1) and the outer dynein arm docking complex (ODA-DC). Studies using Chlamydomonas mutants have suggested that the individual sites have rather weak affinities for microtubules, and therefore strong OAD attachment to microtubules is achieved by their cooperation. To test this idea, we examined interactions between IC1, IC2 (another intermediate chain) and ODA-DC using recombinant proteins. Recombinant IC1 and IC2 were found to form a 1:1 complex, and this complex associated with ODA-DC in vitro. Binding of IC1 to mutant axonemes revealed that there are specific binding sites for IC1. From these data, we propose a novel model of OAD-outer doublet association. PMID:23747306

  18. The Remarkable Reactivity of Aryl Halides with Nucleophiles

    ERIC Educational Resources Information Center

    Bunnett, Joseph F.

    1974-01-01

    Discusses the reactivity of aryl halides with nucleophilic or basic reagents, including nucleophilic attacks on carbon, hydrogen, halogen, and arynes. Suggestions are made concerning revisions of the sections on aryl halide chemistry courses and the corresponding chapters in textbooks. (CC)

  19. Transition metal catalysis and nucleophilic fluorination.

    PubMed

    Hollingworth, Charlotte; Gouverneur, Véronique

    2012-03-21

    Transition metal catalyzed transformations using fluorinating reagents have been developed extensively for the preparation of synthetically valuable fluorinated targets. This is a topic of critical importance to facilitate laboratory and industrial chemical synthesis of fluorine containing pharmaceuticals and agrochemicals. Translation to (18)F-radiochemistry is also emerging as a vibrant research field because functional imaging based on Positron Emission Tomography (PET) is increasingly used for both diagnosis and pharmaceutical development. This review summarizes how fluoride sources have been used for the catalytic nucleophilic fluorination of various substrates inclusive of aryl triflates, alkynes, allylic halides, allylic esters, allylic trichloroacetimidates, benzylic halides, tertiary alkyl halides and epoxides. Until recently, progress in this field of research has been slow in part because of the challenges associated with the dual reactivity profile of fluoride (nucleophile or base). Despite these difficulties, some remarkable breakthroughs have emerged. This includes the demonstration that Pd(0)/Pd(II)-catalyzed nucleophilic fluorination to access fluoroarenes from aryl triflates is feasible, and the first examples of Tsuji-Trost allylic alkylation with fluoride using either allyl chlorides or allyl precursors bearing O-leaving groups. More recently, allylic fluorides were also made accessible under iridium catalysis. Another reaction, which has been greatly improved based on careful mechanistic work, is the catalytic asymmetric hydrofluorination of meso epoxides. Notably, each individual transition metal catalyzed nucleophilic fluorination reported to date employs a different F-reagent, an observation indicating that this area of research will benefit from a larger pool of nucleophilic fluoride sources. In this context, a striking recent development is the successful design, synthesis and applications of a fluoride-derived electrophilic late stage

  20. The electrostatic driving force for nucleophilic catalysis in L-arginine deiminase: a combined experimental and theoretical study.

    PubMed

    Li, Ling; Li, Zhimin; Wang, Canhui; Xu, Dingguo; Mariano, Patrick S; Guo, Hua; Dunaway-Mariano, Debra

    2008-04-22

    L-arginine deiminase (ADI) catalyzes the hydrolysis of L-arginine to form L-citrulline and ammonia via two partial reactions. A working model of the ADI catalytic mechanism assumes nucleophilic catalysis by a stringently conserved active site Cys and general acid-general base catalysis by a stringently conserved active site His. Accordingly, in the first partial reaction, the Cys attacks the substrate guanidino C zeta atom to form a tetrahedral covalent adduct, which is protonated by the His at the departing ammonia group to facilitate the formation of the Cys- S-alkylthiouronium intermediate. In the second partial reaction, the His activates a water molecule for nucleophilic addition at the thiouronium C zeta atom to form the second tetrahedral intermediate, which eliminates the Cys in formation of the L-citrulline product. The absence of a basic residue near the Cys thiol suggested that the electrostatic environment of the Cys thiol, in the enzyme-substrate complex, stabilizes the Cys thiolate anion. The studies described in this paper explore the mechanism of stabilization of the Cys thiolate. First, the log(k(cat)/K(m)) and log k(cat) pH rate profiles were measured for several structurally divergent ADIs to establish the pH range for ADI catalysis. All ADIs were optimally active at pH 5, which suggested that the Cys pKa is strongly perturbed by the prevailing electrostatics of the ADI active site. The p K a of the Bacillus cereus ADI (BcADI) was determined by UV-pH titration to be 9.6. In contrast, the pKa determined by iodoacetamide Cys alkylation is 6.9. These results suggest that the negative electrostatic field from the two opposing Asp carboxylates perturbs the Cys pKa upward in the apoenzyme and that the binding of the iodoacetamide (a truncated analogue of the citrulline product) between the Cys thiol and the two Asp carboxylates shields the Cys thiol, thereby reducing its pKa. It is hypothesized that the bound positively charged guanidinium group of the

  1. A process-based fire parameterization of intermediate complexity in a Dynamic Global Vegetation Model

    NASA Astrophysics Data System (ADS)

    Li, F.; Zeng, X. D.; Levis, S.

    2012-07-01

    A process-based fire parameterization of intermediate complexity has been developed for global simulations in the framework of a Dynamic Global Vegetation Model (DGVM) in an Earth System Model (ESM). Burned area in a grid cell is estimated by the product of fire counts and average burned area of a fire. The scheme comprises three parts: fire occurrence, fire spread, and fire impact. In the fire occurrence part, fire counts rather than fire occurrence probability are calculated in order to capture the observed high burned area fraction in areas of high fire frequency and realize parameter calibration based on MODIS fire counts product. In the fire spread part, post-fire region of a fire is assumed to be elliptical in shape. Mathematical properties of ellipses and some mathematical derivations are applied to improve the equation and assumptions of an existing fire spread parameterization. In the fire impact part, trace gas and aerosol emissions due to biomass burning are estimated, which offers an interface with atmospheric chemistry and aerosol models in ESMs. In addition, flexible time-step length makes the new fire parameterization easily applied to various DGVMs. Global performance of the new fire parameterization is assessed by using an improved version of the Community Land Model version 3 with the Dynamic Global Vegetation Model (CLM-DGVM). Simulations are compared against the latest satellite-based Global Fire Emission Database version 3 (GFED3) for 1997-2004. Results show that simulated global totals and spatial patterns of burned area and fire carbon emissions, regional totals and spreads of burned area, global annual burned area fractions for various vegetation types, and interannual variability of burned area are reasonable, and closer to GFED3 than CLM-DGVM simulations with the commonly used Glob-FIRM fire parameterization and the old fire module of CLM-DGVM. Furthermore, average error of simulated trace gas and aerosol emissions due to biomass burning

  2. PALADYN, a comprehensive land surface-vegetation-carbon cycle model of intermediate complexity

    NASA Astrophysics Data System (ADS)

    Willeit, Matteo; Ganopolski, Andrey

    2016-04-01

    PALADYN is presented, a new comprehensive and computationally efficient land surface-vegetation-carbon cycle model designed to be used in Earth system models of intermediate complexity for long-term simulations and paleoclimate studies. The model treats in a consistent manner the interaction between atmosphere, terrestrial vegetation and soil through the fluxes of energy, water and carbon. Energy, water and carbon are conserved. The model explicitly treats permafrost, both in physical processes and as important carbon pool. The model distinguishes 9 surface types of which 5 are different vegetation types, bare soil, land ice, lake and ocean shelf. Including the ocean shelf allows to treat continuous changes in sea level and shelf area associated with glacial cycles. Over each surface type the model solves the surface energy balance and computes the fluxes of sensible, latent and ground heat and upward shortwave and longwave radiation. It includes a single snow layer. The soil model distinguishes between three different macro surface types which have their own soil column: vegetation and bare soil, ice sheet and ocean shelf. The soil is vertically discretized into 5 layers where prognostic equations for temperature, water and carbon are consistently solved. Phase changes of water in the soil are explicitly considered. A surface hydrology module computes precipitation interception by vegetation, surface runoff and soil infiltration. The soil water equation is based on Darcy's law. Given soil water content, the wetland fraction is computed based on a topographic index. Photosynthesis is computed using a light use efficiency model. Carbon assimilation by vegetation is coupled to the transpiration of water through stomatal conductance. The model includes a dynamic vegetation module with 5 plant functional types competing for the gridcell share with their respective net primary productivity. Each macro surface type has its own carbon pools represented by a litter, a fast

  3. Event attribution using data assimilation in an intermediate complexity atmospheric model

    NASA Astrophysics Data System (ADS)

    Metref, Sammy; Hannart, Alexis; Ruiz, Juan; Carrassi, Alberto; Bocquet, Marc; Ghil, Michael

    2016-04-01

    A new approach, coined DADA (Data Assimilation for Detection and Attribution) has been recently introduced by Hannart et al. 2015, and is potentially useful for near real time, systematic causal attribution of weather and climate-related events The method is purposely designed to allow its operability at meteorological centers by synergizing causal attribution with Data Assimilation (DA) methods usually designed to deal with large nonlinear models. In Hannart et al. 2015, the DADA proposal is illustrated in the context of a low-order nonlinear model (forced three-variable Lorenz model) that is of course not realistic to represent the events considered. As a continuation of this stream of work, we therefore propose an implementation of the DADA approach in a realistic intermediate complexity atmospheric model (ICTP AGCM, nicknamed SPEEDY). The SPEEDY model is based on a spectral dynamical core developed at the Geophysical Fluid Dynamics Laboratory (see Held and Suarez 1994). It is a hydrostatic, r-coordinate, spectral-transform model in the vorticity-divergence form described by Bourke (1974). A synthetic dataset of observations of an extreme precipitation event over Southeastern South America is extracted from a long SPEEDY simulation under present climatic conditions (i.e. factual conditions). Then, following the DADA approach, observations of this event are assimilated twice in the SPEEDY model: first in the factual configuration of the model and second under its counterfactual, pre-industrial configuration. We show that attribution can be performed based on the likelihood ratio as in Hannart et al. 2015, but we further extend this result by showing that the likelihood can be split in space, time and variables in order to help identify the specific physical features of the event that bear the causal signature. References: Hannart A., A. Carrassi, M. Bocquet, M. Ghil, P. Naveau, M. Pulido, J. Ruiz, P. Tandeo (2015) DADA: Data assimilation for the detection and

  4. Wave-induced upper-ocean mixing in a climate model of intermediate complexity

    NASA Astrophysics Data System (ADS)

    Babanin, Alexander V.; Ganopolski, Andrey; Phillips, William R. C.

    Climate modelling, to a great extent, is based on simulating air-sea interactions at larger scales. Small-scale interactions and related phenomena, such as wind-generated waves and wave-induced turbulence are sub-grid processes for such models and therefore cannot be simulated explicitly. In the meantime, the waves play the principal role in the upper-ocean mixing. This role is usually parameterized, mostly to account for the wave-breaking turbulence and to describe downward diffusion of such turbulence. The main purpose of the paper is to demonstrate that an important physical mechanism, that is the ocean mixing due to waves, is presently missing in the climate models, whereas the effect of this mixing is significant. It is argued that the mixing role of the surface waves is not limited to the mere transfer of the wind stress and energy across the ocean interface by means of breaking and surface currents. The waves facilitate two processes in the upper-ocean which can deliver turbulence to the depths of the order of 100 m directly, rather than diffusing it from the surface. The first process is due to capacity of the waves to generate turbulence, unrelated to the wave breaking, at all depths where the wave orbital motion is significant. The second process is Langmuir circulation, triggered by the waves. Such wave-controlled mixing should cause seasonal variations of the mixed-layer depth, which regulates the thermodynamic balance between the ocean and atmosphere. In the present paper, these variations are parameterized in terms of the global winds. The variable mixed-layer depth is then introduced in the climate model of intermediated complexity CLIMBER-2 with a purpose of reproducing the pre-industrial climate. Comparisons are conducted with the NRL global atlas of the mixed layer, and performance of the wave-mixing parameterisations was found satisfactory in circumstances where the mixing is expected to be dominated by the wind-generated waves. It is shown that

  5. Analysis of solvent nucleophile isotope effects: evidence for concerted mechanisms and nucleophilic activation by metal coordination in nonenzymatic and ribozyme-catalyzed phosphodiester hydrolysis.

    PubMed

    Cassano, Adam G; Anderson, Vernon E; Harris, Michael E

    2004-08-17

    Heavy atom isotope effects are a valuable tool for probing chemical and enzymatic reaction mechanisms; yet, they are not widely applied to examine mechanisms of nucleophilic activation. We developed approaches for analyzing solvent (18)O nucleophile isotope effects ((18)k(nuc)) that allow, for the first time, their application to hydrolysis reactions of nucleotides and nucleic acids. Here, we report (18)k(nuc) for phosphodiester hydrolysis catalyzed by Mg(2+) and by the Mg(2+)-dependent RNase P ribozyme and deamination by the Zn(2+)-dependent protein enzyme adenosine deaminase (ADA). Because ADA incorporates a single solvent molecule into the product inosine, this reaction can be used to monitor solvent (18)O/(16)O ratios in complex reaction mixtures. This approach, combined with new methods for analysis of isotope ratios of nucleotide phosphates by whole molecule mass spectrometry, permitted determination of (18)k(nuc) for hydrolysis of thymidine 5'-p-nitrophenyl phosphate and RNA cleavage by the RNase P ribozyme. For ADA, an inverse (18)k(nuc) of 0.986 +/- 0.001 is observed, reflecting coordination of the nucleophile by an active site Zn(2+) ion and a stepwise mechanism. In contrast, the observed (18)k(nuc) for phosphodiester reactions were normal: 1.027 +/- 0.013 and 1.030 +/- 0.012 for the Mg(2+)- and ribozyme-catalyzed reactions, respectively. Such normal effects indicate that nucleophilic attack occurs in the rate-limiting step for these reactions, consistent with concerted mechanisms. However, these magnitudes are significantly less than the (18)k(nuc) observed for nucleophilic attack by hydroxide (1.068 +/- 0.007), indicating a "stiffer" bonding environment for the nucleophile in the transition state. Kinetic analysis of the Mg(2+)-catalyzed reaction indicates that a Mg(2+)-hydroxide complex is the catalytic species; thus, the lower (18)k(nuc), in large part, reflects direct metal ion coordination of the nucleophilic oxygen. A similar value for the RNase P

  6. Reaction of a copper(II)-nitrosyl complex with hydrogen peroxide: phenol ring nitration through a putative peroxynitrite intermediate.

    PubMed

    Kalita, Apurba; Deka, Ramesh C; Mondal, Biplab

    2013-10-07

    Copper(II) complex, 1, with the histidine-derived ligand L (L = methyl 2-(2-hydroxybenzylamino)-3-(1H-imidazol-5-yl)propanoate) has been synthesized and characterized. Single-crystal structure determination reveals a diphenolato-bridged dicopper(II) core in 1. Addition of (•)NO to an acetonitrile solution of 1 affords the corresponding mononuclear copper(II)-nitrosyl complex, 2. In the presence of H2O2, 2 results in formation of the corresponding copper(I)-peroxynitrite. Formation of peroxynitrite ((-)OONO) intermediate is evident from its characteristic phenol ring nitration reaction which resembles the tyrosine nitration in biological systems. Further, isolation of nitrate (NO3(-)) as the decomposition product from 2 at room temperature also supports the involvement of (-)OONO intermediate.

  7. Synthetic mononuclear nonheme iron-oxygen intermediates.

    PubMed

    Nam, Wonwoo

    2015-08-18

    Mononuclear nonheme iron-oxygen species, such as iron-superoxo, -peroxo, -hydroperoxo, and -oxo, are key intermediates involved in dioxygen activation and oxidation reactions catalyzed by nonheme iron enzymes. Because these iron-oxygen intermediates are short-lived due to their thermal instability and high reactivity, it is challenging to investigate their structural and spectroscopic properties and reactivity in the catalytic cycles of the enzymatic reactions themselves. One way to approach such problems is to synthesize biomimetic iron-oxygen complexes and to tune their geometric and electronic structures for structural characterization and reactivity studies. Indeed, a number of biologically important iron-oxygen species, such as mononuclear nonheme iron(III)-superoxo, iron(III)-peroxo, iron(III)-hydroperoxo, iron(IV)-oxo, and iron(V)-oxo complexes, were synthesized recently, and the first X-ray crystal structures of iron(III)-superoxo, iron(III)-peroxo, and iron(IV)-oxo complexes in nonheme iron models were successfully obtained. Thus, our understanding of iron-oxygen intermediates in biological reactions has been aided greatly from the studies of the structural and spectroscopic properties and the reactivities of the synthetic biomimetic analogues. In this Account, we describe our recent results on the synthesis and characterization of mononuclear nonheme iron-oxygen complexes bearing simple macrocyclic ligands, such as N-tetramethylated cyclam ligand (TMC) and tetraamido macrocyclic ligand (TAML). In the case of iron-superoxo complexes, an iron(III)-superoxo complex, [(TAML)Fe(III)(O2)](2-), is described, including its crystal structure and reactivities in electrophilic and nucleophilic oxidative reactions, and its properties are compared with those of a chromium(III)-superoxo complex, [(TMC)Cr(III)(O2)(Cl)](+), with respect to its reactivities in hydrogen atom transfer (HAT) and oxygen atom transfer (OAT) reactions. In the case of iron-peroxo intermediates

  8. Modeling of catalytically active metal complex species and intermediates in reactions of organic halides electroreduction.

    PubMed

    Lytvynenko, Anton S; Kolotilov, Sergey V; Kiskin, Mikhail A; Eremenko, Igor L; Novotortsev, Vladimir M

    2015-02-28

    The results of quantum chemical modeling of organic and metal-containing intermediates that occur in electrocatalytic dehalogenation reactions of organic chlorides are presented. Modeling of processes that take place in successive steps of the electrochemical reduction of representative C1 and C2 chlorides - CHCl3 and Freon R113 (1,1,2-trifluoro-1,2,2-trichloroethane) - was carried out by density functional theory (DFT) and second-order Møller-Plesset perturbation theory (MP2). It was found that taking solvation into account using an implicit solvent model (conductor-like screening model, COSMO) or considering explicit solvent molecules gave similar results. In addition to modeling of simple non-catalytic dehalogenation, processes with a number of complexes and their reduced forms, some of which were catalytically active, were investigated by DFT. Complexes M(L1)2 (M = Fe, Co, Ni, Cu, Zn, L1H = Schiff base from 2-pyridinecarbaldehyde and the hydrazide of 4-pyridinecarboxylic acid), Ni(L2) (H2L2 is the Schiff base from salicylaldehyde and 1,2-ethylenediamine, known as salen) and Co(L3)2Cl2, representing a fragment of a redox-active coordination polymer [Co(L3)Cl2]n (L3 is the dithioamide of 1,3-benzenedicarboxylic acid), were considered. Gradual changes in electronic structure in a series of compounds M(L1)2 were observed, and correlations between [M(L1)2](0) spin-up and spin-down LUMO energies and the relative energies of the corresponding high-spin and low-spin reduced forms, as well as the shape of the orbitals, were proposed. These results can be helpful for determination of the nature of redox-processes in similar systems by DFT. No specific covalent interactions between [M(L1)2](-) and the R113 molecule (M = Fe, Co, Ni, Zn) were found, which indicates that M(L1)2 electrocatalysts act rather like electron transfer mediators via outer-shell electron transfer. A relaxed surface scan of the adducts {M(L1)2·R113}(-) (M = Ni or Co) versus the distance between the

  9. A common intermediate for N2 formation in enzymes and zeolites: side-on Cu-nitrosyl complexes

    SciTech Connect

    Kwak, Ja Hun; Lee, Jong H.; Burton, Sarah D.; Lipton, Andrew S.; Peden, Charles HF; Szanyi, Janos

    2013-09-16

    Understanding the mechanisms of catalytic processes requires the identification of reaction centers and key intermediates, both of which are often achieved by the use of spectroscopic characterization tools. Due to the heterogeneity of active centers in heterogeneous catalysts, it is frequently difficult to identify the specific sites that are responsible for the overall activity. Furthermore, the simultaneous presence of a large number of surface species on the catalyst surface often poses a great challenge for the unambiguous determination of the relevant species in the reaction mechanism. In contrast, enzymes possess catalytically active centers with precisely defined coordination environments that are only able to accommodate intermediates relevant to the specific catalytic process. Here we show that side-on Cu+-NO+ complexes characterized by high magnetic field solid state magic angle spinning nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) spectroscopies are the key intermediates in the selective catalytic reduction of NO over Cu-SSZ-13 zeolite catalysts. Analogous intermediates have been observed and characterized in nitrite reductase enzymes, and shown to be the critical intermediates in the formation of N2 for anaerobic ammonium oxidation reactions.[1] The identification of this key reaction intermediate, combined with the results of our prior kinetic studies, allows us to propose a new reaction mechanism for the selective catalytic reduction of NO with NH3 under oxygen-rich environments over Cu-SSZ-13 zeolites, a key reaction in automotive emission control. The authors acknowledge the US Department of Energy (DOE), Office of Energy Efficiency and Renewable Energy/Vehicle Technologies Program for the support of this work. The research described in this paper was performed at the Environmental Molecular Sciences Laboratory (EMSL), a national scientific user facility sponsored by the DOE’s Office of Biological and Environmental

  10. Interrupting Nazarov Reaction with Different Trapping Modality: Utilizing Potassium Alkynyltrifluoroborate as a σ-Nucleophile.

    PubMed

    William, Ronny; Wang, Siming; Mallick, Asadulla; Liu, Xue-Wei

    2016-09-16

    The putative oxyallyl cation intermediate generated following Nazarov cyclization of dienone has been successfully intercepted with potassium alkynyltrifluoroborates which act as σ-nucleophiles in the presence of BF3·Et2O. This new trapping modality allowed unprecedented introduction of an alkynyl moiety to the cyclopentanone framework by means of an interrupted Nazarov reaction. The α-alkynyl cyclopentanone product can be further transformed into an array of densely functionalized cyclic compounds.

  11. Spectroscopic characterization of the complex between water and the simplest Criegee intermediate CH{sub 2}OO

    SciTech Connect

    Nakajima, Masakazu; Endo, Yasuki

    2014-04-07

    The hydrogen-bonded complex between water and the simplest Criegee intermediate CH{sub 2}OO was detected by Fourier-transform microwave spectroscopy under a jet-cooled condition. Both a-type and b-type rotational transitions were observed for H{sub 2}O–CH{sub 2}OO and D{sub 2}O–CH{sub 2}OO. The determined rotational constants enable us to conclude that the complex has an almost planar ring structure with the terminal oxygen atom of CH{sub 2}OO being a strong proton acceptor.

  12. Study of quinones reactions with wine nucleophiles by cyclic voltammetry.

    PubMed

    Oliveira, Carla M; Barros, António S; Ferreira, António C S; Silva, Artur M S

    2016-11-15

    Quinones are electrophilic species which can react with various nucleophiles, like wine antioxidants, such as sulfur dioxide or ascorbic acid, thiols, amino acids, and numerous polyphenols. These reactions are very important in wine aging because they mediate oxygen reactions during both production and bottle aging phases. In this work, the major challenge was to determine the interaction between ortho-quinones and wine nucleophiles (amino acids, thiols, and the antioxidants SO2 and ascorbic acid), by cyclic voltammetry. Wine-model solutions with gallic acid, caffeic acid, or (+)-catechin and nucleophilic compounds were used. To understand the effect of nucleophilic addition in wine, a white wine with the same added nucleophiles was also analysed. Cyclic voltammograms were taken with glassy carbon electrode or screen-printed carbon electrodes, respectively, for wine-model and white wines solutions, in the absence and in the presence of nucleophiles. A nucleophilic order profile related to the cathodic current intensity decrease was observed.

  13. Identification of intermediates and products in the reaction of porphyrin iron(III) alkyl complexes with dioxygen

    SciTech Connect

    Arasasingham, R.D.; Balch, A.L.; Latos-Grazynski, L.

    1987-09-16

    Unlike most PFe/sup III+/ (P is a porphyrin dianion) complexes, complexes of the type PFe/sup III/CH/sub 2/R (R = H or CH/sub 3/) are reactive toward dioxygen with the ubiquitous PFe/sup III/O-Fe/sup III/P as the only reported product. Here the authors report on /sup 1/H NMR studies of this reaction which focus on the detection of intermediates and the fate of the alkyl group. These results should be viewed in the context of extensive previous studies on model systems for dioxygen activation in biological systems (heme oxygenases) involving reaction of dioxygen with PFe/sup II/ and on the interaction of peracids and hydroperoxides with PFe/sup III/. Through these studies a number of reactive intermediates including the peroxobridge complex, PFe/sup III/-O-O-Fe/sup III/P, and the ferryl complexes, PFe/sup IV/ double bond O, (B)P-Fe/sup IV/ double bond O (B is an amine), and (P)Fe/sup IV/ double bond O/sup +/ (P is a porphyrin radical monoanion), have been detected.

  14. EXAFS structural study of platinum-based anticancer drugs degradation in presence of sulfur nucleophilic species.

    PubMed

    Provost, Karine; Bouvet-Muller, Diane; Crauste-Manciet, Sylvie; Moscovici, Jacques; Olivi, Luca; Vlaic, Gilberto; Michalowicz, Alain

    2009-10-01

    Three platinum complexes, cisplatin, carboplatin and oxaliplatin are currently used worldwide. Investigation of their main structural modifications in presence of sulfur nucleophiles is of particular interest because of the implication of thiol and thioether groups in biochemical mechanism of action, resistance mechanism and in vivo or in vitro detoxification. We present the main structural results we have obtained concerning the reaction of these drugs with diverse sulfur nucleophiles (cysteine, glutathione, methionine, thiosulfate and thiocyanate), monitored in solution or as precipitates by EXAFS spectroscopy. The reactivities of the carboxylate and amine ligands of both carboplatin and oxaliplatin are compared, on the basis of first-coordination sphere modeling. Among the new results of this EXAFS study, we present the first observation of oxaliplatin diaminocyclohexane ligand displacement by sulfur nucleophiles.

  15. Multipotent neural stem cells generate glial cells of the central complex through transit amplifying intermediate progenitors in Drosophila brain development.

    PubMed

    Viktorin, Gudrun; Riebli, Nadia; Popkova, Anna; Giangrande, Angela; Reichert, Heinrich

    2011-08-15

    The neural stem cells that give rise to the neural lineages of the brain can generate their progeny directly or through transit amplifying intermediate neural progenitor cells (INPs). The INP-producing neural stem cells in Drosophila are called type II neuroblasts, and their neural progeny innervate the central complex, a prominent integrative brain center. Here we use genetic lineage tracing and clonal analysis to show that the INPs of these type II neuroblast lineages give rise to glial cells as well as neurons during postembryonic brain development. Our data indicate that two main types of INP lineages are generated, namely mixed neuronal/glial lineages and neuronal lineages. Genetic loss-of-function and gain-of-function experiments show that the gcm gene is necessary and sufficient for gliogenesis in these lineages. The INP-derived glial cells, like the INP-derived neuronal cells, make major contributions to the central complex. In postembryonic development, these INP-derived glial cells surround the entire developing central complex neuropile, and once the major compartments of the central complex are formed, they also delimit each of these compartments. During this process, the number of these glial cells in the central complex is increased markedly through local proliferation based on glial cell mitosis. Taken together, these findings uncover a novel and complex form of neurogliogenesis in Drosophila involving transit amplifying intermediate progenitors. Moreover, they indicate that type II neuroblasts are remarkably multipotent neural stem cells that can generate both the neuronal and the glial progeny that make major contributions to one and the same complex brain structure.

  16. Palladium-catalyzed allylation of acidic and less nucleophilic anilines using allylic alcohols directly.

    PubMed

    Hsu, Yi-Chun; Gan, Kim-Hong; Yang, Shyh-Chyun

    2005-10-01

    The direct activation of C-O bonds in allylic alcohols by palladium complexes has been accelerated by carrying out the reactions in the presence of titanium(IV) isoproxide and 4 A molecular sieves. The acidic and less nucleophilic anilines such as diphenylamine, phenothiazine, 4-cyanoaniline, and nitroanilines are efficiently allylated under palladium catalysis using allylic alcohols as allylating reagents.

  17. Structure of Leishmania major methionyl-tRNA synthetase in complex with intermediate products methionyladenylate and pyrophosphate.

    PubMed

    Larson, Eric T; Kim, Jessica E; Zucker, Frank H; Kelley, Angela; Mueller, Natascha; Napuli, Alberto J; Verlinde, Christophe L M J; Fan, Erkang; Buckner, Frederick S; Van Voorhis, Wesley C; Merritt, Ethan A; Hol, Wim G J

    2011-03-01

    Leishmania parasites cause two million new cases of leishmaniasis each year with several hundreds of millions of people at risk. Due to the paucity and shortcomings of available drugs, we have undertaken the crystal structure determination of a key enzyme from Leishmania major in hopes of creating a platform for the rational design of new therapeutics. Crystals of the catalytic core of methionyl-tRNA synthetase from L. major (LmMetRS) were obtained with the substrates MgATP and methionine present in the crystallization medium. These crystals yielded the 2.0 Å resolution structure of LmMetRS in complex with two products, methionyladenylate and pyrophosphate, along with a Mg(2+) ion that bridges them. This is the first class I aminoacyl-tRNA synthetase (aaRS) structure with pyrophosphate bound. The residues of the class I aaRS signature sequence motifs, KISKS and HIGH, make numerous contacts with the pyrophosphate. Substantial differences between the LmMetRS structure and previously reported complexes of Escherichia coli MetRS (EcMetRS) with analogs of the methionyladenylate intermediate product are observed, even though one of these analogs only differs by one atom from the intermediate. The source of these structural differences is attributed to the presence of the product pyrophosphate in LmMetRS. Analysis of the LmMetRS structure in light of the Aquifex aeolicus MetRS-tRNA(Met) complex shows that major rearrangements of multiple structural elements of enzyme and/or tRNA are required to allow the CCA acceptor triplet to reach the methionyladenylate intermediate in the active site. Comparison with sequences of human cytosolic and mitochondrial MetRS reveals interesting differences near the ATP- and methionine-binding regions of LmMetRS, suggesting that it should be possible to obtain compounds that selectively inhibit the parasite enzyme.

  18. Deformylation Reaction by a Nonheme Manganese(III)-Peroxo Complex via Initial Hydrogen-Atom Abstraction.

    PubMed

    Barman, Prasenjit; Upadhyay, Pranav; Faponle, Abayomi S; Kumar, Jitendra; Nag, Sayanta Sekhar; Kumar, Devesh; Sastri, Chivukula V; de Visser, Sam P

    2016-09-05

    Metal-peroxo intermediates are key species in the catalytic cycles of nonheme metalloenzymes, but their chemical properties and reactivity patterns are still poorly understood. The synthesis and characterization of a manganese(III)-peroxo complex with a pentadentate bispidine ligand system and its reactivity with aldehydes was studied. Manganese(III)-peroxo can react through hydrogen-atom abstraction reactions instead of the commonly proposed nucleophilic addition reaction. Evidence of the mechanism comes from experiments which identify a primary kinetic isotope effect of 5.4 for the deformylation reaction. Computational modeling supports the established mechanism and identifies the origin of the reactivity preference of hydrogen-atom abstraction over nucleophilic addition.

  19. Functionalization of metallabenzenes through nucleophilic aromatic substitution of hydrogen.

    PubMed

    Clark, George R; Ferguson, Lauren A; McIntosh, Amy E; Söhnel, Tilo; Wright, L James

    2010-09-29

    The cationic metallabenzenes [Ir(C(5)H(4){SMe-1})(κ(2)-S(2)CNEt(2))(PPh(3))(2)]PF(6) (1) and [Os(C(5)H(4){SMe-1})(CO)(2)(PPh(3))(2)][CF(3)SO(3)] (2) undergo regioselective nucleophilic aromatic substitution of hydrogen at the metallabenzene ring position γ to the metal in a two-step process that first involves treatment with appropriate nucleophiles and then oxidation. Thus, reaction between compound 1 and NaBH(4), MeLi, or NaOEt gives the corresponding neutral iridacyclohexa-1,4-diene complexes Ir(C(5)H(3){SMe-1}{H-3}{Nu-3})(κ(2)-S(2)CNEt(2))(PPh(3))(2) (Nu = H (3), Me (4), OEt (5)). Similarly, reaction between 2 and NaBH(4) or MeLi gives the corresponding osmacyclohexa-1,4-diene complexes Os(C(5)H(3){SMe-1}{H-3}{Nu-3})(CO)(2)(PPh(3))(2) (Nu = H (8), Me (9)). The metallacyclohexa-1,4-diene rings in all these compounds are rearomatized on treatment with the oxidizing agent O(2), CuCl(2), or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Accordingly, the cationic metallabenzene 1 or 2 is returned after reaction between 3 and DDQ/NEt(4)PF(6) or between 8 and DDQ/NaO(3)SCF(3), respectively. The substituted cationic iridabenzene [Ir(C(5)H(3){SMe-1}{Me-3})(κ(2)-S(2)CNEt(2))(PPh(3))(2)]PF(6) (6) or [Ir(C(5)H(4){SMe-1}{OEt-3})(κ(2)-S(2)CNEt(2))(PPh(3))(2)]PF(6) (7) is produced in a similar manner through reaction between 4 or 5, respectively, and DDQ/NEt(4)PF(6), and the substituted cationic osmabenzene [Os(C(5)H(3){SMe-1}{Me-3})(CO)(2)(PPh(3))(2)]Cl (10) is formed in good yield on treatment of 9 with CuCl(2). The starting cationic iridabenzene 1 is conveniently prepared by treatment of the neutral iridabenzene Ir(C(5)H(4){SMe-1})Cl(2)(PPh(3))(2) with NaS(2)CNEt(2) and NEt(4)PF(6), and the related starting cationic osmabenzene 2 is obtained by treatment of Os(C(5)H(4){S-1})(CO)(PPh(3))(2) with CF(3)SO(3)CH(3) and CO. The stepwise transformations of 1 into 6 or 7 as well as 2 into 10 provide the first examples in metallabenzene chemistry of regioselective

  20. Aryl-phenyl scrambling in intermediate organopalladium complexes: a gas-phase study of the Mizoroki-Heck reaction.

    PubMed

    Fiebig, Lukas; Schlörer, Nils; Schmalz, Hans-Günther; Schäfer, Mathias

    2014-04-22

    The intramolecular aryl-phenyl scrambling reaction within palladium-DPPP-aryl complex (DPPP=1,3-bis(diphenylphosphino)propane) ions was analyzed by state-of-the-art tandem MS, including gas-phase ion/molecule reactions. The Mizoroki-Heck cross-coupling reaction was performed in the gas phase, and the intrinsic reactivity of important intermediates could be examined. Moreover, linear free-energy correlations were applied, and a mechanism for the scrambling reaction proceeding via phosphonium cations was assumed.

  1. Development of a Raman spectroscopy technique to detect alternate transportation fuel hydrocarbon intermediates in complex combustion environments.

    SciTech Connect

    Ekoto, Isaac W.; Barlow, Robert S.

    2012-12-01

    Spontaneous Raman spectra for important hydrocarbon fuels and combustion intermediates were recorded over a range of low-to-moderate flame temperatures using the multiscalar measurement facility located at Sandia/CA. Recorded spectra were extrapolated to higher flame temperatures and then converted into empirical spectral libraries that can readily be incorporated into existing post-processing analysis models that account for crosstalk from overlapping hydrocarbon channel signal. Performance testing of the developed libraries and reduction methods was conducted through an examination of results from well-characterized laminar reference flames, and was found to provide good agreement. The diagnostic development allows for temporally and spatially resolved flame measurements of speciated hydrocarbon concentrations whose parent is more chemically complex than methane. Such data are needed to validate increasingly complex flame simulations.

  2. Nucleophilic Substitution Reactions Using Phosphine Nucleophiles: An Introduction to Phosphorus-31 NMR

    ERIC Educational Resources Information Center

    Sibbald, Paul A.

    2015-01-01

    Nuclear magnetic resonance (NMR) spectroscopy is commonly used in modern synthetic chemistry to monitor the conversion of reactants to products. Since instruction in the use of NMR spectroscopy typically does not occur until after the introduction of nucleophilic substitution reactions, organic chemistry students are not able to take advantage of…

  3. Nucleophilic substitutions of 1-alkenylcyclopropyl esters and 1-alkynylcyclopropyl chlorides catalyzed by palladium (0)

    SciTech Connect

    Stolle, A. |; Ollivier, J.; Salauen, J.

    1992-05-20

    The 1-ethenylcyclopropylsulfonates 2e,f and 2-cyclopropylideneethyl esters 10b,c, readily available from cyclopropanone hemiacetal 1, undergo regioselective Pd(0) catalyzed nucleophilic substitution via the unsymmetric 1,1-dimethylene-{pi}-allyl complex 23. With stabilized anions (enolates of malonic ester, {beta}-dicarbonyl compounds, {beta}-sulfonyl ester, and Schiff bases as well as acetate anion, sulfonamide anion, etc.) the nucleophilic substitution occurs at the terminal vinylic position exclusively, providing cyclopropylideneethyl derivatives as building blocks of high synthetic potential. Competition experiments have disclosed that 1-ethenylcyclopropyl tosylate (2e) and cyclopropylideneethyl acetate (10b) are more reactive than dimethylallyl acetates 19 and 22, respectively. Use of chiral phosphines as ligands in the palladium catalyst can provide optically active methylenecyclopropane derivatives. With phenyl-, methyl-, and even n-butylzinc chloride as nucleophiles, the reaction apparently proceeds with initial transfer of the organic residue to palladium, followed by reductive elimination entailing tertiary substitution on the cyclopropane ring exclusively; the same type of product is obtained with azide and bis(trimethylsilyl)amide. But the site of hydride attack to yield reduction products depends on the hydride source. 1-Alkynylcyclopropyl chlorides 12, 13, and 14 react only with organozinc chlorides (nonstabilized nucleophiles) to provide mixtures of ethenylidenecyclopropanes 65 and alkynylcyclopropanes 66, via the {sigma}-palladium complexes 69 and 70, while chloride 15 undergoes mainly reduction. Other transition metal catalysts (Ni, Mo) also induce substitutions, but with poorer regioselectivity. 81 refs., 9 figs., 3 tabs.

  4. Priming of Simple and Complex Scene Layout: Rapid Function from the Intermediate Level

    ERIC Educational Resources Information Center

    Sanocki, Thomas; Sulman, Noah

    2009-01-01

    Three experiments examined the time course of layout priming with photographic scenes varying in complexity (number of objects). Primes were presented for varying durations (800-50 ms) before a target scene with 2 spatial probes; observers indicated whether the left or right probe was closer to viewpoint. Reaction time was the main measure. Scene…

  5. Electronic Structure of a Cu(II)-Alkoxide Complex Modeling Intermediates in Copper-Catalyzed Alcohol Oxidations.

    PubMed

    Hayes, Ellen C; Porter, Thomas R; Barrows, Charles J; Kaminsky, Werner; Mayer, James M; Stoll, Stefan

    2016-03-30

    In the copper-catalyzed oxidation of alcohols to aldehydes, a Cu(II)-alkoxide (Cu(II)-OR) intermediate is believed to modulate the αC-H bond strength of the deprotonated substrate to facilitate the oxidation. As a structural model for these intermediates, we characterized the electronic structure of the stable compound Tp(tBu)Cu(II)(OCH2CF3) (Tp(tBu) = hydro-tris(3-tert-butyl-pyrazolyl)borate) and investigated the influence of the trifluoroethoxide ligand on the electronic structure of the complex. The compound exhibits an electron paramagnetic resonance (EPR) spectrum with an unusually large gzz value of 2.44 and a small copper hyperfine coupling Azz of 40 × 10(-4) cm(-1) (120 MHz). Single-crystal electron nuclear double resonance (ENDOR) spectra show that the unpaired spin population is highly localized on the copper ion (≈68%), with no more than 15% on the ethoxide oxygen. Electronic absorption and magnetic circular dichroism (MCD) spectra show weak ligand-field transitions between 5000 and 12,000 cm(-1) and an intense ethoxide-to-copper charge transfer (LMCT) transition at 24,000 cm(-1), resulting in the red color of this complex. Resonance Raman (rR) spectroscopy reveals a Cu-O stretch mode at 592 cm(-1). Quantum chemical calculations support the interpretation and assignment of the experimental data. Compared to known Cu(II)-thiolate and Cu(II)-alkylperoxo complexes from the literature, we found an increased σ interaction in the Cu(II)-OR bond that results in the spectroscopic features. These insights lay the basis for further elucidating the mechanism of copper-catalyzed alcohol oxidations.

  6. Electronic Structure of a CuII-Alkoxide Complex Modeling Intermediates in Copper-Catalyzed Alcohol Oxidations

    PubMed Central

    Hayes, Ellen C.; Porter, Thomas R.; Barrows, Charles J.; Kaminsky, Werner; Mayer, James M.; Stoll, Stefan

    2016-01-01

    In the copper-catalyzed oxidation of alcohols to aldehydes, a CuII-alkoxide (CuII-OR) intermediate is believed to modulate the αC-H bond strength of the deprotonated substrate to facilitate the oxidation. As a structural model for these intermediates, we characterized the electronic structure of the stable compound TptBuCuII(OCH2CF3) (TptBu = (hydro-tris (3-tert-butyl-pyrazolyl) borate) and investigated the influence of the trifluoroethoxide ligand on the electronic structure of the complex. The compound exhibits an electron paramagnetic resonance (EPR) spectrum with an unusually large gzz value of 2.44 and a small copper hyperfine coupling Azz of 40·10−4 cm−1 (120 MHz). Single-crystal electron nuclear double resonance (ENDOR) spectra show that the unpaired spin population is highly localized on the copper ion (≈ 68 %), with no more than 15 % on the ethoxide oxygen. Electronic absorption and magnetic circular dichroism (MCD) spectra show weak ligand-field transitions between 5000 and 12000 cm−1 and an intense ethoxide-to-copper charge transfer (LMCT) transition at 24000 cm−1, resulting in the red color of this complex. Resonance Raman (rR) spectroscopy reveals a Cu-O stretch mode at 592 cm−1. Quantum chemical calculations support the interpretation and assignment of the experimental data. Compared to known CuII-thiolate and CuII-alkylperoxo complexes from the literature, we found an increased σ interaction in the CuII-OR bond that results in the spectroscopic features. These insights lay the basis for further elucidating the mechanism of copper-catalyzed alcohol oxidations. PMID:26907976

  7. Structure and function of outer dynein arm intermediate and light chain complex

    PubMed Central

    Oda, Toshiyuki; Abe, Tatsuki; Yanagisawa, Haruaki; Kikkawa, Masahide

    2016-01-01

    The outer dynein arm (ODA) is a molecular complex that drives the beating motion of cilia/flagella. Chlamydomonas ODA is composed of three heavy chains (HCs), two ICs, and 11 light chains (LCs). Although the three-dimensional (3D) structure of the whole ODA complex has been investigated, the 3D configurations of the ICs and LCs are largely unknown. Here we identified the 3D positions of the two ICs and three LCs using cryo–electron tomography and structural labeling. We found that these ICs and LCs were all localized at the root of the outer-inner dynein (OID) linker, designated the ODA-Beak complex. Of interest, the coiled-coil domain of IC2 extended from the ODA-Beak to the outer surface of ODA. Furthermore, we investigated the molecular mechanisms of how the OID linker transmits signals to the ODA-Beak, by manipulating the interaction within the OID linker using a chemically induced dimerization system. We showed that the cross-linking of the OID linker strongly suppresses flagellar motility in vivo. These results suggest that the ICs and LCs of the ODA form the ODA-Beak, which may be involved in mechanosignaling from the OID linker to the HCs. PMID:26864626

  8. A SeCSe-Pd(II) pincer complex as a highly efficient catalyst for allylation of aldehydes with allyltributyltin.

    PubMed

    Yao, Qingwei; Sheets, Matthew

    2006-07-07

    An air- and moisture-stable SeCSe-Pd(II) pincer complex was synthesized and found to catalyze the nucleophilic allylation of aldehydes with allyltributyltin. The allylation of a variety of aromatic and aliphatic aldehydes to give the corresponding homoallyl alcohols was performed at room temperature to 60 degrees C in yields ranging from 50% (for typical aliphatic aldehydes) to up to 97% (for aromatic aldehydes) using 5 x 10(-3) to 1 mol % of the Pd catalyst. NMR spectroscopic study indicated that a sigma-allylpalladium intermediate was formed and possibly functions as the nucleophilic species that undergoes addition to the aldehydes.

  9. Critical analysis of Strattice performance in complex abdominal wall reconstruction: intermediate-risk patients and early complications.

    PubMed

    Patel, Ketan M; Albino, Frank P; Nahabedian, Maurice Y; Bhanot, Parag

    2013-01-01

    The purpose of this study was to analyze the performance of a porcine-derived acellular dermal matrix (Strattice Reconstructive Tissue Matrix) in patients at increased risk for perioperative complications. We reviewed medical records for patients with complex abdominal wall reconstruction (AWR) and Strattice underlay from 2007 to 2010. Intermediate-risk patients were defined as having multiple comorbidities without abdominal infection. Forty-one patients met the inclusion criteria (mean age, 60 years; mean body mass index, 35.5 kg/m(2)). Comorbidities included coronary artery disease (63.4%), diabetes mellitus (36.6%), and chronic obstructive pulmonary disease (17.1%). Fascial closure was achieved in 40 patients (97.6%). Average hospitalization was 6.4 days (range, 1-24 days). Complications included seroma (7.3%), wound dehiscence with Strattice exposure (4.9%), cellulitis (2.4%), and hematoma (2.4%). All patients achieved abdominal wall closure with no recurrent hernias or need for Strattice removal. Patients with multiple comorbidities at intermediate risk of postoperative complications can achieve successful, safe AWR with Strattice.

  10. Intermediates in the assembly of mitotic checkpoint complexes and their role in the regulation of the anaphase-promoting complex

    PubMed Central

    Kaisari, Sharon; Sitry-Shevah, Danielle; Miniowitz-Shemtov, Shirly; Hershko, Avram

    2016-01-01

    The mitotic (or spindle assembly) checkpoint system prevents premature separation of sister chromatids in mitosis and thus ensures the fidelity of chromosome segregation. Kinetochores that are not attached properly to the mitotic spindle produce an inhibitory signal that prevents progression into anaphase. The checkpoint system acts on the Anaphase-Promoting Complex/Cyclosome (APC/C) ubiquitin ligase, which targets for degradation inhibitors of anaphase initiation. APC/C is inhibited by the Mitotic Checkpoint Complex (MCC), which assembles when the checkpoint is activated. MCC is composed of the checkpoint proteins BubR1, Bub3, and Mad2, associated with the APC/C coactivator Cdc20. The intermediary processes in the assembly of MCC are not sufficiently understood. It is also not clear whether or not some subcomplexes of MCC inhibit the APC/C and whether Mad2 is required only for MCC assembly and not for its action on the APC/C. We used purified subcomplexes of mitotic checkpoint proteins to examine these problems. Our results do not support a model in which Mad2 catalytically generates a Mad2-free APC/C inhibitor. We also found that the release of Mad2 from MCC caused a marked (although not complete) decrease in inhibitory action, suggesting a role of Mad2 in MCC for APC/C inhibition. A previously unknown species of MCC, which consists of Mad2, BubR1, and two molecules of Cdc20, contributes to the inhibition of APC/C by the mitotic checkpoint system. PMID:26755599

  11. A Safer, Discovery-Based Nucleophilic Substitution Experiment

    ERIC Educational Resources Information Center

    Horowitz, Gail

    2009-01-01

    A discovery-based nucleophilic substitution experiment is described in which students compare the reactivity of chloride and iodide ions in an S[subscript N]2 reaction. This experiment improves upon the well-known "Competing Nucleophiles" experiment in that it does not involve the generation of hydrogen halide gas. The experiment also introduces…

  12. Competition between glutathione and guanine for a ruthenium(II) arene anticancer complex: detection of a sulfenato intermediate.

    PubMed

    Wang, Fuyi; Xu, Jingjing; Habtemariam, Abraha; Bella, Juraj; Sadler, Peter J

    2005-12-21

    The organometallic anticancer complex [(eta6-bip)Ru(en)Cl]+ (1; bip = biphenyl, en = ethylenediamine) selectively binds to guanine (N7) bases of DNA (Novakova, O.; Chen, H.; Vrana, O.; Rodger, A.; Sadler, P. J.; Brabec, V. Biochemistry 2003, 42, 11544-11554). In this work, competition between the tripeptide glutathione (gamma-L-Glu-L-Cys-Gly; GSH) and guanine (as guanosine 3',5'-cyclic monophosphate, cGMP) for complex 1 was investigated using HPLC, LC-MS and 1H,15N NMR spectroscopy. In unbuffered solution (pH ca. 3), the reaction of 1 with GSH gave rise to three intermediates: an S-bound thiolato adduct [(eta6-bip)Ru(en)(GS-S)] (4) and two carboxylate-bound glutathione products [(eta6-bip)Ru(en)(GSH-O)]+ (5, 6) during the early stages (<6 h), followed by en displacement and formation of a tri-GS-bridged dinuclear Ru(II) complex [((eta6-bip)Ru)2(GS-mu-S)3]2- (7). Under physiologically relevant conditions (micromolar Ru concentrations, pH 7, 22 mM NaCl, 310 K), the thiolato complex 4 was unexpectedly readily oxidized by dioxygen to the sulfenato complex [(eta6-bip)Ru(en)(GS(O)-S)] (8) instead of forming the dinuclear complex 7. Under these conditions, competitive reaction of complex 1 with GSH and cGMP gave rise to the cGMP adduct [(eta6-bip)Ru(en)(cGMP-N7)]+ (10) as the major product, accounting for ca. 62% of total Ru after 72 h, even in the presence of a 250-fold molar excess of GSH. The oxidation of coordinated glutathione in the thiolato complex 4 to the sulfenate in 8 appears to provide a facile route for displacement of S-bound glutathione by G N7. Redox reactions of cysteinyl adducts of these Ru(II) arene anticancer complexes could therefore play a significant role in their biological activity.

  13. Ternary polyplex micelles with PEG shells and intermediate barrier to complexed DNA cores for efficient systemic gene delivery.

    PubMed

    Li, Junjie; Chen, Qixian; Zha, Zengshi; Li, Hui; Toh, Kazuko; Dirisala, Anjaneyulu; Matsumoto, Yu; Osada, Kensuke; Kataoka, Kazunori; Ge, Zhishen

    2015-07-10

    Simultaneous achievement of prolonged retention in blood circulation and efficient gene transfection activity in target tissues has always been a major challenge hindering in vivo applications of nonviral gene vectors via systemic administration. Herein, we constructed novel rod-shaped ternary polyplex micelles (TPMs) via complexation between the mixed block copolymers of poly(ethylene glycol)-b-poly{N'-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} (PEG-b-PAsp(DET)) and poly(N-isopropylacrylamide)-b-PAsp(DET) (PNIPAM-b-PAsp(DET)) and plasmid DNA (pDNA) at room temperature, exhibiting distinct temperature-responsive formation of a hydrophobic intermediate layer between PEG shells and pDNA cores through facile temperature increase from room temperature to body temperature (~37 °C). As compared with binary polyplex micelles of PEG-b-PAsp(DET) (BPMs), TPMs were confirmed to condense pDNA into a more compact structure, which achieved enhanced tolerability to nuclease digestion and strong counter polyanion exchange. In vitro gene transfection results demonstrated TPMs exhibiting enhanced gene transfection efficiency due to efficient cellular uptake and endosomal escape. Moreover, in vivo performance evaluation after intravenous injection confirmed that TPMs achieved significantly prolonged blood circulation, high tumor accumulation, and promoted gene expression in tumor tissue. Moreover, TPMs loading therapeutic pDNA encoding an anti-angiogenic protein remarkably suppressed tumor growth following intravenous injection into H22 tumor-bearing mice. These results suggest TPMs with PEG shells and facilely engineered intermediate barrier to inner complexed pDNA have great potentials as systemic nonviral gene vectors for cancer gene therapy.

  14. The role of reactive oxygen intermediates in nonspecific monocyte cytotoxicity induced by immune complexes.

    PubMed Central

    Geffner, J R; Giordano, M; Serebrinsky, G; Isturiz, M

    1987-01-01

    Normal human monocytes were induced to lyse nonsensitized target cells when triggered by precipitating immune complexes (IC) or soluble heat-aggregated IgG (HAIgG). Catalase, azide, cyanide and three aminoacids employed as quenchers of ClO, significantly inhibited this nonspecific cytotoxicity (NSC), suggesting an important role for the myeloperoxidase (MPO) system. However, HO and/or 1O2 may also be involved in the lysis, since certain scavengers of these species such as mannitol, benzoate, ethanol and histidine, as well as superoxide dismutase (SOD), partially inhibited NSC. Moreover, cyanide and azide were unable to completely abrogate this lytic activity. When NSC was compared to antibody dependent cellular cytotoxicity (ADCC), it was found that neither catalase nor oxygen-species scavengers affected ADCC while azide and cyanide significantly enhanced it. Antibody-coated target cells were also destroyed by IC-triggered monocytes. However, kinetic analysis and studies on the capacity of catalase to inhibit the lysis demonstrated that it was mediated through a NSC-like mechanism. The cytotoxic system described in this report offers a suitable model to study in vitro alternative lytic mechanisms triggered through monocyte receptors for the Fc portion of IgG (Fc gamma R). PMID:3038442

  15. Molecular structure of the acyl-enzyme intermediate in beta-lactam hydrolysis at 1.7 A resolution.

    PubMed

    Strynadka, N C; Adachi, H; Jensen, S E; Johns, K; Sielecki, A; Betzel, C; Sutoh, K; James, M N

    1992-10-22

    The X-ray crystal structure of the molecular complex of penicillin G with a deacylation-defective mutant of the RTEM-1 beta-lactamase from Escherichia coli shows how these antibiotics are recognized and destroyed. Penicillin G is covalently bound to Ser 70 0 gamma as an acyl-enzyme intermediate. The deduced catalytic mechanism uses Ser 70 0 gamma as the attacking nucleophile during acylation. Lys 73 N zeta acts as a general base in abstracting a proton from Ser 70 and transferring it to the thiazolidine ring nitrogen atom via Ser 130 0 gamma. Deacylation is accomplished by nucleophilic attack on the penicilloyl carbonyl carbon by a water molecule assisted by the general base, Glu 166.

  16. 4-Trifluoromethyl-p-quinols as dielectrophiles: three-component, double nucleophilic addition/aromatization reactions.

    PubMed

    Dong, Jinhuan; Shi, Lou; Pan, Ling; Xu, Xianxiu; Liu, Qun

    2016-06-01

    In recent years, numerous methods have emerged for the synthesis of trifluoromethylated arenes based on the late-stage introduction of a trifluoromethyl group onto an aryl ring. In sharp comparison, the synthesis of trifluoromethylated arenes based on the pre-introduction of a trifluoromethyl group onto an "aromatic to be" carbon has rarely been addressed. It has been found that 4-trifluoromethyl-p-quinol silyl ethers, the readily available and relatively stable compounds, can act as dielectrophiles to be applied to multi-component reactions for the synthesis of various trifluoromethylated arenes. Catalyzed by In(OTf)3, 4-trifluoromethyl-p-quinol silyl ethers react with C-, N-, and S-nucleophiles, respectively, in a regiospecific 1,2-addition manner to generate the corresponding highly reactive electrophilic intermediates. Further reaction of the in-situ generated electrophiles with a C-nucleophile followed by spontaneous aromatization enables the construction of functionalized trifluoromethyl arenes. This three-component, double nucleophilic addition/aromatization reaction based on the pre-introduction of a trifluoromethyl group onto an "aromatic to be" carbon provides a divergent strategy for the synthesis of trifluoromethylated arenes under mild reaction conditions in a single operation.

  17. 4-Trifluoromethyl-p-quinols as dielectrophiles: three-component, double nucleophilic addition/aromatization reactions

    PubMed Central

    Dong, Jinhuan; Shi, Lou; Pan, Ling; Xu, Xianxiu; Liu, Qun

    2016-01-01

    In recent years, numerous methods have emerged for the synthesis of trifluoromethylated arenes based on the late-stage introduction of a trifluoromethyl group onto an aryl ring. In sharp comparison, the synthesis of trifluoromethylated arenes based on the pre-introduction of a trifluoromethyl group onto an “aromatic to be” carbon has rarely been addressed. It has been found that 4-trifluoromethyl-p-quinol silyl ethers, the readily available and relatively stable compounds, can act as dielectrophiles to be applied to multi-component reactions for the synthesis of various trifluoromethylated arenes. Catalyzed by In(OTf)3, 4-trifluoromethyl-p-quinol silyl ethers react with C-, N-, and S-nucleophiles, respectively, in a regiospecific 1,2-addition manner to generate the corresponding highly reactive electrophilic intermediates. Further reaction of the in-situ generated electrophiles with a C-nucleophile followed by spontaneous aromatization enables the construction of functionalized trifluoromethyl arenes. This three-component, double nucleophilic addition/aromatization reaction based on the pre-introduction of a trifluoromethyl group onto an “aromatic to be” carbon provides a divergent strategy for the synthesis of trifluoromethylated arenes under mild reaction conditions in a single operation. PMID:27246540

  18. Bicyclo[3.2.1]octane synthons from cyclopropenes: functionalization of cycloadducts by nucleophilic additions.

    PubMed

    Orugunty, Ravi S; Wright, Dennis L; Battiste, Merle A; Helmich, Richard J; Abboud, Khalil

    2004-01-23

    It has been known for several decades that a highly functionalized family of tetrahalobicyclo[3.2.1]octadienes are readily available through the cycloaddition of furan or cyclopentadiene with either tetrachloro- or tetrabromocyclopropene. However, the application of these highly functionalized building blocks in synthesis has remained relatively unexplored in relation to their better-known counterparts derived through oxyallyl cation additions. As a first step toward utilizing these highly versatile intermediates in synthesis, a study of the addition of various nucleophiles to the halogenated nucleus has been conducted. It has been found that these halogenated systems are amenable to a wide range of functionalizations in high yields and with good selectivities.

  19. Synthesis of a Fluorescent Acridone using a Grignard Addition, Oxidation, and Nucleophilic Aromatic Substitution Reaction Sequence.

    PubMed

    Goodrich, Samuel; Patel, Miloni; Woydziak, Zachary R

    2015-07-14

    A three-pot synthesis oriented for an undergraduate organic chemistry laboratory was developed to construct a fluorescent acridone molecule. This laboratory experiment utilizes Grignard addition to an aldehyde, alcohol oxidation, and iterative nucleophilic aromatic substitution steps to produce the final product. Each of the intermediates and the acridone product of the synthesis are analyzed by common techniques available in most undergraduate chemistry laboratories, such as melting point, TLC, IR spectroscopy, UV-Vis spectroscopy, and fluorescence spectroscopy. Yields for each transformation in the synthesis are generally moderately low to good (20-90%) and nearly all of the students (>90%) who attempted the synthesis were able to produce the final acridone product.

  20. Mono- and dinuclear non-heme iron–nitrosyl complexes: Models for key intermediates in bacterial nitric oxide reductases

    SciTech Connect

    Berto, Timothy C.; Speelman, Amy L.; Zheng, Sheng; Lehnert, Nicolai

    2013-01-01

    High-spin non-heme iron–nitrosyls are of direct interest to both the chemical and biological communities as these species exhibit interesting chemical properties and act as direct models for enzymatic intermediates. The electronic ground state of the ferrous NO complexes, {Fe–NO}7, is best described as high-spin FeIII antiferromagnetically coupled to NO-, generating the spectroscopically observed S = 3/2 ground state. These species have been identified as catalytically relevant to a variety of NO-reducing enzymes such as bacterial nitric oxide reductase (NorBC) and flavo(rubredoxin) nitric oxide reductase (FNOR). Recently, the corresponding one-electron reduced {Fe–NO}8 (nitroxyl) complexes have also been implicated as biologically significant species. In this review the available spectroscopic data for {Fe–NO}7 and {Fe–NO}8 mono- and dinuclear non-heme iron–nitrosyls are summarized, and the implications of these results with respect to the electronic structures and reactivities of these species, in particular towards NO reduction, are discussed.

  1. A General Ligand Design for Gold Catalysis allowing Ligand-Directed Anti Nucleophilic Attack of Alkynes

    PubMed Central

    Wang, Yanzhao; Wang, Zhixun; Li, Yuxue; Wu, Gongde; Cao, Zheng; Zhang, Liming

    2014-01-01

    Most homogenous gold catalyses demand ≥0.5 mol % catalyst loading. Due to the high cost of gold, these reactions are unlikely to be applicable in medium or large scale applications. Here we disclose a novel ligand design based on the privileged biphenyl-2-phosphine framework that offers a potentially general approach to dramatically lowering catalyst loading. In this design, an amide group at the 3’ position of the ligand framework directs and promotes nucleophilic attack at the ligand gold complex-activated alkyne, which is unprecedented in homogeneous gold catalysis considering the spatial challenge of using ligand to reach antiapproaching nucleophile in a linear P-Au-alkyne centroid structure. With such a ligand, the gold(I) complex becomes highly efficient in catalyzing acid addition to alkynes, with a turnover number up to 99,000. Density functional theory calculations support the role of the amide moiety in directing the attack of carboxylic acid via hydrogen bonding. PMID:24704803

  2. Nucleophilic behaviour of dioxo- and thiooxophosphorane complexes [MoCp(CO)2{E,P-EP(O)(2,4,6-C6H2(t)Bu3)}](-) (E = O, S).

    PubMed

    Alonso, María; Alvarez, M Angeles; García, M Esther; García-Vivó, Daniel; Ruiz, Miguel A

    2014-11-14

    The title anions were prepared as (DBU-H)(+) salts upon reaction of the oxophosphinidene complex (H-DBU)[MoCp(CO)2{P(O)R*}] with either dimethyldioxirane or elemental sulphur (R* = 2,4,6-C6H2(t)Bu3; Cp = η(5)-C5H5, DBU = 1,8-diazabicyclo[5.4.0]undec-7-ene). The dioxophosphorane complex failed to react with MeI at room temperature, but reacted readily with (Me3O)BF4 to give the phosphonite complex [MoCp{O,P-OP(OMe)R*}(CO)2]. In contrast, the thiooxophosphorane complex reacted with MeI to give the thiolophosphinide derivative [MoCp{S,P-(MeS)P(O)R*}(CO)2], whereas its reaction with (Me3O)BF4 gave a mixture of the latter complex and the phosphonothiolate isomer [MoCp{S,P-SP(OMe)R*}(CO)2] in similar amounts. Other electrophiles were added selectively to the terminal O atom of the R*POS ligand. Thus the thiooxophosphorane complex reacted with ClC(O)C2H3, [NH4]PF6, ClSiMe3, ClSnMe3 and [ZrCp2Cl2] to give the corresponding derivatives [MoCp{S,P-SP(OX)R*}(CO)2] (X = C(O)C2H3, H, SiMe3, SnMe3, ZrCp2Cl). The structure of two of these products (X = C(O)C2H3, SiMe3) was determined by single-crystal X-ray diffraction studies. Density functional theory (DFT) calculations of the title anions and some of their derivatives indicated that attachment of an external electrophile to the terminal O atom of the thiooxophosphorane ligand is favoured under the conditions of charge control, while the sulphur atom is the favoured site under the conditions of orbital control, although it leads to less stable products.

  3. Transition Metal Donor-Peptide-Acceptor Complexes: From Intramolecular Electron Transfer Reactions to the Study of Reactive Intermediates

    SciTech Connect

    Isied, Stephan S.

    2003-03-11

    The trans-polyproline (PII) oligomers (Figure 1) are unusually rigid peptide structures which have been extensively studied by our group for peptide mediated intramolecular electron transfer (ET) at long distances. We have previously studied ET across a series of metal ion donor (D) acceptor (A) oligoproline peptides with different distances, driving forces and reorganizational energies. The majority of these experiments involve generating the ET intermediate using pulse radiolysis methods, although more recently photochemical methods are also used. Results of these studies showed that ET across peptides can vary by more than twelve orders of magnitude. Using ruthenium bipyridine donors, ET reaction rate constants across several proline residues (n = 4 - 9) occurred in the millisecond (ms) to {micro}s timescale, thus limiting the proline peptide conformational motions to only minor changes (far smaller than the large changes that occur on the ms to sec timescale, such as trans to cis proline isomerization). The present report describes our large data base of experimental results for D-peptide-A complexes in terms of a model where the involvement of both superexchange and hopping (hole and electron) mechanisms account for the long range ET rate constants observed. Our data shows that the change from superexchange to hopping mechanisms occurs at different distances depending on the type of D and A and their interactions with the peptides. Our model is also consistent with generalized models for superexchange and hopping which have been put forward by a number of theoretical groups to account for long range ET phenomena.

  4. Geology, geophysics and age of a late Miocene, intermediate-silicic, collapsed stratovolcano complex in the northern Mojave Desert, CA

    SciTech Connect

    Sabin, A.E. ); Monastero, F.C.; Katzenstein, A.M. ); Snee, L.W. . Branch of Isotope Geochemistry)

    1993-04-01

    Geologic mapping has revealed that the Myrick Spring-Eagle Crags area of the northern Mojave Desert is an intermediate to silicic volcanic center covering nearly 100 square km. A complex series of flows, tuffs, dikes, sills and flow breccias ranging in composition from calc-alkaline basalt to high slica rhyolite were extruded through at least three different types of NW- to W-trending vents. Alteration associated with these vents includes silicic, propylitic, argillic and minor carbonate. The most intensely altered zones are vent-proximal and are controlled by a set of conjugate NW- and NE-trending fractures. Preliminary analyses reveal anomalously high concentrations of Hg, Sb and Ba with no detectable Au or Ag within these zones. Up to 500 m of vertical offset along an arcuate fault scarp in the central portion of this region describes the topographic rim of a half-graben style caldera with an infered diameter of at least 5 km. The outlow facies to the south of the rim is dominated by thick sequences of volcaniclastic breccias with interlayered rhyolite tuffs. Preliminary results of a detailed gravity survey have precisely delineated one of the largest gravity lows in the region ([minus]140 mgals). This low directly coincides with the topographic rim of the caldera. [sup 40]Ar/[sup 39] Ar age dating of biotite, sanidine and hornblende from dacite and rhyolite flows and tuffs preliminarily bracket the age of this volcanic center between 12.4 [+-].04 and 14.5 [+-].05 Ma.

  5. Subcomplexes of Ancestral Respiratory Complex I Subunits Rapidly Turn Over in Vivo as Productive Assembly Intermediates in Arabidopsis*

    PubMed Central

    Li, Lei; Nelson, Clark J.; Carrie, Chris; Gawryluk, Ryan M. R.; Solheim, Cory; Gray, Michael W.; Whelan, James; Millar, A. Harvey

    2013-01-01

    Subcomplexes of mitochondrial respiratory complex I (CI; EC 1.6.5.3) are shown to turn over in vivo, and we propose a role in an ancestral assembly pathway. By progressively labeling Arabidopsis cell cultures with 15N and isolating mitochondria, we have identified CI subcomplexes through differences in 15N incorporation into their protein subunits. The 200-kDa subcomplex, containing the ancestral γ-carbonic anhydrase (γ-CA), γ-carbonic anhydrase-like, and 20.9-kDa subunits, had a significantly higher turnover rate than intact CI or CI+CIII2. In vitro import of precursors for these CI subunits demonstrated rapid generation of subcomplexes and revealed that their specific abundance varied when different ancestral subunits were imported. Time course studies of precursor import showed the further assembly of these subcomplexes into CI and CI+CIII2, indicating that the subcomplexes are productive intermediates of assembly. The strong transient incorporation of new subunits into the 200-kDa subcomplex in a γ-CA mutant is consistent with this subcomplex being a key initiator of CI assembly in plants. This evidence alongside the pattern of coincident occurrence of genes encoding these particular proteins broadly in eukaryotes, except for opisthokonts, provides a framework for the evolutionary conservation of these accessory subunits and evidence of their function in ancestral CI assembly. PMID:23271729

  6. Seasonal and spatial variations of 17Oexcess and dexcess in Antarctic precipitation: Insights from an intermediate complexity isotope model

    NASA Astrophysics Data System (ADS)

    Schoenemann, Spruce W.; Steig, Eric J.

    2016-10-01

    An intermediate complexity model (ICM) is used to investigate the sensitivity of water isotope ratios in precipitation, including 17Oexcess, to climate variations in the Southern Hemisphere. The ICM is forced with boundary conditions from seasonal National Centers for Environmental Prediction/Department of Energy II reanalysis data. Perturbations to the surface temperature and humidity fields are used to investigate the isotopic sensitivity. The response of 17Oexcess to a uniform temperature change is insignificant over the ocean, while there is a large magnitude response over the ice sheet, particularly in East Antarctica. A decrease of ocean surface relative humidity produces increased 17Oexcess and dexcess, with a coherent response over both the ocean and Antarctica. For interior East Antarctica, the model simulates a seasonal cycle in 17Oexcess that is positively correlated with δ18O and of large magnitude ( 50 per meg), consistent with the observations from Vostok. The seasonal cycle in 17Oexcess for interior West Antarctica is predicted to be considerably smaller in magnitude (12 per meg), and is negatively correlated with δ18O, consistent with new data from a firn core near the West Antarctic Ice Sheet Divide site. Over the ocean, the ICM predicts much smaller seasonal cycles in 17Oexcess. Oceanic source changes (i.e., humidity) are insufficient to explain the amplitude of the simulated seasonal cycle over the Antarctic continent. Spatial differences in the seasonal response of 17Oexcess to local temperature reflect the balance of equilibrium and kinetic fractionation during snow formation.

  7. Evaluating key parameters for the initiation of a Neoproterozoic Snowball Earth with a single Earth System Model of intermediate complexity

    NASA Astrophysics Data System (ADS)

    Spiegl, T. C.; Paeth, H.; Frimmel, H. E.

    2015-04-01

    Even after more than two decades of intense research the main drivers for a potential Neoproterozoic Snowball Earth continue to be discussed controversially. In this study we present results from 37 sensitivity experiments that were performed with the Planet Simulator (PlaSim), an Earth System Model of intermediate complexity. In contrast to previous studies, in which only a limited number of potential climate-controlling parameters were assessed with different climate models, we tested our presumed key parameters within one single model. This approach makes it easier to compare the influence of the various parameters on extreme climate change as postulated for the Neoproterozoic Era. Furthermore we compare the results obtained to most recent high complexity state-of-the-art approaches. This comparison helps to estimate, which internal model interactions and physics are crucial for a Snowball Earth simulation and hence should be included into a model that is capable of realistically simulating a Neoproterozoic climate. To this effect we carried out simulations that involved reduced solar irradiation, land-sea distributions, atmospheric CO2 concentrations, relief of the land surface and length of day. In addition, we focus on different land surface albedo values, which were most likely exceptionally low and similar to the Martian albedo, and obliquity changes between 23.5° and 80°. Our findings suggest that changes in land surface albedo are a strong climate driver that can compensate a much lower Neoproterozoic total solar irradiance if it is combined with shifts in obliquity or atmospheric CO2 levels. We also obtained a critical threshold for increased obliquities beyond which a Snowball Earth situation turns into an extreme greenhouse climate with almost absent cryosphere, and furthermore, obliquity values that lead to a tropical ice age with sea ice spreading from the equator to high latitudes.

  8. Intermediate complex morphophysiological dormancy in seeds of the cold desert sand dune geophyte Eremurus anisopterus (Xanthorrhoeaceae; Liliaceae s.l.)

    PubMed Central

    Mamut, Jannathan; Tan, Dun Yan; Baskin, Carol C.; Baskin, Jerry M.

    2014-01-01

    Background and Aims Little is known about morphological (MD) or morphophysiological (MPD) dormancy in cold desert species and in particular those in Liliaceae sensu lato, an important floristic element in the cold deserts of Central Asia with underdeveloped embyos. The primary aim of this study was to determine if seeds of the cold desert liliaceous perennial ephemeral Eremurus anisopterus has MD or MPD, and, if it is MPD, then at what level. Methods Embryo growth and germination was monitored in seeds subjected to natural and simulated natural temperature regimes and the effects of after-ripening and GA3 on dormancy break were tested. In addition, the temperature requirements for embryo growth and dormancy break were investigated. Key Results At the time of seed dispersal in summer, the embryo length:seed length (E:S) ratio was 0·73, but it increased to 0·87 before germination. Fresh seeds did not germinate during 1 month of incubation in either light or darkness over a range of temperatures. Thus, seeds have MPD, and, after >12 weeks incubation at 5/2 °C, both embryo growth and germination occurred, showing that they have a complex level of MPD. Since both after-ripening and GA3 increase the germination percentage, seeds have intermediate complex MPD. Conclusions Embryos in after-ripened seeds of E. anisopterus can grow at low temperatures in late autumn, but if the soil is dry in autumn then growth is delayed until snowmelt wets the soil in early spring. The ecological advantage of embryo growth phenology is that seeds can germinate at a time (spring) when sand moisture conditions in the desert are suitable for seedling establishment. PMID:25180288

  9. Structure of Naegleria Tet-like dioxygenase (NgTet1) in complexes with a reaction intermediate 5-hydroxymethylcytosine DNA

    DOE PAGES

    Hashimoto, Hideharu; Pais, June E.; Dai, Nan; ...

    2015-08-31

    The family of ten-eleven translocation (Tet) dioxygenases is widely distributed across the eukaryotic tree of life, from mammals to the amoeboflagellate Naegleria gruberi. Like mammalian Tet proteins, the Naegleria Tet-like protein, NgTet1, acts on 5-methylcytosine (5mC) and generates 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in three consecutive, Fe(II)- and α-ketoglutarate-dependent oxidation reactions. The two intermediates, 5hmC and 5fC, could be considered either as the reaction product of the previous enzymatic cycle or the substrate for the next cycle. Here we present a new crystal structure of NgTet1 in complex with DNA containing a 5hmC. Along with the previously solvedmore » NgTet1–5mC structure, the two complexes offer a detailed picture of the active site at individual stages of the reaction cycle. In the crystal, the hydroxymethyl (OH-CH2-) moiety of 5hmC points to the metal center, representing the reaction product of 5mC hydroxylation. The hydroxyl oxygen atom could be rotated away from the metal center, to a hydrophobic pocket formed by Ala212, Val293 and Phe295. Such rotation turns the hydroxyl oxygen atom away from the product conformation, and exposes the target CH2 towards the metal-ligand water molecule, where a dioxygen O2 molecule would occupy to initiate the next round of reaction by abstracting a hydrogen atom from the substrate. The Ala212-to-Val (A212V) mutant profoundly limits the product to 5hmC, probably due to the reduced hydrophobic pocket size restricts the binding of 5hmC as a substrate.« less

  10. Organolithium compounds in the nucleophilic substitution of hydrogen in arenes and hetarenes

    NASA Astrophysics Data System (ADS)

    Kovalev, I. S.; Kopchuk, D. S.; Zyryanov, G. V.; Rusinov, V. L.; Chupakhin, O. N.; Charushin, V. N.

    2015-12-01

    The review considers the most typical examples of the direct non-activated non-catalytic C-C bond formation in arenes and their metal complexes activated by electron-withdrawing substituents in the aromatic nucleus and in hetarenes (azines and their N-oxides, porphyrins, etc.) upon the reactions with aliphatic and (hetero)aromatic (hetero)organolithium nucleophiles. Particular attention is given to the direct introduction of nitroxide radicals and (hetero)organic moieties into mono-, di- and triazines and their N-oxides. The influence of the structures of the (hetero)aromatic substrate and the (hetero)organolithium nucleophile on the reaction pathway and rate and on the structure of the reaction product is analyzed. The bibliography includes 237 references. Dedicated to Academician N S Zefirov on the occasion of 80th birthday.

  11. A common intermediate for N2 formation in enzymes and zeolites: side-on Cu-nitrosyl complexes.

    PubMed

    Kwak, Ja Hun; Lee, Jong H; Burton, Sarah D; Lipton, Andrew S; Peden, Charles H F; Szanyi, János

    2013-09-16

    Side on! Combined FTIR and NMR studies revealed the presence of a side-on nitrosyl species in the zeolite Cu-SSZ-13. This intermediate is very similar to those found in nitrite reductase enzyme systems. The identification of this intermediate led to the proposal of a reaction mechanism that is fully consistent with the results of both kinetic and spectroscopic studies.

  12. Activation of dinitrogen-derived hafnium nitrides for nucleophilic N-C bond formation with a terminal isocyanate.

    PubMed

    Semproni, Scott P; Chirik, Paul J

    2013-12-02

    Better by Hf: Anion coordination to a bridging hafnocene nitride complex, prepared from CO-induced N2 cleavage, increases the nucleophilicity of the nitrogen atom, thus promoting additional NC bond formation with a typically inert terminal isocyanate ligand. This cascade sequence allows synthesis of otherwise challenging mono-substituted ureas using N2 , CO, and an appropriate electrophile.

  13. Nucleophile-Assisted Alkene Activation: Olefins Alone Are Often Incompetent.

    PubMed

    Ashtekar, Kumar Dilip; Vetticatt, Mathew; Yousefi, Roozbeh; Jackson, James E; Borhan, Babak

    2016-07-06

    Emerging work on organocatalytic enantioselective halocyclizations naturally draws on conditions where both new bonds must be formed under delicate control, the reaction regime where the concerted nature of the AdE3 mechanism is of greatest importance. Without assistance, many simple alkene substrates react slowly or not at all with conventional halenium donors under synthetically relevant reaction conditions. As demonstrated earlier by Shilov, Cambie, Williams, Fahey, and others, alkenes can undergo a concerted AdE3-type reaction via nucleophile participation, which sets the configuration of the newly created stereocenters at both ends in one step. Herein, we explore the modulation of alkene reactivity and halocyclization rates by nucleophile proximity and basicity, through detailed analyses of starting material spectroscopy, addition stereopreferences, isotope effects, and nucleophile-alkene interactions, all obtained in a context directly relevant to synthesis reaction conditions. The findings build on the prior work by highlighting the reactivity spectrum of halocyclizations from stepwise to concerted, and suggest strategies for design of new reactions. Alkene reactivity is seen to span the range from the often overgeneralized "sophomore textbook" image of stepwise electrophilic attack on the alkene and subsequent nucleophilic bond formation, to the nucleophile-assisted alkene activation (NAAA) cases where electron donation from the nucleophilic addition partner activates the alkene for electrophilic attack. By highlighting the factors that control reactivity across this range, this study suggests opportunities to explain and control stereo-, regio-, and organocatalytic chemistry in this important class of alkene additions.

  14. Nucleophilic aromatic substitution on aryl-amido ligands promoted by oxidizing osmium(IV) centers.

    PubMed

    Soper, Jake D; Saganic, Erik; Weinberg, David; Hrovat, David A; Benedict, Jason B; Kaminsky, Werner; Mayer, James M

    2004-09-20

    Addition of amine nucleophiles to acetonitrile solutions of the OsIV anilido complex TpOs(NHPh)Cl2 (1) [Tp = hydrotris(1-pyrazolyl)borate] gives products with derivatized anilido ligands, i.e., TpOs[NH-p-C6H4(N(CH2)5)]Cl2 (2) from piperidine and TpOs[NH-p-C6H4N(CH2)4]Cl2 (3) from pyrrolidine. These materials are formed in approximately 30% yield under anaerobic conditions, together with approximately 60% yields of the OsIII aniline complex TpOs(NH2Ph)Cl2 (5). Formation of the para-substituted materials 2 or 3 from 1 involves oxidative removal of two hydrogen atoms (two H+ and two e-). The oxidation can be accomplished by 1, forming 5, or by O2. Related reactions have been observed with other amines and with the 2-naphthylamido derivative, which gives an ortho-substituted product. Kinetic studies indicate an addition-elimination mechanism involving initial attack of the amine nucleophile on the anilido ligand. These are unusual examples of nucleophilic aromatic substitution of hydrogen. Ab initio calculations on 1 show that the LUMO has significant density at the ortho and para positions of the anilido ligand, resembling the LUMO of nitrobenzene. By analogy with nucleophilic aromatic substitution, 2 is quantitatively formed from piperidine and the p-chloroanilide TpOs(NH-p-C6H4Cl)Cl2 (7). Binding the anilide ligands to an oxidizing OsIV center thus causes a remarkable umpolung or inversion of chemical character from a typically electron-rich anilido to an electron-deficient aromatic functionality. This occurs because of the coupling of redox changes at the TpOsIV center with bond formation at the coordinated ligand.

  15. Response of the South Pacific Convergence Zone to imposed circulation and moisture perturbations in an intermediate level complexity model

    NASA Astrophysics Data System (ADS)

    Niznik, M. J.; Lintner, B. R.

    2014-12-01

    Previous research has identified a connection between the strength of low-level trade wind inflow from the relatively dry southeastern Pacific basin and the position of the South Pacific Convergence Zone (SPCZ). This circulation-precipitation relationship has been noted in composite analysis applied to reanalysis data as well as to output from current generation climate models, although the causality is ambiguous. Additionally, given that prior studies exhibit deep vertical structures associated with changes to low-level inflow east of the SPCZ, the relationship between low-level inflow variability and the propagation of upper level mid-latitude synoptic disturbances into the SPCZ remains unclear. Thus, forcing models with prescribed circulation and moisture anomalies may be instructive for untangling the dynamic and thermodynamic contributions to such interactions, as well as their potential causality. To that end, we use the Quasi-equilibrium Tropical Circulation Model 2 (QTCM2), an intermediate complexity model with a separate boundary layer of fixed height imposed at the base of the free troposphere, to explore the response of the SPCZ, and more broadly convection across the South Pacific, to perturbed low- and upper-level circulation and moisture fields east of its climatological position. Preliminary results suggest a strong precipitation response to strengthened low-level trade wind inflow, hypothesized to be the result of increased convergence in the climatological SPCZ, with an associated decrease in Intertropical Convergence Zone (ITCZ) precipitation. Conversely, there is a limited precipitation response to weakened low-level trade wind inflow despite a notable (2-3 g kg-1) increase in specific humidity, suggesting the climatological low-level inflow is already associated with the necessary moisture threshold for deep convection. Ultimately, these results suggest dynamics play a stronger role than thermodynamics in the interaction as modeled by QTCM2.

  16. Nucleophilic substitution at centers other than carbon: reaction at the chlorine of N-chloroacetanilides with triethylamine as the nucleophile

    SciTech Connect

    Underwood, G.R.; Dietze, P.E.

    1984-12-28

    The reaction between triethylamine (TEA) and a series of para-substituted N-chloroacetanilides has been studied in aqueous solution buffered to pHs between 1 and 5. The exclusive product derived from the aromatic moiety is the corresponding acetanilide. The reaction occurs via two parallel pseudo-second-order paths, one acid catalyzed (the Orton-like mechanism), the other uncatalyzed. The uncatalyzed reaction is accelerated by the presence of electron-withdrawing substituents on the aromatic ring and can best be represented as nucleophilic displacement at chlorine. It therefore appears to be the prototype of a convenient class of reactions for the study of displacement reactions at chlorine. The rho value for this reaction is 3.87, indicating substantial negative charge buildup in the aromatic ring during of the transition state. The acid-catalyzed reaction is more complex, presumable involving a protonation equilibrium for the N-chloroacetanilide prior to the rate-determining step similar to that in the Orton reaction. 15 references, 2 figures, 3 tables.

  17. Nucleophile Assisting Leaving Groups: A Strategy for Aliphatic 18F-Fluorination

    PubMed Central

    Lu, Shuiyu; Lepore, Salvatore D.; Li, Song Ye; Mondal, Deboprosad; Cohn, Pamela C.; Bhunia, Anjan K.; Pike, Victor W.

    2009-01-01

    A series of arylsulfonate nucleophile assisting leaving groups (NALGs) were prepared in which the metal chelating unit is attached to the aryl ring via an ether linker. These NALGs exhibited significant rate enhancements in halogenation reactions using metal halides. Studies with a NALG containing a macrocyclic ether unit suggest that rate enhancements of these nucleophilic halogenation reactions are facilitated by stabilization of charge in the transition state rather than through strong pre-complexation with metal cation. In several cases, a primary substrate containing one of the new leaving groups rivaled or surpassed the reactivity of triflates when exposed to nucleophile but was otherwise highly stable and isolable. These and previously disclosed chelating leaving groups were used in 18F-fluorination reactions using no-carrier-added [18F]fluoride ion (t1/2 = 109.7 min, β+ = 97%) in CH3CN. Under microwave irradiation and without the assistance of a cryptand, such as K2.2.2, primary substrates with select NALGs led to a substantial improvement (2 to 3 fold) in radiofluorination yields over traditional leaving groups. PMID:19572583

  18. Optimality principles reveal a complex interplay of intermediate toxicity and kinetic efficiency in the regulation of prokaryotic metabolism

    PubMed Central

    Ewald, Jan; Bartl, Martin; Kaleta, Christoph

    2017-01-01

    A precise and rapid adjustment of fluxes through metabolic pathways is crucial for organisms to prevail in changing environmental conditions. Based on this reasoning, many guiding principles that govern the evolution of metabolic networks and their regulation have been uncovered. To this end, methods from dynamic optimization are ideally suited since they allow to uncover optimality principles behind the regulation of metabolic networks. We used dynamic optimization to investigate the influence of toxic intermediates in connection with the efficiency of enzymes on the regulation of a linear metabolic pathway. Our results predict that transcriptional regulation favors the control of highly efficient enzymes with less toxic upstream intermediates to reduce accumulation of toxic downstream intermediates. We show that the derived optimality principles hold by the analysis of the interplay between intermediate toxicity and pathway regulation in the metabolic pathways of over 5000 sequenced prokaryotes. Moreover, using the lipopolysaccharide biosynthesis in Escherichia coli as an example, we show how knowledge about the relation of regulation, kinetic efficiency and intermediate toxicity can be used to identify drug targets, which control endogenous toxic metabolites and prevent microbial growth. Beyond prokaryotes, we discuss the potential of our findings for the development of antifungal drugs. PMID:28212377

  19. Analysis of the Nucleophilic Solvation Effects in Isopropyl Chlorothioformate Solvolysis

    PubMed Central

    D’Souza, Malcolm J.; Mahon, Brian P.; Kevill, Dennis N.

    2010-01-01

    Correlation of the solvent effects through application of the extended Grunwald-Winstein equation to the solvolysis of isopropyl chlorothioformate results in a sensitivity value of 0.38 towards changes in solvent nucleophilicity (l) and a sensitivity value of 0.72 towards changes in solvent ionizing power (m). This tangible l value coupled with the negative entropies of activation observed indicates a favorable predisposition towards a modest rear-side nucleophilic solvation of a developing carbocation. Only in 100% ethanol was the bimolecular pathway dominant. These observations are very different from those obtained for the solvolysis of isopropyl chloroformate, where dual reaction channels were proposed, with the addition-elimination reaction favored in the more nucleophilic solvents and a unimolecular fragmentation-ionization mechanism favored in the highly ionizing solvents. PMID:20717524

  20. The SMC-5/6 Complex and the HIM-6 (BLM) Helicase Synergistically Promote Meiotic Recombination Intermediate Processing and Chromosome Maturation during Caenorhabditis elegans Meiosis.

    PubMed

    Hong, Ye; Sonneville, Remi; Agostinho, Ana; Meier, Bettina; Wang, Bin; Blow, J Julian; Gartner, Anton

    2016-03-01

    Meiotic recombination is essential for the repair of programmed double strand breaks (DSBs) to generate crossovers (COs) during meiosis. The efficient processing of meiotic recombination intermediates not only needs various resolvases but also requires proper meiotic chromosome structure. The Smc5/6 complex belongs to the structural maintenance of chromosome (SMC) family and is closely related to cohesin and condensin. Although the Smc5/6 complex has been implicated in the processing of recombination intermediates during meiosis, it is not known how Smc5/6 controls meiotic DSB repair. Here, using Caenorhabditis elegans we show that the SMC-5/6 complex acts synergistically with HIM-6, an ortholog of the human Bloom syndrome helicase (BLM) during meiotic recombination. The concerted action of the SMC-5/6 complex and HIM-6 is important for processing recombination intermediates, CO regulation and bivalent maturation. Careful examination of meiotic chromosomal morphology reveals an accumulation of inter-chromosomal bridges in smc-5; him-6 double mutants, leading to compromised chromosome segregation during meiotic cell divisions. Interestingly, we found that the lethality of smc-5; him-6 can be rescued by loss of the conserved BRCA1 ortholog BRC-1. Furthermore, the combined deletion of smc-5 and him-6 leads to an irregular distribution of condensin and to chromosome decondensation defects reminiscent of condensin depletion. Lethality conferred by condensin depletion can also be rescued by BRC-1 depletion. Our results suggest that SMC-5/6 and HIM-6 can synergistically regulate recombination intermediate metabolism and suppress ectopic recombination by controlling chromosome architecture during meiosis.

  1. Nucleophilic substitution reactions of N-chloramines: evidence for a change in mechanism with increasing nucleophile reactivity.

    PubMed

    Calvo, Paula; Crugeiras, Juan; Ríos, Ana; Ríos, Miguel A

    2007-04-27

    Third-order rate constants (kNu)H (M-2 s-1) for the hydronium ion catalyzed reactions of a range of nucleophiles with N-chlorotaurine (1) in water at 25 degrees C and I=0.5 (NaClO4) are reported. The solvent deuterium isotope effects on hydronium ion catalysis of the reaction with 1 of bromide and iodide ion are (kBr)H/(kBr)D=0.30 and (kI)H/(kI)D=0.54, respectively. The inverse nature of these isotope effects and the absence of general acid catalysis are consistent with a stepwise mechanism involving protonation of 1 in a fast preequilibrium step. The appearance of strong catalysis by general acids for the reaction of the more nucleophilic SO(3)2- and HOCH2CH2S- with the chloramine indicates a change to a concerted mechanism, with protonation of the chloramine at nitrogen and chlorine transfer to the nucleophile occurring in a single step. A rough estimate of the lifetime of the protonated chloramine in the presence of the thiolate anion suggests that the concerted mechanism is enforced by the absence of a significant lifetime of the protonated substrate in contact with the nucleophile. Theoretical calculations provide evidence against an electron-transfer mechanism for chlorination of the nucleophiles by protonated 1.

  2. Nucleophilic Tetrafluoroethylation Employing in Situ Formed Organomagnesium Reagents.

    PubMed

    Budinská, Alena; Václavík, Jiří; Matoušek, Václav; Beier, Petr

    2016-11-18

    Tetrafluoroalkyl bromides are metalated with equimolar iPrMgCl·LiCl (Turbo Grignard) to form organomagnesium compounds which are stable at low temperatures and react with various electrophiles (aldehydes, ketones, CO2, cyclic sulfate and sulfamidate, N-sulfonylimines, nitrone, chlorophosphate, nonaflyl azide) to afford novel functionalized tetrafluoroethylene-containing products. Ease of operation, excellent selectivity, high nucleophilicity, and enhanced stability of the reactive species together with a broad substrate scope comprise a highly attractive nucleophilic tetrafluoroethylation protocol affording unique synthetic building blocks.

  3. Nucleophilic Polymers and Gels in Hydrolytic Degradation of Chemical Warfare Agents.

    PubMed

    Bromberg, Lev; Creasy, William R; McGarvey, David J; Wilusz, Eugene; Hatton, T Alan

    2015-10-07

    Water- and solvent-soluble polymeric materials based on polyalkylamines modified with nucleophilic groups are introduced as catalysts of chemical warfare agent (CWA) hydrolysis. A comparative study conducted at constant pH and based on the criteria of the synthetic route simplicity, aqueous solubility, and rate of hydrolysis of CWA mimic, diisopropylfluorophosphate (DFP), indicated that 4-aminopyridine-substituted polyallylamine (PAAm-APy) and polyvinylamine substituted with 4-aminopyridine (PVAm-APy) were advantageous over 4-pyridinealdoxime-modified PVAm and PAAm, poly(butadiene-co-pyrrolidinopyridine), and PAAm modified with bipyridine and its complex with Cu(II). The synthesis of PVAm-APy and PAAm-APy involved generation of a betaine derivative of acrylamide and its covalent attachment onto the polyalkylamine chain followed by basic hydrolysis. Hydrogel particles of PAAm-APy and PVAm-APy cross-linked by epichlorohydrin exhibited pH-dependent swelling and ionization patterns that affected the rate constants of DFP nucleophilic hydrolysis. Deprotonation of the aminopyridine and amine groups increased the rates of the nucleophilic hydrolysis. The second-order rate of nucleophilic hydrolysis was 5.5- to 10-fold higher with the nucleophile-modified gels compared to those obtained by cross-linking of unmodified PAAm, throughout the pH range. Testing of VX and soman (GD) was conducted in 2.5-3.7 wt % PVAm-APy suspensions or gels swollen in water or DMSO/water mixtures. The half-lives of GD in aqueous PVAm-APy were 12 and 770 min at pH 8.5 and 5, respectively. Addition of VX into 3.5-3.7 wt % suspensions of PVAm-APy in DMSO-d6 and D2O at initial VX concentration of 0.2 vol % resulted in 100% VX degradation in less than 20 min. The unmodified PVAm and PAAm were 2 orders of magnitude less active than PVAm-APy and PAAm-APy, with VX half-lives in the range of 24 h. Furthermore, the PVAm-APy and PAAm-APy gels facilitated the dehydrochlorination reaction of sulfur mustard

  4. PALADYN v1.0, a comprehensive land surface-vegetation-carbon cycle model of intermediate complexity

    NASA Astrophysics Data System (ADS)

    Willeit, Matteo; Ganopolski, Andrey

    2016-10-01

    PALADYN is presented; it is a new comprehensive and computationally efficient land surface-vegetation-carbon cycle model designed to be used in Earth system models of intermediate complexity for long-term simulations and paleoclimate studies. The model treats in a consistent manner the interaction between atmosphere, terrestrial vegetation and soil through the fluxes of energy, water and carbon. Energy, water and carbon are conserved. PALADYN explicitly treats permafrost, both in physical processes and as an important carbon pool. It distinguishes nine surface types: five different vegetation types, bare soil, land ice, lake and ocean shelf. Including the ocean shelf allows the treatment of continuous changes in sea level and shelf area associated with glacial cycles. Over each surface type, the model solves the surface energy balance and computes the fluxes of sensible, latent and ground heat and upward shortwave and longwave radiation. The model includes a single snow layer. Vegetation and bare soil share a single soil column. The soil is vertically discretized into five layers where prognostic equations for temperature, water and carbon are consistently solved. Phase changes of water in the soil are explicitly considered. A surface hydrology module computes precipitation interception by vegetation, surface runoff and soil infiltration. The soil water equation is based on Darcy's law. Given soil water content, the wetland fraction is computed based on a topographic index. The temperature profile is also computed in the upper part of ice sheets and in the ocean shelf soil. Photosynthesis is computed using a light use efficiency model. Carbon assimilation by vegetation is coupled to the transpiration of water through stomatal conductance. PALADYN includes a dynamic vegetation module with five plant functional types competing for the grid cell share with their respective net primary productivity. PALADYN distinguishes between mineral soil carbon, peat carbon, buried

  5. Determination of gas-phase nucleophilicities and electrophilicities using B⋯HX bond critical point properties of AIM analysis

    NASA Astrophysics Data System (ADS)

    Ebrahimi, Ali; Roohi, Hosein; Habibi, Mostafa; Hasannejad, Mehdi

    2006-09-01

    The values of nucleophilicity and electrophilicity have been established in gas phase for some nucleophiles (B = CH 3CN, CO, H 2O, H 2S, HCN, N 2, NH 3, PH 3) and electrophiles (HX = HF, HCl, HBr, HCN HCF 3) from properties of bond critical points of atoms in molecules (AIM) analysis. On the basis of the meaningful relationship, the recent method has been applied to electron density ( ρ), Laplacian of electron density (∇ρ2), and electronic kinetic energy density ( G), of B⋯HX bond critical point. AIM analysis has been performed on the obtained wave functions at MP2/6-311++G(d,p) level of theory. The correlation between averaged calculated values of nucleophilicity (or electrophilicity), using different properties of B⋯HX bond critical points, and complexation energies (Δ Ecomp) is satisfactory. The best correlation coefficient between nucleophilicity and Δ Ecomp is related to ρ values of bond critical points. But, the best correlation coefficient between electrophilicity and Δ Ecomp is allied to ∇ρ2 and G values of bond critical points.

  6. Recent Developments in Metal-Catalyzed Additions of Oxygen Nucleophiles to Alkenes and Alkynes

    NASA Astrophysics Data System (ADS)

    Hintermann, Lukas

    Progress in the field of metal-catalyzed redox-neutral additions of oxygen nucleophiles (water, alcohols, carboxylic acids, and others) to alkenes, alkynes, and allenes between 2001 and 2009 is critically reviewed. Major advances in reaction chemistry include development of chiral Lewis acid catalyzed asymmetric oxa-Michael additions and Lewis-acid catalyzed hydro-alkoxylations of nonactivated olefins, as well as further development of Markovnikov-selective cationic gold complex-catalyzed additions of alcohols or water to alkynes and allenes.

  7. Mono-nuclear copper complexes mimicking the intermediates for the binuclear copper center of the subunit II of cytochrome oxidase: a peptide based approach.

    PubMed

    Dutta Gupta, Dwaipayan; Usharani, Dandamudi; Mazumdar, Shyamalava

    2016-11-28

    Three stable copper complexes of peptides derived from the copper ion binding loop of the subunit II of cytochrome c oxidase have been prepared and characterized by various spectroscopic techniques. These stable copper complexes of peptides were found to exhibit cysteine, histidine and/or methionine ligation, which has predominant σ-contribution in the Cys-Cu charge transfer. The copper(ii) peptide complexes showed type-2 EPR spectra, which is uncommon in copper-cysteinate complexes. UV-visible spectra, Raman and EPR results support a tetragonal structure of the coordination geometry around the copper ion. The copper complex of the 9-amino acid peptide suggested the formation of a 'red' copper center while the copper complexes of the 12- and 11-amino acid peptides showed the formation of a 'green' copper center. The results provide insights on the first stable models of the copper complexes formed in the peptide scaffold that mimic the mono-nuclear copper bound protein intermediates proposed during the formation of the binuclear Cu2S2 core of the enzyme. These three copper complexes of peptides derived from the metal ion binding loop of the CuA center of the subunit II of cytochrome c oxidase showed novel spectroscopic properties which have not so far been reported in any stable small complex.

  8. Molecular orbital studies of enzyme activity: I: Charge relay system and tetrahedral intermediate in acylation of serine proteinases.

    PubMed Central

    Scheiner, S; Kleier, D A; Lipscomb, W N

    1975-01-01

    The charge relay ststem and its role in the acylation of serine proteinases is studied using the partial retention of diatomic differential overlap (PRDDO) technique to perform approximate ab initio molecular orbital calculations on a model of the enzyme-substrate complex. The aspartate in the charge relay system is seen to act as the ultimate proton acceptor during the charging of the serine nucleophile. A projection of the potential energy surface is obtained in a subspace corresponding to this charge transfer and to the coupled motions of active site residues and the substrate. These results together with extended basis set results for cruder models suggest that a concerted transfer of protons from Ser-195 to His-57 and from His-57 to Asp-102 occurs with an energy barrier of 20-25 kcal/mole (84-105 kJ/mole). The subsequent nucleophilic attack on the scissile peptide linkage by the charged serine is then seen to proceed energetically downhill to the tetrahedral intermediate. The formation of the tetrahedral intermediate from the Michaelis complex is calculated to be nearly thermoneutral. PMID:1058476

  9. Structural Studies of E. coli Topoisomerase III-DNA Complexes Reveal a Novel Type IA Topoisomerase-DNA Conformational Intermediate

    SciTech Connect

    Changela, Anita; DiGate, Russell J.; Mondragon, Alfonso

    2010-03-05

    Escherichia coli DNA topoisomerase III belongs to the type IA family of DNA topoisomerases, which transiently cleave single-stranded DNA (ssDNA) via a 5{prime} phosphotyrosine intermediate. We have solved crystal structures of wild-type E. coli topoisomerase III bound to an eight-base ssDNA molecule in three different pH environments. The structures reveal the enzyme in three distinct conformational states while bound to DNA. One conformation resembles the one observed previously with a DNA-bound, catalytically inactive mutant of topoisomerase III where DNA binding realigns catalytic residues to form a functional active site. Another conformation represents a novel intermediate in which DNA is bound along the ssDNA-binding groove but does not enter the active site, which remains in a catalytically inactive, closed state. A third conformation shows an intermediate state where the enzyme is still in a closed state, but the ssDNA is starting to invade the active site. For the first time, the active site region in the presence of both the catalytic tyrosine and ssDNA substrate is revealed for a type IA DNA topoisomerase, although there is no evidence of ssDNA cleavage. Comparative analysis of the various conformational states suggests a sequence of domain movements undertaken by the enzyme upon substrate binding.

  10. Pd-catalyzed C-H fluorination with nucleophilic fluoride.

    PubMed

    McMurtrey, Kate B; Racowski, Joy M; Sanford, Melanie S

    2012-08-17

    The palladium-catalyzed C-H fluorination of 8-methylquinoline derivatives with nucleophilic fluoride is reported. This transformation involves the use of AgF as the fluoride source in combination with a hypervalent iodine oxidant. Both the scope and mechanism of the reaction are discussed.

  11. Nucleophilicity-periodic trends and connection to basicity.

    PubMed

    Uggerud, Einar

    2006-01-23

    The potential energy profiles of 18 identity S(N)2 reactions have been estimated by using G2-type quantum-chemical calculations. The reactions are: X- + CH3-X --> X-CH3 + X- and XH + CH3-XH+ --> +HX-CH3 + XH (X = NH2, OH, F, PH2, SH, Cl, AsH2, SeH, Br). Despite the charge difference, the barrier heights and the geometrical requirements upon going from the reactant to the transition structure are surprisingly similar for X- and XH. The barrier heights decrease on going from left to right in the periodic table, and increasing ionization energy (of X- and XH) is correlated with decreasing barrier. The observed trends are explained in terms of substrates with stronger electrostatic character giving rise to lower energetic barriers due to decreased electron repulsion in the transition structure. On the basis of this study, the relationship between the kinetic concept of nucleophilicity and the thermodynamic concept of basicity has been analyzed and clarified. Since the trends in intrinsic nucleophilicity (only defined for identity reactions) and basicity are opposite, overall nucleophilicity (defined for any reaction) will be determined by the relative contribution of the two factors. Only for strongly exothermic reactions will basicity and nucleophilicity be matching.

  12. Nucleophilic substitution reaction for post-functionalization of polyoxometalates

    DOE PAGES

    Yin, Panchao; Li, Qiang; Zhang, Jin; ...

    2015-07-06

    In this study, a hexamolybdate-based organic inorganic hybrid molecule containing a chloralkane fragment is synthesized and its Cl atom can be substituted by iodine and nitrate through nucleophilic substitution reactions in high yields, which provide a post-functionalization protocol to bring in various additional functional groups into polyoxometalate-based hybrid materials under mild conditions.

  13. Dynamic Origin of the Stereoselectivity of a Nucleophilic Substitution Reaction

    PubMed Central

    Bogle, Xavier S.; Singleton, Daniel A.

    2012-01-01

    A nucleophilic substitution on a dichlorovinyl ketone was studied experimentally and computationally. A mixture of products is observed experimentally, but a conventional computational analysis does not account for the formation of the minor stereoisomer. Instead, the product mixture is predicted accurately from a dynamic trajectory study on a bifurcating energy surface. The dynamic origin of the stereoselectivity of the reaction is discussed. PMID:22540965

  14. Reactivity of the insecticide fenitrothion toward O and N nucleophiles.

    PubMed

    Rougier, Natalia M; Vico, Raquel V; de Rossi, Rita H; Buján, Elba I

    2010-05-21

    The reactivity of Fenitrothion (1) toward several O- and N-based nucleophiles, including ambident and alpha-nucleophiles, was investigated in basic media at 25 degrees C in water containing 2% 1,4-dioxane. In the reactions with HO(-) and HOO(-) quantitative formation of 3-methyl-4-nitrophenoxide (2) was observed indicating a S(N)2(P) pathway. In the reactions with NH(2)OH, NH(2)O(-), and BuNH(2), demethylfenitrothion (4) was formed along with 2, indicating competition between the S(N)2(P) and S(N)2(C) pathways; no evidence of a S(N)Ar pathway was observed in any case. The observed rate constants were dissected into the values corresponding to the S(N)2(P) and S(N)2(C) pathways. The yield of 4 depends on the nucleophile and on the pH of the reaction, being the main product in the case of BuNH(2). With HOO(-), NH(2)OH, and NH(2)O(-) a significant alpha-effect was observed, confirming the participation of the nucleophile in the rate-limiting step of the reaction.

  15. Snapshots of enzymatic Baeyer-Villiger catalysis: oxygen activation and intermediate stabilization.

    PubMed

    Orru, Roberto; Dudek, Hanna M; Martinoli, Christian; Torres Pazmiño, Daniel E; Royant, Antoine; Weik, Martin; Fraaije, Marco W; Mattevi, Andrea

    2011-08-19

    Baeyer-Villiger monooxygenases catalyze the oxidation of carbonylic substrates to ester or lactone products using NADPH as electron donor and molecular oxygen as oxidative reactant. Using protein engineering, kinetics, microspectrophotometry, crystallography, and intermediate analogs, we have captured several snapshots along the catalytic cycle which highlight key features in enzyme catalysis. After acting as electron donor, the enzyme-bound NADP(H) forms an H-bond with the flavin cofactor. This interaction is critical for stabilizing the oxygen-activating flavin-peroxide intermediate that results from the reaction of the reduced cofactor with oxygen. An essential active-site arginine acts as anchoring element for proper binding of the ketone substrate. Its positively charged guanidinium group can enhance the propensity of the substrate to undergo a nucleophilic attack by the flavin-peroxide intermediate. Furthermore, the arginine side chain, together with the NADP(+) ribose group, forms the niche that hosts the negatively charged Criegee intermediate that is generated upon reaction of the substrate with the flavin-peroxide. The fascinating ability of Baeyer-Villiger monooxygenases to catalyze a complex multistep catalytic reaction originates from concerted action of this Arg-NADP(H) pair and the flavin subsequently to promote flavin reduction, oxygen activation, tetrahedral intermediate formation, and product synthesis and release. The emerging picture is that these enzymes are mainly oxygen-activating and "Criegee-stabilizing" catalysts that act on any chemically suitable substrate that can diffuse into the active site, emphasizing their potential value as toolboxes for biocatalytic applications.

  16. A general phosphoric acid-catalyzed desymmetrization of meso-aziridines with silylated selenium nucleophiles.

    PubMed

    Senatore, Matilde; Lattanzi, Alessandra; Santoro, Stefano; Santi, Claudio; Della Sala, Giorgio

    2011-09-21

    The first example of meso-aziridine desymmetrization with selenium nucleophiles is reported. The reaction, promoted by VAPOL-hydrogen phosphate using (phenylseleno)trimethylsilane as the nucleophile, proves to be very general and highly enantioselective (84-99% ee).

  17. Molecular Dynamics Simulations of Arachidonic Acid-Derived Pentadienyl Radical Intermediate Complexes with COX-1 and COX-2

    PubMed Central

    Furse, Kristina E.; Pratt, Derek A.; Schneider, Claus; Brash, Alan R.; Porter, Ned A.; Lybrand, Terry P.

    2008-01-01

    The two cyclooxygenase enzymes, COX-1 and COX-2, are responsible for the committed step in prostaglandin biosynthesis, and are the targets of the non-steroidal anti-inflammatory drugs aspirin, ibuprofen and the COX-2 selective inhibitors, Celebrex™, Vioxx™ and Bextra™. The enzymes are remarkable in that they catalyze two dioxygenations and two cyclizations of the native substrate, arachidonic acid, with near absolute regio- and stereoselectivity. Several theories have been advanced to explain the nature of enzymatic control over this series of reactions, including suggestions of steric shielding and oxygen channeling. As proposed here, selective radical trapping and spin localization in the substrate-derived pentadienyl radical intermediate can also be envisioned. Herein we describe the results of explicit, 10 ns molecular dynamics simulations of both COX-1 and COX-2 with the substrate-derived pentadienyl radical intermediate bound in the active site. The enzymes’ influence on the conformation of the pentadienyl radical was investigated, along with the accessible space above and below the radical plane, and the width of several channels to the active site that could function as access routes for molecular oxygen. Additional simulations demonstrated the extent of molecular oxygen mobility within the active site. The results suggest that spin localization is unlikely to play a role in enzymatic control of this reaction. Instead, a combination of oxygen channeling, steric shielding and selective radical trapping appears to be responsible. This work adds a dynamic perspective to the strong foundation of static structural data available for these enzymes. PMID:16519515

  18. Enhanced Reactivity in Nucleophilic Acyl Substitution Ion/Ion Reactions Using Triazole-Ester Reagents

    NASA Astrophysics Data System (ADS)

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

    2017-02-01

    The acyl substitution reactions between 1-hydroxy-7-aza-benzotriazole (HOAt)/1-hydroxy-benzotriazole (HOBt) ester reagents and nucleophilic side chains on peptides have been demonstrated in the gas phase via ion/ion reactions. The HOAt/HOBt ester reagents were synthesized in solution and ionized via negative nano-electrospray ionization. The anionic reagents were then reacted with doubly protonated model peptides containing amines, guanidines, and imidazoles in the gas phase. The complexes formed in the reaction cell were further probed with ion trap collision induced dissociation (CID) yielding either a covalently modified analyte ion or a proton transfer product ion. The covalent reaction yield of HOAt/HOBt ester reagents was demonstrated to be higher than the yield with N-hydroxysuccinimide (NHS) ester reagents over a range of equivalent conditions. Density functional theory (DFT) calculations were performed with a primary amine model system for both triazole-ester and NHS-ester reactants, which indicated a lower transition state barrier for the former reagent, consistent with experiments. The work herein demonstrates that the triazole-ester reagents are more reactive, and therefore less selective, than the analogous NHS-ester reagent. As a consequence, the triazole-ester reagents are the first to show efficient reactivity with unprotonated histidine residues in the gas phase. For all nucleophilic sites and all reagents, covalent reactions are favored under long time, low amplitude activation conditions. This work presents a novel class of reagents capable of gas-phase conjugation to nucleophilic sites in analyte ions via ion/ion chemistry.

  19. The Wacker process: inner- or outer-sphere nucleophilic addition? New insights from ab initio molecular dynamics.

    PubMed

    Comas-Vives, Aleix; Stirling, András; Lledós, Agustí; Ujaque, Gregori

    2010-08-02

    The Wacker process consists of the oxidation of ethylene catalyzed by a Pd(II) complex. The reaction mechanism has been largely debated in the literature; two modes for the nucleophilic addition of water to a Pd-coordinated alkene have been proposed: syn-inner- and anti-outer-sphere mechanisms. These reaction steps have been theoretically evaluated by means of ab initio molecular dynamics combined with metadynamics by placing the [Pd(C(2)H(4))Cl(2)(H(2)O)] complex in a box of water molecules, thereby resembling experimental conditions at low [Cl(-)]. The nucleophilic addition has also been evaluated for the [Pd(C(2)H(4))Cl(3)](-) complex, thus revealing that the water by chloride ligand substitution trans to ethene is kinetically favored over the generally assumed cis species in water. Hence, the resulting trans species can only directly undertake the outer-sphere nucleophilic addition, whereas the inner-sphere mechanism is hindered since the attacking water is located trans to ethene. In addition, all the simulations from the [Pd(C(2)H(4))Cl(2)(H(2)O)] species (either cis or trans) support an outer-sphere mechanism with a free-energy barrier compatible with that obtained experimentally, whereas that for the inner-sphere mechanism is significantly higher. Moreover, additional processes for a global understanding of the Wacker process in solution have also been identified, such as ligand substitutions, proton transfers that involve the aquo ligand, and the importance of the trans effect of the ethylene in the nucleophilic addition attack.

  20. Pd-Catalyzed Nucleophilic Fluorination of Aryl Bromides

    PubMed Central

    2015-01-01

    On the basis of mechanism-driven reaction design, a Pd-catalyzed nucleophilic fluorination of aryl bromides and iodides has been developed. The method exhibits a broad substrate scope, especially with respect to nitrogen-containing heteroaryl bromides, and proceeds with minimal formation of the corresponding reduction products. A facilitated ligand modification process was shown to be critical to the success of the reaction. PMID:24559304

  1. HBF4-Catalysed Nucleophilic Substitutions of Propargylic Alcohols

    PubMed Central

    Barreiro, Elena; Sanz-Vidal, Alvaro; Tan, Eric; Lau, Shing-Hing; Sheppard, Tom D; Díez-González, Silvia

    2015-01-01

    The activity of HBF4 (aqueous solution) as a catalyst in propargylation reactions is presented. Diverse types of nucleophiles were employed in order to form new C–O, C–N and C–C bonds in technical acetone and in air. Good to excellent yields and good chemoselectivities were obtained using low acid loading (typically 1 mol-%) under simple reaction conditions. PMID:26693210

  2. The intraflagellar transport dynein complex of trypanosomes is made of a heterodimer of dynein heavy chains and of light and intermediate chains of distinct functions.

    PubMed

    Blisnick, Thierry; Buisson, Johanna; Absalon, Sabrina; Marie, Alexandra; Cayet, Nadège; Bastin, Philippe

    2014-09-01

    Cilia and flagella are assembled by intraflagellar transport (IFT) of protein complexes that bring tubulin and other precursors to the incorporation site at their distal tip. Anterograde transport is driven by kinesin, whereas retrograde transport is ensured by a specific dynein. In the protist Trypanosoma brucei, two distinct genes encode fairly different dynein heavy chains (DHCs; ∼40% identity) termed DHC2.1 and DHC2.2, which form a heterodimer and are both essential for retrograde IFT. The stability of each heavy chain relies on the presence of a dynein light intermediate chain (DLI1; also known as XBX-1/D1bLIC). The presence of both heavy chains and of DLI1 at the base of the flagellum depends on the intermediate dynein chain DIC5 (FAP133/WDR34). In the IFT140(RNAi) mutant, an IFT-A protein essential for retrograde transport, the IFT dynein components are found at high concentration at the flagellar base but fail to penetrate the flagellar compartment. We propose a model by which the IFT dynein particle is assembled in the cytoplasm, reaches the base of the flagellum, and associates with the IFT machinery in a manner dependent on the IFT-A complex.

  3. The aerobic oxidation of a Pd(II) dimethyl complex leads to selective ethane elimination from a Pd(III) intermediate.

    PubMed

    Khusnutdinova, Julia R; Rath, Nigam P; Mirica, Liviu M

    2012-02-01

    Oxidation of the Pd(II) complex (N4)Pd(II)Me(2) (N4 = N,N'-di-tert-butyl-2,11-diaza[3.3](2,6)pyridinophane) with O(2) or ROOH (R = H, tert-butyl, cumyl) produces the Pd(III) species [(N4)Pd(III)Me(2)](+), followed by selective formation of ethane and the monomethyl complex (N4)Pd(II)Me(OH). Cyclic voltammetry studies and use of 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trap suggest an inner-sphere mechanism for (N4)Pd(II)Me(2) oxidation by O(2) to generate a Pd(III)-superoxide intermediate. In addition, reaction of (N4)Pd(II)Me(2) with cumene hydroperoxide involves a heterolytic O-O bond cleavage, implying a two-electron oxidation of the Pd(II) precursor and formation of a transient Pd(IV) intermediate. Mechanistic studies of the C-C bond formation steps and crossover experiments are consistent with a nonradical mechanism that involves methyl group transfer and transient formation of a Pd(IV) species. Moreover, the (N4)Pd(II)Me(OH) complex formed upon ethane elimination reacts with weakly acidic C-H bonds of acetone and terminal alkynes, leading to formation of a new Pd(II)-C bond. Overall, this study represents the first example of C-C bond formation upon aerobic oxidation of a Pd(II) dimethyl complex, with implications in the development of Pd catalysts for aerobic oxidative coupling of C-H bonds.

  4. A rationale on the role of intermediate Au(III)-vitamin C complexation in the production of gold nanoparticles

    NASA Astrophysics Data System (ADS)

    Zümreoglu-Karan, B.

    2009-07-01

    Preparation of gold nanoparticles, particularly gold nanorods, by wet chemistry processes involves gold seeds, an Au(III) salt, structure directing surfactants, and metal ion additives in the growth solution into which a weak reducing agent is added. The most commonly employed weak reducing agent is l-ascorbic acid (vitamin C) which is known to reduce many metal ions in the solution phase and form complexes with relatively low stability constants. A purple-gray gold-ascorbate compound, obtained from the reaction of sodium tetrachloroaurate(III) with sodium ascorbate, is now reported. The compound possesses the expected structural features of vitamin C-metal complexes as verified by its 13C CP-MAS NMR spectrum. A discussion is also presented on the possibility of gold-ascorbate complexation operating in gold nanoparticle formation.

  5. Pentacoordinated carboxylate π-allyl nickel complexes as key intermediates for the Ni-catalyzed direct amination of allylic alcohols.

    PubMed

    Kita, Yusuke; Sakaguchi, Hironobu; Hoshimoto, Yoichi; Nakauchi, Daisuke; Nakahara, Yasuhito; Carpentier, Jean-François; Ogoshi, Sensuke; Mashima, Kazushi

    2015-10-05

    Direct amination of allylic alcohols with primary and secondary amines catalyzed by a system made of [Ni(1,5-cyclooctadiene)2 ] and 1,1'-bis(diphenylphosphino)ferrocene was effectively enhanced by adding nBu4 NOAc and molecular sieves, affording the corresponding allyl amines in high yield with high monoallylation selectivity for primary amines and high regioselectivity for monosubstituted allylic alcohols. Such remarkable additive effects of nBu4 NOAc were elucidated by isolating and characterizing some nickel complexes, manifesting the key role of a charge neutral pentacoordinated η(3) -allyl acetate complex in the present system, in contrast to usual cationic tetracoordinated complexes earlier reported in allylic substitution reactions.

  6. Apparent anti-Woodward-Hoffmann addition to a nickel bis(dithiolene) complex: the reaction mechanism involves reduced, dimetallic intermediates.

    PubMed

    Dang, Li; Shibl, Mohamed F; Yang, Xinzheng; Harrison, Daniel J; Alak, Aiman; Lough, Alan J; Fekl, Ulrich; Brothers, Edward N; Hall, Michael B

    2013-04-01

    Nickel dithiolene complexes have been proposed as electrocatalysts for alkene purification. Recent studies of the ligand-based reactions of Ni(tfd)2 (tfd = S2C2(CF3)2) and its anion [Ni(tfd)2](-) with alkenes (ethylene and 1-hexene) showed that in the absence of the anion, the reaction proceeds most rapidly to form the intraligand adduct, which decomposes by releasing a substituted dihydrodithiin. However, the presence of the anion increases the rate of formation of the stable cis-interligand adduct, and decreases the rate of dihydrodithiin formation and decomposition. In spite of both computational and experimental studies, the mechanism, especially the role of the anion, remained somewhat elusive. We are now providing a combined experimental and computational study that addresses the mechanism and explains the role of the anion. A kinetic study (global analysis) for the reaction of 1-hexene is reported, which supports the following mechanism: (1) reversible intraligand addition, (2) oxidation of the intraligand addition product prior to decomposition, and (3) interligand adduct formation catalyzed by Ni(tfd)2(-). Density functional theory (DFT) calculations were performed on the Ni(tfd)2/Ni(tfd)2(-)/ethylene system to shed light on the selectivity of adduct formation in the absence of anion and on the mechanism in which Ni(tfd)2(-) shifts the reaction from intraligand addition to interligand addition. Computational results show that in the neutral system the free energy of activation for intraligand addition is lower than that for interligand addition, in agreement with the experimental results. The computations predict that the anion enhances the rate of the cis-interligand adduct formation by forming a dimetallic complex with the neutral complex. The [(Ni(tfd)2)2](-) dimetallic complex then coordinates ethylene and isomerizes to form a Ni,S-bound ethylene complex, which then rapidly isomerizes to the stable interligand adduct but not to the intraligand adduct

  7. Neuromuscular synapse integrity requires linkage of acetylcholine receptors to postsynaptic intermediate filament networks via rapsyn–plectin 1f complexes

    PubMed Central

    Mihailovska, Eva; Raith, Marianne; Valencia, Rocio G.; Fischer, Irmgard; Banchaabouchi, Mumna Al; Herbst, Ruth; Wiche, Gerhard

    2014-01-01

    Mutations in the cytolinker protein plectin lead to grossly distorted morphology of neuromuscular junctions (NMJs) in patients suffering from epidermolysis bullosa simplex (EBS)-muscular dystrophy (MS) with myasthenic syndrome (MyS). Here we investigated whether plectin contributes to the structural integrity of NMJs by linking them to the postsynaptic intermediate filament (IF) network. Live imaging of acetylcholine receptors (AChRs) in cultured myotubes differentiated ex vivo from immortalized plectin-deficient myoblasts revealed them to be highly mobile and unable to coalesce into stable clusters, in contrast to wild-type cells. We found plectin isoform 1f (P1f) to bridge AChRs and IFs via direct interaction with the AChR-scaffolding protein rapsyn in an isoform-specific manner; forced expression of P1f in plectin-deficient cells rescued both compromised AChR clustering and IF network anchoring. In conditional plectin knockout mice with gene disruption in muscle precursor/satellite cells (Pax7-Cre/cKO), uncoupling of AChRs from IFs was shown to lead to loss of postsynaptic membrane infoldings and disorganization of the NMJ microenvironment, including its invasion by microtubules. In their phenotypic behavior, mutant mice closely mimicked EBS-MD-MyS patients, including impaired body balance, severe muscle weakness, and reduced life span. Our study demonstrates that linkage to desmin IF networks via plectin is crucial for formation and maintenance of AChR clusters, postsynaptic NMJ organization, and body locomotion. PMID:25318670

  8. A pentacoordinated norbornenyl-acyl-rhodium(iii) complex as a likely intermediate in the catalytic hydroacylation of norbornadiene.

    PubMed

    Almenara, N; Ibarlucea, L; Mendicute-Fierro, C; Seco, J M; Rodríguez-Diéguez, A; Garralda, M A; Huertos, M A

    2016-11-22

    [RhCl(NCO)(nbyl)(PR3)] (nbyl = σ-norbornenyl; NCO = quinoline-8-acyl; R = p-F-C6H4) (1) has been synthesized by the reaction of [Rh(nbd)Cl]2 (nbd = norbornadiene) with 2 equivalents of NCHO (quinoline-8-carbaldehyde) and 2 equivalents of PR3. Compound 1 has been fully characterized in solution and also in the solid state by X-ray diffraction. Compound 1 shows low stability in solution and undergoes slow ring closure isomerization to [RhCl(NCO)(ntyl)(PR3)] (ntyl = σ-nortricyclyl) (2) after 12 hours. Reaction of 1 with an extra equivalent of aldehyde (NCHO) and PR3 led to the formation of [RhCl(H)(NCO)(PR3)2] (3) and an equivalent of ketone, which is a hydroacylation product. The catalytic activity of 3 in the hydroacylation of nbd with NCHO is reported as well as the catalytic activity of compound 1. Compounds 1 and 3 are proposed as intermediate species in the catalytic hydroacylation of norbornadiene with NCHO.

  9. Nucleotides as nucleophiles: reactions of nucleotides with phosphoimidazolide activated guanosine

    NASA Technical Reports Server (NTRS)

    Kanavarioti, A.; Rosenbach, M. T.; Hurley, T. B.

    1991-01-01

    An earlier study of the reaction of phosphoimidazolide activated nucleosides (ImpN) in aqueous phosphate buffers indicated two modes of reaction of the phosphate monoanion and dianion. The first mode is catalysis of the hydrolysis of the P-N bond in ImpN's which leads to imidazole and nucleoside 5'-monophosphate. The second represents a nucleophilic substitution of the imidazole to yield the nucleoside 5'-diphosphate. This earlier study thus served as a model for the reaction of ImpN with nucleoside monophosphates (pN) because the latter can be regarded as phosphate derivatives. In the present study we investigated the reaction of guanosine 5'-phosphate-2-methylimidazolide, 2-MeImpG, in the presence of pN (N = guanosine, adenosine and uridine) in the range 6.9 less than or equal to pH less than or equal to 7.7. We observed that pN's do act as nucleophiles to form NppG, and as general base to enhance the hydrolysis of the P-N bond in 2-MeImpG, i.e. pN show the same behavior as inorganic phosphate. The kinetic analysis yields the following rate constants for the dianion pN2-: knpN = 0.17 +/- 0.02 M-1 h-1 for nucleophilic attack and khpN = 0.11 +/- 0.07 M-1 h-1 for general base catalysis of the hydrolysis. These rate constants which are independent of the nucleobase compare with kp.2 = 0.415 M-1 h-1 and khp2. = 0.217 M-1 h-1 for the reactions of HPO4(2-). In addition, this study shows that under conditions where pN presumably form stacks, the reaction mechanism remains unchanged although in quantitative terms stacked pN are somewhat less reactive. Attack by the 2'-OH and 3'-OH groups of the ribose moiety in amounts greater than or equal to 1% is not observed; this is attributed to the large difference in nucleophilicity in the neutral pH range between the phosphate group and the ribose hydroxyls. This nucleophilicity rank is not altered by stacking.

  10. Electrochemical nucleophilic synthesis of di-tert-butyl-(4-[18F]fluoro-1,2-phenylene)-dicarbonate.

    PubMed

    He, Qinggang; Wang, Ying; Alfeazi, Ines; Sadeghi, Saman

    2014-09-01

    An electrochemical method with the ability to conduct (18)F-fluorination of aromatic molecules through direct nucleophilic fluorination of cationic intermediates is presented in this paper. The reaction was performed on a remote-controlled automatic platform. Nucleophilic electrochemical fluorination of tert-butyloxycarbonyl (Boc) protected catechol, an intermediate model molecule for the positron emission tomography (PET) probe (3,4-dihydroxy-6-[(18)F]fluoro-L-phenylalanine), was performed. Fluorination was achieved under potentiostatic anodic oxidation in acetonitrile containing Et3N·3HF and other supporting electrolytes. Radiofluorination efficiency was influenced by a number of variables, including the concentration of the precursor, concentration of Et3N·3HF, type of supporting electrolyte, temperature and time, as well as applied potentials. Radio-fluorination efficiency of 10.4±0.6% (n=4) and specific activity of up to 43GBq/mmol was obtained after 1h electrolysis of 0.1M of 4-tert-butyl-diboc-catechol in the acetonitrile solution of Et3N·3HF (0.033M) and NBu4PF6 (0.05M). Density functional theory (DFT) was employed to explain the tert-butyl functional group facilitation of electrochemical oxidation and subsequent fluorination.

  11. Mechanism of SN2 disulfide bond cleavage by phosphorus nucleophiles. Implications for biochemical disulfide reducing agents.

    PubMed

    Dmitrenko, Olga; Thorpe, Colin; Bach, Robert D

    2007-10-26

    The B3LYP variant of DFT has been used to study the mechanism of S-S bond scission in dimethyl disulfide by a phosphorus nucleophile, trimethylphospine (TMP). The reaction is highly endothermic in the gas phase and requires significant external stabilization of the charged products. DFT calculations (B3LYP) were performed with explicit (water molecules added) and implicit solvent corrections (COSMO model). The transition structures for this SN2 displacement reaction in a number of model systems have been located and fully characterized. The reaction barriers calculated with different approaches for different systems are quite close (around 11 kcal/mol). Remarkably, the calculations suggest that the reaction is almost barrierless with respect to the preorganized reaction complex and that most of the activation energy is required to rearrange the disulfide and TMP to its most effective orientation for the SMe group transfer way. Different reactivities of different phosphorus nucleophiles were suggested to be the result of steric effects, as manifested largely by varying amounts of hindrance to solvation of the initial product phosphonium ion. These data indicate that the gas-phase addition of a phosphine to the disulfide moiety will most likely form a phosphonium cation-thiolate anion salt, in the presence of four or more water molecules, that provide sufficient H-bonding stabilization to allow displacement of the thiolate anion, a normal uncomplicated SN2 transition state is to be expected.

  12. An altered mechanism of hydrolysis for a metal-complexed phosphate diester.

    PubMed

    Humphry, Tim; Forconi, Marcello; Williams, Nicholas H; Hengge, Alvan C

    2002-12-18

    Isotope effects in the nucleophile and in the leaving group were measured to gain information about the mechanism and transition state of the hydrolysis of methyl p-nitrophenyl phosphate complexed to a dinuclear cobalt complex. The complexed diester undergoes hydrolysis about 1011 times faster than the corresponding uncomplexed diester. The kinetic isotope effects indicate that this rate acceleration is accompanied by a change in mechanism. A large inverse 18O isotope effect in the bridging hydroxide nucleophile (0.937 +/- 0.002) suggests that nucleophilic attack occurs before the rate-determining step. Large isotope effects in the nitrophenyl leaving group (18Olg = 1.029 +/- 0.002, 15N = 1.0026 +/- 0.0002) indicate significant fission of the P-O ester bond in the transition state of the rate-determining step. The data indicate that in contrast to uncomplexed diesters, which undergo hydrolysis by a concerted mechanism, the reaction of the complexed diester likely proceeds via an addition-elimination mechanism. The rate-limiting step is expulsion of the p-nitrophenyl leaving group from the intermediate, which proceeds by a late transition state with extensive bond fission to the leaving group. This represents a substantial change in mechanism from the hydrolysis of uncomplexed aryl phosphate diesters.

  13. Complexity of expression of the intermediate filaments of six new human ovarian carcinoma cell lines: new expression of cytokeratin 20.

    PubMed Central

    Yanagibashi, T.; Gorai, I.; Nakazawa, T.; Miyagi, E.; Hirahara, F.; Kitamura, H.; Minaguchi, H.

    1997-01-01

    Six permanent human ovarian carcinoma cell lines (OVISE, OVTOKO, OVMANA and OVSAYO from clear cell adenocarcinoma, and OVSAHO and OVKATE from serous papillary adenocarcinoma) were established from solid tumours. The cell lines have been in culture for 5-8 years, the passage number varying from 62 to 246. Immunohistochemical analysis has shown that five of the six cell lines express at least six cytokeratin (CK) polypeptides. OVISE and OVSAYO expressed CKs 6, 7, 8, 18, 19 and 15 and/or 16. OVTOKO was positive for CKs 7, 8, 18, 19 and 15 and/or 16. OVSAHO expressed CKs 6, 7, 8, 14, 18, 19 and 15 and/or 16. OVMANA expressed CKs 6, 7, 8, 18, 19, 20 and 15 and/or 16. OVKATE expressed CKs 6, 7, 8, 13, 17, 18, 19, 20 and 15 and/or 16. The expression of CK7, additional expression of vimentin, and clinical and histopathological findings enabled us to confirm that six cell lines had been established from primary ovarian cancers. Two of the six cell lines were positive for CK20, although CK20 was not expressed in the original tumours. The heterotransplanted tumours produced by CK20-positive cells also expressed CK20. This is the first report of ovarian carcinoma cell lines that express CK20 irrespective of their histological type. CK20 has been found in all colon carcinoma cell lines, but only in the mucinous type of ovarian tumours. These new ovarian carcinoma cell lines will therefore provide a relevant experimental system for elucidating the regulatory control mechanisms of intermediate filament expression. Images Figure 1 Figure 2 Figure 3 PMID:9328139

  14. Hyperpolarized 89Y NMR spectroscopic detection of yttrium ion and DOTA macrocyclic ligand complexation: pH dependence and Y-DOTA intermediates

    NASA Astrophysics Data System (ADS)

    Ferguson, Sarah; Kiswandhi, Andhika; Niedbalski, Peter; Parish, Christopher; Kovacs, Zoltan; Lumata, Lloyd

    Dissolution dynamic nuclear polarization (DNP) is a rapidly emerging physics technique used to enhance the signal strength in nuclear magnetic resonance (NMR) and imaging (MRI) experiments for nuclear spins such as yttrium-89 by >10,000-fold. One of the most common and stable MRI contrast agents used in the clinic is Gd-DOTA. In this work, we have investigated the binding of the yttrium and DOTA ligand as a model for complexation of Gd ion and DOTA ligand. The macrocyclic ligand DOTA is special because its complexation with lanthanide ions such as Gd3+ or Y3+ is highly pH dependent. Using this physics technology, we have tracked the complexation kinetics of hyperpolarized Y-triflate and DOTA ligand in real-time and detected the Y-DOTA intermediates. Different kinds of buffers were used (lactate, acetate, citrate, oxalate) and the pseudo-first order complexation kinetic calculations will be discussed. The authors would like to acknowledge the support by US Dept of Defense Award No. W81XWH-14-1-0048 and Robert A. Welch Foundation Grant No. AT-1877.

  15. Nucleophilic and general acid catalysis at physiological pH by a designed miniature esterase.

    PubMed

    Nicoll, Andrew J; Allemann, Rudolf K

    2004-08-07

    A 31-residue peptide (Art-Est) was designed to catalyse the hydrolysis of p-nitrophenyl esters through histidine catalysis on the solvent exposed face of the alpha-helix of bovine pancreatic polypeptide. NMR spectroscopy indicated that Art-Est adopted a stable 3-dimensional structure in solution. Art-Est was an efficient catalyst with second order rate constants of up to 0.050 M(-1) s(-1). The activity of Art-Est was a consequence of the increased nucleophilicity of His-22, which had a reduced pK(a) value of 5.5 as a consequence of its interaction with His-18 and the positively charged Arg-25 and Arg-26. Mass spectrometry and NMR spectroscopy confirmed that the Art-Est catalysed hydrolysis of p-nitrophenyl esters proceeded through an acyl-enzyme intermediate. A solvent kinetic isotope effect of 1.8 indicated that the transition state preceding the acyl intermediate was stabilised through interaction with the protonated side-chain of His-18 and indicated a reaction mechanism similar to that generally observed for natural esterases. The involvement in the reaction of two histidine residues with different pK(a) values led to a bell-shaped dependence of the reaction rate on the pH of the solution. The catalytic behaviour of Art-Est indicated that designed miniature enzymes can act in a transparent mechanism based fashion with enzyme-like behaviour through the interplay of several amino acid residues.

  16. Intermediate number of major histocompatibility complex class IIB length variants relates to enlarged perivisceral fat deposits in the blunt-head cichlid Tropheus moorii.

    PubMed

    Hablützel, P I; Vanhove, M P M; Grégoir, A F; Hellemans, B; Volckaert, F A M; Raeymaekers, J A M

    2014-10-01

    Studying the genetic basis of host-parasite interactions represents an outstanding opportunity to observe eco-evolutionary processes. Established candidates for such studies in vertebrates are immunogenes of the major histocompatibility complex (MHC). The MHC has been reported to reach high intra- and interindividual diversity, and a diverse MHC might be advantageous when facing infections from multiple parasites. However, other studies indicated that individuals with an intermediate number of MHC alleles are less infected with parasites or have other fitness advantages. In this study, we assessed the optimal number of MHC alleles in the blunt-head cichlid Tropheus moorii from Lake Tanganyika. We investigated the influence of the interindividual variation in number of MHC length variants on parasite infection and body condition, measured by the amount of perivisceral fat reserves. Surprisingly, there was no correlation between parasite infection and number of MHC length variants or perivisceral fat deposits. However, the individual number of MHC length variants significantly correlated with the amount of perivisceral fat deposits in males, suggesting that male individuals with an intermediate number of alleles might be able to use their fat reserves more efficiently.

  17. Xyloglucan endotransglycosylase: evidence for the existence of a relatively stable glycosyl-enzyme intermediate.

    PubMed

    Sulová, Z; Takácová, M; Steele, N M; Fry, S C; Farkas, V

    1998-03-15

    Xyloglucan endotransglycosylases (XETs) catalyse the breakdown of xyloglucan molecules predominantly by transglycosylation. In this process, fragments of cleaved polysaccharide are preferentially transferred to other xyloglucan molecules or their oligosaccharide subunits, with overall retention of the anomeric configuration of the glycosidic bond. In accordance with the theory, we propose that the cleavage and re-formation of the glycosidic bond in xyloglucan involves the formation of a glycosyl-enzyme intermediate which decomposes by transfer of the glycosyl moiety to a suitable carbohydrate acceptor. XETs from nasturtium seed cotyledons, mung bean hypocotyls and cauliflower florets interacted with xyloglucan to form complexes of high Mr as judged by gel-permeation chromatography. The nasturtium enzyme also showed evidence of XET-xyloglucan complex-formation according to anion-exchange chromatography and adsorption of the complex to filter paper on the basis of affinity of its xyloglucan moiety for cellulose. The XET-xyloglucan complex was stable in water, 6 M urea and acidic and alkaline buffers (pH 2.5-9.5), but readily decomposed by transferring its glycosyl moiety to xyloglucan-derived oligosaccharides or by incubation with the strong nucleophile imidazole at pH 3.8-9.6. These results strongly support the assumption that XET forms a relatively stable covalently linked glycosyl-enzyme intermediate.

  18. Fragmentation of protonated 2-(2-phenylethyl)chromones from agarwood: the diagnostic role of ion/neutral complexes as reactive intermediates.

    PubMed

    Yang, Delan; Xia, Bing; Jiang, Yan; Mei, Wenli; Kuck, Dietmar

    2015-01-01

    A positive-ion electrospray ionisation collision-induced dissociation mass spectrometric study on the fragmentation of the [M + H](+) ions of 2-(2-phenylethyl)chromone and a set of nine hydroxyl- and/or methoxy-substituted derivatives has revealed a highly prominent fragmentation channel, the loss of benzoquinomethanes or a benzaldehyde, respectively, as a diagnostic feature for 2-(2-phenylethyl)chromones that bear a hydroxyl group at the para- (4'-), ortho- (2'-) and/or benzylic (α-) position of the phenylethyl residue. Derivatives that bear only a meta- (3'-) hydroxyl group do not undergo this elimination. The intermediacy of ion/neutral complexes (INCs) is invoked to explain this fragmentation, which involves the remarkable intra-complex proton or hydrogen atom transfer from the remote 4'-OH (or the 2'- or α-OH) functionalities. Density functional theory (B3LYP/6-31G(d)) calculations confirm the energetic preference for these elimination channels and agree with the limited thermochemical data known for para- and ortho- benzoquinomethanes. The INC-mediated losses of the benzaldehydes from the [M + H](+) ions of the α-hydroxy-substituted 2-(2-phenylethyl)chromones correspond to a particularly facile (vinylogous) Grob fragmentation. The study may be viewed as a telling example of the diagnostic role of ion/neutral complexes as intermediates for the structural assignment of constitutional isomers by mass spectrometry.

  19. Trans-eQTLs Reveal That Independent Genetic Variants Associated with a Complex Phenotype Converge on Intermediate Genes, with a Major Role for the HLA

    PubMed Central

    Fehrmann, Rudolf S. N.; Arends, Danny; Bonder, Marc Jan; Fu, Jingyuan; Deelen, Patrick; Groen, Harry J. M.; Smolonska, Asia; Weersma, Rinse K.; Hofstra, Robert M. W.; Buurman, Wim A.; Rensen, Sander; Wolfs, Marcel G. M.; Platteel, Mathieu; Zhernakova, Alexandra; Elbers, Clara C.; Festen, Eleanora M.; Trynka, Gosia; Hofker, Marten H.; Saris, Christiaan G. J.; Ophoff, Roel A.; van den Berg, Leonard H.; van Heel, David A.; Wijmenga, Cisca; te Meerman, Gerard J.; Franke, Lude

    2011-01-01

    For many complex traits, genetic variants have been found associated. However, it is still mostly unclear through which downstream mechanism these variants cause these phenotypes. Knowledge of these intermediate steps is crucial to understand pathogenesis, while also providing leads for potential pharmacological intervention. Here we relied upon natural human genetic variation to identify effects of these variants on trans-gene expression (expression quantitative trait locus mapping, eQTL) in whole peripheral blood from 1,469 unrelated individuals. We looked at 1,167 published trait- or disease-associated SNPs and observed trans-eQTL effects on 113 different genes, of which we replicated 46 in monocytes of 1,490 different individuals and 18 in a smaller dataset that comprised subcutaneous adipose, visceral adipose, liver tissue, and muscle tissue. HLA single-nucleotide polymorphisms (SNPs) were 10-fold enriched for trans-eQTLs: 48% of the trans-acting SNPs map within the HLA, including ulcerative colitis susceptibility variants that affect plausible candidate genes AOAH and TRBV18 in trans. We identified 18 pairs of unlinked SNPs associated with the same phenotype and affecting expression of the same trans-gene (21 times more than expected, P<10−16). This was particularly pronounced for mean platelet volume (MPV): Two independent SNPs significantly affect the well-known blood coagulation genes GP9 and F13A1 but also C19orf33, SAMD14, VCL, and GNG11. Several of these SNPs have a substantially higher effect on the downstream trans-genes than on the eventual phenotypes, supporting the concept that the effects of these SNPs on expression seems to be much less multifactorial. Therefore, these trans-eQTLs could well represent some of the intermediate genes that connect genetic variants with their eventual complex phenotypic outcomes. PMID:21829388

  20. Human 2-Oxoglutarate Dehydrogenase Complex E1 Component Forms a Thiamin-derived Radical by Aerobic Oxidation of the Enamine Intermediate*

    PubMed Central

    Nemeria, Natalia S.; Ambrus, Attila; Patel, Hetalben; Gerfen, Gary; Adam-Vizi, Vera; Tretter, Laszlo; Zhou, Jieyu; Wang, Junjie; Jordan, Frank

    2014-01-01

    Herein are reported unique properties of the human 2-oxoglutarate dehydrogenase multienzyme complex (OGDHc), a rate-limiting enzyme in the Krebs (citric acid) cycle. (a) Functionally competent 2-oxoglutarate dehydrogenase (E1o-h) and dihydrolipoyl succinyltransferase components have been expressed according to kinetic and spectroscopic evidence. (b) A stable free radical, consistent with the C2-(C2α-hydroxy)-γ-carboxypropylidene thiamin diphosphate (ThDP) cation radical was detected by electron spin resonance upon reaction of the E1o-h with 2-oxoglutarate (OG) by itself or when assembled from individual components into OGDHc. (c) An unusual stability of the E1o-h-bound C2-(2α-hydroxy)-γ-carboxypropylidene thiamin diphosphate (the “ThDP-enamine”/C2α-carbanion, the first postdecarboxylation intermediate) was observed, probably stabilized by the 5-carboxyl group of OG, not reported before. (d) The reaction of OG with the E1o-h gave rise to superoxide anion and hydrogen peroxide (reactive oxygen species (ROS)). (e) The relatively stable enzyme-bound enamine is the likely substrate for oxidation by O2, leading to the superoxide anion radical (in d) and the radical (in b). (f) The specific activity assessed for ROS formation compared with the NADH (overall complex) activity, as well as the fraction of radical intermediate occupying active centers of E1o-h are consistent with each other and indicate that radical/ROS formation is an “off-pathway” side reaction comprising less than 1% of the “on-pathway” reactivity. However, the nearly ubiquitous presence of OGDHc in human tissues, including the brain, makes these findings of considerable importance in human metabolism and perhaps disease. PMID:25210035

  1. The first alkene-platinum-silyl complexes: lifting the hydrosilation mechanism shroud with long-lived precatalytic intermediates and true pt catalysts.

    PubMed

    Roy, Aroop K; Taylor, Richard B

    2002-08-14

    The synthesis, characterization, and exploratory chemistry of two classes of alkene-platinum-silyl complexes, which have been postulated as hydrosilation intermediates, are described in this report. The unique dimeric complexes 1, [R(3)Si(mu-Cl)(eta(2)-COD)Pt](2) [R(3)Si = Et(3)Si, MeCl(2)Si, Me(2)ClSi, "(EtO)(3)Si", PhMe(2)Si, and (Me(3)SiO)Me(2)Si; COD = cycloocta-1,5-diene], and the bis-silyl complexes 2, (eta(4)-COD)Pt(SiR(3))(2) (R(3)Si = Cl(3)Si, MeCl(2)Si, Me(2)ClSi, and PhMe(2)Si), are formed from the sequential reaction of 2 and 4 equiv of the corresponding hydrosilanes, respectively, with Pt(COD)Cl(2) in the presence of a small excess of COD. Complexes 1 are stable for many days in solution at room temperature but decompose via slow elimination of chlorosilane. Some of the bis-silyl compounds 2 are stable for extended periods under inert atmosphere and especially below 0 degrees C, either in the solid state or in solution (in the presence of a small excess of free COD). Complexes 2 display catalytic activity as discrete, molecular, and mononuclear species for hydrosilation and isomerization reactions. Compound 2c (R(3)Si = MeCl(2)Si) was fully characterized via multinuclear NMR spectroscopy and X-ray crystal structure analysis. The facile H-transfer rather than Si-transfer to bound COD provides experimental support for the sequence of insertive steps in the Chalk-Harrod catalytic cycle, at least for Pt-catalyzed hydrosilation.

  2. Mechanism of host-guest complex formation and identification of intermediates through NMR titration and diffusion NMR spectroscopy.

    PubMed

    Lamm, Jan-Hendrik; Niermeier, Philipp; Mix, Andreas; Chmiel, Jasmin; Neumann, Beate; Stammler, Hans-Georg; Mitzel, Norbert W

    2014-07-21

    The formation of host-guest (H-G) complexes between 1,8-bis[(diethylgallanyl)ethynyl]anthracene (H) and the N-heterocycles pyridine and pyrimidine (G) was studied in solution using a combination of NMR titration and diffusion NMR experiments. For the latter, diffusion coefficients of potential host-guest structures in solution were compared with those of tailor-made reference compounds of similar shape (synthesized and characterized by NMR, HRMS, and in part XRD). Highly dynamic behavior was observed in both cases, but with different host-guest species and equilibria. With increasing concentrations of the pyridine guest, the equilibrium H2⇄H2κ(1)-G1⇄HG2 is observed (in the second step a host dimer coordinates one guest molecule); for pyrimidine the equilibrium H2→H1κ(2)-G1⇄HG2 is observed (the formation of a 1:1 aggregate is the second step).

  3. Advantages of paramagnetic chemical exchange saturation transfer (CEST) complexes having slow to intermediate water exchange properties as responsive MRI agents.

    PubMed

    Soesbe, Todd C; Wu, Yunkou; Dean Sherry, A

    2013-07-01

    Paramagnetic chemical exchange saturation transfer (PARACEST) complexes are exogenous contrast agents that have great potential to further extend the functional and molecular imaging capabilities of magnetic resonance. As a result of the presence of a central paramagnetic lanthanide ion (Ln(3+) ≠ La(3+) , Gd(3+) , Lu(3+) ) within the chelate, the resonance frequencies of exchangeable protons bound to the PARACEST agent are shifted far away from the bulk water frequency. This large chemical shift, combined with an extreme sensitivity to the chemical exchange rate, make PARACEST agents ideally suited for the reporting of significant biological metrics, such as temperature, pH and the presence of metabolites. In addition, the ability to turn PARACEST agents 'off' and 'on' using a frequency-selective saturation pulse gives them a distinct advantage over Gd(3+) -based contrast agents. A current challenge for PARACEST research is the translation of the promising in vitro results into in vivo systems. This short review article first describes the basic theory behind PARACEST contrast agents, their benefits over other contrast agents and their applications to MRI. It then describes some of the recent PARACEST research results: specifically, pH measurements using water molecule exchange rate modulation, T2 exchange contrast caused by water molecule exchange, the use of ultrashort TEs (TE < 10 µs) to overcome T2 exchange line broadening and the potential application of T2 exchange as a new contrast mechanism for MRI.

  4. The efficiency of the metal catalysts in the nucleophilic substitution of alcohols is dependent on the nucleophile and not on the electrophile.

    PubMed

    Biswas, Srijit; Samec, Joseph S M

    2013-05-01

    In this study, we investigate the effect of the electrophiles and the nucleophiles for eight catalysts in the catalytic SN 1 type substitution of alcohols with different degree of activation by sulfur-, carbon-, oxygen-, and nitrogen-centered nucleophiles. The catalysts do not show any general variance in efficiency or selectivity with respect to the alcohols and follow the trend of alcohol reactivity. However, when it comes to the nucleophile, the eight catalysts show general and specific variances in the efficiency and selectivity to perform the desired substitution. Interestingly, the selectivity of the alcohols to produce the desired substitution products was found to be independent of the electrophilicity of the generated carbocations but highly dependent on the ease of formation of the cation. Catalysts based on iron(III), bismuth(III), and gold(III) show higher conversions for S-, C-, and N-centered nucleophiles, and Bi(III) was the most efficient catalyst in all combinations. Catalysts based on rhenium(I) or rhenium(VII), palladium(II), and lanthanum(III) were the most efficient in performing the nucleophilic substitution on the various alcohols with the O-centered nucleophiles. These catalysts generate the symmetrical ether as a by-product from the reactions of S-, C-, and N-centered nucleophiles as well, resulting in lower chemoselectivity.

  5. Diverse Reactivity of an Electrophilic Phosphasilene towards Anionic Nucleophiles: Substitution or Metal-Amino Exchange.

    PubMed

    Willmes, Philipp; Junk, Lukas; Huch, Volker; Yildiz, Cem B; Scheschkewitz, David

    2016-08-26

    The reaction of MesLi (Mes=2,4,6-trimethylphenyl) with the electrophilic phosphasilene R2 (NMe2 )Si-RSi=PNMe2 (2, R=Tip=2,4,6-triisopropylphenyl) cleanly affords R2 (NMe2 )Si-RSi=PMes and thus provides the first example of a substitution reaction at an unperturbed Si=P bond. In toluene, the reaction of 2 with lithium disilenide, R2 Si=Si(R)Li (1), apparently proceeds via an initial nucleophilic substitution step as well (as suggested by DFT calculations), but affords a saturated bicyclo[1.1.0]butane analogue as the final product, which was further characterized as its Fe(CO)4 complex. In contrast, in 1,2-dimethoxyethane the reaction of 1 with 2 results in an unprecedented metal-amino exchange reaction.

  6. Synthesis and nucleophilic aromatic substitution of 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzene

    PubMed Central

    Ajenjo, Javier; Greenhall, Martin; Zarantonello, Camillo

    2016-01-01

    Summary 3-Fluoro-5-nitro-1-(pentafluorosulfanyl)benzene was prepared by three different ways: as a byproduct of direct fluorination of 1,2-bis(3-nitrophenyl)disulfane, by direct fluorination of 4-nitro-1-(pentafluorosulfanyl)benzene, and by fluorodenitration of 3,5-dinitro-1-(pentafluorosulfanyl)benzene. The title compound was subjected to a nucleophilic aromatic substitution of the fluorine atom with oxygen, sulfur and nitrogen nucleophiles affording novel (pentafluorosulfanyl)benzenes with 3,5-disubstitution pattern. Vicarious nucleophilic substitution of the title compound with carbon, oxygen, and nitrogen nucleophiles provided 3-fluoro-5-nitro-1-(pentafluorosulfanyl)benzenes substituted in position four. PMID:26977178

  7. Reactions of (chloroethynyl)phosphonates with neutral nucleophiles

    SciTech Connect

    Garibina, V.A.; Leonov, A.A.; Dogadina, A.V.; Ionin, B.I.; Petrov, A.A.

    1987-12-20

    The authors studied reactions of (chloroethynyl)phosphonates with a number of neutral nucleophiles containing a primary amino group together with a second nucleophilic center. The phosphorylated benzimidazoles are crystalline substances. The chemical shift of phosphorus in these compounds, delta/sub p/ +22.0 ppm, is characteristic for compounds containing an sp/sup 3/-hybridized carbon atom attached to phosphorus. The PMR spectra of the compounds contain a characteristic signal of the protons of a methylene group attached to phosphorus, delta 2.8, /sup 2/J/sub HP/ 22.0 Hz. The /sup 13/C NMR spectrum of the compounds contain the signals of a methoxy group on phosphorus delta/sub C/(CH/sub 3/O) 49.50 ppm, J/sub CP/ 6.9 Hz; and a doublet signal of the carbon atom of the methylene group delta/sub C/ 23.16 ppm, J/sub CP/ 138.8 Hz; and a doublet of carbon of the benzimidazole ring delta/sub C/ 141.6 ppm, J/sub CP/ 8.7 Hz; the carbon atoms of the benzene ring resonate in the weak field.

  8. The reaction of indole with the aminoacrylate intermediate of Salmonella typhimurium tryptophan synthase: observation of a primary kinetic isotope effect with 3-[(2)H]indole.

    PubMed

    Cash, Michael T; Miles, Edith W; Phillips, Robert S

    2004-12-15

    The bacterial tryptophan synthase alpha(2)beta(2) complex catalyzes the final reactions in the biosynthesis of L-tryptophan. Indole is produced at the active site of the alpha-subunit and is transferred through a 25-30 A tunnel to the beta-active site, where it reacts with an aminoacrylate intermediate. Lane and Kirschner proposed a two-step nucleophilic addition-tautomerization mechanism for the reaction of indole with the aminoacrylate intermediate, based on the absence of an observed kinetic isotope effect (KIE) when 3-[(2)H]indole reacts with the aminoacrylate intermediate. We have now observed a KIE of 1.4-2.0 in the reaction of 3-[(2)H]indole with the aminoacrylate intermediate in the presence of monovalent cations, but not when an alpha-subunit ligand, disodium alpha-glycerophosphate (Na(2)GP), is present. Rapid-scanning stopped flow kinetic studies were performed of the reaction of indole and 3-[(2)H]indole with tryptophan synthase preincubated with L-serine, following the decay of the aminoacrylate intermediate at 350 nm, the formation of the quinonoid intermediate at 476 nm, and the formation of the L-Trp external aldimine at 423 nm. The addition of Na(2)GP dramatically slows the rate of reaction of indole with the alpha-aminoacrylate intermediate. A primary KIE is not observed in the reaction of 3-[(2)H]indole with the aminoacrylate complex of tryptophan synthase in the presence of Na(2)GP, suggesting binding of indole with tryptophan synthase is rate limiting under these conditions. The reaction of 2-methylindole does not show a KIE, either in the presence of Na(+) or Na(2)GP. These results support the previously proposed mechanism for the beta-reaction of tryptophan synthase, but suggest that the rate limiting step in quinonoid intermediate formation from indole and the aminoacrylate intermediate is deprotonation.

  9. Amino acids as novel nucleophiles for silver nanoparticle-luminol chemiluminescence.

    PubMed

    Li, Na; Ni, Shubiao

    2014-12-01

    The use of noble metal nanoparticles (NPs) as reductants in chemiluminescence (CL) has been reported only rarely owing to their high oxidation potentials. Interestingly, nucleophiles could dramatically lower the oxidation potential of Ag NPs, such that in the presence of nucleophiles Ag NPS could be used as reductants to induce the CL emission of luminol, an important CL reagent widely used in forensic analysis for the detection of trace amounts of blood. Although nucleophiles are indispensible in Ag NP-luminol CL, only inorganic nucleophiles such as Cl(-), Br(-), I(-) and S2O3 (2-) have been shown to be efficient. The effects of organic nucleophiles on CL remain unexplored. In this study, 20 standard amino acids were evaluated as novel organic nucleophiles in Ag NP-luminol CL. Histidine, lysine and arginine could initiate CL emission; the others could not. It is proposed that the different behaviors of 20 standard amino acids in the CL reactions derive from the interface chemistry between Ag NPs and these amino acids. UV/vis absorption spectra were studied to validate the interface chemistry. In addition, imidazole and histidine were chosen as a model pair to compare the behavior of the monodentate nucleophile with that of the corresponding multidentate nucleophile in Ag NP-luminol CL.

  10. Amination of electrophilic aromatic compounds by vicarious nucleophilic substitution

    SciTech Connect

    Mitchell, Alexander R.; Pagoria, Philip F.; Schmidt, Robert D.

    2000-01-01

    The present invention relates to a process to aminate electrophilic aromatic compounds by vicarious nucleophilic substitution of hydrogen using quaternary hydrazinium salts. The use of trialkylhydrazinium halide, e.g., trimethylhydrazinium iodide, as well as hydroxylamine, alkoxylamines, and 4-amino-1,2,4-triazole to produce aminated aromatic structures, such as 1,3-diamino-2,4,6-trinitrobenzene (DATB), 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) and 3,5-diamino-2,4,6-trinitrotoluene (DATNT), is described. DATB and TATB are useful insensitive high explosives. TATB is also used for the preparation of benzenehexamine, a starting material for the synthesis of novel materials (optical imaging devices, liquid crystals, ferromagnetic compounds).

  11. Poly(N-arylenebenzimidazole)s via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Jr., Joseph G. (Inventor)

    1996-01-01

    Novel poly(N-arylenebenzimidazole)s (PNABls) are prepared by the aromatic nucleophilic displacement reaction of novel di(hydroxyphenyl-N-arylene benzimidazole) monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl-N-arylenebenzimidazole) monomers are synthesized by reacting phenyl-4-hydroxybenzoate with bis(2-aminoanilino)arylenes in diphenylsulfone. Moderate molecular weight PNABIs of new chemical structures were prepared that exhibit a favorable combination of physical and mechanical properties. The use of the novel di(hydroxyphenyI-N-arylenebenzimidazole)s permits a more economical and easier way to prepare PNABIs than previous routes.

  12. Poly(1,3,4-oxadiazoles) via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Wolf, Peter (Inventor)

    1992-01-01

    Poly(1,3,4-oxadiazoles) (POX) are prepared by the aromatic nucleophilic displacement reaction of di(hydroxyphenyl) 1,3,4-oxadiazole monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The polymerizations are carried out in polar aprotic solvents such as sulfolane or diphenylsulfone using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl) 1,3,4-oxadiazole monomers are synthesized by reacting 4-hydroxybenzoic hydrazide with phenyl 4-hydrobenzoate in the melt and also by reacting aromatic dihydrazides with two moles of phenyl 4-hydroxybenzoate in the melt. This synthetic route has provided high molecular weight POX of new chemical structure, is economically and synthetically more favorable than other routes, and allows for facile chemical structure variation due to the large variety of activated aromatic dihalides which are available.

  13. Poly(N-arylenbenzimidazoles) via aromatic nucleophilic displacement

    NASA Technical Reports Server (NTRS)

    Connell, John W. (Inventor); Hergenrother, Paul M. (Inventor); Smith, Joseph G., Jr. (Inventor)

    1995-01-01

    Novel poly(N-arylenebenzimidazole)s (PNABIs) are prepared by the aromatic nucleophilic displacement reaction of novel di(hydroxyphenyl-N-arylene benzimidazole) monomers with activated aromatic dihalides or activated aromatic dinitro compounds. The polymerizations are carried out in polar aprotic solvents such as N-methyl-2-pyrrolidinone or N,N-dimethylacetamide using alkali metal bases such as potassium carbonate at elevated temperatures under nitrogen. The di(hydroxyphenyl N-arylenebenzimidazole) monomers are synthesized by reacting phenyl 4-hydroxybenzoate with bis(2-aminoanilino) arylenes in diphenylsulfone. Moderate molecular weight PNABIs of new chemical structures were prepared that exhibit a favorable combination of physical and mechanical properties. The use of the novel di(hydroxyphenyl N-arylenebenzimidazole)s permits a more economical and easier way to prepare PNABIs than previous routes.

  14. Nucleophilic activation by positioning in phosphoryl transfer catalyzed by nucleoside diphosphate kinase.

    PubMed

    Admiraal, S J; Schneider, B; Meyer, P; Janin, J; Véron, M; Deville-Bonne, D; Herschlag, D

    1999-04-13

    The nonenzymatic reaction of ATP with a nucleophile to generate ADP and a phosphorylated product proceeds via a dissociative transition state with little bond formation to the nucleophile. Consideration of the dissociative nature of the nonenzymatic transition state leads to the following question: To what extent can the nucleophile be activated in enzymatic phosphoryl transfer? We have addressed this question for the NDP kinase reaction. A mutant form of the enzyme lacking the nucleophilic histidine (H122G) can be chemically rescued for ATP attack by imidazole or other exogenous small nucleophiles. The ATP reaction is 50-fold faster with the wild-type enzyme, which has an imidazole nucleophile positioned for reaction by a covalent bond, than with H122G, which employs a noncovalently bound imidazole nucleophile [(kcat/KM)ATP]. Further, a 4-fold advantage for imidazole positioned in the nucleophile binding pocket created by the mutation is suggested from comparison of the reaction of H122G and ATP with an imidazole versus a water nucleophile, after correction for the intrinsic reactivities of imidazole and water toward ATP in solution. X-ray structural analysis shows no detectable rearrangement of the residues surrounding His 122 upon mutation to Gly 122. The overall rate effect of approximately 10(2)-fold for the covalent imidazole nucleophile relative to water is therefore attributed to positioning of the nucleophile with respect to the reactive phosphoryl group. This is underscored by the more deleterious effect of replacing ATP with AlphaTauPgammaS in the wild-type reaction than in the imidazole-rescued mutant reaction, as follows. For the wild-type, AlphaTauPgammaS presumably disrupts positioning between nucleophile and substrate, resulting in a large thio effect of 300-fold, whereas precise alignment is already disrupted in the mutant because there is no covalent bond to the nucleophile, resulting in a smaller thio effect of 10-fold. In summary, the results

  15. Arabidopsis ERG28 Tethers the Sterol C4-Demethylation Complex to Prevent Accumulation of a Biosynthetic Intermediate That Interferes with Polar Auxin Transport[C][W

    PubMed Central

    Mialoundama, Alexis Samba; Jadid, Nurul; Brunel, Julien; Di Pascoli, Thomas; Heintz, Dimitri; Erhardt, Mathieu; Mutterer, Jérôme; Bergdoll, Marc; Ayoub, Daniel; Van Dorsselaer, Alain; Rahier, Alain; Nkeng, Paul; Geoffroy, Philippe; Miesch, Michel; Camara, Bilal; Bouvier, Florence

    2013-01-01

    Sterols are vital for cellular functions and eukaryotic development because of their essential role as membrane constituents. Sterol biosynthetic intermediates (SBIs) represent a potential reservoir of signaling molecules in mammals and fungi, but little is known about their functions in plants. SBIs are derived from the sterol C4-demethylation enzyme complex that is tethered to the membrane by Ergosterol biosynthetic protein28 (ERG28). Here, using nonlethal loss-of-function strategies focused on Arabidopsis thaliana ERG28, we found that the previously undetected SBI 4-carboxy-4-methyl-24-methylenecycloartanol (CMMC) inhibits polar auxin transport (PAT), a key mechanism by which the phytohormone auxin regulates several aspects of plant growth, including development and responses to environmental factors. The induced accumulation of CMMC in Arabidopsis erg28 plants was associated with diagnostic hallmarks of altered PAT, including the differentiation of pin-like inflorescence, loss of apical dominance, leaf fusion, and reduced root growth. PAT inhibition by CMMC occurs in a brassinosteroid-independent manner. The data presented show that ERG28 is required for PAT in plants. Furthermore, it is accumulation of an atypical SBI that may act to negatively regulate PAT in plants. Hence, the sterol pathway offers further prospects for mining new target molecules that could regulate plant development. PMID:24326590

  16. Formation of a ruthenium(IV)-oxo complex by electron-transfer oxidation of a coordinatively saturated ruthenium(II) complex and detection of oxygen-rebound intermediates in C-H bond oxygenation.

    PubMed

    Kojima, Takahiko; Nakayama, Kazuya; Ikemura, Kenichiro; Ogura, Takashi; Fukuzumi, Shunichi

    2011-08-03

    A coordinatively saturated ruthenium(II) complex having tetradentate tris(2-pyridylmethyl)amine (TPA) and bidentate 2,2'-bipyridine (bpy), [Ru(TPA)(bpy)](2+) (1), was oxidized by a Ce(IV) ion in H(2)O to afford a Ru(IV)-oxo complex, [Ru(O)(H(+)TPA)(bpy)](3+) (2). The crystal structure of the Ru(IV)-oxo complex 2 was determined by X-ray crystallography. In 2, the TPA ligand partially dissociates to be in a facial tridentate fashion and the uncoordinated pyridine moiety is protonated. The spin state of 2, which showed paramagnetically shifted NMR signals in the range of 60 to -20 ppm, was determined to be an intermediate spin (S = 1) by the Evans' method with (1)H NMR spectroscopy in acetone-d(6). The reaction of 2 with various oraganic substrates in acetonitrile at room temperature afforded oxidized and oxygenated products and a solvent-bound complex, [Ru(H(+)TPA)(bpy)(CH(3)CN)], which is intact in the presence of alcohols. The oxygenation reaction of saturated C-H bonds with 2 proceeds by two-step processes: the hydrogen abstraction with 2, followed by the dissociation of the alcohol products from the oxygen-rebound complexes, Ru(III)-alkoxo complexes, which were successfully detected by ESI-MS spectrometry. The kinetic isotope effects in the first step for the reaction of dihydroanthrathene (DHA) and cumene with 2 were determined to be 49 and 12, respectively. The second-order rate constants of C-H oxygenation in the first step exhibited a linear correlation with bond dissociation energies of the C-H bond cleavage.

  17. Crystal structure of activated tobacco rubisco complexed with the reaction-intermediate analogue 2-carboxy-arabinitol 1,5-bisphosphate.

    PubMed Central

    Schreuder, H. A.; Knight, S.; Curmi, P. M.; Andersson, I.; Cascio, D.; Sweet, R. M.; Brändén, C. I.; Eisenberg, D.

    1993-01-01

    The crystal structure of activated tobacco rubisco, complexed with the reaction-intermediate analogue 2-carboxy-arabinitol 1,5-bisphosphate (CABP) has been determined by molecular replacement, using the structure of activated spinach rubisco (Knight, S., Andersson, I., & Brändén, C.-I., 1990, J. Mol. Biol. 215, 113-160) as a model. The R-factor after refinement is 21.0% for 57,855 reflections between 9.0 and 2.7 A resolution. The local fourfold axis of the rubisco hexadecamer coincides with a crystallographic twofold axis. The result is that the asymmetric unit of the crystals contains half of the L8S8 complex (molecular mass 280 kDa in the asymmetric unit). The activated form of tobacco rubisco is very similar to the activated form of spinach rubisco. The root mean square difference is 0.4 A for 587 equivalent C alpha atoms. Analysis of mutations between tobacco and spinach rubisco revealed that the vast majority of mutations concerned exposed residues. Only 7 buried residues were found to be mutated versus 54 residues at or near the surface of the protein. The crystal structure suggests that the Cys 247-Cys 247 and Cys 449-Cys 459 pairs are linked via disulfide bridges. This pattern of disulfide links differ from the pattern of disulfide links observed in crystals of unactivated tobacco rubisco (Curmi, P.M.G., et al., 1992, J. Biol. Chem. 267, 16980-16989) and is similar to the pattern observed for activated spinach tobacco. PMID:8358296

  18. Structure of Naegleria Tet-like dioxygenase (NgTet1) in complexes with a reaction intermediate 5-hydroxymethylcytosine DNA

    SciTech Connect

    Hashimoto, Hideharu; Pais, June E.; Dai, Nan; Corrêa, Jr., Ivan R.; Zhang, Xing; Zheng, Yu; Cheng, Xiaodong

    2015-08-31

    The family of ten-eleven translocation (Tet) dioxygenases is widely distributed across the eukaryotic tree of life, from mammals to the amoeboflagellate Naegleria gruberi. Like mammalian Tet proteins, the Naegleria Tet-like protein, NgTet1, acts on 5-methylcytosine (5mC) and generates 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) in three consecutive, Fe(II)- and α-ketoglutarate-dependent oxidation reactions. The two intermediates, 5hmC and 5fC, could be considered either as the reaction product of the previous enzymatic cycle or the substrate for the next cycle. Here we present a new crystal structure of NgTet1 in complex with DNA containing a 5hmC. Along with the previously solved NgTet1–5mC structure, the two complexes offer a detailed picture of the active site at individual stages of the reaction cycle. In the crystal, the hydroxymethyl (OH-CH2-) moiety of 5hmC points to the metal center, representing the reaction product of 5mC hydroxylation. The hydroxyl oxygen atom could be rotated away from the metal center, to a hydrophobic pocket formed by Ala212, Val293 and Phe295. Such rotation turns the hydroxyl oxygen atom away from the product conformation, and exposes the target CH2 towards the metal-ligand water molecule, where a dioxygen O2 molecule would occupy to initiate the next round of reaction by abstracting a hydrogen atom from the substrate. The Ala212-to-Val (A212V) mutant profoundly limits the product to 5hmC, probably due to the reduced hydrophobic pocket size restricts the binding of 5hmC as a substrate.

  19. A new approach to cyclic hydroxamic acids: Intramolecular cyclization of N-benzyloxy carbamates with carbon nucleophiles

    PubMed Central

    Liu, Yuan; Jacobs, Hollie K.

    2011-01-01

    N-Alkyl-N-benzyloxy carbamates, 2, undergo facile intramolecular cyclization with a variety of carbon nucleophiles to give functionalized 5- and 6-membered protected cyclic hydroxamic acids, 3, in good to excellent yields. This method can be extended to prepare seven-membered cyclic hydroxamic acids in moderate yields. The sulfone intermediates 3 from this study can be alkylated while the corresponding phosphonates have been shown to undergo HWE reaction. The α,β-unsaturated synthon, 8, prepared by thermal elimination of sulfoxide 3m, undergoes Michael addition with secondary amines. The usefulness of this approach to prepare polydentate chelators has been demonstrated by the synthesis of bis cyclic hydroxamic acids 12, 14, and 15. PMID:21499514

  20. Reaction profiles of the interaction between sarin and acetylcholinesterase and the S203C mutant: model nucleophiles and QM/MM potential energy surfaces.

    PubMed

    Beck, Jeremy M; Hadad, Christopher M

    2010-09-06

    The phosphonylation mechanism of AChE and the S203C mutation by sarin (GB) is evaluated using two reaction schemes: a small model nucleophile (ethoxide, CH(3)CH(2)O(-)) and quantum mechanical/molecular mechanical (QM/MM) simulations. Calculations utilizing small model nucleophiles indicate that the reaction barrier for addition to GB is the rate-limiting step for both ethoxide and ethyl thiolate (CH(3)CH(2)S(-)); moreover, the activation barrier for addition to the phosphorus center of GB by ethyl thiolate is significantly larger (13.2 kcal/mol) than for ethoxide (8.3 kcal/mol). The decomposition transition state for both nucleophiles was determined to be approximately 1 kcal/mol. QM/MM simulations for AChE suggest a similar reaction mechanism for phosphonylation of the catalytic S203; however, the relative energetics are altered significantly compared to the isolated system. QM/MM results indicate that formation of the penta-coordinate intermediate is the rate-limiting step in the enzymatic system, with an activation barrier of 3.6 kcal/mol. Hydrogen-bonding interactions between the fluoride leaving group of GB with Y124 in AChE are observed throughout the reaction profile. The S203C mutation alters the relative energetics of the reaction, increasing the energy barrier for formation of the penta-coordinate intermediate to a value of 4.5 kcal/mol; moreover, the penta-coordinate intermediate (as product) is stabilized by an additional 6 kcal/mol when compared to wild-type AChE.

  1. Reaction Profiles of the Interaction between Sarin and Acetylcholinesterase and the S203C Mutant: Model Nucleophiles and QM/MM Potential Energy Surfaces

    PubMed Central

    Beck, Jeremy M.; Hadad, Christopher M.

    2010-01-01

    The phosphonylation mechanism of AChE and the S203C mutation by sarin (GB) is evaluated using two reaction schemes: a small model nucleophile (ethoxide, CH3CH2O−) and quantum mechanical/molecular mechanical (QM/MM) simulations. Calculations utilizing small model nucleophiles indicate that the reaction barrier for addition to GB is the rate-limiting step for both ethoxide and ethyl thiolate (CH3CH2S−); moreover, the activation barrier for addition to the phosphorus center of GB by ethyl thiolate is significantly larger (13.2 kcal/mol) than for ethoxide (8.3 kcal/mol). The decomposition transition state for both nucleophiles was determined to be ~1 kcal/mol. QM/MM simulations for AChE suggest a similar reaction mechanism for phosphonylation of the catalytic S203; however, the relative energetics are altered significantly compared to the isolated system. QM/MM results indicate that formation of the penta-coordinate intermediate is the rate–limiting step in the enzymatic system, with an activation barrier of 3.6 kcal/mol. Hydrogen-bonding interactions between the fluoride leaving group of GB with Y124 in AChE are observed throughout the reaction profile. The S203C mutation alters the relative energetics of the reaction, increasing the energy barrier for formation of the penta-coordinate intermediate to a value of 4.7 kcal/mol; moreover, the penta-coordinate intermediate (as product) is stabilized by an additional 6 kcal/mol when compared to wild-type AChE. PMID:20156428

  2. Theoretical study of the EPR spectrum of the S3TyrZ(•) metalloradical intermediate state of the O2-evolving complex of photosystem II.

    PubMed

    Zahariou, Georgia; Ioannidis, Nikolaos

    2016-12-01

    The intermediates trapped during the transitions between the consecutive S-states of the oxygen-evolving complex (OEC) of photosystem II (PSII) contain the free radical TyrZ(•) interacting magnetically with the Mn-cluster (Mn4Ca). In this paper, we present a theoretical study of the EPR spectrum of the S3TyrZ(•) metalloradical intermediate state, which has been recently detected in MeOH-containing PSII preparations. For this analysis, we use two different approximations: the first, simpler one, is the point-dipole approach, where the two interacting spins are the S = 1/2 of TyrZ(•) and the ground spin state of S = 3 of the OEC being in the S3 state. The second approximation is based on previous proposals indicating that the ground spin state (S G = 3) of the S3 state arises from an antiferromagnetic exchange coupling between the S = 9/2 of the Mn(IV)3CaO4 and the S = 3/2 of the external Mn(IV) of the OEC. Under the above assumption, the second approximation involves three interacting spins, denoted S A(Mn(IV)3Ca) = 9/2, S B(Mn(IV)) = 3/2 and S C(TyrZ(•)) = 1/2. Accordingly, the tyrosine radical is exposed to dipolar interactions with both fragments of the OEC, while an antiferromagnetic exchange coupling within the "3 + 1" structural motif of the OEC is also considered. By application of the first-point-dipole approach, the inter-spin distance that simulates the experimental spectrum is not consistent with the theoretical models that were recently reported for the OEC in the S3 state. Instead, the recent models are consistent with the results of the analysis that is performed by using the second, more detailed, approach.

  3. Assignment of sweet almond beta-glucosidase as a family 1 glycosidase and identification of its active site nucleophile.

    PubMed

    He, S; Withers, S G

    1997-10-03

    Sweet almond beta-glucosidase is a well studied glycosidase, having been subjected to numerous kinetic analyses and inhibition studies. However, it is not known to which glycosidase family it belongs, nor is the identity of the active site nucleophile known with certainty. It can be inactivated using the specific, mechanism-based enzyme inactivator 2-deoxy-2-fluoro-beta-D-glucopyranosyl fluoride, which functions by forming a stable 2-deoxy-2-fluoro-alpha-D-glucopyranosyl-enzyme intermediate. The glycosylated peptide present in a peptic digest of this trapped glycosyl-enzyme intermediate was identified by use of neutral loss scans on an electrospray ionization triple quadrupole mass spectrometer. Comparative liquid chromatographic/mass spectrometric analysis of peptic digests of labeled and unlabeled enzyme samples confirmed the unique presence of this peptide of m/z = 1041 in the labeled sample. The sequence of this peptide was determined to be Ile-Thr-Glu-Gln-Gly-Val-Asp-Glu by further tandem mass spectrometric analysis in the daughter ion scan mode in conjunction with Edman degradation of the purified peptide. The identity of the labeled side chain was determined by further tandem mass spectrometric analysis in the daughter ion scan mode of a partially purified sample of the labeled peptide subjected to methyl esterification, the fragmentation pattern being consistent only with the first Glu in the sequence being labeled. The sequence around this residue is identical to that surrounding the catalytic nucleophile in many members of glycosidase Family 1, confirming the assignment of this enzyme to that family. The residue labeled is, however, different from that (Asp) identified previously in the enzyme from bitter almonds by use of conduritol epoxide affinity labels, although apparently close in the primary sequence.

  4. Novel Fragmentation Pathways of Anionic Adducts of Steroids Formed by Electrospray Anion Attachment Involving Regioselective Attachment, Regiospecific Decompositions, Charge-Induced Pathways, and Ion-Dipole Complex Intermediates

    NASA Astrophysics Data System (ADS)

    Rannulu, Nalaka S.; Cole, Richard B.

    2012-09-01

    The analysis of several bifunctional neutral steroids, 5-α-pregnane diol (5-α-pregnane-3α-20βdiol), estradiol (3,17α-dihydroxy-1,3,5(10)-estratriene), progesterone (4-pregnene-3,20-dione), lupeol (3β-hydroxy-20(29)-lupene), pregnenolone (5-pregnen-3β-ol-20-one), and pregnenolone acetate (5-pregnen-3β-ol-20-one acetate) was accomplished by negative ion electrospray mass spectrometry (ESI-MS) employing adduct formation with various anions: fluoride, bicarbonate, acetate, and chloride. Fluoride yielded higher abundances of anionic adducts and more substantial abundances of deprotonated molecules compared with other investigated anions. Collision-induced dissociation (CID) of precursor [M + anion]- adducts of these steroids revealed that fluoride adduct [M + F]- precursors first lose HF to produce [M - H]- and then undergo consecutive decompositions to yield higher abundances of structurally-informative product ions than the other tested anions. In addition to charge-remote fragmentations, the majority of CID pathways of estradiol are deduced to occur via charge-induced fragmentation. Most interestingly, certain anions exhibit preferential attachment to a specific site on these bifunctional steroid molecules, which we are calling "regioselective anion attachment." Regioselective anion attachment is evidenced by subsequent regiospecific decomposition. Regioselective attachment of fluoride (and acetate) anions to low (and moderate) acidity functional groups of pregnenolone, respectively, is demonstrated using deuterated compounds. Moreover, the formation of unique intermediate ion-dipole complexes leading to novel fragmentation pathways of fluoride adducts of pregnenolone acetate, and bicarbonate adducts of d4-pregnenolone, are also discussed.

  5. MEDUSA-2.0: an intermediate complexity biogeochemical model of the marine carbon cycle for climate change and ocean acidification studies

    NASA Astrophysics Data System (ADS)

    Yool, A.; Popova, E. E.; Anderson, T. R.

    2013-10-01

    MEDUSA-1.0 (Model of Ecosystem Dynamics, nutrient Utilisation, Sequestration and Acidification) was developed as an "intermediate complexity" plankton ecosystem model to study the biogeochemical response, and especially that of the so-called "biological pump", to anthropogenically driven change in the World Ocean (Yool et al., 2011). The base currency in this model was nitrogen from which fluxes of organic carbon, including export to the deep ocean, were calculated by invoking fixed C:N ratios in phytoplankton, zooplankton and detritus. However, due to anthropogenic activity, the atmospheric concentration of carbon dioxide (CO2) has significantly increased above its natural, inter-glacial background. As such, simulating and predicting the carbon cycle in the ocean in its entirety, including ventilation of CO2 with the atmosphere and the resulting impact of ocean acidification on marine ecosystems, requires that both organic and inorganic carbon be afforded a more complete representation in the model specification. Here, we introduce MEDUSA-2.0, an expanded successor model which includes additional state variables for dissolved inorganic carbon, alkalinity, dissolved oxygen and detritus carbon (permitting variable C:N in exported organic matter), as well as a simple benthic formulation and extended parameterizations of phytoplankton growth, calcification and detritus remineralisation. A full description of MEDUSA-2.0, including its additional functionality, is provided and a multi-decadal spin-up simulation (1860-2005) is performed. The biogeochemical performance of the model is evaluated using a diverse range of observational data, and MEDUSA-2.0 is assessed relative to comparable models using output from the Coupled Model Intercomparison Project (CMIP5).

  6. Design, synthesis, and carbon-heteroatom coupling reactions of organometallic nickel(IV) complexes.

    PubMed

    Camasso, Nicole M; Sanford, Melanie S

    2015-03-13

    Homogeneous nickel catalysis is used for the synthesis of pharmaceuticals, natural products, and polymers. These reactions generally proceed via nickel intermediates in the Ni(0), Ni(I), Ni(II), and/or Ni(III) oxidation states. In contrast, Ni(IV) intermediates are rarely accessible. We report herein the design, synthesis, and characterization of a series of organometallic Ni(IV) complexes, accessed by the reaction of Ni(II) precursors with the widely used oxidant S-(trifluoromethyl)dibenzothiophenium triflate. These Ni(IV) complexes undergo highly selective carbon(sp(3))-oxygen, carbon(sp(3))-nitrogen, and carbon(sp(3))-sulfur coupling reactions with exogenous nucleophiles. The observed reactivity has the potential for direct applications in the development of nickel-catalyzed carbon-heteroatom coupling reactions.

  7. Structures of enzyme-intermediate complexes of yeast Nit2: insights into its catalytic mechanism and different substrate specificity compared with mammalian Nit2.

    PubMed

    Liu, Hejun; Gao, Yongxiang; Zhang, Mengying; Qiu, Xiaoting; Cooper, Arthur J L; Niu, Liwen; Teng, Maikun

    2013-08-01

    The Nit (nitrilase-like) protein subfamily constitutes branch 10 of the nitrilase superfamily. Nit proteins are widely distributed in nature. Mammals possess two members of the Nit subfamily, namely Nit1 and Nit2. Based on sequence similarity, yeast Nit2 (yNit2) is a homologue of mouse Nit1, a tumour-suppressor protein whose substrate specificity is not yet known. Previous studies have shown that mammalian Nit2 (also a putative tumour suppressor) is identical to ω-amidase, an enzyme that catalyzes the hydrolysis of α-ketoglutaramate (α-KGM) and α-ketosuccinamate (α-KSM) to α-ketoglutarate (α-KG) and oxaloacetate (OA), respectively. In the present study, crystal structures of wild-type (WT) yNit2 and of WT yNit2 in complex with α-KG and with OA were determined. In addition, the crystal structure of the C169S mutant of yNit2 (yNit2-C169S) in complex with an endogenous molecule of unknown structure was also solved. Analysis of the structures revealed that α-KG and OA are covalently bound to Cys169 by the formation of a thioester bond between the sulfhydryl group of the cysteine residue and the γ-carboxyl group of α-KG or the β-carboxyl group of OA, reflecting the presumed reaction intermediates. However, an enzymatic assay suggests that α-KGM is a relatively poor substrate of yNit2. Finally, a ligand was found in the active site of yNit2-C169S that may be a natural substrate of yNit2 or an endogenous regulator of enzyme activity. These crystallographic analyses provide information on the mode of substrate/ligand binding at the active site of yNit2 and insights into the catalytic mechanism. These findings suggest that yNit2 may have broad biological roles in yeast, especially in regard to nitrogen homeostasis, and provide a framework for the elucidation of the substrate specificity and biological role of mammalian Nit1.

  8. Formation of diphenylphosphanylbutadienyl complexes by insertion of two P-coordinated alkynylphosphanes into a PtbondC6F5 bond: detection of intermediate and reaction products.

    PubMed

    Ara, Irene; Forniés, Juan; García, Ana; Gómez, Julio; Lalinde, Elena; Moreno, M Teresa

    2002-08-16

    complexes are unstable in solution evolving firstly, through an unexpected formal 4-1 R (Ph, Tol) migration, to the intermediate diphosphanylbutadienyl isomer derivatives [Pt(C(6)F(5))(S)mu-[C(C(6)F(5))doublebondC(PPh(2))C(PPh(2))doublebondC(R)(2)]M(C(6)F(5))(2)] (16, 18) (X-ray, R=Ph, M=Pt) and, finally, to 1-pentafluorophenyl-2,3-bis(diphenylphosphanyl)naphthalene mononuclear complexes (17, 19) by annulation of a phenyl or tolyl group.

  9. Nucleophilic 1,4-additions for natural product discovery.

    PubMed

    Cox, Courtney L; Tietz, Jonathan I; Sokolowski, Karol; Melby, Joel O; Doroghazi, James R; Mitchell, Douglas A

    2014-09-19

    Natural products remain an important source of drug candidates, but the difficulties inherent to traditional isolation, coupled with unacceptably high rates of compound rediscovery, limit the pace of natural product detection. Here we describe a reactivity-based screening method to rapidly identify exported bacterial metabolites that contain dehydrated amino acids (i.e., carbonyl- or imine-activated alkenes), a common motif in several classes of natural products. Our strategy entails the use of a commercially available thiol, dithiothreitol, for the covalent labeling of activated alkenes by nucleophilic 1,4-addition. Modification is easily discerned by comparing mass spectra of reacted and unreacted cell surface extracts. When combined with bioinformatic analysis of putative natural product gene clusters, targeted screening and isolation can be performed on a prioritized list of strains. Moreover, known compounds are easily dereplicated, effectively eliminating superfluous isolation and characterization. As a proof of principle, this labeling method was used to identify known natural products belonging to the thiopeptide, lanthipeptide, and linaridin classes. Further, upon screening a panel of only 23 actinomycetes, we discovered and characterized a novel thiopeptide antibiotic, cyclothiazomycin C.

  10. Nucleophilic Addition of Nitrogen to Aryl Cations: Mimicking Titan Chemistry

    NASA Astrophysics Data System (ADS)

    Li, Anyin; Jjunju, Fred P. M.; Cooks, R. Graham

    2013-11-01

    The reactivity of aryl cations toward molecular nitrogen is studied systematically in an ion trap mass spectrometer at 102 Pascal of nitrogen, the pressure of the Titan main haze layer. Nucleophilic addition of dinitrogen occurs and the nature of aryl group has a significant influence on the reactivity, through inductive effects and by changing the ground state spin multiplicity. The products of nitrogen activation, aryldiazonium ions, react with typical nitriles, aromatic amines, and alkynes (compounds that are relevant as possible Titan atmosphere constituents) to form covalently bonded heterocyclic products. Theoretical calculations at the level [DFT(B3LYP)/6-311++G(d,p)] indicate that the N2 addition reaction is exothermic for the singlet aryl cations but endothermic for their triplet spin isomers. The -OH and -NH2 substituted aryl ions are calculated to have triplet ground states, which is consistent with their decreased nitrogen addition reactivity. The energy needed for the generation of the aryl cations from their protonated precursors (ca. 340 kJ/mol starting with protonated aniline) is far less than that required to directly activate the nitrogen triple bond (the lowest energy excited state of N2 lies ca. 600 kJ/mol above the ground state). The formation of aza-aromatics via arene ionization and subsequent reactions provide a conceivable route to the genesis of nitrogen-containing organic molecules in the interstellar medium and Titan haze layers.

  11. Palladium-Catalyzed Cross Coupling of Secondary and Tertiary Alkyl Bromides with a Nitrogen Nucleophile

    PubMed Central

    2016-01-01

    We report a new class of catalytic reaction: the thermal substitution of a secondary and or tertiary alkyl halide with a nitrogen nucleophile. The alkylation of a nitrogen nucleophile with an alkyl halide is a classical method for the construction of C–N bonds, but traditional substitution reactions are challenging to achieve with a secondary and or tertiary alkyl electrophile due to competing elimination reactions. A catalytic process could address this limitation, but thermal, catalytic coupling of alkyl halides with a nitrogen nucleophile and any type of catalytic coupling of an unactivated tertiary alkyl halide with a nitrogen nucleophile are unknown. We report the coupling of unactivated secondary and tertiary alkyl bromides with benzophenone imines to produce protected primary amines in the presence of palladium ligated by the hindered trialkylphosphine Cy2t-BuP. Mechanistic studies indicate that this amination of alkyl halides occurs by a reversible reaction to form a free alkyl radical. PMID:27725963

  12. REVISITING NUCLEOPHILIC SUBSTITUTION REACTIONS: MICROWAVE-ASSISTED SYNTHESIS OF AZIDES, THIOCYANATES AND SULFONES IN AQUEOUS MEDIUM

    EPA Science Inventory

    A practical, rapid and efficient microwave (MW) promoted synthesis of various azides, thiocyanates and sulfones, is described in aqueous medium. This general and expeditious MW-enhanced nucleophilic substitution approach uses easily accessible starting materials such as halides o...

  13. Effects of electron acceptors and radical scavengers on nonchain radical nucleophilic substitution reactions

    SciTech Connect

    Xianman Zhang; Dilun Yang; Youcheng Liu )

    1993-01-01

    The yields of reaction products from thermal nucleophilic substitution reactions in dimethyl sulfoxide (DMSO) of six o- and p-nitrohalobenzenes with the sodium salt of ethyl [alpha]-cyanoacetate carbanion [Na[sup +][sup [minus

  14. Dehalogenation of arenes via SN2 reactions at bromine: competition with nucleophilic aromatic substitution.

    PubMed

    Gronert, Scott; Garver, John M; Nichols, Charles M; Worker, Benjamin B; Bierbaum, Veronica M

    2014-11-21

    The gas-phase reactions of carbon- and nitrogen-centered nucleophiles with polyfluorobromobenzenes were examined in a selected-ion flow tube (SIFT) and modeled computationally at the MP2/6-31+G(d,p)//MP2/6-31+G(d) level. In the gas-phase experiments, rate constants and branching ratios were determined. The carbon nucleophiles produce expected nucleophilic aromatic substitution (SNAr) and proton transfer products along with unexpected products that result from SN2 reactions at the bromine center (polyfluorophenide leaving group). With nitrogen nucleophiles, the SN2 at bromine channel is suppressed. In the SNAr channels, the "element effect" is observed, and fluoride loss competes with bromide loss. The computational modeling indicates that all the substitution barriers are well below the entrance channel and that entropy and dynamics effects control the product distributions.

  15. Sulfur isotope fractionation during incorporation of sulfur nucleophiles into organic compounds.

    PubMed

    Amrani, Alon; Ma, Qisheng; Ahmad, Ward Said; Aizenshtat, Zeev; Tang, Yongchun

    2008-03-21

    (34)S enrichment is shown to occur during sulfurization reactions and for the first time conclusively attributed to an isotope equilibrium effect rather than selective addition of (34)S enriched nucleophiles.

  16. REACTIONS OF ELECTROPHILES WITH NUCLEOPHILIC THIOLATE SITES: RELEVANCE TO PATHOPHYSIOLOGICAL MECHANISMS AND REMEDIATION

    PubMed Central

    LoPachin, Richard M.; Gavin, Terrence

    2016-01-01

    Electrophiles are electron deficient species that form covalent bonds with electron rich nucleophiles. In biological systems, reversible electrophile-nucleophile interactions mediate basal cytophysiological functions (e.g., enzyme regulation through S-nitrosylation), whereas irreversible electrophilic adduction of cellular macromolecules is involved in pathogenic processes that underlie many disease and injury states. The nucleophiles most often targeted by electrophiles are side chains on protein amino acids (e.g., Cys, His and Lys) and aromatic nitrogen sites on DNA bases (e.g., guanine N7). The sulfhydryl thiol (RSH) side-chain of cysteine residues is a weak nucleophile that can be ionized in specific conditions to a more reactive nucleophilic thiolate (RS−). This review will focus on electrophile interactions with cysteine thiolates and the pathophysiological consequences that result from irreversible electrophile modification of this anionic sulfur. According to the Hard and Soft, Acids and Bases (HSAB) theory of Pearson, electrophiles and nucleophiles can be classified as either soft or hard depending on their relative polarizability. HSAB theory suggests that electrophiles will preferentially and more rapidly form covalent adducts with nucleophiles of comparable softness or hardness. Application of HSAB principles, in conjunction with in vitro and proteomic studies, have indicated that soft electrophiles of broad chemical classes selectively form covalent Michael-type adducts with soft, highly reactive cysteine thiolate nucleophiles. Therefore, these electrophiles exhibit a common mechanism of cytotoxicity. As we will discuss, this level of detailed mechanistic understanding is a necessary prerequisite for the rational development of effective prevention and treatment strategies for electrophile-based pathogenic states. PMID:26559119

  17. Reactions of electrophiles with nucleophilic thiolate sites: relevance to pathophysiological mechanisms and remediation.

    PubMed

    LoPachin, Richard M; Gavin, Terrence

    2016-01-01

    Electrophiles are electron-deficient species that form covalent bonds with electron-rich nucleophiles. In biological systems, reversible electrophile-nucleophile interactions mediate basal cytophysiological functions (e.g. enzyme regulation through S-nitrosylation), whereas irreversible electrophilic adduction of cellular macromolecules is involved in pathogenic processes that underlie many disease and injury states. The nucleophiles most often targeted by electrophiles are side chains on protein amino acids (e.g. Cys, His, and Lys) and aromatic nitrogen sites on DNA bases (e.g. guanine N7). The sulfhydryl thiol (RSH) side chain of cysteine residues is a weak nucleophile that can be ionized in specific conditions to a more reactive nucleophilic thiolate (RS(-)). This review will focus on electrophile interactions with cysteine thiolates and the pathophysiological consequences that result from irreversible electrophile modification of this anionic sulfur. According to the Hard and Soft, Acids and Bases (HSAB) theory of Pearson, electrophiles and nucleophiles can be classified as either soft or hard depending on their relative polarizability. HSAB theory suggests that electrophiles will preferentially and more rapidly form covalent adducts with nucleophiles of comparable softness or hardness. Application of HSAB principles, in conjunction with in vitro and proteomic studies, have indicated that soft electrophiles of broad chemical classes selectively form covalent Michael-type adducts with soft, highly reactive cysteine thiolate nucleophiles. Therefore, these electrophiles exhibit a common mechanism of cytotoxicity. As we will discuss, this level of detailed mechanistic understanding is a necessary prerequisite for the rational development of effective prevention and treatment strategies for electrophile-based pathogenic states.

  18. Synthesis of high specific activity (+)- and (-)-6-( sup 18 F)fluoronorepinephrine via the nucleophilic aromatic substitution reaction

    SciTech Connect

    Ding, Y.S.; Fowler, J.S.; Gatley, S.J.; Dewey, S.L.; Wolf, A.P. )

    1991-02-01

    The first example of a no-carrier-added {sup 18}F-labeled catecholamine, 6-({sup 18}F)fluoronorepinephrine (6-({sup 18}F)FNE), has been synthesized via nucleophilic aromatic substitution. The racemic mixture was resolved on a chiral HPLC column to obtain pure samples of (-)-6-({sup 18}F)FNE and (+)6-({sup 18}F)FNE. Radiochemical yields of 20% at the end of bombardment (EOB) for the racemic mixture (synthesis time 93 min), 6% for each enantiomer (synthesis time 128 min) with a specific activity of 2-5 Ci/mumol at EOB were obtained. Chiral HPLC peak assignment for the resolved enantiomers was achieved by using two independent methods: polarimetric determination and reaction with dopamine beta-hydroxylase. Positron emission tomography (PET) studies with racemic 6-({sup 18}F)FNE show high uptake and retention in the baboon heart. This work demonstrates that nucleophilic aromatic substitution by ({sup 18}F)fluoride ion is applicable to systems having electron-rich aromatic rings, leading to high specific activity radiopharmaceuticals. Furthermore, the suitably protected dihydroxynitrobenzaldehyde 1 may serve as a useful synthetic precursor for the radiosynthesis of other complex {sup 18}F-labeled radiotracers.

  19. The Effects of Guided Careful Online Planning on Complexity, Accuracy and Fluency in Intermediate EFL Learners' Oral Production: The Case of English Articles

    ERIC Educational Resources Information Center

    Ahmadian, Mohammad Javad

    2012-01-01

    The purpose of the study reported in this article was twofold: First, to see whether guided careful online planning assists intermediate learners of English as a foreign language (EFL) in accurate oral production of English articles ("an/a" and "the"); and, second, to see whether guided careful online planning has any effects…

  20. Kinetic isotope effects for RNA cleavage by 2'-O- transphosphorylation: Nucleophilic activation by specific base

    PubMed Central

    Harris, Michael E; Dai, Qing; Gu, Hong; Kellerman, Dan; Piccirilli, Joseph A; Anderson, Vernon E

    2010-01-01

    To better understand the interactions between catalysts and transition states during RNA strand cleavage, primary 18O kinetic isotope effects and solvent D2O isotope effects were measured to probe the mechanism of base-catalyzed 2'-O-transphosphorylation of the RNA dinucleotide 5'-UpG-3'. The observed 18O KIEs for the nucleophilic 2'-O and in the 5'-O leaving group at pH 14 are both large relative to reactions of phosphodiesters with good leaving groups, indicating that the reaction catalyzed by hydroxide has a transition state (TS) with advanced phosphorus-oxygen bond fission to the leaving group (18kLG = 1.034 ± 0.004) and phosphorous-nucleophile bond formation (18kNUC = 0.984 ± 0.004). A breakpoint in the pH dependence of the 2'-O-transphosphorylation rate to a pH independent phase above pH 13 has been attributed to the pKa of the 2'-OH nucleophile. A smaller nucleophile KIE is observed at pH 12 (18kNUC = 0.995 ± 0.004) that is interpreted as the combined effect of the equilibrium isotope effect (~1.02) on deprotonation of the 2′-hydroxyl nucleophile and the intrinsic KIE on the nucleophilic addition step (ca. 0.981). An alternative mechanism in which the hydroxide ion acts as a general base is considered unlikely given the lack of a solvent deuterium isotope effect above the breakpoint in the pH versus rate profile. These results represent the first direct analysis of the transition state for RNA strand cleavage. The primary 18O KIE results and the lack of a kinetic solvent deuterium isotope effect together provide strong evidence for a late transition state and 2'-O nucleophile activation by specific base catalysis. PMID:20669950

  1. Role of the reaction intermediates in determining PHIP (parahydrogen induced polarization) effect in the hydrogenation of acetylene dicarboxylic acid with the complex [Rh (dppb)]{sup +} (dppb: 1,4-bis(diphenylphosphino)butane)

    SciTech Connect

    Reineri, F.; Aime, S.; Gobetto, R.; Nervi, C.

    2014-03-07

    This study deals with the parahydrogenation of the symmetric substrate acetylene dicarboxylic acid catalyzed by a Rh(I) complex bearing the chelating diphosphine dppb (1,4-bis(diphenylphosphino)butane). The two magnetically equivalent protons of the product yield a hyperpolarized emission signal in the {sup 1}H-NMR spectrum. Their polarization intensity varies upon changing the reaction solvent from methanol to acetone. A detailed analysis of the hydrogenation pathway is carried out by means of density functional theory calculations to assess the structure of hydrogenation intermediates and their stability in the two solvents. The observed polarization effects have been accounted on the basis of the obtained structures. Insights into the lifetime of a short-lived reaction intermediate are also obtained.

  2. Role of the reaction intermediates in determining PHIP (parahydrogen induced polarization) effect in the hydrogenation of acetylene dicarboxylic acid with the complex [Rh (dppb)]+ (dppb: 1,4-bis(diphenylphosphino)butane).

    PubMed

    Reineri, F; Aime, S; Gobetto, R; Nervi, C

    2014-03-07

    This study deals with the parahydrogenation of the symmetric substrate acetylene dicarboxylic acid catalyzed by a Rh(I) complex bearing the chelating diphosphine dppb (1,4-bis(diphenylphosphino)butane). The two magnetically equivalent protons of the product yield a hyperpolarized emission signal in the (1)H-NMR spectrum. Their polarization intensity varies upon changing the reaction solvent from methanol to acetone. A detailed analysis of the hydrogenation pathway is carried out by means of density functional theory calculations to assess the structure of hydrogenation intermediates and their stability in the two solvents. The observed polarization effects have been accounted on the basis of the obtained structures. Insights into the lifetime of a short-lived reaction intermediate are also obtained.

  3. Nucleophile sensitivity of Drosophila TRPA1 underlies light-induced feeding deterrence.

    PubMed

    Du, Eun Jo; Ahn, Tae Jung; Wen, Xianlan; Seo, Dae-Won; Na, Duk L; Kwon, Jae Young; Choi, Myunghwan; Kim, Hyung-Wook; Cho, Hana; Kang, KyeongJin

    2016-09-22

    Solar irradiation including ultraviolet (UV) light causes tissue damage by generating reactive free radicals that can be electrophilic or nucleophilic due to unpaired electrons. Little is known about how free radicals induced by natural sunlight are rapidly detected and avoided by animals. We discover that Drosophila Transient Receptor Potential Ankyrin 1 (TRPA1), previously known only as an electrophile receptor, sensitively detects photochemically active sunlight through nucleophile sensitivity. Rapid light-dependent feeding deterrence in Drosophila was mediated only by the TRPA1(A) isoform, despite the TRPA1(A) and TRPA1(B) isoforms having similar electrophile sensitivities. Such isoform dependence re-emerges in the detection of structurally varied nucleophilic compounds and nucleophilicity-accompanying hydrogen peroxide (H2O2). Furthermore, these isoform-dependent mechanisms require a common set of TRPA1(A)-specific residues dispensable for electrophile detection. Collectively, TRPA1(A) rapidly responds to natural sunlight intensities through its nucleophile sensitivity as a receptor of photochemically generated radicals, leading to an acute light-induced behavioral shift in Drosophila.

  4. Nucleophile sensitivity of Drosophila TRPA1 underlies light-induced feeding deterrence

    PubMed Central

    Du, Eun Jo; Ahn, Tae Jung; Wen, Xianlan; Seo, Dae-Won; Na, Duk L; Kwon, Jae Young; Choi, Myunghwan; Kim, Hyung-Wook; Cho, Hana; Kang, KyeongJin

    2016-01-01

    Solar irradiation including ultraviolet (UV) light causes tissue damage by generating reactive free radicals that can be electrophilic or nucleophilic due to unpaired electrons. Little is known about how free radicals induced by natural sunlight are rapidly detected and avoided by animals. We discover that Drosophila Transient Receptor Potential Ankyrin 1 (TRPA1), previously known only as an electrophile receptor, sensitively detects photochemically active sunlight through nucleophile sensitivity. Rapid light-dependent feeding deterrence in Drosophila was mediated only by the TRPA1(A) isoform, despite the TRPA1(A) and TRPA1(B) isoforms having similar electrophile sensitivities. Such isoform dependence re-emerges in the detection of structurally varied nucleophilic compounds and nucleophilicity-accompanying hydrogen peroxide (H2O2). Furthermore, these isoform-dependent mechanisms require a common set of TRPA1(A)-specific residues dispensable for electrophile detection. Collectively, TRPA1(A) rapidly responds to natural sunlight intensities through its nucleophile sensitivity as a receptor of photochemically generated radicals, leading to an acute light-induced behavioral shift in Drosophila. DOI: http://dx.doi.org/10.7554/eLife.18425.001 PMID:27656903

  5. Characterization of Metastable Intermediates Formed in the Reaction Between a Mn(II) Complex and Dioxygen, Including a Crystallographic Structure of a Binuclear Mn(III)-Peroxo Species

    PubMed Central

    Coggins, Michael K.; Sun, Xianru; Kwak, Yeonju; Solomon, Edward I.; Rybak-Akimova, Elena; Kovacs, Julie A.

    2013-01-01

    Transition-metal peroxos have been implicated as key intermediates in a variety of critical biological processes involving O2. Due to their highly reactive nature, very few metal-peroxos have been characterized. The dioxygen chemistry of manganese remains largely unexplored despite the proposed involvement of a binuclear Mn-peroxo, either as a precursor to O2, or derived from O2, in both photosynthetic H2O oxidation and DNA biosynthesis, arguably two of the most fundamental processes of life. Neither of these biological intermediates has been observed. Herein we describe the dioxygen chemistry of coordinatively unsaturated [MnII(SMe2N4(6-MeDPEN))] +(1), and the characterization of intermediates formed en route to a binuclear mono-oxo bridged Mn(III) product {[MnIII(SMe2N4(6-MeDPEN)]2-(μ-O)}2+ (2), the oxo atom of which is derived from 18O2. At low-temperatures, a dioxygen intermediate, [Mn(SMe2N4(6-MeDPEN))(O2)]+ (4), is observed (by stopped-flow) to rapidly and irreversibly form in this reaction (k1(−10 °C)= 3780±180M−1s−1, ΔH1‡ = 26.4±1.7 kJ mol−1, ΔS1‡ = − 75.6±6.8 J mol−1K−1), and then convert more slowly (k2(−10 °C)= 417±3.2 M−1s−1, ΔH2‡ = 47.1±1.4 kJ mol−1, ΔS2‡ = − 15.0±5.7 J mol−1K−1) to a species 3 with isotopically sensitive stretches at νo-o (Δ18O) = 819(47) cm−1, kO–O= 3.02 mdyn/Å, and νMn-O(Δ18O) = 611(25) cm−1 consistent with a peroxo. Intermediate 3 releases approximately 0.5 equiv of H2O2 per Mn ion upon protonation, and the rate of conversion of 4 to 3 is dependent on [Mn(II)] concentration, consistent with the formation of a binuclear Mn-peroxo. This was verified by X-ray crystallography, where the peroxo of {[MnIII(SMe2N4(6-Me-DPEN)]2(trans–μ–1,2–O2)}2+ (3) is shown to be bridging between two Mn(III) ions in an end-on trans-μ-1,2-fashion. This represents the first characterized example of a binuclear Mn(III)-peroxo, and a rare case in which more than one intermediate is observed

  6. Alternative nucleophilic substrates for the endonuclease activities of human immunodeficiency virus type 1 integrase

    SciTech Connect

    Ealy, Julie B.; Sudol, Malgorzata; Krzeminski, Jacek; Amin, Shantu; Katzman, Michael

    2012-11-10

    Retroviral integrase can use water or some small alcohols as the attacking nucleophile to nick DNA. To characterize the range of compounds that human immunodeficiency virus type 1 integrase can accommodate for its endonuclease activities, we tested 45 potential electron donors (having varied size and number or spacing of nucleophilic groups) as substrates during site-specific nicking at viral DNA ends and during nonspecific nicking reactions. We found that integrase used 22 of the 45 compounds to nick DNA, but not all active compounds were used for both activities. In particular, 13 compounds were used for site-specific and nonspecific nicking, 5 only for site-specific nicking, and 4 only for nonspecific nicking; 23 other compounds were not used for either activity. Thus, integrase can accommodate a large number of nucleophilic substrates but has selective requirements for its different activities, underscoring its dynamic properties and providing new information for modeling and understanding integrase.

  7. Identification of the nucleophile catalytic residue of GH51 α-l-arabinofuranosidase from Pleurotus ostreatus

    DOE PAGES

    Amore, Antonella; Iadonisi, Alfonso; Vincent, Florence; ...

    2015-12-21

    In this paper, the recombinant α-l-arabinofuranosidase from the fungus Pleurotus ostreatus (rPoAbf) was subjected to site-directed mutagenesis in order to identify the catalytic nucleophile residue. Based on bioinformatics and homology modelling analyses, E449 was revealed to be the potential nucleophilic residue. Thus, the mutant E449G of PoAbf was recombinantly expressed in Pichia pastoris and its recombinant expression level and reactivity were investigated in comparison to the wild-type. The design of a suitable set of hydrolysis experiments in the presence or absence of alcoholic arabinosyl acceptors and/or formate salts allowed to unambiguously identify the residue E449 as the nucleophile residue involvedmore » in the retaining mechanism of this GH51 arabinofuranosidase. 1H NMR analysis was applied for the identification of the products and the assignement of their anomeric configuration.« less

  8. Profiling the Reactivity of Cyclic C-Nucleophiles towards Electrophilic Sulfur in Cysteine Sulfenic Acid

    PubMed Central

    Gupta, Vinayak; Carroll, Kate S.

    2015-01-01

    Oxidation of a protein cysteine thiol to sulfenic acid, termed S-sulfenylation, is a reversible post-translational modification that plays a crucial role in regulating protein function and is correlated with disease states. The majority of reaction-based small molecule and immunochemical probes used for detecting sulfenic acids are based on the 5,5-dimethyl-1,3-cyclohexanedione (dimedone) scaffold, which is selective, but suffers from low reactivity. In addition, mechanistic details and features that diminish or enhance nucleophile reactivity remain largely unknown. A significant hurdle to resolving the aforementioned issues has been the chemically unstable nature of small-molecule sulfenic acid models. Herein, we report a facile mass spectrometry-based assay and repurposed dipeptide-based model to screen a library of cyclic C-nucleophiles for reactivity with sulfenic acid under aqueous conditions. Observed rate constants for ~100 cyclic C-nucleophiles were obtained and, from this collection, we have identified novel compounds with more than 200-fold enhanced reactivity, as compared to dimedone. The increase in reactivity and retention of selectivity of these C-nucleophiles were validated in secondary assays, including a protein model for sulfenic acid. Together, this work represents a significant step toward developing new chemical reporters for detecting protein S-sulfenylation with superior kinetic resolution. The enhanced rates and varied composition of the C-nucleophiles should enable more comprehensive analyses of the sulfenome and serve as the foundation for reversible or irreversible nucleophilic covalent inhibitors that target oxidized cysteine residues in therapeutically important proteins. PMID:26819701

  9. Laser-Induced Dynamics of Peroxo-Dicopper(II) Complexes Vary with Ligand Architecture; One-Photon Two-Electron O2-Ejection and Formation of Mixed-Valent CuICuII-Superoxide Intermediates

    PubMed Central

    Saracini, Claudio; Ohkubo, Kei; Suenobu, Tomoyoshi; Meyer, Gerald J.; Karlin, Kenneth D.; Fukuzumi, Shunichi

    2015-01-01

    The overall one-photon two-electron peroxide-to-dioxygen oxidation chemistry (O22− + 1 hν → O2 + 2e−) was achieved with copper complexes. Interestingly, light excitation of peroxo dinuclear copper(II) complexes with an μ-η2-η2–(side-on) peroxo ligation was found to release dioxygen while those with a trans-1,2 (end-on) geometry did not, even though spectroscopic studies revealed that both reactions proceeded through superoxo intermediates. More specifically, femtosecond laser excitation of acetone solutions of a trans-μ–1,2(end-on) peroxo dinuclear copper(II) complex ([(tmpa)2CuII2(O2)]2+ (1); λmax, 525 & 600 nm) and μ-η2-η2–(side-on) peroxo dinuclear copper(II) complexes ([(N5)CuII2(O2)]2+ (2) and [(N3)CuII2(O2)]2+ (3)) at −80 °C resulted in the rapid formation of an intermediate that was reasonably assigned to be a previously unknown mixed-valent superoxide species, [CuII(O2•−)CuI]2+ (λmax, 685–740 nm). For 1, this intermediate underwent further fast intramolecular electron transfer from the O2•− moiety to the CuII ion to yield an ‘O2-caged’ dicopper(I) adduct, CuI2–O2, with rate constant of (2.8 ± 0.4) × 1012 s−1 but without release of O2. Instead, data consistent with barrierless stepwise back electron transfer to regenerate 1 were observed with the rate constant (1.8 ± 0.1) × 1010 s−1. Femtosecond laser excitation of the side-on peroxide complexes 2 and 3 under the same conditions led to the appearance of transient species well formulated as [CuII(O2•−)CuI]2+ intermediates that underwent further intramolecular electron-transfer from the O2•− center to the CuII ion resulting in complete O2 release to produce the corresponding dicopper(I) compounds with rate constants of (3.9 ± 0.3) × 109 s−1 and (7.3 ± 0.3) × 109 s−1 for 2 and 3, respectively. Such remarkable differences in reaction pathways for the peroxo dinuclear copper(II) complexes likely result from the ligand-derived stability of the CuI vs

  10. Enantioselective Nucleophile-Catalyzed Synthesis of Tertiary Alkyl Fluorides via the α-Fluorination of Ketenes: Synthetic and Mechanistic Studies

    PubMed Central

    2015-01-01

    The catalytic asymmetric synthesis of alkyl fluorides, particularly α-fluorocarbonyl compounds, has been the focus of substantial effort in recent years. While significant progress has been described in the formation of enantioenriched secondary alkyl fluorides, advances in the generation of tertiary alkyl fluorides have been more limited. Here, we describe a method for the catalytic asymmetric coupling of aryl alkyl ketenes with commercially available N-fluorodibenzenesulfonimide (NFSI) and C6F5ONa to furnish tertiary α-fluoroesters. Mechanistic studies are consistent with the hypothesis that the addition of an external nucleophile (C6F5ONa) is critical for turnover, releasing the catalyst (PPY*) from an N-acylated intermediate. The available data can be explained by a reaction pathway wherein the enantioselectivity is determined in the turnover-limiting transfer of fluorine from NFSI to a chiral enolate derived from the addition of PPY* to the ketene. The structure and the reactivity of the product of this proposed elementary step, an α-fluoro-N-acylpyridinium salt, have been examined. PMID:24922581

  11. An Artificial Enzyme Made by Covalent Grafting of an Fe(II) Complex into β-Lactoglobulin: Molecular Chemistry, Oxidation Catalysis, and Reaction-Intermediate Monitoring in a Protein.

    PubMed

    Buron, Charlotte; Sénéchal-David, Katell; Ricoux, Rémy; Le Caër, Jean-Pierre; Guérineau, Vincent; Méjanelle, Philippe; Guillot, Régis; Herrero, Christian; Mahy, Jean-Pierre; Banse, Frédéric

    2015-08-17

    An artificial metalloenzyme based on the covalent grafting of a nonheme Fe(II) polyazadentate complex into bovine β-lactoglobulin has been prepared and characterized by using various spectroscopic techniques. Attachment of the Fe(II) catalyst to the protein scaffold is shown to occur specifically at Cys121. In addition, spectrophotometric titration with cyanide ions based on the spin-state conversion of the initial high spin (S=2) Fe(II) complex into a low spin (S=0) one allows qualitative and quantitative characterization of the metal center's first coordination sphere. This biohybrid catalyst activates hydrogen peroxide to oxidize thioanisole into phenylmethylsulfoxide as the sole product with an enantiomeric excess of up to 20 %. Investigation of the reaction between the biohybrid system and H2 O2 reveals the generation of a high spin (S=5/2) Fe(III) (η(2) -O2 ) intermediate, which is proposed to be responsible for the catalytic sulfoxidation of the substrate.

  12. Structures of the Michaelis Complex (1.2A) and the Covalent Acyl Intermediate (2.0A ) of Cefamandole Bound in the Active Sites of the Mycobacterium tuberculosis beta-Lactamase K72A and E166A Mutants

    SciTech Connect

    L Tremblay; h Xu; J Blanchard

    2011-12-31

    The genome of Mycobacterium tuberculosis (TB) contains a gene that encodes a highly active {beta}-lactamase, BlaC, that imparts TB with resistance to {beta}-lactam chemotherapy. The structure of covalent BlaC-{beta}-lactam complexes suggests that active site residues K73 and E166 are essential for acylation and deacylation, respectively. We have prepared the K73A and E166A mutant forms of BlaC and have determined the structures of the Michaelis complex of cefamandole and the covalently bound acyl intermediate of cefamandole at resolutions of 1.2 and 2.0 {angstrom}, respectively. These structures provide insight into the details of the catalytic mechanism.

  13. Lewis Acid Mediated Vinylogous Additions of Enol Nucleophiles into an α,β-Unsaturated Platinum Carbene

    PubMed Central

    Allegretti, Paul A.; Huynh, Khoi; Ozumerzifon, Tarik J.; Ferreira, Eric M.

    2016-01-01

    A variety of substituted indoles and benzofurans are accessed via a platinum catalyzed annulation and vinylogous addition of enol nucleophiles. Several β-dicarbonyl compounds participate in the reaction, as do α-nitro and α-cyano carbonyl species. Subjecting the indole products to acidic conditions results in the formation of fused heterocycles. PMID:26652926

  14. Nucleophilic Aromatic Substitution Reactions Described by the Local Electron Attachment Energy.

    PubMed

    Stenlid, Joakim H; Brinck, Tore

    2017-03-17

    A local multiorbital electrophilicity descriptor, the local electron attachment energy [E(r)], is used to study the nucleophilic aromatic substitution reactions of SNAr and VNS (vicarious nucleophilic substitution). E(r) considers all virtual orbitals below the free electron limit and is determined on the molecular isodensity contour of 0.004 atomic units. Good (R(2) = 0.83) to excellent (R(2) = 0.98) correlations are found between descriptor values and experimental reactivity data for six series of electron deficient arenes. These include homo- and heteroarenes, rings of five to six atoms, and a variety of fluorine, bromine, and hydride leaving groups. The solvent, temperature, and nucleophile are in addition varied across the series. The surface E(r) [ES(r)] is shown to provide reactivity predictions better than those of transition-state calculations for a concerted SNAr reaction with a bromine nucleofug, gives correlations substantially stronger than those of LUMO energies, and is overall more reliable than the molecular electrostatic potential. With the use of ES(r), one can identify the various electrophilic sites within a molecule and correctly predict isomeric distributions. Since the calculations of ES(r) are computationally inexpensive, the descriptor offers fast but accurate reactivity predictions for the important nucleophilic aromatic substitution class of reactions. Applications in, e.g., drug discovery, synthesis, and toxicology studies are envisaged.

  15. REVISITING CLASSICAL NUCLEOPHILIC SUBSTITUTIONS IN AQUEOUS MEDIUM: MICROWAVE-ASSISTED SYNTHESIS OF ALKYL AZIDES

    EPA Science Inventory

    An efficient and clean synthesis of alkyl azides using microwave (MW) radiation is described in aqueous medium by reacting alkyl halides or tosylates with alkali azides. This general and expeditious MW-enhanced approach to nucleophilic substitution reactions is applicable to the ...

  16. Highly diastereoselective nucleophilic addition to myrtenal. Straightforward synthesis of an enantiopure scorpionate ligand.

    PubMed

    Otero, Antonio; Fernandez-Baeza, Juan; Antiñolo, Antonio; Tejeda, Juan; Lara-Sanchez, Agustín; Sanchez-Barba, Luis F; Sanchez-Molina, Margarita; Franco, Sonia; López-Solera, Maria I; Rodríguez, Ana M

    2007-10-15

    The work described here represents the first example in which an efficient and highly diastereoselective nucleophilic 1,2-addition of an organolithium reagent has been performed on a carbonylic prostereogenic center to give an enantiopure scorpionate ligand in only one step.

  17. Preparation of 6-substituted quinoxaline JSP-1 inhibitors by microwave accelerated nucleophilic substitution.

    PubMed

    Zhang, Li; Qiu, Beiying; Li, Xin; Wang, Xin; Li, Jingya; Zhang, Yongliang; Liu, Jian; Li, Jia; Shen, Jingkang

    2006-12-21

    A small library of 6-aminoquinoxalines has been prepared by nucleophilic substitution of 6-fluoroquinoxaline with amines and nitrogen-containing heterocycles under computer-controlled microwave irradiation. Some compounds were found to be potent inhibitors of JNK Stimulatory Phosphatase-1 (JSP-1) in an in vitro biological assay.

  18. Gold(I)-catalyzed amination of allylic alcohols with cyclic ureas and related nucleophiles.

    PubMed

    Mukherjee, Paramita; Widenhoefer, Ross A

    2010-03-19

    A 1:1 mixture of [P(t-Bu)(2)-o-biphenyl]AuCl and AgSbF(6) catalyzes the intermolecular amination of allylic alcohols with 1-methylimidazolidin-2-one and related nucleophiles that, in the case of gamma-unsubstituted or gamma-methyl-substituted allylic alcohols, occurs with high gamma-regioselectivity and syn-stereoselectivity.

  19. Organic Chemistry Students' Ideas about Nucleophiles and Electrophiles: The Role of Charges and Mechanisms

    ERIC Educational Resources Information Center

    Anzovino, Mary E.; Bretz, Stacey Lowery

    2015-01-01

    Organic chemistry students struggle with reaction mechanisms and the electron-pushing formalism (EPF) used by practicing organic chemists. Faculty have identified an understanding of nucleophiles and electrophiles as one conceptual prerequisite to mastery of the EPF, but little is known about organic chemistry students' knowledge of nucleophiles…

  20. Quantitative Structure-Activity Relationships for the Nucleophilicity of Trivalent Boron Compounds.

    PubMed

    García-López, Diego; Cid, Jessica; Marqués, Ruben; Fernández, Elena; Carbó, Jorge J

    2017-04-11

    We describe herein the development of quantitative structure-activity relationships (QSAR) for the nucleophilicity of trivalent boron compounds covering boryl fragments bonded to alkali and alkaline-earth metals, to transition metals, and to sp(3) boron units in diboron reagents. We used the charge of the boryl fragment (q[B]) and the boron p/s population ratio (p/s) to describe the electronic structures of boryl moieties, whereas the distance-weighted volume (Vw ) descriptor was used to evaluate the steric effects. The three-term easy-to-interpret QSAR model showed statistical significance and predictive ability (r(2) =0.88, q(2) =0.83). The use of chemically meaningful descriptors has allowed identification of the factors governing the boron nucleophilicity and indicates that the most efficient nucleophiles are those with enhanced the polarization of the B-X bond towards the boron atom and reduced steric bulk. A detailed analysis of the potential energy surfaces of different types of boron substituents has provided insight into the mechanism and established an order of nucleophilicity for boron in B-X: X=Li>Cu>B(sp(3) )>Pd. Finally, we used the QSAR model to make a priori predictions of experimentally untested compounds.

  1. Spectroscopic and computational characterization of CuII-OOR (R = H or cumyl) complexes bearing a Me6-tren ligand.

    PubMed

    Choi, Yu Jin; Cho, Kyung-Bin; Kubo, Minoru; Ogura, Takashi; Karlin, Kenneth D; Cho, Jaeheung; Nam, Wonwoo

    2011-03-14

    A copper(II)-hydroperoxo complex, [Cu(Me(6)-tren)(OOH)](+) (2), and a copper(ii)-cumylperoxo complex, [Cu(Me(6)-tren)(OOC(CH(3))(2)Ph)](+) (3), were synthesized by reacting [Cu(Me(6)-tren)(CH(3)CN)](2+) (1) with H(2)O(2) and cumyl-OOH, respectively, in the presence of triethylamine. These intermediates, 2 and 3, were successfully characterized by various physicochemical methods such as UV-vis, ESI-MS, resonance Raman and EPR spectroscopies, leading us to propose structures of the Cu(II)-OOR species with a trigonal-bipyramidal geometry. Density functional theory (DFT) calculations provided geometric and electronic configurations of 2 and 3, showing trigonal bipyramidal copper(II)-OOR geometries. These copper(II)-hydroperoxo and -cumylperoxo complexes were inactive in electrophilic and nucleophilic oxidation reactions.

  2. Reactions of stabilized Criegee Intermediates

    NASA Astrophysics Data System (ADS)

    Vereecken, Luc; Harder, Hartwig; Novelli, Anna

    2014-05-01

    Carbonyl oxides (Criegee intermediates) were proposed as key intermediates in the gas phase ozonolysis of alkenes in 1975 by Rudolf Criegee. Despite the importance of ozonolysis in atmospheric chemistry, direct observation of these intermediates remained elusive, with only indirect experimental evidence for their role in the oxidation of hydrocarbons, e.g. through scavenging experiments. Direct experimental observation of stabilized CI has only been achieved since 2008. Since then, a concerted effort using experimental and theoretical means is in motion to characterize the chemistry and kinetics of these reactive intermediates. We present the results of theoretical investigations of the chemistry of Criegee intermediates with a series of coreactants which may be of importance in the atmosphere, in experimental setups, or both. This includes the CI+CI cross-reaction, which proceeds with a rate coefficient near the collision limit and can be important in experimental conditions. The CI + alkene reactions show strong dependence of the rate coefficient depending on the coreactants, but is generally found to be rather slow. The CI + ozone reaction is sufficiently fast to occur both in experiment and the free troposphere, and acts as a sink for CI. The reaction of CI with hydroperoxides, ROOH, is complex, and leads both to the formation of oligomers, as to the formation of reactive etheroxides, with a moderately fast rate coefficient. The importance of these reactions is placed in the context of the reaction conditions in different atmospheric environments ranging from unpolluted to highly polluted.

  3. Photodissociation of carbon monoxide and dioxygen forms of synthetic heme complexes studied by using picosecond absorption spectroscopy. Evidence of a pseudo-four-coordinate intermediate

    SciTech Connect

    Caldwell, K.; Noe, L.J.; Ciccone, J.D.; Traylor, T.G.

    1986-10-01

    The authors have studied the photodissociation of the CO and O/sub 2/ forms of a number of synthetic heme complexes by using 531-nm, 8-ps pulses from a mode-locked Nd-phosphate glass laser employing the standard pump-probe technique. These complexes closely mimic the R and T states of hemoglobin depending on whether the imidazole-heme steric interaction is strain free or not. Such variations in the proximal imidazole-heme geometry allow one to explore the effects of tertiary constraint of this type on the dissociation. The results of this work are complementary to their earlier work on the natural compounds, hemoglobin and myoglobin, and show that the effects of strain on the heme are manifest in the dynamics and mechanism of the photodissociation. For both the natural and synthetic compounds, they have identified certain predissociative and postdissociative photointermediates as they sequentially evolve by monitoring the ..pi pi../sup */ porphyrin Soret absorption changes as a function of time. Their kinetic analysis indicates that it takes from 2 to 16 ps for the synthetic complexes to dissociate depending on whether the Fe-imidazole bond is strain free or not. They also suggest that a pseudo-four-coordinate complex may be present as a photointermediate in the compounds having the strained Fe-imidazole linkage.

  4. Cyclopalladation of dimesityl selenide: synthesis, reactivity, structural characterization, isolation of an intermediate complex with C-H···Pd intra-molecular interaction and computational studies.

    PubMed

    Kolay, Siddhartha; Wadawale, Amey; Das, Dasarathi; Kisan, Hemanta K; Sunoj, Raghavan B; Jain, Vimal K

    2013-08-14

    The reaction of dimesityl selenide (Mes2Se) with either PdCl2(PhCN)2 in toluene or PdCl2 in toluene-acetonitrile yields a chloro-bridged binuclear palladium complex, [Pd2Cl2(μ-Cl)2(Mes2Se)2] (1), whereas with Na2PdCl4 in refluxing ethanol, a cyclometallated palladium complex, [Pd2(μ-Cl)2{MesSeC6H2(Me2)CH2}2] (2) is afforded. 2 can also be obtained when 1 is refluxed in ethanol. On treatment with Pb(Epy)2 in dichloromethane, 2 afforded the Epy-bridged binuclear complexes, [Pd2(μ-Epy)2{MesSeC6H2(Me2)CH2}2] (3; E = S (3a) or Se (3b)). Treatment of 2 with PPh3 yields a bridge-cleaved monomeric complex, [PdCl{MesSeC6H2(Me2)CH2}(PPh3)]. The molecular structures of 1-3 were established by X-ray diffraction analyses. All the complexes are dimeric, with the palladium atoms acquiring a distorted square planar configuration. There are intra-molecular C-H···Pd interactions (d(M-H): 2.75 Å and

  5. A DFT study on the reaction pathways for carbon-carbon bond-forming reactions between propargylic alcohols and alkenes or ketones catalyzed by thiolate-bridged diruthenium complexes.

    PubMed

    Sakata, Ken; Miyake, Yoshihiro; Nishibayashi, Yoshiaki

    2009-01-05

    The reaction pathways of two types of the carbon-carbon bond-forming reactions catalyzed by thiolate-bridged diruthenium complexes have been investigated by density-functional-theory calculations. It is clarified that both carbon-carbon bond-forming reactions proceed through a ruthenium-allenylidene complex as a common reactive intermediate. The attack of pi electrons on propene or the vinyl alcohol on the ruthenium-allenylidene complex is the first step of the reaction pathways. The reaction pathways are different after the attack of nucleophiles on the ruthenium-alkynyl complex. In the reaction with propene, the carbon-carbon bond-forming reaction proceeds through a stepwise process, whereas in the reaction with vinyl alcohol, it proceeds through a concerted process. The interactions between the ruthenium-allenylidene complex and propene or vinyl alcohol have been investigated by applying a simple way of looking at orbital interactions.

  6. Simultaneous capture of two distinct radical ion intermediates generated from the EDA complexes of three-membered compounds with TCNE by photoexcitation and in the dark

    SciTech Connect

    Miyashi, T.; Kamata, M.; Mukai, T.

    1987-04-29

    Irradiation of the electron donor-acceptor (EDA) complexes of 2,2-diaryl-1-methylenecyclopropanes, 1,1,2,2-tetraarylcyclopropanes, 2,3-diaryloxiranes, or 2,3-diarylaziridines with tetracyanoethylene (TCNE) under aerated conditions involved oxygenation and/or the (3 + 2) cycloaddition with TCNE. The same oxygenation took place in the dark when the EDA complexes of 2,2-diaryl-1-methylenecyclopropanes or 1,1,2,2-tetraarylcyclopropanes with TCNE were simply stirred in oxygen-saturated solvents. Oxygenation occurred much more efficiently as the solvent polarity and the electron-donative nature of donor substrates increased. 1,2,4,5-Tetramethoxybenzene (TMB) used as a quencher efficiently suppressed oxygenation but not the (3 + 2) cycloaddition at all. Oxygenation occurs through the solvent-separated radical cations diffused from the photogenerated geminate radical ion pairs, whereas the cage coupling of the radical ion pairs involves the (3 + 2) cycloaddition with TCNE.

  7. A family of Group 4 metal alkoxo complexes with an M3(mu3-O) core relevant to Ziegler-Natta catalyst intermediates.

    PubMed

    Utko, Józef; Przybylak, Szymon; Jerzykiewicz, Lucjan B; Szafert, Sławomir; Sobota, Piotr

    2003-01-03

    Reactions of [Mg(thffo)(2)] (1) or [Ca(thffo)(2)] (2) with ZrCl(4) or HfCl(4) in a CH(2)Cl(2)/THF/CH(3)CN mixture give thermally stable neutral heterobimetallic tetranuclear complexes [M(3)M'(mu(x)-O)(mu,eta(2)-thffo)(6)(Cl)(6)] (thffo=tetrahydrofurfuroxide; M/M'/x: 3, Zr/Mg/3; 4, Hf/Mg/3; 5, Zr/Ca/4; 6, Hf/Ca/4) as colorless crystals in 75-82 % yield. X-ray diffraction studies show complexes 3-5 to contain oxo-bridged M(3) triangles that are capped by an alkaline earth metal-containing moiety to form species of C(3) symmetry. Reactions of ZrCl(4) and HfCl(4) with pure tetrahydrofurfuryl alcohol in EtOH and MeOH provide ionic complexes [M(3)(mu(3)-O)(mu,eta(2)-thffo)(3)(L)(3)(Cl)(6)]Cl (M/L: 8, Zr/EtOH; 9, Hf/EtOH; 10, Zr/MeOH) in 66-79 % yield. Complexes 8-10 consist of M(3) triangles that are analogous to those in 3-6 and possess similar overall symmetry, as shown by X-ray crystallography. Changes in the reaction conditions afforded the asymmetric neutral dimer [Zr(2)(mu-thffo)(2)(thffoH)(Cl)(6)] (7) and the homometallic [Zr(3)(mu(3)-O)(mu,eta(2)-thp)(3)(thf)(2)(Cl)(7)] (11).

  8. Isolation and characterization of a dimeric ruthenium(II) complex. An intermediate in the ruthenium-catalyzed oxygen oxidation of thioethers to sulfoxides

    SciTech Connect

    Riley, D.P.; Thompson, M.R.; Lyon, J. III

    1988-12-01

    Complexes of the type Ru/sup II/X/sub 2/(MeSO)/sub 2 or 3/(PR/sub 3/) are excellent catalysts for the selective oxygen oxidation of thioethers to sulfoxides. The complex RuCl/sub 2/(Me/sub 2/SO)/sub 3/(PPh/sub 3/) is an example of such a catalyst, and its solution chemistry under simulated catalytic conditions reveals that only one detectable complex is present. This presumed catalytic complex has been isolated and characterized by /sup 1/H, /sup 13/C, and /sup 31/P NMR and by an x-ray structure determination to be the chlorotri-/mu/-chlorotris(dimethyl sulfoxide)bis(triphenylphosphine)diruthenium, 2. Single crystals of 2 are monoclinic with space group P/sub 2/sub 1//c/ with a = 16.662(3)/angstrom/, b = 16.576(3)/angstrom/, c = 19.282(3)/angstrom/, and /beta/ = 98.86(1)/degree/. Both Ru centers are coordinated in a distorted octahedral fashion having three /mu/-bridged chlorine atoms shared between them. Ru/sub 1/ possesses three terminal ligands, one chloride, one triphenylphosphine and a dimethyl sulfoxide. Ru/sub 2/ is terminally bonded to two Me/sub 2/SO centers and one triphenylphosphine. The /mu/-bridged chlorine atoms are bonded in an asymmetric fashion due to the differing trans-influences of the Cl/sup /minus//, (CH/sub 3/)/sub 2/SO and PPh/sub 3/ ligands bonded to the metal centers. Ru-/mu/Cl distances range from 2.436(2)/angstrom/ to 2.490(2)/angstrom/, and Ru-S distances from 2.205(2)/angstrom/ to 2.269(2)/angstrom/.

  9. Performance study of magnesium-sulfur battery using a graphene based sulfur composite cathode electrode and a non-nucleophilic Mg electrolyte

    NASA Astrophysics Data System (ADS)

    Vinayan, B. P.; Zhao-Karger, Zhirong; Diemant, Thomas; Chakravadhanula, Venkata Sai Kiran; Schwarzburger, Nele I.; Cambaz, Musa Ali; Behm, R. Jürgen; Kübel, Christian; Fichtner, Maximilian

    2016-02-01

    Here we report for the first time the development of a Mg rechargeable battery using a graphene-sulfur nanocomposite as the cathode, a Mg-carbon composite as the anode and a non-nucleophilic Mg based complex in tetraglyme solvent as the electrolyte. The graphene-sulfur nanocomposites are prepared through a new pathway by the combination of thermal and chemical precipitation methods. The Mg/S cell delivers a higher reversible capacity (448 mA h g-1), a longer cyclability (236 mA h g-1 at the end of the 50th cycle) and a better rate capability than previously described cells. The dissolution of Mg polysulfides to the anode side was studied by X-ray photoelectron spectroscopy. The use of a graphene-sulfur composite cathode electrode, with the properties of a high surface area, a porous morphology, a very good electronic conductivity and the presence of oxygen functional groups, along with a non-nucleophilic Mg electrolyte gives an improved battery performance.Here we report for the first time the development of a Mg rechargeable battery using a graphene-sulfur nanocomposite as the cathode, a Mg-carbon composite as the anode and a non-nucleophilic Mg based complex in tetraglyme solvent as the electrolyte. The graphene-sulfur nanocomposites are prepared through a new pathway by the combination of thermal and chemical precipitation methods. The Mg/S cell delivers a higher reversible capacity (448 mA h g-1), a longer cyclability (236 mA h g-1 at the end of the 50th cycle) and a better rate capability than previously described cells. The dissolution of Mg polysulfides to the anode side was studied by X-ray photoelectron spectroscopy. The use of a graphene-sulfur composite cathode electrode, with the properties of a high surface area, a porous morphology, a very good electronic conductivity and the presence of oxygen functional groups, along with a non-nucleophilic Mg electrolyte gives an improved battery performance. Electronic supplementary information (ESI) available

  10. Trifunctional metal ion-catalyzed solvolysis: Cu(II)-promoted methanolysis of N,N-bis(2-picolyl) benzamides involves unusual Lewis acid activation of substrate, delivery of coordinated nucleophile, powerful assistance of the leaving group departure.

    PubMed

    Raycroft, Mark A R; Maxwell, Christopher I; Oldham, Robyn A A; Andrea, Areen Saffouri; Neverov, Alexei A; Brown, R Stan

    2012-10-01

    The methanolyses of Cu(II) complexes of a series of N,N-bis(2-picolyl) benzamides (4a-g) bearing substituents X on the aromatic ring were studied under (s)(s)pH-controlled conditions at 25 °C. The active form of the complexes at neutral (s)(s)pH has a stoichiometry of 4:Cu(II):((-)OCH(3))(HOCH(3)) and decomposes unimolecularly with a rate constant k(x). A Hammett plot of log(k(x)) vs σ(x) values has a ρ(x) of 0.80 ± 0.05. Solvent deuterium kinetic isotope effects of 1.12 and 1.20 were determined for decomposition of the 4-nitro and 4-methoxy derivatives, 4b:Cu(II):((-)OCH(3))(HOCH(3)) and 4g:Cu(II):((-)OCH(3))(HOCH(3)), in the plateau region of the (s)(s)pH/log(k(x)) profiles in both CH(3)OH and CH(3)OD. Activation parameters for decomposition of these complexes are ΔH(++) = 19.1 and 21.3 kcal mol(-1) respectively and ΔS(++) = -5.1 and -2 cal K(-1) mol(-1). Density functional theory (DFT) calculations for the reactions of the Cu(II):((-)OCH(3))(HOCH(3)) complexes of 4a,b and g (4a, X = 3,5-dinitro) were conducted to probe the relative transition state energies and geometries of the different states. The experimental and computational data support a mechanism where the metal ion is coordinated to the N,N-bis(2-picolyl) amide unit and positioned so that it permits delivery of a coordinated Cu(II):((-)OCH(3)) nucleophile to the C═O in the rate-limiting transition state (TS) of the reaction. This proceeds to a tetrahedral intermediate INT, occupying a shallow minimum on the free energy surface with the Cu(II) coordinated to both the methoxide and the amidic N. Breakdown of INT is a virtually barrierless process, involving a Cu(II)-assisted departure of the bis(2-picolyl)amide anion. The analysis of the data points to a trifunctional role for the metal ion in the solvolysis mechanism where it activates intramolecular nucleophilic attack on the C═O group by coordination to an amidic N in the first step of the reaction and subsequently assists leaving group

  11. Sequential metabolism of secondary alkyl amines to metabolic-intermediate complexes: opposing roles for the secondary hydroxylamine and primary amine metabolites of desipramine, (s)-fluoxetine, and N-desmethyldiltiazem.

    PubMed

    Hanson, Kelsey L; VandenBrink, Brooke M; Babu, Kantipudi N; Allen, Kyle E; Nelson, Wendel L; Kunze, Kent L

    2010-06-01

    Three secondary amines desipramine (DES), (S)-fluoxetine [(S)-FLX], and N-desmethyldiltiazem (MA) undergo N-hydroxylation to the corresponding secondary hydroxylamines [N-hydroxydesipramine, (S)-N-hydroxyfluoxetine, and N-hydroxy-N-desmethyldiltiazem] by cytochromes P450 2C11, 2C19, and 3A4, respectively. The expected primary amine products, N-desmethyldesipramine, (S)-norfluoxetine, and N,N-didesmethyldiltiazem, are also observed. The formation of metabolic-intermediate (MI) complexes from these substrates and metabolites was examined. In each example, the initial rates of MI complex accumulation followed the order secondary hydroxylamine > secondary amine > primary amine, suggesting that the primary amine metabolites do not contribute to formation of MI complexes from these secondary amines. Furthermore, the primary amine metabolites, which accumulate in incubations of the secondary amines, inhibit MI complex formation. Mass balance studies provided estimates of the product ratios of N-dealkylation to N-hydroxylation. The ratios were 2.9 (DES-CYP2C11), 3.6 [(S)-FLX-CYP2C19], and 0.8 (MA-CYP3A4), indicating that secondary hydroxylamines are significant metabolites of the P450-mediated metabolism of secondary alkyl amines. Parallel studies with N-methyl-d(3)-desipramine and CYP2C11 demonstrated significant isotopically sensitive switching from N-demethylation to N-hydroxylation. These findings demonstrate that the major pathway to MI complex formation from these secondary amines arises from N-hydroxylation rather than N-dealkylation and that the primary amines are significant competitive inhibitors of MI complex formation.

  12. Complex, compound inversion/translocation polymorphism in an ape: presumptive intermediate stage in the karyotypic evolution of the agile gibbon Hylobates agilis.

    PubMed

    Van Tuinen, P; Mootnick, A R; Kingswood, S C; Hale, D W; Kumamoto, A T

    1999-10-01

    Karyotypic variation in five gibbon species of the subgenus Hylobates (2n = 44) was assessed in 63 animals, 23 of them wild born. Acquisition of key specimens of Hylobates agilis (agile gibbon), whose karyotype had been problematic due to unresolved structural polymorphisms, led to disclosure of a compound inversion/translocation polymorphism. A polymorphic region of chromosome 8 harboring two pericentric inversions, one nested within the other, was in turn bissected by one breakpoint of a reciprocal translocation. In double-inversion + translocation heterozygotes, the theoretical meiotic pairing configuration is a double inversion loop, with four arms of a translocation quadrivalent radiating from the loop. Electron-microscopic analysis of synaptonemal complex configurations consistently revealed translocation quadrivalents but no inversion loops. Rather, nonhomologous pairing was evident in the inverted region, a condition that should preclude crossing over and the subsequent production of duplication-deficiency gametes. This is corroborated by the existence of normal offspring of compound heterozygotes, indicating that fertility may not be reduced despite the topological complexity of this polymorphic system. The distribution of inversion and translocation morphs in these taxa suggests application of cytogenetics in identifying gibbon specimens and avoiding undesirable hybridization in captive breeding efforts.

  13. Transition metal-catalyzed/mediated reaction of allenes with a nucleophilic functionality connected to the alpha-carbon atom.

    PubMed

    Ma, Shengming

    2003-09-01

    Allenes with a nucleophilic functionality connected to the alpha-carbon atom have been shown to be versatile building blocks for the syn-thesis of gamma-butenolides, gamma-lactams, gamma-iminolactones, vinylic epoxides, 4-amino-2-alkenols, 2-amino-3-alkenols, 2,5-dihydrofurans, furans, vinylic cyclopropanes, and cyclopentenes, depending on the nature of the nucleophilic centers. The reaction may proceed via the carbometalation-nucleophilic attack mechanism or nucleometallation-reductive elimination. The stereochemical outcomes by these two pathways are different.

  14. Breaking the dogma of aldolase specificity: Simple aliphatic ketones and aldehyde are nucleophiles for fructose-6-phosphate aldolase.

    PubMed

    Roldán, Raquel; Sanchez-Moreno, Israel; Scheidt, Thomas; Hélaine, Virgil; Lemaire, Marielle; Parella, Teodor; Clapés, Pere; Fessner, Wolf-Dieter; Guérard-Hélaine, Christine

    2017-03-07

    D-Fructose-6-phosphate aldolase (FSA) was probed for extended nucleophile promiscuity by using a series of fluorogenic substrates to reveal retro-aldol activity. Four nucleophiles ethanal, propanone, butanone and cyclopentanone were subsequently confirmed to be non-natural substrates in the synthesis direction using the wild type enzyme and its D6H variant. This exceptional widening of the nucleophile substrate scope offers a rapid entry, in good yields and high stereoselectivity, to less oxygenated alkyl ketones and aldehydes, which was hitherto impossible.

  15. Mechanismic investigation on the cleavage of phosphate monoester catalyzed by unsymmetrical macrocyclic dinuclear complexes: the selection of metal centers and the intrinsic flexibility of the ligand.

    PubMed

    Zhang, Xuepeng; Zhu, Yajie; Zheng, Xiaowei; Phillips, David Lee; Zhao, Cunyuan

    2014-04-07

    The hydrolysis mechanisms of phosphor-monoester monoanions NPP(-) (p-nitrophenyl phosphate) catalyzed by unsymmetrical bivalent dinuclear complexes are explored using DFT calculations in this report. Four basic catalyst-substrate binding modes are proposed, and two optional compartments for the location of the nucleophile-coordinated metal center are also considered. Five plausible mechanisms are examined in this computational study. Mechanisms 1, 2, and 3 employ an unsymmetrical dizinc complex. All three mechanisms are based on concerted SN2 addition-substitution pathways. Mechanism 1, which involves more electronegative oxygen atoms attached to the imine nitrogen atoms in the nucleophile-coordinated compartment, was found to be more competitive compared to the other two mechanisms. Mechanisms 4 and 5 are based on consideration of the substitution of the bivalent metal centers and the intrinsic flexibility of the ligand. Both mechanisms 4 and 5 are based on stepwise SN2-type reactions. Magnesium ions with hard base properties and more available coordination sites were found to be good candidates as a substitute in the M(II) dinuclear phosphatases. The reaction energy barriers for the more distorted complexes are lower than those of the less distorted complexes. The proper intermediate distance and a functional second coordination sphere lead to significant catalytic power in the reactions studied. More importantly, the mechanistic differences between the concerted and the stepwise pathways suggest that a better nucleophile with more available coordination sites (from either the metal centers or a functional second coordination sphere) favors concerted mechanisms for the reactions of interest. The results reported in the paper are consistent with and provide a reasonable interpretation for experimental observations in the literature. More importantly, our present results provide some practical suggestions for the selection of the metal centers and how to approach

  16. Probing the Ser-Ser-Lys catalytic triad mechanism of peptide amidase: computational studies of the ground state, transition state, and intermediate.

    PubMed

    Valiña, Anna Liza B; Mazumder-Shivakumar, Devleena; Bruice, Thomas C

    2004-12-21

    Peptide amidase (Pam), a hydrolytic enzyme that belongs to the amidase signature (AS) family, selectively catalyzes the hydrolysis of the C-terminal amide bond (CO-NH(2)) of peptides. The recent availability of the X-ray structures of Pam, fatty acid amide hydrolase, and malonamidase E2 has led to the proposal of a novel Ser-Ser-Lys catalytic triad mechanism for the amide hydrolysis by the AS enzymes. The molecular dynamics (MD) simulations using the CHARMM force field were performed to explore the catalytic mechanism of Pam. The 1.8 A X-ray crystal structure of Pam in complex with the amide analogue of chymostatin was chosen for the initial coordinates for the MD simulations. The five systems that were investigated are as follows: (i) enzyme.substrate with Lys123-NH(2), (ii) enzyme.substrate with Lys123-NH(3)(+), (iii) enzyme.substrate with Lys123-NH(3)(+) and Ser226-O(-), (iv) enzyme.transition state, and (v) enzyme.tetrahedral intermediate. Our data support the presence of the hydrogen bonding network among the catalytic triad residues, Ser226, Ser202, and Lys123, where Ser226 acts as the nucleophile and Ser202 bridges Ser226 and Lys123. The MD simulation supports the catalytic role of the crystallographic waters, Wat1 and Wat2. In all the systems that have been studied, the backbone amide nitrogens of Asp224 and Thr223 create an oxyanion hole by hydrogen bonding to the terminal amide oxygen of the substrate, and stabilize the oxyanion tetrahedral intermediate. The results from both our computational investigation and previously published experimental pH profile support two mechanisms. In a mechanism that is relevant at lower pH, the Lys123-NH(3)(+)-Ser202 dyad provides structural support to the catalytic residue Ser226, which in turn carries out a nucleophilic attack at the substrate amide carbonyl in concert with Wat1-mediated deprotonation and stabilization of the tetrahedral transition state by the oxyanion hole. In the mechanism operating at higher pH, the

  17. Theoretical vibrational spectroscopy of intermediates and the reaction mechanism of the guanosine triphosphate hydrolysis by the protein complex Ras-GAP

    NASA Astrophysics Data System (ADS)

    Khrenova, Maria G.; Grigorenko, Bella L.; Nemukhin, Alexander V.

    2016-09-01

    The structures and vibrational spectra of the reacting species upon guanosine triphosphate (GTP) hydrolysis to guanosine diphosphate and inorganic phosphate (Pi) trapped inside the protein complex Ras-GAP were analyzed following the results of QM/MM simulations. The frequencies of the phosphate vibrations referring to the reactants and to Pi were compared to those observed in the experimental FTIR studies. A good correlation between the theoretical and experimental vibrational data provides a strong support to the reaction mechanism of GTP hydrolysis by the Ras-GAP enzyme system revealed by the recent QM/MM modeling. Evolution of the vibrational bands associated with the inorganic phosphate Pi during the elementary stages of GTP hydrolysis is predicted.

  18. The intermediate filament protein vimentin binds specifically to a recombinant integrin {alpha}2/{beta}1 cytoplasmic tail complex and co-localizes with native {alpha}2/{beta}1 in endothelial cell focal adhesions

    SciTech Connect

    Kreis, Stephanie; Schoenfeld, Hans-Joachim; Melchior, Chantal; Steiner, Beat; Kieffer, Nelly . E-mail: kieffer@cu.lu

    2005-04-15

    Integrin receptors are crucial players in cell adhesion and migration. Identification and characterization of cellular proteins that interact with their short {alpha} and {beta} cytoplasmic tails will help to elucidate the molecular mechanisms by which integrins mediate bi-directional signaling across the plasma membrane. Integrin {alpha}2{beta}1 is a major collagen receptor but to date, only few proteins have been shown to interact with the {alpha}2 cytoplasmic tail or with the {alpha}2{beta}1 complex. In order to identify novel binding partners of a {alpha}2{beta}1cytoplasmic domain complex, we have generated recombinant GST-fusion proteins, incorporating the leucine zipper heterodimerization cassettes of Jun and Fos. To ascertain proper functionality of the recombinant proteins, interaction with natural binding partners was tested. GST-{alpha}2 and GST-Jun {alpha}2 bound His-tagged calreticulin while GST-{beta}1 and GST-Fos {beta}1 proteins bound talin. In screening assays for novel binding partners, the immobilized GST-Jun {alpha}2/GST-Fos {beta}1 heterodimeric complex, but not the single subunits, interacted specifically with endothelial cell-derived vimentin. Vimentin, an abundant intermediate filament protein, has previously been shown to co-localize with {alpha}v{beta}3-positive focal contacts. Here, we provide evidence that this interaction also occurs with {alpha}2{beta}1-enriched focal adhesions and we further show that this association is lost after prolonged adhesion of endothelial cells to collagen.

  19. Chemoselective nucleophilic fluorination induced by selective solvation of the SN2 transition state.

    PubMed

    Pliego, Josefredo R; Piló-Veloso, Dorila

    2007-02-22

    Reaction of the fluoride ion with secondary alkyl halides leads to 90% of elimination reaction and only 10% of nucleophilic substitution in dipolar aprotic solvents. Adding water to the organic phase, the SN2 yield increases in the cost of decreased reactivity. Using ab initio calculations, we have shown that it is possible to increase the reaction rate and the selectivity toward the SN2 process through supramolecular organocatalysis. The catalytic concept is based on selective solvation of the transition state through two hydrogen bonds provided by the 1,4-benzenedimethanol. The two hydrogen bonds between the catalyst and the SN2 transition state favor this pathway while just one strong hydrogen bond between the catalyst and the fluoride ion leads to a lower stabilization of the nucleophile, resulting in a higher reaction rate. Our calculations predict that the substitution product increases to 40% yield because of the selective catalysis provided by the 1,4-benzenedimethanol.

  20. Specific anion binding to sulfobetaine micelles and kinetics of nucleophilic reactions.

    PubMed

    Marte, Luisa; Beber, Rosane C; Farrukh, M Akhyar; Micke, Gustavo A; Costa, Ana C O; Gillitt, Nicholas D; Bunton, Clifford A; Di Profio, Pietro; Savelli, Gianfranco; Nome, Faruk

    2007-08-23

    With fully micellar bound substrates reactions of OH- with benzoic anhydride, Bz(2)O, and of Br- with methyl naphthalene-2-sulfonate, MeONs, in micellized sulfobetaines are strongly inhibited by NaClO4 which displaces the nucleophilic anions from the micellar pseudophases. Micellar incorporations of ClO4- and Br- are estimated with an ion-selective electrode and by electrophoresis, and partitioning of Br- between water and micelles is related to changes in NMR spectral (79)Br- line widths. Extents of inhibition by ClO4- of these nucleophilic reactions in the micellar pseudophase are related to quantitative displacement of the reactive anions from the micelles by ClO4-. The kinetic data are correlated with physical evidence on the strong interactions between sulfobetaines and ClO4-, which turn sulfobetaine micelles anionic and effectively provoke displacement of OH- and Br-.

  1. Biological matching of chemical reactivity: pairing indole nucleophilicity with electrophilic isoprenoids.

    PubMed

    Walsh, Christopher T

    2014-12-19

    The indole side chain of tryptophan has latent nucleophilic reactivity at both N1 and all six (nonbridgehead) carbons, which is not generally manifested in post-translational reactions of proteins. On the other hand, all seven positions can be prenylated by the primary metabolite Δ(2)-isopentenyl diphosphate by dimethyallyl transferase (DMATs) family members as initial steps in biosynthetic pathways to bioactive fungal alkaloids including ergots and tremorgens. These are formulated as regioselective capture of isopentenyl allylic cationic transition states by the indole side chain as a nucleophile. The balance of regiospecificity and promiscuity among these indole prenyltransferases continues to raise questions about possible Cope and azaCope rearrangements of nascent products. In addition to these two electron reaction manifolds, there is evidence for one electron reaction manifolds in indole ring biosynthetic functionalization.

  2. Chemoselective Boron-Catalyzed Nucleophilic Activation of Carboxylic Acids for Mannich-Type Reactions.

    PubMed

    Morita, Yuya; Yamamoto, Tomohiro; Nagai, Hideoki; Shimizu, Yohei; Kanai, Motomu

    2015-06-10

    The carboxyl group (COOH) is an omnipresent functional group in organic molecules, and its direct catalytic activation represents an attractive synthetic method. Herein, we describe the first example of a direct catalytic nucleophilic activation of carboxylic acids with BH3·SMe2, after which the acids are able to act as carbon nucleophiles, i.e. enolates, in Mannich-type reactions. This reaction proceeds with a mild organic base (DBU) and exhibits high levels of functional group tolerance. The boron catalyst is highly chemoselective toward the COOH group, even in the presence of other carbonyl moieties, such as amides, esters, or ketones. Furthermore, this catalytic method can be extended to highly enantioselective Mannich-type reactions by using a (R)-3,3'-I2-BINOL-substituted boron catalyst.

  3. Nucleophilic Additions to Coordinated 1,10-Phenanthroline: Intramolecular, Intermolecular, Reversible, and Irreversible.

    PubMed

    Arévalo, Rebeca; Menéndez, M Isabel; López, Ramón; Merino, Isabel; Riera, Lucía; Pérez, Julio

    2016-12-12

    KN(SiMe3 )2 reacts with [Re(CO)3 (phen)(PMe3 )]OTf via reversible addition to the phen ligand and irreversible deprotonation of the PMe3 ligand followed by intramolecular attack to phen by the deprotonated phosphane, whereas MeLi irreversibly adds to phen. The addition of MeLi has been shown to be intermolecular, unlike previously known nucleophilic additions to pyridines.

  4. Transition-Metal-Free Stereospecific Cross-Coupling with Alkenylboronic Acids as Nucleophiles.

    PubMed

    Li, Chengxi; Zhang, Yuanyuan; Sun, Qi; Gu, Tongnian; Peng, Henian; Tang, Wenjun

    2016-08-31

    We herein report a transition-metal-free cross-coupling between secondary alkyl halides/mesylates and aryl/alkenylboronic acid, providing expedited access to a series of nonchiral/chiral coupling products in moderate to good yields. Stereospecific SN2-type coupling is developed for the first time with alkenylboronic acids as pure nucleophiles, offering an attractive alternative to the stereospecific transition-metal-catalyzed C(sp(2))-C(sp(3)) cross-coupling.

  5. ortho-Lithium/magnesium carboxylate-driven aromatic nucleophilic substitution reactions on unprotected naphthoic acids.

    PubMed

    Aissaoui, Regadia; Nourry, Arnaud; Coquel, Ariane; Dao, Thi Thanh Hà; Derdour, Aicha; Helesbeux, Jean-Jacques; Duval, Olivier; Castanet, Anne-Sophie; Mortier, Jacques

    2012-01-06

    Substitution of an ortho-fluoro or methoxy group in 1- and 2-naphthoic acids furnishing substituted naphthoic acids occurs in good to excellent yields upon reaction with alkyl/vinyl/aryl organolithium and Grignard reagents, in the absence of a metal catalyst without the need to protect the carboxyl (CO(2)H) group. This novel nucleophilic aromatic substitution is presumed to proceed via a precoordination of the organometallic with the substrate, followed by an addition/elimination.

  6. Asymmetric catalysis for the construction of quaternary carbon centres: nucleophilic addition on ketones and ketimines.

    PubMed

    Riant, Olivier; Hannedouche, Jérôme

    2007-03-21

    There is a growing need in organic synthesis for efficient methodologies for the asymmetric synthesis of quaternary carbon centres. One of the most attractive and straightforward methods focuses on the use of asymmetric catalysis for the addition of various types of nucleophiles on prochiral ketones and ketimines. A view of the literature from this growing area of research will be presented in this review, with an emphasis on the pioneer works and milestones brought by the main players in this field.

  7. Novel nucleophiles enhance the human serum paraoxonase 1 (PON1)-mediated detoxication of organophosphates.

    PubMed

    Chambers, Janice E; Chambers, Howard W; Meek, Edward C; Funck, Kristen E; Bhavaraju, Manikanthan H; Gwaltney, Steven R; Pringle, Ronald B

    2015-01-01

    Paraoxonase 1 (PON1) is a calcium-dependent hydrolase associated with serum high-density lipoprotein particles. PON1 hydrolyzes some organophosphates (OPs), including some nerve agents, through nucleophilic attack of hydroxide ion (from water) in the active site. Most OPs are hydrolyzed inefficiently. This project seeks to identify nucleophiles that can enhance PON1-mediated OP degradation. A series of novel nucleophiles, substituted phenoxyalkyl pyridinium oximes, has been synthesized which enhance the degradation of surrogates of sarin (nitrophenyl isopropyl methylphosphonate; NIMP) and VX (nitrophenyl ethyl methylphosphonate; NEMP). Two types of in vitro assays have been conducted, a direct assay using millimolar concentrations of substrate with direct spectrophotometric quantitation of a hydrolysis product (4-nitrophenol) and an indirect assay using submicromolar concentrations of substrate with quantitation by the level of inhibition of an exogenous source of acetylcholinesterase from non-hydrolyzed substrate. Neither NIMP nor NEMP is hydrolyzed effectively by PON1 if one of these novel oximes is absent. However, in the presence of eight novel oximes, PON1-mediated degradation of both surrogates occurs. Computational modeling has created a model of PON1 embedded in phospholipid and has indicated general agreement of the binding enthalpies with the relative efficacy as PON1 enhancers. PON1 enhancement of degradation of OPs could be a unique and unprecedented mechanism of antidotal action.

  8. Detoxication of sulfur half-mustards by nucleophilic scavengers: robust activity of thiopurines

    PubMed Central

    Liu, Jinyun; Powell, K. Leslie; Thames, Howard D.; MacLeod, Michael C.

    2010-01-01

    Sulfur mustard (bis-(2-chloroethyl)sulfide) has been used in chemical warfare since World War I, and is well known as an acutely toxic vesicant. It has been implicated as a carcinogen after chronic low-level exposure, and is known to form inter-strand crosslinks in DNA. Sulfur and nitrogen mustards are currently of interest as potential chemical threat agents for terrorists due to ease of synthesis. Sulfur mustard and monofunctional analogs (half-mustards, 2-[chloroethyl] alkyl sulfides) react as electrophiles, damaging cellular macromolecules, and thus are potentially subject to scavenging by nucleophilic agents. We have determined rate constants for the reaction of four purine derivatives that contain nucleophilic thiol moieties with several sulfur-half-mustards. Three of these compounds, 2,6-dithiopurine, 2,6-dithiouric acid, and 9-methyl-6-mercaptopurine, exhibit facile reaction with the electrophilic mustard compounds. At near neutral pH, these thiopurines are much better nucleophilic scavengers of mustard electrophiles than other low molecular weight thiols such as N-acetyl cysteine and glutathione. Progress curves calculated by numerical integration techniques indicate that equimolar concentrations of thiopurine provide significant reductions in the overall exposure to the episulfonium ions, which are the major reactive, electrophiles produced when sulfur mustards are dissolved in aqueous solution. PMID:20050632

  9. Local Electron Attachment Energy and Its Use for Predicting Nucleophilic Reactions and Halogen Bonding.

    PubMed

    Brinck, Tore; Carlqvist, Peter; Stenlid, Joakim H

    2016-12-22

    A new local property, the local electron attachment energy [E(r)], is introduced and is demonstrated to be a useful guide to predict intermolecular interactions and chemical reactivity. The E(r) is analogous to the average local ionization energy but indicates susceptibility toward interactions with nucleophiles rather than electrophiles. The functional form E(r) is motivated based on Janak's theorem and the piecewise linear energy dependence of electron addition to atomic and molecular systems. Within the generalized Kohn-Sham method (GKS-DFT), only the virtual orbitals with negative eigenvalues contribute to E(r). In the present study, E(r) has been computed from orbitals obtained from GKS-DFT computations with a hybrid exchange-correlation functional. It is shown that E(r) computed on a molecular isodensity surface, ES(r), reflects the regioselectivity and relative reactivity for nucleophilic aromatic substitution, nucleophilic addition to activated double bonds, and formation of halogen bonds. Good to excellent correlations between experimental or theoretical measures of interaction strengths and minima in ES(r) (ES,min) are demonstrated.

  10. Detoxication of sulfur half-mustards by nucleophilic scavengers: robust activity of thiopurines.

    PubMed

    Liu, Jinyun; Powell, K Leslie; Thames, Howard D; MacLeod, Michael C

    2010-03-15

    Sulfur mustard (bis-(2-chloroethyl)sulfide) has been used in chemical warfare since World War I and is well known as an acutely toxic vesicant. It has been implicated as a carcinogen after chronic low-level exposure and is known to form interstrand cross-links in DNA. Sulfur and nitrogen mustards are currently of interest as potential chemical threat agents for terrorists because of ease of synthesis. Sulfur mustard and monofunctional analogues (half-mustards, 2-[chloroethyl] alkyl sulfides) react as electrophiles, damaging cellular macromolecules, and thus are potentially subject to scavenging by nucleophilic agents. We have determined rate constants for the reaction of four purine derivatives that contain nucleophilic thiol moieties with several sulfur-half-mustards. Three of these compounds, 2,6-dithiopurine, 2,6-dithiouric acid, and 9-methyl-6-mercaptopurine, exhibit facile reaction with the electrophilic mustard compounds. At near neutral pH, these thiopurines are much better nucleophilic scavengers of mustard electrophiles than other low molecular weight thiols such as N-acetyl cysteine and glutathione. Progress curves calculated by numerical integration techniques indicate that equimolar concentrations of thiopurine provide significant reductions in the overall exposure to the episulfonium ions, which are the major reactive, electrophiles produced when sulfur mustards are dissolved in aqueous solution.

  11. Reactivity of Aziridinomitosene Derivatives Related to FK317 in the Presence of Protic Nucleophiles

    PubMed Central

    Wiedner, Susan D.; Vedejs, Edwin

    2012-01-01

    The syntheses and reactivity of N-TBDPS and N-trityl protected derivatives of an aziridinomitosene corresponding to FK317 are described. New reactivity patterns were observed for these highly sensitive and functionally dense heterocycles under mild nucleophilic conditions approaching the threshold for degradation. Thus, the silyl or trityl protected aziridinomitosene reacted with Cs2CO3/CD3OD to give isomeric products where substitution occurred at C(10) and C(9a) (mitomycin numbering) providing a CD3 ether and a CD3 hemiaminal respectively. These findings show that heterolysis at C(10) is faster than at aziridine C(1), in contrast to the behavior of typical aziridinomitosenes in the mitomycin series. The labile N-TBDPS hemiaminal and the more stable N-trityl hemiaminal resemble the mitomycin K substitution pattern. A reagent consisting of CsF in CF3CH2OH/CH3CN desilylated a simple N-TBDPS aziridine, but caused nucleophilic cleavage at C(1) as well as C(10) without cleavage of the N-TBPDS group in the fully functionalized penultimate aziridinomitosene. The high reactivity of the C(10) carbamate with nucleophiles precludes the use of deprotection methodology that requires N-protonation for fully functionalized aziridinomitosenes in the FK317 series. PMID:22208619

  12. Gold-Catalyzed Reactions via Cyclopropyl Gold Carbene-like Intermediates.

    PubMed

    Dorel, Ruth; Echavarren, Antonio M

    2015-08-07

    Cycloisomerizations of 1,n-enynes catalyzed by gold(I) proceed via electrophilic species with a highly distorted cyclopropyl gold(I) carbene-like structure, which can react with different nucleophiles to form a wide variety of products by attack at the cyclopropane or the carbene carbons. Particularly important are reactions in which the gold(I) carbene reacts with alkenes to form cyclopropanes either intra- or intermolecularly. In the absence of nucleophiles, 1,n-enynes lead to a variety of cycloisomerized products including those resulting from skeletal rearrangements. Reactions proceeding through cyclopropyl gold(I) carbene-like intermediates are ideally suited for the bioinspired synthesis of terpenoid natural products by the selective activation of the alkyne in highly functionalized enynes or polyenynes.

  13. Gold-Catalyzed Reactions via Cyclopropyl Gold Carbene-like Intermediates

    PubMed Central

    2015-01-01

    Cycloisomerizations of 1,n-enynes catalyzed by gold(I) proceed via electrophilic species with a highly distorted cyclopropyl gold(I) carbene-like structure, which can react with different nucleophiles to form a wide variety of products by attack at the cyclopropane or the carbene carbons. Particularly important are reactions in which the gold(I) carbene reacts with alkenes to form cyclopropanes either intra- or intermolecularly. In the absence of nucleophiles, 1,n-enynes lead to a variety of cycloisomerized products including those resulting from skeletal rearrangements. Reactions proceeding through cyclopropyl gold(I) carbene-like intermediates are ideally suited for the bioinspired synthesis of terpenoid natural products by the selective activation of the alkyne in highly functionalized enynes or polyenynes. PMID:26061916

  14. 1,1,1-Trimethylhydrazinium iodide: A novel, highly reactive reagent for aromatic amination via vicarious nucleophilic substitution of hydrogen

    SciTech Connect

    Pagoria, P.F.; Mitchell, A.R.; Schmidt, R.D.

    1996-05-03

    1,1,1-Trimethylhydrazinium iodide, TMHI, has been shown to be a novel vicarious nucleophilic substitution aminating reagent. It can be used to obtain isomers not produced by reaction with other nucleophilic aminating reagents. It is easily prepared from 1,1-dimethylhydrazine, or directly from hydrazine. Further studies on the use of TMHI and related quaternary hydrazines as nucleophlic aminating reagents are in progress. 1 tab.

  15. Diastereocontrolled construction of pactamycin's complex ureido triol functional array.

    PubMed

    Malinowski, Justin T; McCarver, Stefan J; Johnson, Jeffrey S

    2012-06-01

    An advanced intermediate in a projected synthesis of pactamycin has been prepared. Early installation of the C1-dimethylurea functionality allows for its participation in a diastereoselective, chelation-controlled addition of organometal nucleophiles to the C5 prochiral ketone. Four of the molecule's six stereocenters are set with a ketone functional handle provided for subsequent manipulation.

  16. Complexity.

    PubMed

    Gómez-Hernández, J Jaime

    2006-01-01

    It is difficult to define complexity in modeling. Complexity is often associated with uncertainty since modeling uncertainty is an intrinsically difficult task. However, modeling uncertainty does not require, necessarily, complex models, in the sense of a model requiring an unmanageable number of degrees of freedom to characterize the aquifer. The relationship between complexity, uncertainty, heterogeneity, and stochastic modeling is not simple. Aquifer models should be able to quantify the uncertainty of their predictions, which can be done using stochastic models that produce heterogeneous realizations of aquifer parameters. This is the type of complexity addressed in this article.

  17. A mutation in the E2 subunit of the mitochondrial pyruvate dehydrogenase complex in Arabidopsis reduces plant organ size and enhances the accumulation of amino acids and intermediate products of the TCA cycle.

    PubMed

    Yu, Hailan; Du, Xiaoqiu; Zhang, Fengxia; Zhang, Fang; Hu, Yong; Liu, Shichang; Jiang, Xiangning; Wang, Guodong; Liu, Dong

    2012-08-01

    The mitochondrial pyruvate dehydrogenase complex (mtPDC) plays a pivotal role in controlling the entry of carbon into the tricarboxylic acid (TCA) cycle for energy production. This multi-enzyme complex consists of three components: E1, E2, and E3. In Arabidopsis, there are three genes, mtE2-1, mtE2-2, and mtE2-3, which encode the putative mtPDC E2 subunit but how each of them contributes to the total mtPDC activity remains unknown. In this work, we characterized an Arabidopsis mutant, m132, that has abnormal small organs. Molecular cloning indicated that the phenotype of m132 is caused by a mutation in the mtE2-1 gene, which results in a truncation of 109 amino acids at the C-terminus of the encoded protein. In m132, mtPDC activity is only 30% of the WT and ATP production is severely impaired. The mutation in the mtE2-1 gene also leads to the over-accumulation of most intermediate products of the TCA cycle and of all the amino acids for protein synthesis. Our results suggest that, among the three mtE2 genes, mtE2-1 is a major contributor to the function of Arabidopsis mtPDC and that the functional disruption of mtE2-1 profoundly affects plant growth and development, as well as its metabolism.

  18. 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 O2 , 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 O2 -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).

  19. Anionic polymerization of oxadiazole-containing 2-vinylpyridine by precisely tuning nucleophilicity and the polyelectrolyte characteristics of the resulting polymers

    DOE PAGES

    Goodwin, Andrew; Goodwin, Kimberly M.; Wang, Weiyu; ...

    2016-09-01

    Anionic polymerization is one of the most powerful techniques for preparation of well-defined polymers. However, this well-known and widely employed polymerization technique encounters major limitations for the polymerization of functional monomers containing heteroatoms. This work presents the anionic polymerization of 2-phenyl-5-(6-vinylpyridin-3-yl)-1,3,4-oxadiazole (VPyOzP), a heteroatom monomer that contains both oxadiazole and pyridine substituents within the same pendant group, using various initiating systems based on diphenylmethyl potassium (DPM-K) and triphenylmethyl potassium (TPM-K). Remarkably, well-defined poly(2-phenyl-5-(6-vinylpyridin-3-yl)-1,3,4-oxadiazole) (PVPyOzP) polymers having predicted molecular weights (MW) ranging from 2200 to 21 100 g/mol and polydispersity indices (PDI) ranging from 1.11 to 1.15 were prepared with TPM-K,more » without any additional additives, at –78 °C. The effect of temperature on the polymerization of PVPyOzP was also studied at –78, –45, 0, and 25 °C, and it was observed that increasing the polymerization temperature produced materials with unpredictable MW’s and broader molecular weight distributions. Furthermore, the nucleophilicity of PVPyOzP was investigated through copolymerization with methyl methacrylate and acrylonitrile, where only living poly(methyl methacrylate) (PMMA) prepared by DPM-K/VPPy and in the absence of additives such as lithium chloride (LiCl) and diethyl zinc (ZnEt2) could be used to produce the well-defined block copolymer of PMMA-b-PVPyOzP. It was also demonstrated by sequential monomer addition that the nucleophilicity of living PVPyOzP is located between that of living PMMA and polyacrylonitrile (PAN). Here, the pyridine moiety of the pendant group also allowed for quaternization and produced PQVPyOzP homopolymer using methyl iodide (CH3I) and bis(trifluoromethylsulfonyl)amide [Tf2N–]. The resulting charged polymer and counterion complexes were manipulated and investigated

  20. Anionic polymerization of oxadiazole-containing 2-vinylpyridine by precisely tuning nucleophilicity and the polyelectrolyte characteristics of the resulting polymers

    SciTech Connect

    Goodwin, Andrew; Goodwin, Kimberly M.; Wang, Weiyu; Yu, Yong -Guen; Lee, Jae -Suk; Mahurin, Shannon M.; Dai, Sheng; Mays, Jimmy W.; Kang, Nam -Goo

    2016-09-01

    Anionic polymerization is one of the most powerful techniques for preparation of well-defined polymers. However, this well-known and widely employed polymerization technique encounters major limitations for the polymerization of functional monomers containing heteroatoms. This work presents the anionic polymerization of 2-phenyl-5-(6-vinylpyridin-3-yl)-1,3,4-oxadiazole (VPyOzP), a heteroatom monomer that contains both oxadiazole and pyridine substituents within the same pendant group, using various initiating systems based on diphenylmethyl potassium (DPM-K) and triphenylmethyl potassium (TPM-K). Remarkably, well-defined poly(2-phenyl-5-(6-vinylpyridin-3-yl)-1,3,4-oxadiazole) (PVPyOzP) polymers having predicted molecular weights (MW) ranging from 2200 to 21 100 g/mol and polydispersity indices (PDI) ranging from 1.11 to 1.15 were prepared with TPM-K, without any additional additives, at –78 °C. The effect of temperature on the polymerization of PVPyOzP was also studied at –78, –45, 0, and 25 °C, and it was observed that increasing the polymerization temperature produced materials with unpredictable MW’s and broader molecular weight distributions. Furthermore, the nucleophilicity of PVPyOzP was investigated through copolymerization with methyl methacrylate and acrylonitrile, where only living poly(methyl methacrylate) (PMMA) prepared by DPM-K/VPPy and in the absence of additives such as lithium chloride (LiCl) and diethyl zinc (ZnEt2) could be used to produce the well-defined block copolymer of PMMA-b-PVPyOzP. It was also demonstrated by sequential monomer addition that the nucleophilicity of living PVPyOzP is located between that of living PMMA and polyacrylonitrile (PAN). Here, the pyridine moiety of the pendant group also allowed for quaternization and produced PQVPyOzP homopolymer using methyl iodide (CH3I) and bis(trifluoromethylsulfonyl)amide [Tf2N]. The resulting charged polymer and counterion complexes

  1. Nucleophilic reactions at a vinylic center. XVI. Investigation of the nucleophilic exchange of fluorine in. beta. -fluoroacrylonitriles by the MINDO/3 method

    SciTech Connect

    Shainyan, B.A.

    1986-01-10

    The potential energy surfaces of the reactions of F/sup -/ with cis- and trans-..beta..-fluoroacrylonitriles were calculated by the MINDO/3 method. It was shown that three reaction paths can be realized in the system, i.e., attack by the nucleophile at the ..beta..-carbon atom, the elimination of a proton from the ..cap alpha.. position, and the elimination of a proton from the ..beta.. position. All three reaction paths are exothermic in the gas phase, and the elimination of the proton from the ..cap alpha.. position is 70 kJ/mole more favorable than from the ..beta.. position. Allowance for the effect of the medium in terms of an unconcerted solvation model modes not lead to the appearance of an activation barrier, in contrast to the reactions of anions with ethylene.

  2. Stepwise Catalytic Mechanism via Short-Lived Intermediate Inferred from Combined QM/MM MERP and PES Calculations on Retaining Glycosyltransferase ppGalNAcT2

    PubMed Central

    Trnka, Tomáš; Kozmon, Stanislav; Tvaroška, Igor; Koča, Jaroslav

    2015-01-01

    The glycosylation of cell surface proteins plays a crucial role in a multitude of biological processes, such as cell adhesion and recognition. To understand the process of protein glycosylation, the reaction mechanisms of the participating enzymes need to be known. However, the reaction mechanism of retaining glycosyltransferases has not yet been sufficiently explained. Here we investigated the catalytic mechanism of human isoform 2 of the retaining glycosyltransferase polypeptide UDP-GalNAc transferase by coupling two different QM/MM-based approaches, namely a potential energy surface scan in two distance difference dimensions and a minimum energy reaction path optimisation using the Nudged Elastic Band method. Potential energy scan studies often suffer from inadequate sampling of reactive processes due to a predefined scan coordinate system. At the same time, path optimisation methods enable the sampling of a virtually unlimited number of dimensions, but their results cannot be unambiguously interpreted without knowledge of the potential energy surface. By combining these methods, we have been able to eliminate the most significant sources of potential errors inherent to each of these approaches. The structural model is based on the crystal structure of human isoform 2. In the QM/MM method, the QM region consists of 275 atoms, the remaining 5776 atoms were in the MM region. We found that ppGalNAcT2 catalyzes a same-face nucleophilic substitution with internal return (SNi). The optimized transition state for the reaction is 13.8 kcal/mol higher in energy than the reactant while the energy of the product complex is 6.7 kcal/mol lower. During the process of nucleophilic attack, a proton is synchronously transferred to the leaving phosphate. The presence of a short-lived metastable oxocarbenium intermediate is likely, as indicated by the reaction energy profiles obtained using high-level density functionals. PMID:25849117

  3. Enhanced nucleophilicity and depressed electrophilicity of peroxide by zinc(II), aluminum(III) and lanthanum(III) ions.

    PubMed

    Nishino, S; Kobayashi, T; Matsushima, H; Tokii, T; Nishida, Y

    2001-01-01

    The binuclear zinc(II) complex, [Zn2(HPTP)(CH3COO)]2+ was found highly active to cleave DNA (double-strand super-coiled DNA, pBR322 and phix174) in the presence of hydrogen peroxide. However, no TBARS (2-thiobarbituric acid reactive substance) formation was detected in a solution containing 2-deoxyribose (or 2'-deoxyguanosine, etc); where (HPTP) represents N,N,N'-N'-tetrakis(2-pyridylmethyl)-1,3-diamino-2-propanol. These facts imply that DNA cleavage reaction by the binuclear Zn(II)/H2O2 system should be due to a hydrolytic mechanism, which may be attributed to the enhanced nucleophilicity but depressed electrophilicity of the peroxide ion coordinated to the zinc(II) ion. DFT (density-functional theory) calculations on the peroxide adduct of monomeric zinc(II) have supported the above consideration. Similar DFT calculations on the peroxide adducts of the Al(III) and La(III) compounds have revealed that electrophilicity of the peroxide ion in these compounds is strongly reduced. This gives an important information to elucidate the fact that La3+ can enhance the growth of plants under certain conditions.

  4. Structural insights into catalysis and inhibition of O-acetylserine sulfhydrylase from Mycobacterium tuberculosis. Crystal structures of the enzyme alpha-aminoacrylate intermediate and an enzyme-inhibitor complex.

    PubMed

    Schnell, Robert; Oehlmann, Wulf; Singh, Mahavir; Schneider, Gunter

    2007-08-10

    Cysteine biosynthetic genes are up-regulated in the persistent phase of Mycobacterium tuberculosis, and the corresponding enzymes are therefore of interest as potential targets for novel antibacterial agents. cysK1 is one of these genes and has been annotated as coding for an O-acetylserine sulfhydrylase. Recombinant CysK1 is a pyridoxal phosphate (PLP)-dependent enzyme that catalyzes the conversion of O-acetylserine to cysteine. The crystal structure of the enzyme was determined to 1.8A resolution. CysK1 belongs to the family of fold type II PLP enzymes and is similar in structure to other O-acetylserine sulfhydrylases. We were able to trap the alpha-aminoacrylate reaction intermediate and determine its structure by cryocrystallography. Formation of the aminoacrylate complex is accompanied by a domain rotation resulting in active site closure. The aminoacrylate moiety is bound in the active site via the covalent linkage to the PLP cofactor and by hydrogen bonds of its carboxyl group to several enzyme residues. The catalytic lysine residue is positioned such that it can protonate the Calpha-carbon atom of the aminoacrylate only from the si-face, resulting in the formation of L-cysteine. CysK1 is competitively inhibited by a four-residue peptide derived from the C-terminal of serine acetyl transferase. The crystallographic analysis reveals that the peptide binds to the enzyme active site, suggesting that CysK1 forms an bi-enzyme complex with serine acetyl transferase, in a similar manner to other bacterial and plant O-acetylserine sulfhydrylases. The structure of the enzyme-peptide complex provides a framework for the design of strong binding inhibitors.

  5. Synthesis of Some "Cobaloxime" Derivatives: A Demonstration of "Umpolung" in the Reactivity of an Organometallic Complex

    NASA Astrophysics Data System (ADS)

    Jameson, Donald L.; Grzybowski, Joseph J.; Hammels, Deb E.; Castellano, Ronald K.; Hoke, Molly E.; Freed, Kimberly; Basquill, Sean; Mendel, Angela; Shoemaker, William J.

    1998-04-01

    This article describes a four-reaction sequence for the synthesis of two organometallic "cobaloxime" derivatives. The concept of "Umpolung" or reversal of reactivity is demonstrated in the preparation of complexes. The complex Co(dmgH)2(4-t-BuPy)Et is formed by the reaction of a cobalt (I) intermediate (cobalt in the role of nucleophile) with ethyl iodide. The complex Co(dmgH)2(4-t-BuPy)Ph is formed by the reaction of PhMgBr with a cobalt (III) intermediate (cobalt in the role of electrophile). All the products contain cobalt in the diamagnetic +3 oxidation state and are readily characterized by proton and carbon NMR. The four reaction sequence may be completed in two 4-hour lab periods. Cobaloximes are well known as model complexes for Vitamin B-12 and the experiment exposes students to aspects of classical coordination chemistry, organometallic chemistry and bioinorganic chemistry. The experiment also illustrates an important reactivity parallel between organic and organometallic chemistry.

  6. Nucleophilic displacement reactions of 5′-derivatised nucleosides in a vibration ball mill

    PubMed Central

    Eguaogie, Olga; Conlon, Patrick F; Ravalico, Francesco; Sweet, Jamie S T; Elder, Thomas B; Conway, Louis P; Lennon, Marc E; Hodgson, David R W

    2017-01-01

    Vibration ball-milling in a zirconia-lined vessel afforded clean and quantitative nucleophilic displacement reactions between 4-methoxybenzylthiolate salts and nucleoside 5′-halides or 5′-tosylates in five to 60 minutes. Under these conditions, commonly-encountered nucleoside cyclisation byproducts (especially of purine nucleosides) were not observed. Liquid-assisted grinding of the same 5'-iodide and 5′-tosylate substrates with potassium selenocyanate in the presence of DMF produced the corresponding 5′-selenocyanates in variable yields over the course of between one and eleven hours thereby avoiding the preparation and use of hygroscopic tetrabutylammonium salts. PMID:28179952

  7. Synthesis of Allenamides by Copper-Catalyzed Coupling of Propargylic Bromides and Nitrogen Nucleophiles.

    PubMed

    Demmer, Charles S; Benoit, Emeline; Evano, Gwilherm

    2016-03-18

    An efficient and general synthesis of allenamides derived from oxazolidinones and hydantoins is reported. Upon activation with a combination of a copper catalyst and a 2,2'-bipyridine derivative in the presence of an inorganic base, propargylic bromides were found to be suitable reagents for the direct allenylation of nitrogen nucleophiles by a formal copper-catalyzed S(N)2' reaction. Besides the availability of the starting materials, notable features of this route to allenamides are its mild reaction conditions, the reaction being performed at room temperature in most cases, and its applicability to the preparation of mono-, di-, as well as trisubstituted allenamides.

  8. Highly efficient "on water" catalyst-free nucleophilic addition reactions using difluoroenoxysilanes: dramatic fluorine effects.

    PubMed

    Yu, Jin-Sheng; Liu, Yun-Lin; Tang, Jing; Wang, Xin; Zhou, Jian

    2014-09-01

    A remarkable fluorine effect on "on water" reactions is reported. The CF⋅⋅⋅HO interactions between suitably fluorinated nucleophiles and the hydrogen-bond network at the phase boundary of oil droplets enable the formation of a unique microstructure to facilitate on water catalyst-free reactions, which are difficult to realize using nonfluorinated substrates. Accordingly, a highly efficient on water, catalyst-free reaction of difluoroenoxysilanes with aldehydes, activated ketones, and isatylidene malononitriles was developed, thus leading to the highly efficient synthesis of a variety of α,α-difluoro-β-hydroxy ketones and quaternary oxindoles.

  9. Molecular structure of a barley alpha-amylase-inhibitor complex: implications for starch binding and catalysis.

    PubMed

    Kadziola, A; Søgaard, M; Svensson, B; Haser, R

    1998-04-24

    alpha-Amylases are widely occurring, multidomain proteins with a catalytic (beta/alpha)8-barrel. In barley alpha-amylase, insight into the catalytic mechanism is gained from the X-ray crystal structure of its molecular complex with acarbose, a pseudotetrasaccharide that acts like a transition-state analogue and which is shown to bind at two specific regions of the enzyme. The structure of the complex has been refined to an R-factor of 15.1% for all observations with Fo>sigma(Fo) between 10 and 2.8 A resolution. A difference Fourier map produced after refinement of the native structure against the data of the acarbose complex clearly revealed density corresponding to two oligosaccharide-binding sites. One of these is defined as the surface-located starch granule-binding site characteristic of cereal alpha-amylases. It involves stacking of two acarbose rings on Trp276 and Trp277. The other binding region is the active site covering subsites -1, +1 and +2. Here, Glu204 is positioned to act in general acid/base catalysis protonating the glucosidic oxygen atom assisted by Asp289. A water molecule that bridges Glu204 and Asp289 is found at the entrance cavity containing a total of five water molecules. This water molecule is proposed to reprotonate Glu204 and supply the hydroxyl ion for nucleophilic attack on the glucosyl C1 atom. Asp 179 acts as the nucleophile that can bind covalently to the substrate intermediate after bond cleavage. The present complex structure together with the conservation of active-site residues among alpha-amylases and related enzymes, are consistent with a common catalytic mechanism for this class of retaining carbohydrases.

  10. Trapping and characterization of covalent intermediates of mutant retaining glycosyltransferases.

    PubMed

    Soya, Naoto; Fang, Ying; Palcic, Monica M; Klassen, John S

    2011-05-01

    The enzymatic mechanism by which retaining glycosyltransferases (GTs) transfer monosaccharides with net retention of the anomeric configuration has, so far, resisted elucidation. Here, direct detection of covalent glycosyl-enzyme intermediates for mutants of two model retaining GTs, the human blood group synthesizing α-(1 → 3)-N-acetylgalactosaminyltransferase (GTA) and α-(1 → 3)-galactosyltransferase (GTB) mutants, by mass spectrometry (MS) is reported. Incubation of mutants of GTA or GTB, in which the putative catalytic nucleophile Glu(303) was replaced with Cys (i.e. GTA(E303C) and GTB(E303C)), with their respective donor substrate results in a covalent intermediate. Tandem MS analysis using collision-induced dissociation confirmed Cys(303) as the site of glycosylation. Exposure of the glycosyl-enzyme intermediates to a disaccharide acceptor results in the formation of the corresponding enzymatic trisaccharide products. These findings suggest that the GTA(E303C) and GTB(E303C) mutants may operate by a double-displacement mechanism.

  11. Synthesis, Structure, and Reactivity of Anionic sp(2) -sp(3) Diboron Compounds: Readily Accessible Boryl Nucleophiles.

    PubMed

    Pietsch, Sabrina; Neeve, Emily C; Apperley, David C; Bertermann, Rüdiger; Mo, Fanyang; Qiu, Di; Cheung, Man Sing; Dang, Li; Wang, Jianbo; Radius, Udo; Lin, Zhenyang; Kleeberg, Christian; Marder, Todd B

    2015-05-04

    Lewis base adducts of tetra-alkoxy diboron compounds, in particular bis(pinacolato)diboron (B2 pin2 ), have been proposed as the active source of nucleophilic boryl species in metal-free borylation reactions. We report the isolation and detailed structural characterization (by solid-state and solution NMR spectroscopy and X-ray crystallography) of a series of anionic adducts of B2 pin2 with hard Lewis bases, such as alkoxides and fluoride. The study was extended to alternative Lewis bases, such as acetate, and other diboron reagents. The B(sp(2) )-B(sp(3) ) adducts exhibit two distinct boron environments in the solid-state and solution NMR spectra, except for [(4-tBuC6 H4 O)B2 pin2 ](-) , which shows rapid site exchange in solution. DFT calculations were performed to analyze the stability of the adducts with respect to dissociation. Stoichiometric reaction of the isolated adducts with two representative series of organic electrophiles-namely, aryl halides and diazonium salts-demonstrate the relative reactivities of the anionic diboron compounds as nucleophilic boryl anion sources.

  12. Covalent binding of aniline to humic substances. 2. 15N NMR studies of nucleophilic addition reactions

    USGS Publications Warehouse

    Thorn, K.A.; Pettigrew, P.J.; Goldenberg, W.S.; Weber, E.J.

    1996-01-01

    Aromatic amines are known to undergo covalent binding with humic substances in the environment. Although previous studies have examined reaction conditions and proposed mechanisms, there has been no direct spectroscopic evidence for the covalent binding of the amines to the functional groups in humic substances. In order to further elucidate the reaction mechanisms, the Suwannee River and IHSS soil fulvic and humic acids were reacted with 15N-labeled aniline at pH 6 and analyzed using 15N NMR spectrometry. Aniline underwent nucleophilic addition reactions with the quinone and other carbonyl groups in the samples and became incorporated in the form of anilinohydroquinone, anilinoquinone, anilide, imine, and heterocyclic nitrogen, the latter comprising 50% or more of the bound amine. The anilide and anilinohydroquinone nitrogens were determined to be susceptible to chemical exchange by ammonia. In the case of Suwannee River fulvic acid, reaction under anoxic conditions and pretreatment with sodium borohydride or hydroxylamine prior to reaction under oxic conditions resulted in a decrease in the proportion of anilinohydroquinone nitrogen incorporated. The relative decrease in the incorporation of anilinohydroquinone nitrogen with respect to anilinoquinone nitrogen under anoxic conditions suggested that inter- or intramolecular redox reactions accompanied the nucleophilic addition reactions.

  13. The second-shell metal ligands of human arginase affect coordination of the nucleophile and substrate.

    PubMed

    Stone, Everett M; Chantranupong, Lynne; Georgiou, George

    2010-12-14

    The active sites of eukaryotic arginase enzymes are strictly conserved, especially the first- and second-shell ligands that coordinate the two divalent metal cations that generate a hydroxide molecule for nucleophilic attack on the guanidinium carbon of l-arginine and the subsequent production of urea and l-ornithine. Here by using comprehensive pairwise saturation mutagenesis of the first- and second-shell metal ligands in human arginase I, we demonstrate that several metal binding ligands are actually quite tolerant to amino acid substitutions. Of >2800 double mutants of first- and second-shell residues analyzed, we found more than 80 unique amino acid substitutions, of which four were in first-shell residues. Remarkably, certain second-shell mutations could modulate the binding of both the nucleophilic water/hydroxide molecule and substrate or product ligands, resulting in activity greater than that of the wild-type enzyme. The data presented here constitute the first comprehensive saturation mutagenesis analysis of a metallohydrolase active site and reveal that the strict conservation of the second-shell metal binding residues in eukaryotic arginases does not reflect kinetic optimization of the enzyme during the course of evolution.

  14. Surprising unreactivity of cholesterol-5,6-epoxides towards nucleophiles[S

    PubMed Central

    Paillasse, Michael R.; Saffon, Nathalie; Gornitzka, Heinz; Silvente-Poirot, Sandrine; Poirot, Marc; de Medina, Philippe

    2012-01-01

    We recently established that drugs used for the treatment and the prophylaxis of breast cancers, such as tamoxifen, were potent inhibitors of cholesterol-5,6-epoxide hydrolase (ChEH), which led to the accumulation of 5,6α-epoxy-cholesterol (5,6α-EC) and 5,6β-epoxy-cholesterol (5,6β-EC). This could be considered a paradox because epoxides are known as alkylating agents with putative carcinogenic properties. We report here that, as opposed to the carcinogen styrene-oxide, neither of the ECs reacted spontaneously with nucleophiles. Under catalytic conditions, 5,6β-EC remains unreactive whereas 5,6α-EC gives cholestan-3β,5α-diol-6β-substituted compounds. These data showed that 5,6-ECs are stable epoxides and unreactive toward nucleophiles in the absence of a catalyst, which contrasts with the well-known reactivity of aromatic and aliphatic epoxides. These data rule out 5,6-EC acting as spontaneous alkylating agents. In addition, these data support the existence of a stereoselective metabolism of 5,6α-EC. PMID:22285872

  15. Reduced Reactivity of Amines against Nucleophilic Substitution via Reversible Reaction with Carbon Dioxide.

    PubMed

    Mohammed, Fiaz S; Kitchens, Christopher L

    2015-12-23

    The reversible reaction of carbon dioxide (CO₂) with primary amines to form alkyl-ammonium carbamates is demonstrated in this work to reduce amine reactivity against nucleophilic substitution reactions with benzophenone and phenyl isocyanate. The reversible formation of carbamates has been recently exploited for a number of unique applications including the formation of reversible ionic liquids and surfactants. For these applications, reduced reactivity of the carbamate is imperative, particularly for applications in reactions and separations. In this work, carbamate formation resulted in a 67% reduction in yield for urea synthesis and 55% reduction for imine synthesis. Furthermore, the amine reactivity can be recovered upon reversal of the carbamate reaction, demonstrating reversibility. The strong nucleophilic properties of amines often require protection/de-protection schemes during bi-functional coupling reactions. This typically requires three separate reaction steps to achieve a single transformation, which is the motivation behind Green Chemistry Principle #8: Reduce Derivatives. Based upon the reduced reactivity, there is potential to employ the reversible carbamate reaction as an alternative method for amine protection in the presence of competing reactions. For the context of this work, CO₂ is envisioned as a green protecting agent to suppress formation of n-phenyl benzophenoneimine and various n-phenyl-n-alky ureas.

  16. A Trapped Covalent Intermediate of a Glycoside Hydrolase on the Pathway to Transglycosylation. Insights from Experiments and Quantum Mechanics/Molecular Mechanics Simulations.

    PubMed

    Raich, Lluís; Borodkin, Vladimir; Fang, Wenxia; Castro-López, Jorge; van Aalten, Daan M F; Hurtado-Guerrero, Ramón; Rovira, Carme

    2016-03-16

    The conversion of glycoside hydrolases (GHs) into transglycosylases (TGs), i.e., from enzymes that hydrolyze carbohydrates to enzymes that synthesize them, represents a promising solution for the large-scale synthesis of complex carbohydrates for biotechnological purposes. However, the lack of knowledge about the molecular details of transglycosylation hampers the rational design of TGs. Here we present the first crystallographic structure of a natural glycosyl-enzyme intermediate (GEI) of Saccharomyces cerevisiae Gas2 in complex with an acceptor substrate and demonstrate, by means of quantum mechanics/molecular mechanics metadynamics simulations, that it is tuned for transglycosylation (ΔG(⧧) = 12 kcal/mol). The 2-OH···nucleophile interaction is found to be essential for catalysis: its removal raises the free energy barrier significantly (11 and 16 kcal/mol for glycosylation and transglycosylation, respectively) and alters the conformational itinerary of the substrate (from (4)C1 → [(4)E](⧧) → (1,4)B/(4)E to (4)C1 → [(4)H3](⧧) → (4)C1). Our results suggest that changes in the interactions involving the 2-position could have an impact on the transglycosylation activity of several GHs.

  17. Identification of the nucleophile catalytic residue of GH51 α-l-arabinofuranosidase from Pleurotus ostreatus

    SciTech Connect

    Amore, Antonella; Iadonisi, Alfonso; Vincent, Florence; Faraco, Vincenza

    2015-12-21

    In this paper, the recombinant α-l-arabinofuranosidase from the fungus Pleurotus ostreatus (rPoAbf) was subjected to site-directed mutagenesis in order to identify the catalytic nucleophile residue. Based on bioinformatics and homology modelling analyses, E449 was revealed to be the potential nucleophilic residue. Thus, the mutant E449G of PoAbf was recombinantly expressed in Pichia pastoris and its recombinant expression level and reactivity were investigated in comparison to the wild-type. The design of a suitable set of hydrolysis experiments in the presence or absence of alcoholic arabinosyl acceptors and/or formate salts allowed to unambiguously identify the residue E449 as the nucleophile residue involved in the retaining mechanism of this GH51 arabinofuranosidase. 1H NMR analysis was applied for the identification of the products and the assignement of their anomeric configuration.

  18. MATERIALS FOR INTERMEDIATE TELUGU.

    ERIC Educational Resources Information Center

    KELLEY, GERALD B.

    ONE OF THE FOUR DRAVIDIAN LANGUAGES RECOGNIZED BY THE INDIAN CONSTITUTION OF 1950 AS OFFICIAL LANGUAGES OF THE COUNTRY, TELUGU IS SPOKEN BY 42 MILLION PEOPLE IN ANDHRA PRADESH. THESE INSTRUCTIONAL MATERIALS ARE DESIGNED FOR THE INTERMEDIATE STUDENT OF TELUGU AND ARE DIVIDED INTO NEWSPAPER READINGS AND DIALOGUES OF EVERYDAY CONVERSATION. SUBJECTS…

  19. Intermediate Pashto. Textbook.

    ERIC Educational Resources Information Center

    Tegey, Habibullah; Robson, Barbara

    The textbook for intermediate level Pashto instruction consists of 14 units (15-28) on a variety of cultural topics and linguistic structures. Cultural topics include engagement and marriage, children's education, agriculture and related subjects, the family, Pashtun history, genealogies of major Pashtun tribes, the Pashtun code of behavior,…

  20. Sara Intermediate Course.

    ERIC Educational Resources Information Center

    Thayer, James E.; Maraby, Julien

    This volume consists of an intermediate course in Sara, a language of the Chad Republic of Africa. It is designed for native speakers of English and includes forty reading selections in Sara and an English translation of each selection. The readings are followed by a corresponding set of dialogues in Sara, accompanied by an English translation.…

  1. SPACE: Intermediate Level Modules.

    ERIC Educational Resources Information Center

    Indiana State Dept. of Education, Indianapolis. Center for School Improvement and Performance.

    These modules were developed to assist teachers at the intermediate level to move away from extensive skill practice and toward more meaningful interdisciplinary learning. This packet, to be used by teachers in the summer Extended Learning Program, provides detailed thematic lesson plans matched to the Indiana Curriculum Proficiency Guide. The…

  2. Hispanic American Heritage, Intermediate.

    ERIC Educational Resources Information Center

    Shepherd, Mike

    This resource book features the cultural heritage of Hispanics living within the United States and includes ideas, materials, and activities to be used with students in the intermediate grades and middle school. This book explores the definition of the term "Hispanic Americans" and suggests a multilayered population with a variety of cultural…

  3. Density functional theory studies on the mechanism of the reduction of CO2 to CO catalyzed by copper(I) boryl complexes.

    PubMed

    Zhao, Haitao; Lin, Zhenyang; Marder, Todd B

    2006-12-13

    The detailed reaction mechanism for the reduction of CO2 to CO catalyzed by (NHC)Cu(boryl) complexes (NHC = N-heterocyclic carbene) was studied with the aid of DFT by calculating the relevant intermediates and transition state structures. Our DFT calculations show that the reaction occurs through CO2 insertion into the Cu-B bond to give a Cu-OC(=O)-boryl species (i.e., containing Cu-O and C-B bonds), and subsequent boryl migration from C to O, followed by alpha-bond metathesis between pinB-Bpin (B2pin2, pin = pinacolate = OCMe2CMe2O) and (NHC)Cu(OBpin). The overall reaction is exergonic by 38.0 kcal/mol. It is the nucleophilicity of the Cu-B bond, a function of the very strong alpha-donor properties of the boryl ligand, rather than the oxophilicity of boron, which determines the direction of the CO2 insertion process. The boryl migration from C to O, which releases the product CO, is the rate-determining step and involves the "vacant" orbital orbital on boron. The (NHC)Cu(boryl) complexes show unique activity in the catalytic process. For the analogous (NHC)Cu(alkyl) complexes, the CO2 insertion into the Cu-C bond giving a copper acetate intermediate occurs with a readily achievable barrier. However, the elimination of CO from the acetate intermediate through a methyl migration from C to O is energetically inaccessible.

  4. Acid catalyzed alcoholysis of sulfinamides: unusual stereochemistry, kinetics and a question of mechanism involving sulfurane intermediates and their pseudorotation.

    PubMed

    Bujnicki, Bogdan; Drabowicz, Józef; Mikołajczyk, Marian

    2015-02-11

    The synthesis of optically active sulfinic acid esters has been accomplished by the acid catalyzed alcoholysis of optically active sulfinamides. Sulfinates are formed in this reaction with a full or predominant inversion of configuration at chiral sulfur or with predominant retention of configuration. The steric course of the reaction depends mainly on the size of the dialkylamido group in the sulfinamides and of the alcohols used as nucleophilic reagents. It has been found that bulky reaction components preferentially form sulfinates with retention of configuration. It has been demonstrated that the stereochemical outcome of the reaction can be changed from inversion to retention and vice versa by adding inorganic salts to the acidic reaction medium. The unusual stereochemistry of this typical bimolecular nucleophilic substitution reaction, as confirmed by kinetic measurements, has been rationalized in terms of the addition-elimination mechanism, A-E, involving sulfuranes as intermediates which undergo pseudorotations.

  5. Comprehensive theoretical studies on the gas phase SN2 reactions of anionic nucleophiles toward chloroamine and N-chlorodimethylamine with inversion and retention mechanisms.

    PubMed

    Ren, Yi; Geng, Song; Wei, Xi-Guang; Wong, Ning-Bew; Li, Wai-Kee

    2011-12-01

    The anionic S(N)2 reactions at neutral nitrogen, Nu(-) + NR(2)Cl → NR(2)Nu + Cl(-) (R = H, Me; Nu = F, Cl, Br, OH, SH, SeH, NH(2), PH(2), AsH(2)) have been systematically studied computationally at the modified G2(+) level. Two reaction mechanisms, inversion and retention of configuration, have been investigated. The main purposes of this work are to explore the reactivity trend of anions toward NR(2)Cl (R = H, Me), the steric effect on the potential energy surfaces, and the leaving ability of the anion in S(N)2@N reactions. Our calculations indicate that the complexation energies are determined by the gas basicity (GB) of the nucleophile and the electronegativity (EN) of the attacking atom, and the overall reaction barrier in the inversion pathway is basically controlled by the GB value of the nucleophile. The retention pathway in the reactions of NR(2)Cl with Nu(-) (Nu = F, Cl, Br, OH, SH, SeH) is energetically unfavorable due to the barriers being larger than those in the inversion pathway by more than 120 kJ mol(-1). Activation strain model analyses show that a higher deformation energy and a weaker interaction between deformed reactants lead to higher overall barriers in the reactions of NMe(2)Cl than those in the reactions of NH(2)Cl. Our studies on the reverse process of the title reactions suggest that the leaving ability of the anion in the gas phase anionic S(N)2@N reactions is mainly determined by the strength of the N-LG bond, which is related to the negative hyperconjugation inherent in NR(2)Nu (R = H, Me; Nu = HO, HS, HSe, NH(2), PH(2), AsH(2)).

  6. The Intermediate Neutrino Program

    SciTech Connect

    Adams, C.; et al.

    2015-03-23

    The US neutrino community gathered at the Workshop on the Intermediate Neutrino Program (WINP) at Brookhaven National Laboratory February 4-6, 2015 to explore opportunities in neutrino physics over the next five to ten years. Scientists from particle, astroparticle and nuclear physics participated in the workshop. The workshop examined promising opportunities for neutrino physics in the intermediate term, including possible new small to mid-scale experiments, US contributions to large experiments, upgrades to existing experiments, R&D plans and theory. The workshop was organized into two sets of parallel working group sessions, divided by physics topics and technology. Physics working groups covered topics on Sterile Neutrinos, Neutrino Mixing, Neutrino Interactions, Neutrino Properties and Astrophysical Neutrinos. Technology sessions were organized into Theory, Short-Baseline Accelerator Neutrinos, Reactor Neutrinos, Detector R&D and Source, Cyclotron and Meson Decay at Rest sessions.This report summarizes discussion and conclusions from the workshop.

  7. Intermediate water recovery system

    NASA Technical Reports Server (NTRS)

    Deckman, G.; Anderson, A. R. (Editor)

    1973-01-01

    A water recovery system for collecting, storing, and processing urine, wash water, and humidity condensates from a crew of three aboard a spacecraft is described. The results of a 30-day test performed on a breadboard system are presented. The intermediate water recovery system produced clear, sterile, water with a 96.4 percent recovery rate from the processed urine. Recommendations for improving the system are included.

  8. Unexpected Behavior of the Heaviest Halogen Astatine in the Nucleophilic Substitution of Aryliodonium Salts.

    PubMed

    Guérard, François; Lee, Yong-Sok; Baidoo, Kwamena; Gestin, Jean-François; Brechbiel, Martin W

    2016-08-22

    Aryliodonium salts have become precursors of choice for the synthesis of (18) F-labeled tracers for nuclear imaging. However, little is known on the reactivity of these compounds with heavy halides, that is, radioiodide and astatide, at the radiotracer scale. In the first comparative study of radiohalogenation of aryliodonium salts with (125) I(-) and (211) At(-) , initial experiments on a model compound highlight the higher reactivity of astatide compared to iodide, which could not be anticipated from the trends previously observed within the halogen series. Kinetic studies indicate a significant difference in activation energy (Ea =23.5 and 17.1 kcal mol(-1) with (125) I(-) and (211) At(-) , respectively). Quantum chemical calculations suggest that astatination occurs via the monomeric form of an iodonium complex whereas iodination occurs via a heterodimeric iodonium intermediate. The good to excellent regioselectivity of halogenation and high yields achieved with diversely substituted aryliodonium salts indicate that this class of compounds is a promising alternative to the stannane chemistry currently used for heavy radiohalogen labeling of tracers in nuclear medicine.

  9. Terminating Catalytic Asymmetric Heck Cyclizations by Stereoselective Intramolecular Capture of η3-Allylpalladium Intermediates: Total Synthesis of (−)-Spirotryprostatin B and Three Stereoisomers

    PubMed Central

    Overman, Larry E.; Rosen, Mark D.

    2010-01-01

    A catalytic intramolecular Heck reaction, followed by capture of the resulting η3-allylpalladium intermediate by a tethered diketopiperazine, is the central step in a concise synthetic route to (−)-spirotryprostatin B and three stereoisomers. This study demonstrates that an acyclic, chiral η3-allylpalladium fragment generated in a catalytic asymmetric Heck cyclization can be trapped by even a weakly nucleophilic diketopiperazine more rapidly than it undergoes diastereomeric equilibration. PMID:20725641

  10. Conversion of the rocket propellant UDMH to a reagent useful in vicarious nucleophilic substitution reactions

    SciTech Connect

    Mitchell, A.R.; Pagoria, P.F.; Schmidt, R.D.

    1995-11-10

    The objective of our program is to develop novel, innovative solutions for the disposal of surplus energetic materials resulting from the demilitarization of conventional and nuclear munitions. In this report we describe the use of surplus propellant (UDMH) and explosives (TNT, Explosive D) as chemical precursors for higher value products. The conversion of UDMH to 1,1,1-trimethylhydrazinium iodide (TMHI) provides a new aminating reagent for use in Vicarious Nucleophilic Substitution (VNS) reactions. When TMHI is reacted with various nitroarenes the amino functionality is introduced in good to excellent yields. Thus, 2,4,6-trinitroaniline (picramide) reacts with TMHI to give 1,3,5-triamino-2,4,6-trinitroaniline (TATB) while 2,4,6-trinitrotoluene (TNT) reacts with TMHI to give 3,5-diamino-2,4,6-trinitrotoluene (DATNT). The advantages, scope and limitations of the VNS approach and the use of TMHI are discussed.

  11. Taming of fluoroform: direct nucleophilic trifluoromethylation of Si, B, S, and C centers.

    PubMed

    Prakash, G K Surya; Jog, Parag V; Batamack, Patrice T D; Olah, George A

    2012-12-07

    Fluoroform (CF(3)H), a large-volume by-product of the manufacture of Teflon, refrigerants, polyvinylidene fluoride (PVDF), fire-extinguishing agents, and foams, is a potent and stable greenhouse gas that has found little practical use despite the growing importance of trifluoromethyl (CF3) functionality in more structurally elaborate pharmaceuticals, agrochemicals, and materials. Direct nucleophilic trifluoromethylation using CF(3)H has been a challenge. Here, we report on a direct trifluoromethylation protocol using close to stoichiometric amounts of CF(3)H in common organic solvents such as tetrahydrofuran (THF), diethyl ether, and toluene. The methodology is widely applicable to a variety of silicon, boron, and sulfur-based electrophiles, as well as carbon-based electrophiles.

  12. Modeling DNA Replication Intermediates

    SciTech Connect

    Broyde, S.; Roy, D.; Shapiro, R.

    1997-06-01

    While there is now available a great deal of information on double stranded DNA from X-ray crystallography, high resolution NMR and computer modeling, very little is known about structures that are representative of the DNA core of replication intermediates. DNA replication occurs at a single strand/double strand junction and bulged out intermediates near the junction can lead to frameshift mutations. The single stranded domains are particularly challenging. Our interest is focused on strategies for modeling the DNA of these types of replication intermediates. Modeling such structures presents special problems in addressing the multiple minimum problem and in treating the electrostatic component of the force field. We are testing a number of search strategies for locating low energy structures of these types and we are also investigating two different distance dependent dielectric functions in the coulombic term of the force field. We are studying both unmodified DNA and DNA damaged by aromatic amines, carcinogens present in the environment in tobacco smoke, barbecued meats and automobile exhaust. The nature of the structure adopted by the carcinogen modified DNA at the replication fork plays a key role in determining whether the carcinogen will cause a mutation during replication that can initiate the carcinogenic process. In the present work results are presented for unmodified DNA.

  13. Replacing Conventional Carbon Nucleophiles with Electrophiles: Nickel-Catalyzed Reductive Alkylation of Aryl Bromides and Chlorides

    PubMed Central

    2012-01-01

    A general method is presented for the synthesis of alkylated arenes by the chemoselective combination of two electrophilic carbons. Under the optimized conditions, a variety of aryl and vinyl bromides are reductively coupled with alkyl bromides in high yields. Under similar conditions, activated aryl chlorides can also be coupled with bromoalkanes. The protocols are highly functional-group tolerant (−OH, −NHTs, −OAc, −OTs, −OTf, −COMe, −NHBoc, −NHCbz, −CN, −SO2Me), and the reactions are assembled on the benchtop with no special precautions to exclude air or moisture. The reaction displays different chemoselectivity than conventional cross-coupling reactions, such as the Suzuki–Miyaura, Stille, and Hiyama–Denmark reactions. Substrates bearing both an electrophilic and nucleophilic carbon result in selective coupling at the electrophilic carbon (R–X) and no reaction at the nucleophilic carbon (R–[M]) for organoboron (−Bpin), organotin (−SnMe3), and organosilicon (−SiMe2OH) containing organic halides (X–R–[M]). A Hammett study showed a linear correlation of σ and σ(−) parameters with the relative rate of reaction of substituted aryl bromides with bromoalkanes. The small ρ values for these correlations (1.2–1.7) indicate that oxidative addition of the bromoarene is not the turnover-frequency determining step. The rate of reaction has a positive dependence on the concentration of alkyl bromide and catalyst, no dependence upon the amount of zinc (reducing agent), and an inverse dependence upon aryl halide concentration. These results and studies with an organic reductant (TDAE) argue against the intermediacy of organozinc reagents. PMID:22463689

  14. Reaction of Hydrogen Sulfide with Disulfide and Sulfenic Acid to Form the Strongly Nucleophilic Persulfide.

    PubMed

    Cuevasanta, Ernesto; Lange, Mike; Bonanata, Jenner; Coitiño, E Laura; Ferrer-Sueta, Gerardo; Filipovic, Milos R; Alvarez, Beatriz

    2015-11-06

    Hydrogen sulfide (H2S) is increasingly recognized to modulate physiological processes in mammals through mechanisms that are currently under scrutiny. H2S is not able to react with reduced thiols (RSH). However, H2S, more precisely HS(-), is able to react with oxidized thiol derivatives. We performed a systematic study of the reactivity of HS(-) toward symmetric low molecular weight disulfides (RSSR) and mixed albumin (HSA) disulfides. Correlations with thiol acidity and computational modeling showed that the reaction occurs through a concerted mechanism. Comparison with analogous reactions of thiolates indicated that the intrinsic reactivity of HS(-) is 1 order of magnitude lower than that of thiolates. In addition, H2S is able to react with sulfenic acids (RSOH). The rate constant of the reaction of H2S with the sulfenic acid formed in HSA was determined. Both reactions of H2S with disulfides and sulfenic acids yield persulfides (RSSH), recently identified post-translational modifications. The formation of this derivative in HSA was determined, and the rate constants of its reactions with a reporter disulfide and with peroxynitrite revealed that persulfides are better nucleophiles than thiols, which is consistent with the α effect. Experiments with cells in culture showed that treatment with hydrogen peroxide enhanced the formation of persulfides. Biological implications are discussed. Our results give light on the mechanisms of persulfide formation and provide quantitative evidence for the high nucleophilicity of these novel derivatives, setting the stage for understanding the contribution of the reactions of H2S with oxidized thiol derivatives to H2S effector processes.

  15. The development of catalytic nucleophilic additions of terminal alkynes in water.

    PubMed

    Li, Chao-Jun

    2010-04-20

    One of the major research endeavors in synthetic chemistry over the past two decades is the exploration of synthetic methods that work under ambient atmosphere with benign solvents, that maximize atom utilization, and that directly transform natural resources, such as renewable biomass, from their native states into useful chemical products, thus avoiding the need for protecting groups. The nucleophilic addition of terminal alkynes to various unsaturated electrophiles is a classical (textbook) reaction in organic chemistry, allowing the formation of a C-C bond while simultaneously introducing the alkyne functionality. A prerequisite of this classical reaction is the stoichiometric generation of highly reactive metal acetylides. Over the past decade, our laboratory and others have been exploring an alternative, the catalytic and direct nucleophilic addition of terminal alkynes to unsaturated electrophiles in water. We found that various terminal alkynes can react efficiently with a wide range of such electrophiles in water (or organic solvent) in the presence of simple and readily available catalysts, such as copper, silver, gold, iron, palladium, and others. In this Account, we describe the development of these synthetic methods, focusing primarily on results from our laboratory. Our studies include the following: (i) catalytic reaction of terminal alkynes with acid chloride, (ii) catalytic addition of terminal alkynes to aldehydes and ketones, (iii) catalytic addition of alkynes to C=N bonds, and (iv) catalytic conjugate additions. Most importantly, these reactions can tolerate various functional groups and, in many cases, perform better in water than in organic solvents, clearly defying classical reactivities predicated on the relative acidities of water, alcohols, and terminal alkynes. We further discuss multicomponent and enantioselective reactions that were developed. These methods provide an alternative to the traditional requirement of separate steps in

  16. Use of phosphoimidazolide-activated guanosine to investigate the nucleophilicity of spermine and spermidine

    NASA Technical Reports Server (NTRS)

    Kanavarioti, A.; Baird, E. E.; Smith, P. J.

    1995-01-01

    Guanosine 5'-phosphate 2-methylimidazolide (2-MeImpG), a labile phosphoimidazolide analog of guanosine triphosphate, was used to test the reactivity of the natural polyamines (PAs), spermine (spm) and spermidine (spd). The products are the guanosine 5'-phosphate-polyamine derivatives (PA-pG: spd-pG and spm-pG) which are quite stable in the range 4 < pH < 11. Our study is the first of which we are aware that reports on the nucleophilicity of these amines. The main findings are as follows. (i) HPLC analysis of the products indicates the formation of only two of the three possible spd products and only one of the two possible spm products. These results can be explained if only the primary amino groups of the two polyamines are reactive, while the secondary amino groups are rendered unreactive by a steric effect. The reactions of 2-MeImpG and other phosphoimidazolide derivatives of nucleosides (ImpNs) with primary and secondary monoamines support this interpretation (Kanavarioti et al. J. Org. Chem. 1995, 60, 632). (ii) The product ratio of the two spd-pG adducts derived from the primary amino groups varies between 2.40 and 0.71 in the range 6.1 < or equal to pH < or equal to 11.9. Such small variation in the product ratio can only be rationalized by the similar, but not identical, basicity of the two primary amino groups and provides strong support for a previously reported model for polyamine ionization (Onasch et. al. Biophys. Chem. 1984, 19, 245). (iii) On the basis of our kinetic determinations conditions at which the nucleophilicity of these amines is at a minimum and at which other interactions with ImpNs could be tested can be chosen.

  17. Steric, hydrogen-bonding and structural heterogeneity effects on the nucleophilic substitution of N-(p-fluorophenyldiphenylmethyl)-4-picolinium chloride in ionic liquids.

    PubMed

    Weber, Cameron C; Masters, Anthony F; Maschmeyer, Thomas

    2013-04-21

    The nucleophilic substitution of N-(p-fluorophenyldiphenylmethyl)-4-picolinium chloride was investigated using water and a range of alcoholic nucleophiles in ionic liquid solvents. The reactivity patterns across the nucleophiles examined could be attributed to steric factors, which mediated the relative nucleophilicities. Reducing the hydrogen-bond acidity of the ionic liquid cation was found to generally increase the rate of reaction, however, the magnitude of this rate effect could be influenced by the steric bulk of the nucleophile and the structural heterogeneity of the ionic liquid. Preferential solvation phenomena in binary mixtures of ionic liquids were examined and suggest that the mechanism behind the hydrogen-bond solvation phenomenon arises from direct cation-mediated, rather than indirect anion-mediated, effects.

  18. Photochemistry of RuII 4,4′-Bi-1,2,3-triazolyl (btz) Complexes: Crystallographic Characterization of the Photoreactive Ligand-Loss Intermediate trans-[Ru(bpy)(κ2-btz)(κ1-btz)(NCMe)]2+

    PubMed Central

    Welby, Christine E; Armitage, Georgina K; Bartley, Harry; Wilkinson, Aaron; Sinopoli, Alessandro; Uppal, Baljinder S; Rice, Craig R; Elliott, Paul I P

    2014-01-01

    We report the unprecedented observation and unequivocal crystallographic characterization of the meta-stable ligand loss intermediate solvento complex trans-[Ru(bpy)(κ2-btz)(κ1-btz)(NCMe)]2+ (1 a) that contains a monodentate chelate ligand. This and analogous complexes can be observed during the photolysis reactions of a family of complexes of the form [Ru()(btz)2]2+ (1 a–d: btz=1,1′-dibenzyl-4,4′-bi-1,2,3-triazolyl; =a) 2,2′-bipyridyl (bpy), b) 4,4′-dimethyl-2,2′-bipyridyl (dmbpy), c) 4,4′-dimethoxy-2,2′-bipyridyl (dmeobpy), d) 1,10-phenanthroline (phen)). In acetonitrile solutions, 1 a–d eventually convert to the bis-solvento complexes trans-[Ru()(btz)(NCMe)2]2+ (3 a–d) along with one equivalent of free btz, in a process in which the remaining coordinated bidentate ligands undergo a new rearrangement such that they become coplanar. X-ray crystal structure of 3 a and 3 d confirmed the co-planar arrangement of the and btz ligands and the trans coordination of two solvent molecules. These conversions proceed via the observed intermediate complexes 2 a–d, which are formed quantitatively from 1 a–d in a matter of minutes and to which they slowly revert back on being left to stand in the dark over several days. The remarkably long lifetime of the intermediate complexes (>12 h at 40 °C) allowed the isolation of 2 a in the solid state, and the complex to be crystallographically characterized. Similarly to the structures adopted by complexes 3 a and d, the bpy and κ2-btz ligands in 2 a coordinate in a square-planar fashion with the second monodentate btz ligand coordinated trans to an acetonitrile ligand. PMID:24889966

  19. ortho-Quinol Acetate Chemistry - Reactivity towards Aryl-Based Nucleophiles and Applications to the Synthesis of Natural Products.

    PubMed

    Companys, Simon; Pouységu, Laurent; Peixoto, Philippe A; Chassaing, Stefan; Quideau, Stephane

    2017-03-10

    Two model ortho-quinol acetates were easily prepared by iodane-mediated acetoxylative phenol dearomatization and evaluated for their reactivity towards various aryl-based nucleophiles, i.e., aryl metallic reagents and phenolic derivatives. Novel modes of reactivity, allowing the formation of biaryl linkages, were revealed and here exploited for the synthesis of two natural phenolics.

  20. Reaction of 6H-6-oxo-3(5)-halogenoanthra(1,9-cd)isoxazoles with inorganic nucleophiles

    SciTech Connect

    Gornostaev, L.M.; Zeibert, G.F.

    1986-11-20

    The reaction of 6H-6-oxo-3(5)-halogenoanthral(1,9-cd)isoxazoles with sodium azide in DMFA and also the potassium fluoride in acetonitrile in the presence of crown ethers leads to nucleophilic substitution of the halogen by the azide and fluoride ion respectively.

  1. 1,2,3,4-Tetrahydro-8-hydroxyquinoline-promoted copper-catalyzed coupling of nitrogen nucleophiles and aryl bromides.

    PubMed

    Wang, Huifeng; Li, Yaming; Sun, Fangfang; Feng, Yang; Jin, Kun; Wang, Xiuna

    2008-11-07

    Based on the dramatic accelerating effect of 2-aminophenol, three ligands derived from 2-aminophenol were developed. Copper-catalyzed coupling reaction of nitrogen-containing nucleophiles with aryl bromides was efficiently carried out under mild conditions using 1,2,3,4-tetrahydro-8-hydroxyquinoline as a novel, simple, and versatile ligand.

  2. Direct sp(3)C-H acroleination of N-aryl-tetrahydroisoquinolines by merging photoredox catalysis with nucleophilic catalysis.

    PubMed

    Feng, Zhu-Jia; Xuan, Jun; Xia, Xu-Dong; Ding, Wei; Guo, Wei; Chen, Jia-Rong; Zou, You-Quan; Lu, Liang-Qiu; Xiao, Wen-Jing

    2014-04-07

    Sequence catalysis merging photoredox catalysis (PC) and nucleophilic catalysis (NC) has been realized for the direct sp(3) C-H acroleination of N-aryl-tetrahydroisoquinoline (THIQ). The reaction was performed under very mild conditions and afforded products in 50-91% yields. A catalytic asymmetric variant was proved to be successful with moderate enantioselectivities (up to 83 : 17 er).

  3. Citrus Peel Additives for One-Pot Triazole Formation by Decarboxylation, Nucleophilic Substitution, and Azide-Alkyne Cycloaddition Reactions

    ERIC Educational Resources Information Center

    Mendes, Desiree E.; Schoffstall, Allen M.

    2011-01-01

    This undergraduate organic laboratory experiment consists of three different reactions occurring in the same flask: a cycloaddition reaction, preceded by decarboxylation and nucleophilic substitution reactions. The decarboxylation and cycloaddition reactions occur using identical Cu(I) catalyst and conditions. Orange, lemon, and other citrus fruit…

  4. Organic Chemistry Students' Fragmented Ideas about the Structure and Function of Nucleophiles and Electrophiles: A Concept Map Analysis

    ERIC Educational Resources Information Center

    Anzovino, Mary E.; Bretz, Stacey Lowery

    2016-01-01

    Organic chemistry students struggle with multiple aspects of reaction mechanisms and the curved arrow notation used by organic chemists. Many faculty believe that an understanding of nucleophiles and electrophiles, among other concepts, is required before students can develop fluency with the electronpushing formalism (EPF). An expert concept map…

  5. Selective activation/coupling of polyhalogenated nucleophiles in ni/cr-mediated reactions: synthesis of c1-c19 building block of halichondrin bs.

    PubMed

    Yan, Wuming; Li, Zhanjie; Kishi, Yoshito

    2015-05-20

    The C1-C19 building block 46 of halichondrin Bs was synthesized via a selective activation/coupling of β-bromoenone 34 with aldehyde 35 in a Ni/Cr-mediated reaction. The first phase of study was a method development to effect a coupling of a "naked" vinylogous anion with an aldehyde. The study with the coupling of 9 + 10 → 11 revealed: (1) β-bromoenone 9b is a better nucleophile than the corresponding β-iodo- and β-chloroenones 9a,c; (2) (Me)2Phen(OMe)2·NiCl2 13b is a better Ni-catalyst than (Me)2Phen(H)2·NiCl2 13a; and (3) a low Ni-catalyst loading, for example, 0.05-0.1 mol % Ni-catalyst against 10 mol % Cr-catalyst, is crucial for an effective coupling. The second phase of study was a method development to realize a selective activation/coupling of polyhalogenated nucleophiles such as 34. The competition experiment of 10 + 9b over 10 + 31a-c revealed: (1) (Me)2Phen(OMe)2·NiCl2 13b is more effective than (Me)2Phen(H)2·NiCl2 13a for the required selective activation/coupling; (2) a low Ni-catalyst loading, for example, 0.05-0.1 mol % Ni-catalyst against 10 mol % Cr-catalyst, is crucial for discriminating β-bromoenone 9b from the three types of vinyl iodides 31a-c. The third phase of study was an application of the developed method to execute the proposed coupling of 34 + 35 → 36. For this application, a polyether-type Ni-catalyst 37c, readily soluble in the reaction medium, was introduced to achieve the selective activation/coupling with higher efficiency. With use of ion-exchange resin-based device, the coupling product 36 was transformed to the C1-C19 building block 46 of halichondrin Bs without purification/separation of the intermediates.

  6. Unexpected Reactivity of [(η(5) -1,2,4-tBu3 C5 H2 )Ni(η(3) -P3 )] towards Main Group Nucleophiles and by Reduction.

    PubMed

    Mädl, Eric; Balázs, Gábor; Peresypkina, Eugenia V; Scheer, Manfred

    2016-06-27

    The reduction of [Cp'''Ni(η(3) -P3 )] (1; Cp'''=η(5) -1,2,4-tBu3 C5 H2 ) with potassium produces the complex anion [(Cp'''Ni)2 (μ,η(2:2) -P8 )](2-) (2), which contains a realgar-like P8 unit. The anionic triple-decker sandwich complex [(Cp'''Ni)2 (μ,η(3:3) -P3 )](-) (3) with a cyclo-P3 middle deck is obtained when 1 is treated with NaNH2 as a nucleophile. Na[3] can subsequently be oxidized with AgOTf to the neutral triple-decker complex [(Cp'''Ni)2 (μ,η(3:3) -P3 )] (4). In contrast, 1 reacts with LiPPh2 to give the anionic compound [(Cp'''Ni)2 (μ,η(2:2) -P6 PPh2 )](-) (5), a complex containing a bicyclic P7 fragment capped by two Cp'''Ni units. Protonation of Li[5] with HBF4 leads to the neutral complex [(Cp'''Ni)2 (μ,η(2:2) -(HP6 PPh2 )] (6). Adding LiNMe2 to 1 results in [Cp'''Ni(η(2) -P3 NMe2 )](-) (7) becoming accessible, a complex which forms as a result of nucleophilic attack at the cyclo-P3 ring of 1. The complexes K2 [2], Na[3], 4, 6, and Li[7] were fully characterized and their structures determined by single-crystal X-ray diffraction.

  7. Intermediate Filaments and Polarization in the Intestinal Epithelium

    PubMed Central

    Coch, Richard A.; Leube, Rudolf E.

    2016-01-01

    The cytoplasmic intermediate filament cytoskeleton provides a tissue-specific three-dimensional scaffolding with unique context-dependent organizational features. This is particularly apparent in the intestinal epithelium, in which the intermediate filament network is localized below the apical terminal web region and is anchored to the apical junction complex. This arrangement is conserved from the nematode Caenorhabditis elegans to humans. The review summarizes compositional, morphological and functional features of the polarized intermediate filament cytoskeleton in intestinal cells of nematodes and mammals. We emphasize the cross talk of intermediate filaments with the actin- and tubulin-based cytoskeleton. Possible links of the intermediate filament system to the distribution of apical membrane proteins and the cell polarity complex are highlighted. Finally, we discuss how these properties relate to the establishment and maintenance of polarity in the intestine. PMID:27429003

  8. Substrate Activation by Iron Superoxo Intermediates

    PubMed Central

    van der Donk, Wilfred A.; Krebs, Carsten; Bollinger, J. Martin

    2010-01-01

    A growing number of non-heme-iron oxygenases and oxidases catalyze reactions for which the well-established mechanistic paradigm involving a single C-H-bond cleaving intermediate of the Fe(IV)-oxo (ferryl) type [1] is insufficient to explain the chemistry. It is becoming clear that, in several of these cases, Fe(III)-superoxide complexes formed by simple addition of O2 to the reduced [Fe(II)] cofactor initiate substrate oxidation by abstracting hydrogen [2]. This substrate-oxidizing entry route into high-valent-iron intermediates makes possible an array of complex and elegant oxidation reactions without consumption of valuable reducing equivalents. Examples of this novel mechanistic strategy are discussed with the goal of bringing forth unifying principles. PMID:20951572

  9. Detoxification of biomass hydrolysates with nucleophilic amino acids enhances alcoholic fermentation.

    PubMed

    Xie, Rui; Tu, Maobing; Carvin, Jamarius; Wu, Yonnie

    2015-06-01

    Carbonyl compounds generated in biomass pretreatment hinder the biochemical conversion of biomass hydrolysates to biofuels. A novel approach of detoxifying hydrolysates with amino acids for ethanol production was developed. Among the 20 amino acids assessed for their detoxification efficiency and nucleophilicity, cysteine was the most effective one. It increased both ethanol productivity and final yield of biomass hydrolysates from 0.18 (untreated) to 1.77 g/L/h and from 0.02 to 0.42 g/g, respectively. Detoxification efficiency was followed by histidine and it increased the final yield to 0.42 g/g, then by lysine, tryptophan and asparagine. It was observed all five effective amino acids contained reactive side-chain functional groups, which played important roles in the amino acid detoxification reaction. The study further showed cysteine and glycine detoxifications were temperature and pH dependent. The mechanistic study using mass spectrometry revealed thiazolidine carboxylic acid, a Schiff base, was formed by condensation of aldehyde and cysteine.

  10. Fluorescent "turn-on" detecting CN- by nucleophilic addition induced Schiff-base hydrolysis

    NASA Astrophysics Data System (ADS)

    Lin, Qi; Cai, Yi; Li, Qiao; Shi, Bing-Bing; Yao, Hong; Zhang, You-Ming; Wei, Tai-Bao

    2015-04-01

    A new chemosensor Sz based on Schiff-base group as recognition site and naphthalene as the fluorescence signal group was designed and synthesised. It could fluorescent "turn-on" detect cyanide (CN-) via a novel mechanism of nucleophilic addition induced Schiff-base hydrolysis. Adding the CN- into the solution of Sz could induce Sz to emit blue fluorescence at 435 nm instantly. Moreover, Sz could also colorimetric detect CN-. Upon the addition of CN-, the Sz showed dramatic color change from yellow to colorless. These sensing procedures could not be interfered by other coexistent competitive anions such as F-, AcO-, H2PO4- and SCN-. In addition, Sz showed high sensitivity for CN-, the detection limits is 3.42 × 10-8 M of CN-, which is far lower than the WHO guideline of CN- in drinking water (less than 1.9 × 10-6 M). The CN- test strips based on Sz could act as a convenient CN- test kits.

  11. 1,3,2,5-Diazadiborinine featuring nucleophilic and electrophilic boron centres

    PubMed Central

    Wu, Di; Kong, Lingbing; Li, Yongxin; Ganguly, Rakesh; Kinjo, Rei

    2015-01-01

    The seminal discovery in 1865 by Kekulé that benzene nucleus exists with cyclic skeleton is considered to be the beginning of aromatic chemistry. Since then, a myriad of cyclic molecules displaying aromatic property have been synthesized. Meanwhile, borazine (B3N3H6), despite the isostructural and isoelectronic relationships with benzene, exhibits little aromaticity. Herein, we report the synthesis of a 1,3,2,5-diazadiborinine (B2C2N2R6) derivative, a hybrid inorganic/organic benzene, and we present experimental and computational evidence for its aromaticity. In marked contrast to the reactivity of benzene, borazine, and even azaborinines previously reported, 1,3,2,5-diazadiborinine readily forms the adducts with methyl trifluoromethanesulfonate and phenylacetylene without any catalysts. Moreover, 1,3,2,5-diazadiborine activates carbon dioxide giving rise to a bicycle[2,2,2] product, and the binding process was found to be reversible. These results, thus, demonstrate that 1,3,2,5-diazadiborinine features both nucleophilic and electrophilic boron centres, with a formal B(+I)/B(+III) mixed valence system, in the aromatic six-membered B2C2N2 ring. PMID:26073993

  12. Nucleophilic stabilization of water-based reactive ink for titania-based thin film inkjet printing

    NASA Astrophysics Data System (ADS)

    Gadea, C.; Marani, D.; Esposito, V.

    2017-02-01

    Drop on demand deposition (DoD) of titanium oxide thin films (<500 nm) is performed via a novel titanium-alkoxide-based solution that is tailored as a reactive ink for inkjet printing. The ink is developed as water-based solution by a combined use of titanium isopropoxide and n-methyldiethanolamine (MDEA) used as nucleophilic ligand. The function of the ligand is to control the fast hydrolysis/condensation reactions in water for the metal alkoxide before deposition, leading to formation of the TiO2 only after the jet process. The evolution of the titanium-ligand interactions at increasing amount of MDEA is here elucidated in terms of long term stability. The ink printability parameter (Z) is optimized, resulting in a reactive solution with printability, Z, >1, and chemical stability up to 600 h. Thin titanium oxide films (<500 nm) are proved on different substrates. Pure anatase phase is obtained after annealing at low temperature (ca. 400 °C).

  13. A Rh(II)-catalyzed multicomponent reaction by trapping an α-amino enol intermediate in a traditional two-component reaction pathway

    PubMed Central

    Liu, Shunying; Yao, Wenfeng; Liu, Yuan; Wei, Qinghua; Chen, Jianghui; Wu, Xiang; Xia, Fei; Hu, Wenhao

    2017-01-01

    Multicomponent reactions (MCRs) represent an ideal organic synthesis tool for the rapid construction of complex molecules due to their step and atom economy. Compared to two-component reactions, the development of new MCRs has been greatly limited during the 170 years since the first MCR was reported. Theoretically, the trapping of an active intermediate generated from two components by a third component could change the traditional two-component reaction pathway, leading to the discovery of MCRs. We report an example of the trapping of α-imino enols generated in situ from 1-sulfonyl-1,2,3-triazoles via α-imino metal carbene species by vinylimine ions using C(2)-substituted indoles and paraformaldehyde as precursors in the presence of a rhodium(II) catalyst. The traditional enol-ketone transformation pathway was suspended by the trapping procedure and efficiently switched to an MCR pathway to produce α-amino-β-indole ketones in moderate to good yields. Unexpectedly, the resulting products and the theoretical density functional theory (DFT) calculation results indicated that the enolic carbon had a stronger nucleophilicity than the well-known traditional enamic carbon in the trapping process. The reaction mechanism was investigated using control experiments and detailed DFT calculations, and the synthetic application of the products was also illustrated. The developed strategy provides a mild and rapid access to α-amino-β-indole ketones and suggests a rationale for the discovery of MCRs by trapping an active intermediate with a third component in a traditional two-component reaction pathway. PMID:28345053

  14. S(N)2 reaction of sulfur nucleophiles with hindered sulfamidates: enantioselective synthesis of alpha-methylisocysteine.

    PubMed

    Avenoza, Alberto; Busto, Jesús H; Jiménez-Osés, Gonzalo; Peregrina, Jesús M

    2006-02-17

    The work described here demonstrates that the five-membered cyclic alpha-methylisoserine-derived sulfamidate, (R)-1, behaves as an excellent chiral building block for the ring-opening reaction by S(N)2 attack with sulfur nucleophiles at the quaternary carbon. As a synthetic application of this methodology, and to show that this sulfamidate is a valuable starting material, the synthesis of two new alpha-methylisocysteine derivatives has been carried out to cover the lack of alpha- and beta-methylated amino acids that incorporate the cysteine or isocysteine skeleton. These compounds are two new alpha,alpha-disubstituted beta-amino acids (beta(2,2)-amino acids), and the synthetic routes involve nucleophilic ring opening followed by acid hydrolysis.

  15. sp(2)-sp(3) diboranes: astounding structural variability and mild sources of nucleophilic boron for organic synthesis.

    PubMed

    Dewhurst, Rian D; Neeve, Emily C; Braunschweig, Holger; Marder, Todd B

    2015-06-14

    Despite the widespread use of organoborane reagents in organic synthesis and catalysis, a major challenge still remains: very few boron-centered nucleophiles exist for the direct construction of B-C bonds. Perhaps the most promising emerging solution to this problem is the use of sp(2)-sp(3) diboranes, in which one boron atom of a conventional diborane(4) is quaternised by either a neutral or anionic nucleophile. These compounds, either isolated or generated in situ, serve as relatively mild and convenient sources of the boryl anion [BR2](-) for use in organic synthesis and have already proven their efficacy in metal-free as well as metal-catalysed borylation reactions. This Feature article documents the history of sp(2)-sp(3) diborane synthesis, their properties and surprising structural variability, and their burgeoning utility in organic synthesis.

  16. Enzyme-like catalysis via ternary complex mechanism: alkoxy-bridged dinuclear cobalt complex mediates chemoselective O-esterification over N-amidation.

    PubMed

    Hayashi, Yukiko; Santoro, Stefano; Azuma, Yuki; Himo, Fahmi; Ohshima, Takashi; Mashima, Kazushi

    2013-04-24

    Hydroxy group-selective acylation in the presence of more nucleophilic amines was achieved using acetates of first-row late transition metals, such as Mn, Fe, Co, Cu, and Zn. Among them, cobalt(II) acetate was the best catalyst in terms of reactivity and selectivity. The combination of an octanuclear cobalt carboxylate cluster [Co4(OCOR)6O]2 (2a: R = CF3, 2b: R = CH3, 2c: R = (t)Bu) with nitrogen-containing ligands, such as 2,2'-bipyridine, provided an efficient catalytic system for transesterification, in which an alkoxide-bridged dinuclear complex, Co2(OCO(t)Bu)2(bpy)2(μ2-OCH2-C6H4-4-CH3)2 (10), was successfully isolated as a key intermediate. Kinetic studies and density functional theory calculations revealed Michaelis-Menten behavior of the complex 10 through an ordered ternary complex mechanism similar to dinuclear metallo-enzymes, suggesting the formation of alkoxides followed by coordination of the ester.

  17. Trimethylsilyl chloride promoted synthesis of α-branched amines by nucleophilic addition of organozinc halides to nitrones.

    PubMed

    Fu, Ying; Liu, Yanhua; Chen, Yaojuan; Hügel, Helmut M; Wang, Minzhu; Huang, Danfeng; Hu, Yulai

    2012-10-14

    A general procedure for the nucleophilic addition of organozinc halides with nitrones in the presence of trimethylsilyl chloride has been developed. Trimethylsilyl chloride was found to be both an indispensable reaction promoter and a ready hydroxylamine protective agent in these reactions. The produced O-(trimethylsilyl)hydroxylamines can be easily reduced into corresponding amines just by a zinc-copper couple in saturated aqueous NH(4)Cl solution.

  18. Catalysis of hydrolysis and nucleophilic substitution at the P-N bond of phosphoimidazolide-activated nucleotides in phosphate buffers

    NASA Technical Reports Server (NTRS)

    Kanavarioti, A.; Rosenbach, M. T.

    1991-01-01

    Phosphoimidazolide-activated derivatives of guanosine and cytidine 5'-monophosphates, henceforth called ImpN's, exhibit enhanced rates of degradation in the presence of aqueous inorganic phosphate in the range 4.0 < or = pH < or = 8.6. This degradation is been attributed to (i) nucleophilic substitution of the imidazolide and (ii) catalysis of the P-N bond hydrolysis by phosphate. The first reaction results in the formation of nucleoside 5'-diphosphate and the second in nucleoside 5'-monophosphate. Analysis of the observed rates as well as the product ratios as a function of pH and phosphate concentration allow distinction between various mechanistic possibilities. The results show that both H2PO4- and HPO4(2-) participate in both hydrolysis and nucleophilic substitution. Statistically corrected biomolecular rate constants indicate that the dianion is 4 times more effective as a general base than the monoanion, and 8 times more effective as nucleophile. The low Bronsted value beta = 0.15 calculated for these phosphate species, presumed to act as general bases in facilitating water attack, is consistent with the fact that catalysis of the hydrolysis of the P-N bond in ImpN's has not been detected before. The beta nuc = 0.35 calculated for water, H2PO4-, HPO4(2-), and hydroxide acting as nucleophiles indicates a more associative transition state for nucleotidyl (O2POR- with R = nucleoside) transfers than that observed for phosphoryl (PO3(2-)) transfers (beta nuc = 0.25). With respect to the stability/reactivity of ImpN's under prebiotic conditions, our study shows that these materials would not suffer additional degradation due to inorganic phosphate, assuming the concentrations of phosphate, Pi, on prebiotic Earth were similar to those in the present oceans ([Pi] approximately 2.25 micromoles).

  19. Predicting solvent stability in aprotic electrolyte Li-air batteries: nucleophilic substitution by the superoxide anion radical (O2(•-)).

    PubMed

    Bryantsev, Vyacheslav S; Giordani, Vincent; Walker, Wesley; Blanco, Mario; Zecevic, Strahinja; Sasaki, Kenji; Uddin, Jasim; Addison, Dan; Chase, Gregory V

    2011-11-10

    There is increasing evidence that cyclic and linear carbonates, commonly used solvents in Li ion battery electrolytes, are unstable in the presence of superoxide and thus are not suitable for use in rechargeable Li-air batteries employing aprotic electrolytes. A detailed understanding of related decomposition mechanisms provides an important basis for the selection and design of stable electrolyte materials. In this article, we use density functional theory calculations with a Poisson-Boltzmann continuum solvent model to investigate the reactivity of several classes of aprotic solvents in nucleophilic substitution reactions with superoxide. We find that nucleophilic attack by O(2)(•-) at the O-alkyl carbon is a common mechanism of decomposition of organic carbonates, sulfonates, aliphatic carboxylic esters, lactones, phosphinates, phosphonates, phosphates, and sulfones. In contrast, nucleophilic reactions of O(2)(•-) with phenol esters of carboxylic acids and O-alkyl fluorinated aliphatic lactones proceed via attack at the carbonyl carbon. Chemical functionalities stable against nucleophilic substitution by superoxide include N-alkyl substituted amides, lactams, nitriles, and ethers. The results establish that solvent reactivity is strongly related to the basicity of the organic anion displaced in the reaction with superoxide. Theoretical calculations are complemented by cyclic voltammetry to study the electrochemical reversibility of the O(2)/O(2)(•-) couple containing tetrabutylammonium salt and GCMS measurements to monitor solvent stability in the presence of KO(2)(•) and a Li salt. These experimental methods provide efficient means for qualitatively screening solvent stability in Li-air batteries. A clear correlation between the computational and experimental results is established. The combination of theoretical and experimental techniques provides a powerful means for identifying and designing stable solvents for rechargeable Li-air batteries.

  20. Prostaglandin synthase-mediated metabolism of carcinogens and a potential role for peroxyl radicals as reactive intermediates

    SciTech Connect

    Marnett, L.J. )

    1990-08-01

    Prostaglandin-H synthase is unique among enzymes of the plant and animal kingdom in its ability to biosynthesize and metabolize hydroperoxides. Higher oxidation states of the peroxidase oxidize reducing substrates to electron-deficient derivatives that react with macromolecular nucleophiles. In the case of aromatic amines, the electron-deficient derivatives are mutagenic to bacterial and mammalian cells. {beta}-Dicarbonyl compounds and retinoic acid are oxidized to carbon-centered radicals that react with O{sub 2} to form peroxyl free radicals. Peroxyl radicals are the most stable oxy radicals and are able to diffuse some distance from the site of their generation. Peroxyl radicals are also formed during lipid peroxidation and in the reaction of polyunsaturated fatty acid hydroperoxides with metal complexes and metalloproteins. Peroxyl radicals epoxidize isolated doubled bonds of compounds such as 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (BP-7,8-diol); 3,4-dihydroxy-3,4-dihydrobenzo(a)anthracene; and aflatoxin B{sub 1}. The epoxide products represent the ultimate carcinogenic forms of the respective compounds. Techniques for quantitating the extent of peroxidase dependent or peroxyl radical-dependent metabolism in vivo make use of differences in the structure or stereochemistry of reactive intermediates formed by peroxidases relative to cytochromes P-450. Differences in the relative amounts of hydrolysis products and DNA adducts derived from anti- and syn-dihydrodiolepoxides following application of BP-7,8-diol to mouse skin in vivo indicate peroxyl radicals play a significant role in metabolism of BP-7,8-diol in uninduced animals.

  1. Prostaglandin synthase-mediated metabolism of carcinogens and a potential role for peroxyl radicals as reactive intermediates.

    PubMed Central

    Marnett, L J

    1990-01-01

    Prostaglandin-H synthase is unique among enzymes of the plant and animal kingdom in its ability to biosynthesize and metabolize hydroperoxides. Its cyclooxygenase activity oxygenates polyunsaturated fatty acids to hydroperoxy endoperoxides, and its peroxidase activity reduces the hydroperoxy group to hydroxy groups. Higher oxidation states of the peroxidase oxidize reducing substrates to electron-deficient derivatives that react with macromolecular nucleophiles. In the case of aromatic amines, the electron-deficient derivatives are mutagenic to bacterial and mammalian cells. beta-Dicarbonyl compounds and retinoic acid are oxidized to carbon-centered radicals that react with O2 to form peroxyl free radicals. Peroxyl radicals are the most stable oxy radicals and are able to diffuse some distance from the site of their generation. Peroxyl radicals are also formed during lipid peroxidation and in the reaction of polyunsaturated fatty acid hydroperoxides with metal complexes and metalloproteins. Peroxyl radicals epoxidize isolated doubled bonds of compounds such as 7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (BP-7,8-diol); 3,4-dihydroxy-3,4-dihydrobenzo(a)anthracene; and aflatoxin B1. The epoxide products represent the ultimate carcinogenic forms of the respective compounds. Techniques for quantitating the extent of peroxidase dependent or peroxyl radical-dependent metabolism in vivo make use of differences in the structure or stereochemistry of reactive intermediates formed by peroxidases relative to cytochromes P-450. Differences in the relative amounts of hydrolysis products and DNA adducts derived from anti- and syn-dihydrodiolepoxides following application of BP-7,8-diol to mouse skin in vivo indicate peroxyl radicals play a significant role in metabolism of BP-7,8-diol in uninduced animals. PMID:2125560

  2. Electrophilic, Ambiphilic, and Nucleophilic C-H bond Activation. Understanding the electronic continuum of C-H bond activation through transition-state and reaction pathway interaction energy decompositions

    SciTech Connect

    Ess, Daniel H.; Goddard, William A.; Periana, Roy A.

    2010-10-29

    The potential energy and interaction energy profiles for metal- and metal-ligand-mediated alkane C-H bond activation were explored using B3LYP density functional theory (DFT) and the absolutely localized molecular orbital energy decomposition analysis (ALMO-EDA). The set of complexes explored range from late transition metal group 10 (Pt and Pd) and group 11 (Au) metal centers to group 7-9 (Ir, Rh, Ru, and W) metal centers as well as a group 3 Sc complex. The coordination geometries, electron metal count (d8, d6, d4, and d0), and ligands (N-heterocycles, O-donor, phosphine, and Cp*) are also diverse. Quantitative analysis using ALMO-EDA of both directions of charge-transfer stabilization (occupied to unoccupied orbital stabilization) energies between the metal-ligand fragment and the coordinated C-H bond in the transition state for cleavage of the C-H bond allows classification of C-H activation reactions as electrophilic, ambiphilic, or nucleophilic on the basis of the net direction of charge-transfer energy stabilization. This bonding pattern transcends any specific mechanistic or bonding paradigm, such as oxidative addition, σ-bond metathesis, or substitution. Late transition metals such as Au(III), Pt(II), Pd(II), and Rh(III) metal centers with N-heterocycle, halide, or O-donor ligands show electrophilically dominated reaction profiles with forward charge-transfer from the C-H bond to the metal, leading to more stabilization than reverse charge transfer from the metal to the C-H bond. Transition states and reaction profiles for d6 Ru(II) and Ir(III) metals with Tp and acac ligands were found to have nearly equal forward and reverse charge-transfer energy stabilization. This ambiphilic region also includes the classically labeled electrophilic cationic species Cp*(PMe3)Ir(Me). Nucleophilic character, where the metal to C-H bond charge-transfer interaction is most stabilizing, was found in

  3. Laboratory determination of the carbon kinetic isotope effects (KIEs) for reactions of methyl halides with various nucleophiles in solution

    USGS Publications Warehouse

    Baesman, S.M.; Miller, L.G.

    2005-01-01

    Large carbon kinetic isotope effects (KIEs) were measured for reactions of methyl bromide (MeBr), methyl chloride (MeCl), and methyl iodide (MeI) with various nucleophiles at 287 and 306 K in aqueous solutions. Rates of reaction of MeBr and MeI with H2O (neutral hydrolysis) or Cl- (halide substitution) were consistent with previous measurements. Hydrolysis rates increased with increasing temperature or pH (base hydrolysis). KIEs for hydrolysis were 51 ?? 6??? for MeBr and 38 ?? 8??? for MeI. Rates of halide substitution increased with increasing temperature and greater reactivity of the attacking nucleophile, with the fastest reaction being that of MeI with Br-. KIEs for halide substitution were independent of temperature but varied with the reactant methyl halide and the attacking nucleophile. KIEs were similar for MeBr substitution with Cl- and MeCl substitution with Br- (57 ?? 5 and 60 ?? 9??? respectively). The KIE for halide exchange of MeI was lower overall (33 ?? 8??? and was greater for substitution with Br- (46 ?? 6???) than with Cl- (29 ?? 6???). ?? Springer Science + Business Media, Inc. 2005.

  4. Nucleophilic reactivities of hydrazines and amines: the futile search for the α-effect in hydrazine reactivities.

    PubMed

    Nigst, Tobias A; Antipova, Anna; Mayr, Herbert

    2012-09-21

    The kinetics of the reactions of amines, hydrazines, hydrazides, and hydroxylamines with benzhydrylium ions and quinone methides were studied in acetonitrile and water by UV-vis spectroscopy, using conventional spectrometers and stopped-flow and laser-flash techniques. From the second-order rate constants k(2) of these reactions, the nucleophilicity parameters N and s(N) were determined according to the linear free energy relationship log k(2) = s(N)(N + E). While methyl groups increase the reactivities of the α-position of hydrazines, they decrease the reactivities of the β-position. Despite the 10(2) times lower reactivities of amines and hydrazines in water than in acetonitrile, the relative reactivities of differently substituted amines and hydrazines are almost identical in the two solvents. In both solvents hydrazine has a reactivity similar to that of methylamine. This observation implies that replacement of one hydrogen in ammonia by Me increases the nucleophilicity more than introduction of an amino group, if one takes into account that hydrazine has two reactive centers. Plots of log k(2) versus the corresponding equilibrium constants (log K) or Brønsted basicities (pK(aH)) do not show enhanced nucleophilicities (α-effect) for either hydrazines or hydroxylamine relative to alkylamines.

  5. Nucleophilic selectivity of alkylating agents and their hypermutability in Drosophila as predictors of carcinogenic potency in rodents.

    PubMed

    Vogel, E W; Barbin, A; Nivard, M J; Bartsch, H

    1990-12-01

    The nucleophilic selectivity (Swain-Scott s constant or initial 7-alkylguanine/O6-alkylguanine ratio in DNA) of 60 alkylating agents, mostly monofunctional or cross-linking was compared to their carcinogenic potency in rodents (median TD50 estimates) and to two genotoxicity indices in Drosophila: (i) hypermutability, measured by the increased frequency of induced sex-linked recessive lethal mutations (SLRL) in a strain defective in DNA excision repair (exr-), as compared to the wild-type (exr+); (ii) relative clastogenic efficiency, expressed by the ratio of chromosomal aberrations (ring-X loss) to SLRL determined in the exr+ strain. For a subset of direct-acting, monofunctional alkylating agents, nucleophilic selectivity and TD50 values or hypermutability indices were linearly correlated. In addition, the hypermutability indices in Drosophila by methylating or ethylating procarcinogens were similar to the corresponding values of their ultimate metabolites. In contrast, cross-linking agents, including antitumour drugs, did not show these positive correlations. The relative clastogenic efficiencies in Drosophila of 26 direct-acting, alkylating carcinogens increased with both their cross-linking activity and nucleophilic selectivity. By analyzing mutational spectra in Drosophila induced in the vermilion gene by four monofunctional alkylating agents with contrasting s values, critical DNA lesions, i.e. type of base pair substitution mutations, deletions, insertions, involved in genotoxicity were pinpointed. Thus, these multi-endpoint analyses should, as a new approach, assist in the quantitative risk evaluation of genotoxic agents.

  6. Intramolecular long-distance nucleophilic reactions as a rapid fluorogenic switch applicable to the detection of enzymatic activity.

    PubMed

    Baba, Reisuke; Hori, Yuichiro; Kikuchi, Kazuya

    2015-03-16

    Long-distance intramolecular nucleophilic reactions are promising strategies for the design of fluorogenic probes to detect enzymatic activity involved in lysine modifications. However, such reactions have been challenging and hence have not been established. In this study, we have prepared fluorogenic peptides that induce intramolecular reactions between lysine nucleophiles and electrophiles in distal positions. These peptides contain a lysine and fluorescence-quenched fluorophore with a carbonate ester, which triggers nucleophilic transesterification resulting in fluorogenic response. Transesterification occurred under mild aqueous conditions despite the presence of a long nine-amino-acid spacer between the lysine and fluorophore. In addition, one of the peptides showed the fastest reaction kinetics with a half-life time of 3.7 min. Furthermore, the incorporation of this fluorogenic switch into the probes allowed rapid fluorogenic detection of histone deacetylase (HDAC) activity. These results indicate that the transesterification reaction has great potential for use as a general fluorogenic switch to monitor the activity of lysine-targeting enzymes.

  7. Nucleophilic substitution reactions of alcohols with use of montmorillonite catalysts as solid Brønsted acids.

    PubMed

    Motokura, Ken; Nakagiri, Nobuaki; Mizugaki, Tomoo; Ebitani, Kohki; Kaneda, Kiyotomi

    2007-08-03

    We have developed an environmentally benign synthetic approach to nucleophilic substitution reactions of alcohols that minimizes or eliminates the formation of byproducts, resulting in a highly atom-efficient chemical process. Proton- and metal-exchanged montmorillonites (H- and Mn+-mont) were prepared easily by treating Na+-mont with an aqueous solution of hydrogen chloride or metal salt, respectively. The H-mont possessed outstanding catalytic activity for nucleophilic substitution reactions of a variety of alcohols with anilines, because the unique acidity of the H-mont catalyst effectively prevents the neutralization by the basic anilines. In addition, amides, indoles, 1,3-dicarbonyl compounds, and allylsilane act as nucleophiles for the H-mont-catalyzed substitutions of alcohols, which allowed efficient formation of various C-N and C-C bonds. The solid H-mont was reusable without any appreciable loss in its catalytic activity and selectivity. Especially, an Al3+-mont showed high catalytic activity for the alpha-benzylation of 1,3-dicarbonyl compounds with primary alcohols due to cooperative catalysis between a protonic acid site and a Lewis acidic Al3+ species in its interlayer spaces.

  8. Ligand Intermediates in Metal-Catalyzed Reactions

    SciTech Connect

    Gladysz, John A.

    1999-07-31

    The longest-running goal of this project has been the synthesis, isolation, and physical chemical characterization of homogeneous transition metal complexes containing ligand types believed to be intermediates in the metal-catalyzed conversion of CO/H{sub 2}, CO{sub 2}, CH{sub 4}, and similar raw materials to organic fuels, feedstocks, etc. In the current project period, complexes that contain unusual new types of C{sub x}(carbide) and C{sub x}O{sub y} (carbon oxide) ligands have been emphasized. A new program in homogeneous fluorous phase catalysis has been launched as described in the final report.

  9. Ring-opening reactions of 1,4-diazabicyclo[2.2.2]octane (DABCO) derived quaternary ammonium salts with phenols and related nucleophiles.

    PubMed

    Maraš, Nenad; Polanc, Slovenko; Kočevar, Marijan

    2012-02-14

    1,4-Diazabicyclo[2.2.2]octane (DABCO) has been evaluated as a starting material for the synthesis of 1-alkyl-4-(2-phenoxyethyl)piperazines and related derivatives. We found that 1-alkyl-1,4-diazabicyclo[2.2.2]octan-1-ium salts, resulting from the alkylation of DABCO, efficiently react with a variety of nucleophiles in polyethyleneglycol (PEG) or diglyme at high temperatures to give piperazine products resulting from the nucleophilic ring-opening reaction. The benzylation side reaction was found to be relevant with softer nucleophiles when using 1-benzyl-1,4-diazabicyclo[2.2.2]octan-1-ium salts, while other types of alkylations were not observed. One-pot methodologies allow for the synthesis of piperazines directly from primary alcohols, alkyl halides or sulfonates, using phenols, or other nucleophile sources, and DABCO.

  10. Intermediate inputs and economic productivity.

    PubMed

    Baptist, Simon; Hepburn, Cameron

    2013-03-13

    Many models of economic growth exclude materials, energy and other intermediate inputs from the production function. Growing environmental pressures and resource prices suggest that this may be increasingly inappropriate. This paper explores the relationship between intermediate input intensity, productivity and national accounts using a panel dataset of manufacturing subsectors in the USA over 47 years. The first contribution is to identify sectoral production functions that incorporate intermediate inputs, while allowing for heterogeneity in both technology and productivity. The second contribution is that the paper finds a negative correlation between intermediate input intensity and total factor productivity (TFP)--sectors that are less intensive in their use of intermediate inputs have higher productivity. This finding is replicated at the firm level. We propose tentative hypotheses to explain this association, but testing and further disaggregation of intermediate inputs is left for further work. Further work could also explore more directly the relationship between material inputs and economic growth--given the high proportion of materials in intermediate inputs, the results in this paper are suggestive of further work on material efficiency. Depending upon the nature of the mechanism linking a reduction in intermediate input intensity to an increase in TFP, the implications could be significant. A third contribution is to suggest that an empirical bias in productivity, as measured in national accounts, may arise due to the exclusion of intermediate inputs. Current conventions of measuring productivity in national accounts may overstate the productivity of resource-intensive sectors relative to other sectors.

  11. [Intermediate endpoints in clinical research].

    PubMed

    Peters, Sanne A E; Groenwold, Rolf H H; Bots, Michiel L

    2013-01-01

    An intermediate variable such as blood pressure is part of the causal pathway of mechanisms to a clinical outcome, e.g. myocardial infarction. An intervention affects a clinical outcome through its effect on that intermediate variable. In studies designed to assess the effects of interventions an intermediate variable may be used as surrogate for clinical outcomes. Such an endpoint is also known as an intermediate endpoint. Intervention studies with intermediate endpoints are commonly performed in medical research to evaluate the effects of an intervention on clinical outcomes. Intervention studies with an intermediate endpoint are conducted in a smaller study population and with a shorter duration of follow-up than studies using clinical outcomes. An intermediate variable is not eligible as an intermediate endpoint when the intervention also affects other biological mechanisms that subsequently affect the clinical endpoint. Due to a smaller sample size and shorter study duration, side effects of intervention are more difficult to evaluate in studies with an intermediate endpoint than in studies with clinical endpoints.

  12. Intermediate Filaments: Structure and Assembly.

    PubMed

    Herrmann, Harald; Aebi, Ueli

    2016-11-01

    Proteins of the intermediate filament (IF) supergene family are ubiquitous structural components that comprise, in a cell type-specific manner, the cytoskeleton proper in animal tissues. All IF proteins show a distinctly organized, extended α-helical conformation prone to form two-stranded coiled coils, which are the basic building blocks of these highly flexible, stress-resistant cytoskeletal filaments. IF proteins are highly charged, thus representing versatile polyampholytes with multiple functions. Taking vimentin, keratins, and the nuclear lamins as our prime examples, we present an overview of their molecular and structural parameters. These, in turn, document the ability of IF proteins to form distinct, highly diverse supramolecular assemblies and biomaterials found, for example, at the inner nuclear membrane, throughout the cytoplasm, and in highly complex extracellular appendages, such as hair and nails, of vertebrate organisms. Ultimately, our aim is to set the stage for a more rational understanding of the immediate effects that missense mutations in IF genes have on cellular functions and for their far-reaching impact on the development of the numerous IF diseases caused by them.

  13. Reactions of a Ruthenium Complex with Substituted N-Propargyl Pyrroles.

    PubMed

    Chia, Pi-Yeh; Huang, Shou-Ling; Liu, Yi-Hong; Lin, Ying-Chih

    2016-04-05

    In an investigation into the chemical reactions of N-propargyl pyrroles 1 a-c, containing aldehyde, keto, and ester groups on the pyrrole ring, with [Ru]-Cl ([Ru]=Cp(PPh3 )2 Ru; Cp=C5 H5 ), an aldehyde group in the pyrrole ring is found to play a crucial role in stimulating the cyclization reaction. The reaction of 1 a, containing an aldehyde group, with [Ru]-Cl in the presence of NH4 PF6 yields the vinylidene complex 2 a, which further reacts with allyl amine to give the carbene complex 6 a with a pyrrolizine group. However, if 1 a is first reacted with allyl amine to yield the iminenyne 8 a, then the reaction of 8 a with [Ru]-Cl in the presence of NH4 PF6 yields the ruthenium complex 9 a, containing a cationic pyrrolopyrazinium group, which has been fully characterized by XRD analysis. These results can be adequately explained by coordination of the triple bond of the propargyl group to the ruthenium metal center first, followed by two processes, that is, formation of a vinylidene intermediate or direct nucleophilic attack. Additionally, the deprotonation of 2 a by R4 NOH yields the neutral acetylide complex 3 a. In the presence of NH4 PF6 , the attempted alkylation of 3 a resulted in the formation the Fischer-type amino-carbene complex 5 a as a result of the presence of NH3, which served as a nucleophile. With KPF6, the alkylation of 3 a with ethyl and benzyl bromoacetates afforded the disubstituted vinylidene complexes 10 a and 11 a, containing ester groups, which underwent deprotonation reactions to give the furyl complexes 12 a and 13 a, respectively. For 13 a, containing an O-benzyl group, subsequent 1,3-migration of the benzyl group was observed to yield product 14 a with a lactone unit. Similar reactivity was not observed for the corresponding N-propargyl pyrroles 1 b and 1 c, which contained keto and ester groups, respectively, on the pyrrole ring.

  14. Intermediate BL Lac objects

    NASA Astrophysics Data System (ADS)

    Bondi, M.; Marchã, M. J. M.; Dallacasa, D.; Stanghellini, C.

    2001-08-01

    The 200-mJy sample, defined by Marchã et al., contains about 60 nearby, northern, flat-spectrum radio sources. In particular, the sample has proved effective at finding nearby radio-selected BL Lac objects with radio luminosities comparable to those of X-ray-selected objects, and low-luminosity flat-spectrum weak emission-line radio galaxies (WLRGs). The 200-mJy sample contains 23 BL Lac objects (including 6 BL Lac candidates) and 19 WLRGs. We will refer to these subsamples as the 200-mJy BL Lac sample and the 200-mJy WLRG sample, respectively. We have started a systematic analysis of the morphological pc-scale properties of the 200-mJy radio sources using VLBI observations. This paper presents VLBI observations at 5 and 1.6GHz of 14 BL Lac objects and WLRGs selected from the 200-mJy sample. The pc-scale morphology of these objects is briefly discussed. We derive the radio beaming parameters of the 200-mJy BL Lac objects and WLRGs and compare them with those of other BL Lac samples and with a sample of FR I radio galaxies. The overall broad-band radio, optical and X-ray properties of the 200-mJy BL Lac sample are discussed and compared with those of other BL Lac samples, radio- and X-ray-selected. We find that the 200-mJy BL Lac objects fill the gap between HBL and LBL objects in the colour-colour plot, and have intermediate αXOX as expected in the spectral energy distribution unification scenario. Finally, we briefly discuss the role of the WLRGs.

  15. Nucleophilic substitution by amide nitrogen in the aromatic rings of [zn - H]˙⁺ ions; the structures of the [b₂ - H - 17]˙⁺ and [c1 - 17]⁺ ions.

    PubMed

    Mu, Xiaoyan; Lau, Justin Kai-Chi; Lai, Cheuk-Kuen; Siu, K W Michael; Hopkinson, Alan C; Chu, Ivan K

    2016-04-28

    Peptide radical cations that contain an aromatic amino acid residue cleave to give [zn - H]˙⁺ ions with [b2 - H - 17]˙⁺ and [c1 - 17](+) ions, the dominant products in the dissociation of [zn - H]˙⁺, also present in lower abundance in the CID spectra. Isotopic labeling in the aromatic ring of [Yπ˙GG](+) establishes that in the formation of [b2 - H - 17]˙⁺ ions a hydrogen from the δ-position of the Y residue is lost, indicating that nucleophilic substitution on the aromatic ring has occurred. A preliminary DFT investigation of nine plausible structures for the [c1 - 17](+) ion derived from [Y(π)˙GG](+) shows that two structures resulting from attack on the aromatic ring by oxygen and nitrogen atoms from the peptide backbone have significantly better energies than other isomers. A detailed study of [Y(π)˙GG](+) using two density functionals, B3LYP and M06-2X, with a 6-31++G(d,p) basis set gives a higher barrier for attack on the aromatic ring of the [zn - H]˙⁺ ion by nitrogen than by the carbonyl oxygen. However, subsequent rearrangements involving proton transfers are much higher in energy for the oxygen-substituted isomer leading to the conclusion that the [c1 - 17](+) ions are the products of nucleophilic attack by nitrogen, protonated 2,7-dihydroxyquinoline ions. The [b2 - H - 17]˙⁺ ions are formed by loss of glycine from the same intermediates involved in the formation of the [c1 - 17](+) ions.

  16. Competitive reaction pathways for o-anilide aryl radicals: 1,5- or 1,6-hydrogen transfer versus nucleophilic coupling reactions. A novel rearrangement to afford an amidyl radical.

    PubMed

    Rey, Valentina; Pierini, Adriana B; Peñéñory, Alicia B

    2009-02-06

    The photoinduced reactions of o-iodoanilides (o-IC6H4N(Me)COR, 4a-d) with sulfur nucleophiles such as thiourea anion (1, -SCNH(NH2)), thioacetate anion (2, MeCOS-), and sulfide anion (3, S(2-)) follow different reaction channels, giving the sulfides by a radical nucleophilic substitution or the dehalogenated products by hydrogen atom transfer pathways. After an initial photoinduced electron transfer (PET) from 1 to iodide 4, the o-amide aryl radicals 12 are generated. These aryl radicals 12 afford alternative reaction pathways depending on the structure of the alpha-carbonyl moiety: (a) 12b (R = Me) adds to 1 to render the methylthio-substituted compounds by quenching the thiolate anion intermediate with MeI after irradiation; (b) 12c (R = -CH2Ph) follows a 1,5-hydrogen transfer to give a stabilized alpha-carbonyl radical (17); and (c) 12d (R = t-Bu) affords 1,6-hydrogen transfer, followed by a 1,4-aryl migration to render an amidyl radical (20), which is reduced to the N-benzyl-N,2-dimethylpropanamide (10). Together with this last rearranged product, the ipso substitution derivative was also observed. Similar results were obtained in the PET reactions of 4d (R = t-Bu) with anions 2 and 3 under entrainment conditions with the enolate anion from cyclohexenone (5) or the tert-butoxide anion (6). From this novel rearrangement, and only under reductive conditions by PET reaction with anion 5, iodide 4d (R = t-Bu) affords quantitatively the propanamide 10. The energetic of the intramolecular rearrangements followed by radicals 12b-d were rationalized by B3LYP/6-31+G* calculations.

  17. Printing. Performance Objectives. Intermediate Course.

    ERIC Educational Resources Information Center

    Seivert, Chester

    Several intermediate performance objectives and corresponding criterion measures are listed for each of 13 terminal objectives for an intermediate printing course. The materials were developed for a two-semester (3 hours daily) course with specialized classroom, shop, and practical experiences designed to enable the student to develop proficiency…

  18. Masonry. Performance Objectives. Intermediate Course.

    ERIC Educational Resources Information Center

    Thompson, Moses

    Several intermediate performance objectives and corresponding criterion measures are listed for each of 13 terminal objectives for an intermediate masonry course. These materials, developed for a two-semester (3 hours daily) course, are designed to provide the student with the skills and knowledge necessary for entry level employment in the field…

  19. Welding. Performance Objectives. Intermediate Course.

    ERIC Educational Resources Information Center

    Vincent, Kenneth

    Several intermediate performance objectives and corresponding criterion measures are listed for each of nine terminal objectives for an intermediate welding course. The materials were developed for a 36-week (3 hours daily) course designed to prepare the student for employment in the field of welding. Electric welding and specialized (TIG & MIG)…

  20. Dee-Mack Intermediate School

    ERIC Educational Resources Information Center

    Northwest Evaluation Association, 2012

    2012-01-01

    Frank Reliford, the Principal at Dee-Mack Intermediate since 2005, is familiar to almost every child in the community. 260 Students attend Reliford's school, and their status is a point of pride: Dee-Mack Intermediate is consistently one of the highest performing schools in the state. The change in student performance correlates to the…

  1. Thiol-ene "click" reaction triggered by neutral ionic liquid: the "ambiphilic" character of [hmim]Br in the regioselective nucleophilic hydrothiolation.

    PubMed

    Kumar, Rajesh; Saima; Shard, Amit; Andhare, Nitin H; Richa; Sinha, Arun K

    2015-01-12

    Thiol-ene "click" chemistry has emerged as a powerful strategy to construct carbon-heteroatom (C-S) bonds, which generally results in the formation of two regioisomers. To this end, the neutral ionic liquid [hmim]Br has been explored as a solvent cum catalyst for the synthesis of linear thioethers from activated and inactivated styrene derivatives or secondary benzyl alcohols and thiols without the requirement of using a metal complex, base, or free radical initiator. Furthermore, detailed mechanistic investigations using (1)H NMR spectroscopy and quadrupole time-of-flight electrospray ionization mass spectrometry (Q-TOF ESI-MS) revealed that the "ambiphilic" character of the ionic liquid promotes the nucleophilic addition of thiol to styrene through an anti-Markovnikov pathway. The catalyst recyclability and the extension of the methodology for thiol-yne click chemistry are additional benefits. A competitive study among thiophenol, styrene, and phenyl acetylene revealed that the rate of reaction is in the order of thiol-yne>thiol-ene>dimerization of thiol in [hmim]Br.

  2. Impact of Lewis base on chemical reactivity and separation efficiency for hydrated fourth-row transition metal (II) complexes: an ONIOM DFT/MM study.

    PubMed

    He, Dingsheng; Ma, Ming

    2014-04-24

    In this paper, two-layer ONIOM combinations of high-level quantum mechanics (QM) and inexpensive molecular mechanics (MM) are successfully used to investigate the structural characters of metal (M, all the transition metals in the fourth period)-H2O-Lewis base (A(-)) complexes. Global and local descriptors of chemical reactivity and selectivity from conceptual density functional theory are employed to show the properties of the active complexes of M(H2O)2A2 and to study the effect of the Lewis base for the separation of transition metal ions. It is shown that chemical potential, hardness, electrophilicity, as well as the dual and multiphilic descriptors are adequate for characterizing the global and local reactivity trends of the M(H2O)2A2 complex. It is found that the reactivity is well localized at the metallic center in M(H2O)2A2 and the dual descriptor (ΔfM(r)) can also be used to characterize the directional attack of the electrophile and nucleophile except for the selectivity of the reaction. On the basis of the values of ωM and Δsk, and the sign of ΔfM(r), the selectivity of the nucleophilic reagent (R(-)) for M(II) in M(H2O)2A2 (from high to low) follows this order: Cu(II) > Ni(II) > Co(II) > Fe(II) ≫ Mn(II) > Zn(II) > Cr(II). The Lewis base (A(-)) improves chemical reactivity and selectivity because of changing the reaction path and forming an intermediate, which possesses the higher antibonding character and the larger HOMO/LUMO gap. NBO or AIMALL analysis and Frontier orbital theory results presented here provided more theoretical support for the above reactivity and selectivity studies.

  3. Intermediate dosimetric quantities.

    PubMed

    Kellerer, A M; Hahn, K; Rossi, H H

    1992-04-01

    The transfer of energy from ionizing radiation to matter involves a series of steps. In wide ranges of their energy spectra photons and neutrons transfer energy to an irradiated medium almost exclusively by the production of charged particles which ionize and thereby produce electrons that can ionize in turn. The examination of these processes leads to a series of intermediate quantities. One of these is kerma, which has long been employed as a measure of the energy imparted in the first of the interactions. It depends only on the fluence of uncharged particles and is therefore--unlike absorbed dose and electron fluence--insensitive to local differences of receptor geometry and composition. An analogous quantity for charged-particle fields, cema (converted energy per unit mass), is defined, which quantifies the energy imparted in terms of the interactions of charged particles, disregarding energy dissipation by secondary electrons. Cema can be expressed as an integral over the fluence of ions times their stopping power. However, complications arise when the charged particles are electrons, and when their fluence cannot be separated from that of the secondaries. The resulting difficulty can be circumvented by the definition of reduced cema. This quantity corresponds largely to the concept employed in the cavity theory of Spencer and Attix. In reduced cema not all secondary electrons but all electrons below a chosen cutoff energy, delta, are considered to be absorbed locally. When the cutoff energy is reduced, cema approaches absorbed dose and thereby becomes sensitive to highly local differences in geometry or composition. With larger values of delta, reduced cema is a useful parameter to specify the dose-generating potential of a charged-particle field 'free in air' or in vacuo. It is nearly equal to the mean absorbed dose in a sphere with radius equal to the range of electrons of energy delta. Reduced cema is a function of the fluence at the specified location at

  4. Differential protein labeling based on electrochemically generated reactive intermediates.

    PubMed

    Büter, Lars; Faber, Helene; Wigger, Tina; Vogel, Martin; Karst, Uwe

    2015-10-06

    A specific labeling method for cysteine moieties in proteins was developed. Electrochemical oxidation of phenolic compounds such as phenol or acetaminophen leads to the generation of the reactive intermediates benzoquinone and N-acetyl-p-benzoquinone imine, which can subsequently react with nucleophilic thiol functions in peptides or proteins. Differential labeling of cysteine residues was successfully demonstrated with native as well as heavy-isotope labeled forms of the corresponding labeling compounds. The specific mass differences on the peptide level were successfully analyzed by mass spectrometry for the tripeptide glutathione. Free cysteines in various proteins such as β-lactoglobulin A, human serum albumin, hemoglobin, and human carbonic anhydrase I were successfully labeled. Tryptic digestion of differentially labeled carbonic anhydrase I and hemoglobin allowed the identification of the binding site in the proteins. The obtained mass difference allowed an easy identification of the cysteine containing peptides. With these experiments, it was successfully demonstrated that the developed method can serve as a tool for counting cysteine moieties in proteins and, thus, be used as an additional technique in protein identification experiments.

  5. Isoporphyrin Intermediate in Heme Oxygenase Catalysis

    PubMed Central

    Evans, John P.; Niemevz, Fernando; Buldain, Graciela; de Montellano, Paul Ortiz

    2008-01-01

    Human heme oxygenase-1 (hHO-1) catalyzes the O2- and NADPH-dependent oxidation of heme to biliverdin, CO, and free iron. The first step involves regiospecific insertion of an oxygen atom at the α-meso carbon by a ferric hydroperoxide and is predicted to proceed via an isoporphyrin π-cation intermediate. Here we report spectroscopic detection of a transient intermediate during oxidation by hHO-1 of α-meso-phenylheme-IX, α-meso-(p-methylphenyl)-mesoheme-III, and α-meso-(p-trifluoromethylphenyl)-mesoheme-III. In agreement with previous experiments (Wang, J., Niemevz, F., Lad, L., Huang, L., Alvarez, D. E., Buldain, G., Poulos, T. L., and Ortiz de Montellano, P. R. (2004) J. Biol. Chem. 279, 42593–42604), only the α-biliverdin isomer is produced with concomitant formation of the corresponding benzoic acid. The transient intermediate observed in the NADPH-P450 reductase-catalyzed reaction accumulated when the reaction was supported by H2O2 and exhibited the absorption maxima at 435 and 930 nm characteristic of an isoporphyrin. Product analysis by reversed phase high performance liquid chromatography and liquid chromatography electrospray ionization mass spectrometry of the product generated with H2O2 identified it as an isoporphyrin that, on quenching, decayed to benzoylbiliverdin. In the presence of H218O2, one labeled oxygen atom was incorporated into these products. The hHO-1-isoporphyrin complexes were found to have half-lives of 1.7 and 2.4 h for the p-trifluoromethyl- and p-methyl-substituted phenylhemes, respectively. The addition of NADPH-P450 reductase to the H2O2-generated hHO-1-isoporphyrin complex produced α-biliverdin, confirming its role as a reaction intermediate. Identification of an isoporphyrin intermediate in the catalytic sequence of hHO-1, the first such intermediate observed in hemoprotein catalysis, completes our understanding of the critical first step of heme oxidation. PMID:18487208

  6. Linking chemical electron-proton transfer to proton pumping in cytochrome c oxidase: broken-symmetry DFT exploration of intermediates along the catalytic reaction pathway of the iron-copper dinuclear complex.

    PubMed

    Noodleman, Louis; Han Du, Wen-Ge; Fee, James A; Götz, Andreas W; Walker, Ross C

    2014-07-07

    After a summary of the problem of coupling electron and proton transfer to proton pumping in cytochrome c oxidase, we present the results of our earlier and recent density functional theory calculations for the dinuclear Fe-a3-CuB reaction center in this enzyme. A specific catalytic reaction wheel diagram is constructed from the calculations, based on the structures and relative energies of the intermediate states of the reaction cycle. A larger family of tautomers/protonation states is generated compared to our earlier work, and a new lowest-energy pathway is proposed. The entire reaction cycle is calculated for the new smaller model (about 185-190 atoms), and two selected arcs of the wheel are chosen for calculations using a larger model (about 205 atoms). We compare the structural and redox energetics and protonation calculations with available experimental data. The reaction cycle map that we have built is positioned for further improvement and testing against experiment.

  7. A nucleophilic catalysis step is involved in the hydrolysis of aryl phosphate monoesters by human CT acylphosphatase.

    PubMed

    Paoli, Paolo; Pazzagli, Luigia; Giannoni, Elisa; Caselli, Anna; Manao, Giampaolo; Camici, Guido; Ramponi, Giampietro

    2003-01-03

    Acylphosphatase, one of the smallest enzymes, is expressed in all organisms. It displays hydrolytic activity on acyl phosphates, nucleoside di- and triphosphates, aryl phosphate monoesters, and polynucleotides, with acyl phosphates being the most specific substrates in vitro. The mechanism of catalysis for human acylphosphatase (the organ-common type isoenzyme) was investigated using both aryl phosphate monoesters and acyl phosphates as substrates. The enzyme is able to catalyze phosphotransfer from p-nitrophenyl phosphate to glycerol (but not from benzoyl phosphate to glycerol), as well as the inorganic phosphate-H(2)18O oxygen exchange reaction in the absence of carboxylic acids or phenols. In short, our findings point to two different catalytic pathways for aryl phosphate monoesters and acyl phosphates. In particular, in the aryl phosphate monoester hydrolysis pathway, an enzyme-phosphate covalent intermediate is formed, whereas the hydrolysis of acyl phosphates seems a more simple process in which the Michaelis complex is attacked directly by a water molecule generating the reaction products. The formation of an enzyme-phosphate covalent complex is consistent with the experiments of isotope exchange and transphosphorylation from substrates to glycerol, as well as with the measurements of the Brønsted free energy relationships using a panel of aryl phosphates with different structures. His-25 involvement in the formation of the enzyme-phosphate covalent complex during the hydrolysis of aryl phosphate monoesters finds significant confirmation in experiments performed with the H25Q mutated enzyme.

  8. Modifications of substituted seryl and threonyl residues in phosphopeptides and a polysialoglycoprotein by beta-elimination and nucleophile additions.

    PubMed

    Mega, T; Nakamura, N; Ikenaka, T

    1990-01-01

    The beta-elimination and nucleophile addition reactions of the substituted serine and threonine residues were studied using several synthesized fluorescence-labeled phosphopeptides and a salmon egg polysialoglycoprotein (PSGP). The reagents used were 1 M CH3SH-0.43 M NaOH, 1 M NaBH4-0.1 M NaOH, 1 M CH3NH2-0.1 M NaOH, and 1 M Na2SO3-0.1 M NaOH. The beta-elimination reaction of a phosphoserine peptide, Gly-Ser(PO4)-Glu-AEAP, was about 20 times faster than that of the corresponding phosphothreonine peptide. The carboxyl-side amino acid of the phosphoamino acids in peptides greatly affected the beta-elimination rate. The beta-elimination reaction rates of O-glycosyl serine and threonine in the polysialoglycoprotein were similar and were about a half of that of the phosphoserine peptide. The rates of addition of the three nucleophiles and hydrogen to alpha-aminoacrylic acid (beta-elimination product of substituted serine) in the peptide decreased in the order of CH3SH, Na2SO3, CH3NH2, and H2(NaBH4), and the addition to alpha-aminocrotonic acid (beta-elimination product of substituted threonine) in the order of Na2SO3, CH3NH2, CH3SH, and H2. These results indicated that sulfite is the most recommended nucleophile because of its high addition rate. If sulfite addition is carried out in the presence of NaBH4, sugar chains can be released as alditols, converting the sugar-attaching amino acids to beta-sulfoamino acids.

  9. Tachyon field in intermediate inflation

    SciTech Connect

    Campo, Sergio del; Herrera, Ramon; Toloza, Adolfo

    2009-04-15

    The tachyonic inflationary universe model in the context of intermediate inflation is studied. General conditions for this model to be realizable are discussed. In the slow-roll approximation, we describe in great detail the characteristics of this model.

  10. Tandem SN2' nucleophilic substitution/oxidative radical cyclization of aryl substituted allylic alcohols with 1,3-dicarbonyl compounds.

    PubMed

    Zhang, Zhen; Li, Cheng; Wang, Shao-Hua; Zhang, Fu-Min; Han, Xue; Tu, Yong-Qiang; Zhang, Xiao-Ming

    2017-03-23

    A novel and efficient tandem SN2' nucleophilic substitution/oxidative radical cyclization reaction of aryl substituted allylic alcohols with 1,3-dicarbonyl compounds has been developed by using Mn(OAc)3 as an oxidant, which enables the expeditious synthesis of polysubstituted dihydrofuran (DHF) derivatives in moderate to high yields. The use of weakly acidic hexafluoroisopropanol (HFIP) as the solvent rather than AcOH has successfully improved the yields and expanded the substrate scope of this type of radical cyclization reactions. Mechanistic studies confirmed the cascade reaction process involving a final radical cyclization.

  11. CO2-Mediated Formation of Chiral Carbamates from meso-Epoxides via Polycarbonate Intermediates.

    PubMed

    Liu, Ye; Ren, Wei-Min; He, Ke-Ke; Zhang, Wen-Zhen; Li, Wen-Bing; Wang, Meng; Lu, Xiao-Bing

    2016-10-07

    Carbon dioxide has attracted broad interest as a renewable C1 feedstock for efficient transformation into value-added organic chemicals; nevertheless, far less attention was paid to its stereochemically controlled catalytic fixation/conversion processes. Here, we report a new strategy for the selective synthesis of chiral carbamates from carbon dioxide via polycarbonate intermediates, which are formed by the desymmetric copolymerization of meso-epoxides using enantiopure dinuclear Co(III) catalyst systems with 99% enantioselectivity. Subsequent degradation reaction of the resultant polycarbonates with various primary or secondary amine nucleophiles can afford optically active carbamates, with the complete configuration retention of the two chiral carbon centers. Our accomplishment reported here opens up a new route to prepare a wide range of CO2-based carbamate scaffolds with excellent yields and 99% enantiomeric excess.

  12. Catalytic water oxidation by mononuclear Ru complexes with an anionic ancillary ligand.

    PubMed

    Tong, Lianpeng; Inge, A Ken; Duan, Lele; Wang, Lei; Zou, Xiaodong; Sun, Licheng

    2013-03-04

    Mononuclear Ru-based water oxidation catalysts containing anionic ancillary ligands have shown promising catalytic efficiency and intriguing properties. However, their insolubility in water restricts a detailed mechanism investigation. In order to overcome this disadvantage, complexes [Ru(II)(bpc)(bpy)OH2](+) (1(+), bpc = 2,2'-bipyridine-6-carboxylate, bpy = 2,2'-bipyridine) and [Ru(II)(bpc)(pic)3](+) (2(+), pic = 4-picoline) were prepared and fully characterized, which features an anionic tridentate ligand and has enough solubility for spectroscopic study in water. Using Ce(IV) as an electron acceptor, both complexes are able to catalyze O2-evolving reaction with an impressive rate constant. On the basis of the electrochemical and kinetic studies, a water nucleophilic attack pathway was proposed as the dominant catalytic cycle of the catalytic water oxidation by 1(+), within which several intermediates were detected by MS. Meanwhile, an auxiliary pathway that is related to the concentration of Ce(IV) was also revealed. The effect of anionic ligand regarding catalytic water oxidation was discussed explicitly in comparison with previously reported mononuclear Ru catalysts carrying neutral tridentate ligands, for example, 2,2':6',2″-terpyridine (tpy). When 2(+) was oxidized to the trivalent state, one of its picoline ligands dissociated from the Ru center. The rate constant of picoline dissociation was evaluated from time-resolved UV-vis spectra.

  13. The structure of formylmethanofuran: tetrahydromethanopterin formyltransferase in complex with its coenzymes.

    PubMed

    Acharya, Priyamvada; Warkentin, Eberhard; Ermler, Ulrich; Thauer, Rudolf K; Shima, Seigo

    2006-03-31

    Formylmethanofuran:tetrahydromethanopterin formyltransferase is an essential enzyme in the one-carbon metabolism of methanogenic and sulfate-reducing archaea and of methylotrophic bacteria. The enzyme, which is devoid of a prosthetic group, catalyzes the reversible formyl transfer between the two substrates coenzyme methanofuran and coenzyme tetrahydromethanopterin (H4MPT) in a ternary complex catalytic mechanism. The structure of the formyltransferase without its coenzymes has been determined earlier. We report here the structure of the enzyme in complex with both coenzymes at a resolution of 2.0 A. Methanofuran, characterized for the first time in an enzyme structure, is embedded in an elongated cleft at the homodimer interface and fixed by multiple hydrophobic interactions. In contrast, tetrahydromethanopterin is only weakly bound in a shallow and wide cleft that provides two binding sites. It is assumed that the binding of the bulky coenzymes induces conformational changes of the polypeptide in the range of 3A that close the H4MPT binding cleft and position the reactive groups of both substrates optimally for the reaction. The key residue for substrate binding and catalysis is the strictly conserved Glu245. Glu245, embedded in a hydrophobic region and completely buried upon tetrahydromethanopterin binding, is presumably protonated prior to the reaction and is thus able to stabilize the tetrahedral oxyanion intermediate generated by the nucleophilic attack of the N5 atom of tetrahydromethanopterin onto the formyl carbon atom of formylmethanofuran.

  14. Oxygenation of Organoboronic Acids by a Nonheme Iron(II) Complex: Mimicking Boronic Acid Monooxygenase Activity.

    PubMed

    Chatterjee, Sayanti; Paine, Tapan Kanti

    2015-10-19

    Phenolic compounds are important intermediates in the bacterial biodegradation of aromatic compounds in the soil. An Arthrobacter sp. strain has been shown to exhibit boronic acid monooxygenase activity through the conversion of different substituted phenylboronic acids to the corresponding phenols using dioxygen. While a number of methods have been reported to cleave the C-B bonds of organoboronic acids, there is no report on biomimetic iron complex exhibiting this activity using dioxygen as the oxidant. In that direction, we have investigated the reactivity of a nucleophilic iron-oxygen oxidant, generated upon oxidative decarboxylation of an iron(II)-benzilate complex [(Tp(Ph2))Fe(II)(benzilate)] (Tp(Ph2) = hydrotris(3,5-diphenyl-pyrazol-1-yl)borate), toward organoboronic acids. The oxidant converts different aryl/alkylboronic acids to the corresponding oxygenated products with the incorporation of one oxygen atom from dioxygen. This method represents an efficient protocol for the oxygenation of boronic acids with dioxygen as the terminal oxidant.

  15. Revisiting the Dielectric Constant Effect on the Nucleophile and Leaving Group of Prototypical Backside Sn2 Reactions: a Reaction Force and Atomic Contribution Analysis.

    PubMed

    Pedraza-González, Laura Milena; Galindo, Johan Fabian; Gonzalez, Ronald; Reyes, Andrés

    2016-10-09

    The solvent effect on the nucleophile and leaving group atoms of the prototypical F(-) + CH3Cl → CH3F + Cl(-) backside bimolecular nucleophilic substitution reaction (SN2) is analyzed employing the reaction force and the atomic contributions methods on the intrinsic reaction coordinate (IRC). Solvent effects were accounted for using the polarizable continuum solvent model. Calculations were performed employing eleven dielectric constants, ε, ranging from 1.0 to 78.5, to cover a wide spectrum of solvents. The reaction force data reveals that the solvent mainly influences the region of the IRC preceding the energy barrier, where the structural rearrangement to reach the transition state occurs. A detailed analysis of the atomic role in the reaction as a function of ε reveals that the nucleophile and the carbon atom are the ones that contribute the most to the energy barrier. In addition, we investigated the effect of the choice of nucleophile and leaving group on the ΔE0 and ΔE(↕) of Y(-) + CH3X → YCH3 + X(-) (X,Y= F, Cl, Br, I) in aqueous solution. Our analysis allowed us to find relationships between the atomic contributions to the activation energy and leaving group ability and nucleophilicity.

  16. Facile nucleophilic fluorination reactions using tert-alcohols as a reaction medium: significantly enhanced reactivity of alkali metal fluorides and improved selectivity.

    PubMed

    Kim, Dong Wook; Jeong, Hwan-Jeong; Lim, Seok Tae; Sohn, Myung-Hee; Katzenellenbogen, John A; Chi, Dae Yoon

    2008-02-01

    Although protic solvents are generally not preferred for nucleophilic displacement reactions because of their partial positive charge and hydrogen-bonding capacity that solvate the nucleophile and reduce its reactivity, we recently reported a remarkably beneficial effect of using tertiary alcohols as a reaction media for nucleophilic fluorination with alkali metal fluorides, as well as fluorine-18 radiolabeling with [18F]fluoride ion for the preparation of PET radiopharmaceuticals. In this work, we investigate further the influence of the tert-alcohol reaction medium for nucleophilic fluorination with alkali metal fluorides by studying various interactions among tert-alcohols, the alkali metal fluoride (CsF), and the sulfonyloxy substrate. Factors such as hydrogen bonding between CsF and the tert-alcohol solvent, the formation of a tert-alcohol solvated fluoride, and hydrogen bonding between the sulfonate leaving group and the tert-alcohol appear to contribute to the dramatic increase in the rate of the nucleophilic fluorination reaction in the absence of any kind of catalyst. We found that fluorination of 1-(2-mesyloxyethyl)naphthalene (5) and N-5-bromopentanoyl-3,4-dimethoxyaniline (8) with Bu(4)N(+)F(-) in a tert-alcohol afforded the corresponding fluoro products in much higher yield than obtained by the conventional methods using dipolar aprotic solvents. The protic medium also suppresses formation of byproducts, such as alkenes, ethers, and cyclic adducts.

  17. Linking Chemical Electron–Proton Transfer to Proton Pumping in Cytochrome c Oxidase: Broken-Symmetry DFT Exploration of Intermediates along the Catalytic Reaction Pathway of the Iron–Copper Dinuclear Complex

    PubMed Central

    2015-01-01

    After a summary of the problem of coupling electron and proton transfer to proton pumping in cytochrome c oxidase, we present the results of our earlier and recent density functional theory calculations for the dinuclear Fe-a3–CuB reaction center in this enzyme. A specific catalytic reaction wheel diagram is constructed from the calculations, based on the structures and relative energies of the intermediate states of the reaction cycle. A larger family of tautomers/protonation states is generated compared to our earlier work, and a new lowest-energy pathway is proposed. The entire reaction cycle is calculated for the new smaller model (about 185–190 atoms), and two selected arcs of the wheel are chosen for calculations using a larger model (about 205 atoms). We compare the structural and redox energetics and protonation calculations with available experimental data. The reaction cycle map that we have built is positioned for further improvement and testing against experiment. PMID:24960612

  18. Spectroscopic, Electrochemical and Computational Characterisation of Ru Species Involved in Catalytic Water Oxidation: Evidence for a [Ru(V) (O)(Py2 (Me) tacn)] Intermediate.

    PubMed

    Casadevall, Carla; Codolà, Zoel; Costas, Miquel; Lloret-Fillol, Julio

    2016-07-11

    A new family of ruthenium complexes based on the N-pentadentate ligand Py2 (Me) tacn (N-methyl-N',N''-bis(2-picolyl)-1,4,7-triazacyclononane) has been synthesised and its catalytic activity has been studied in the water-oxidation (WO) reaction. We have used chemical oxidants (ceric ammonium nitrate and NaIO4 ) to generate the WO intermediates [Ru(II) (OH2 )(Py2 (Me) tacn)](2+) , [Ru(III) (OH2 )(Py2 (Me) tacn)](3+) , [Ru(III) (OH)(Py2 (Me) tacn)](2+) and [Ru(IV) (O)(Py2 (Me) tacn)](2+) , which have been characterised spectroscopically. Their relative redox and pH stability in water has been studied by using UV/Vis and NMR spectroscopies, HRMS and spectroelectrochemistry. [Ru(IV) (O)(Py2 (Me) tacn)](2+) has a long half-life (>48 h) in water. The catalytic cycle of WO has been elucidated by using kinetic, spectroscopic, (18) O-labelling and theoretical studies, and the conclusion is that the rate-determining step is a single-site water nucleophilic attack on a metal-oxo species. Moreover, [Ru(IV) (O)(Py2 (Me) tacn)](2+) is proposed to be the resting state under catalytic conditions. By monitoring Ce(IV) consumption, we found that the O2 evolution rate is redox-controlled and independent of the initial concentration of Ce(IV) . Based on these facts, we propose herein that [Ru(IV) (O)(Py2 (Me) tacn)](2+) is oxidised to [Ru(V) (O)(Py2 (Me) tacn)](2+) prior to attack by a water molecule to give [Ru(III) (OOH)(Py2 (Me) tacn)](2+) . Finally, it is shown that the difference in WO reactivity between the homologous iron and ruthenium [M(OH2 )(Py2 (Me) tacn)](2+) (M=Ru, Fe) complexes is due to the difference in the redox stability of the key M(V) (O) intermediate. These results contribute to a better understanding of the WO mechanism and the differences between iron and ruthenium complexes in WO reactions.

  19. Four-mode quantum calculations of resonance states in complex-forming bimolecular reactions: Cl-+CH3Br

    NASA Astrophysics Data System (ADS)

    Schmatz, Stefan

    2005-06-01

    The vibrational resonance states of the complexes formed in the nucleophilic bimolecular substitution (SN2) reaction Cl-+CH3Br→ClCH3+Br- were calculated by means of the filter diagonalization method employing a coupled-cluster potential-energy surface and a Hamiltonian that incorporates an optical potential and is formulated in Radau coordinates for the carbon-halogen stretching modes. The four-dimensional model also includes the totally symmetric vibrations of the methyl group (C-H stretch and umbrella bend). The vast majority of bound states and many resonance states up to the first overtone of the symmetric stretching vibration in the exit channel complex have been calculated, analyzed, and assigned four quantum numbers. The resonances are classified into entrance channel, exit channel, and delocalized states. The resonance widths fluctuate over six orders of magnitude. In addition to a majority of Feshbach-type resonances there are also exceedingly long-lived shape resonances, which are associated with the entrance channel and can only decay by tunneling. The state-selective decay of the resonances was studied in detail. The linewidths of the resonances, and thus the coupling to the energetic continuum, increase with excitation in any mode. Due to the strong mixing of the many progressions in the intermolecular stretching modes of the intermediate complexes, this increase as a function of the corresponding quantum numbers is not monotonic, but exhibits pronounced fluctuations.

  20. Multicomponent reactions of phosphines, diynedioates, and aryl aldehydes generated furans appending reactive phosphorus ylides through cumulated trienoates as key intermediates: a phosphine α-addition-δ-evolvement of an anion pathway.

    PubMed

    Deng, Jie-Cheng; Chuang, Shih-Ching

    2014-11-07

    Multicomponent reactions of phosphines, diynedioates, and aryl aldehydes have been demonstrated, providing trisubstituted furans appending reactive phosphorus ylides, through cumulated trienoates as key intermediates. The proposed trienoate intermediates, 1,5-dipolar species formed via nucleophilic α-attack of phosphines toward diynedioates (α-addition-δ-evolvement of an anion, abbreviated αAδE), undergo addition to aryl aldehydes followed by 5-endo-dig cyclization, proton transfer, and resonance to give trisubstituted furans. Furthermore, the phosphorus ylides are oxidized to α-keto ester furans and utilized as Wittig reagents.

  1. Hydroxylamine as an oxygen nucleophile: substitution of sulfonamide by a hydroxyl group in benzothiazole-2-sulfonamides.

    PubMed

    Kamps, Jos J A G; Belle, Roman; Mecinović, Jasmin

    2013-02-21

    Benzothiazole-2-sulfonamides react with an excess of hydroxylamine in aqueous solutions to form 2-hydroxybenzothiazole, sulfur dioxide, and the corresponding amine. Mechanistic studies that employ a combination of structure-reactivity relationships, oxygen labeling experiments, and (in)direct detection of intermediates and products reveal that the reaction proceeds via oxygen attack, and that oxygen incorporated in the 2-hydroxybenzothiazole product derives from hydroxylamine. The reaction, which is performed under mild conditions, can be used as a deprotection method for cleavage of benzothiazole-2-sulfonyl-protected amino acids.

  2. Porous coordination polymers of diverse topologies based on a twisted tetrapyridylbiaryl: application as nucleophilic catalysts for acetylation of phenols.

    PubMed

    Seth, Saona; Venugopalan, Paloth; Moorthy, Jarugu Narasimha

    2015-01-26

    Porous coordination polymers (CPs) with partially uncoordinated pyridyl rings based on rationally designed polypyridyl linkers are appealing from the point of view of their application as nucleophilic catalysts. A D2d -symmetric tetradentate organic linker L, that is, 2,2',6,6'-tetramethoxy-3,3',5,5'-tetrakis(4-pyridyl)biphenyl, was designed and synthesized for metal-assisted self-assembly aimed at porous CPs. Depending on the nature of the metal ion and the counter anion, the ligand L is found to function as a 3- or 4-connecting building block leading to porous CPs of diverse topologies. The reaction of L with Zn(NO3 )2 and Cd(NO3 )2 yields porous 2 D CPs of "fes" topology, in which the tetrapyridyl linker L serves as a 3-connecting unit with its free pyridyl rings well exposed into the pores. The functional utility of these porous CPs containing uncoordinated pyridyl rings is demonstrated by employing them as efficient heterogeneous nucleophilic catalysts for acetylation of a number of phenols with varying electronic properties and reactivities.

  3. How Do Nutritional Antioxidants Really Work: Nucleophilic Tone and Para-Hormesis Versus Free Radical Scavenging in vivo

    PubMed Central

    Forman, Henry Jay; Davies, Kelvin J. A.; Ursini, Fulvio

    2013-01-01

    We present arguments for an evolution in our understanding of how antioxidants in fruits and vegetables exert their health-protective effects. There is much epidemiological evidence for disease prevention by dietary antioxidants and chemical evidence that such compounds react in one-electron reactions with free radicals in vitro. Nonetheless, kinetic constraints indicate that in vivo scavenging of radicals is ineffective in antioxidant defense. Instead, enzymatic removal of non-radical electrophiles, such as hydroperoxides, in two-electron redox reactions is the major antioxidant mechanism. Furthermore, we propose that a major mechanism of action for nutritional antioxidants is the paradoxical oxidative activation of the Nrf2 (NF-E2-related factor 2) signaling pathway, which maintains protective oxidoreductases and their nucleophilic substrates. This maintenance of ‘Nucleophilic Tone,’ by a mechanism that can be called ‘Para-Hormesis,’ provides a means for regulating physiological non-toxic concentrations of the non-radical oxidant electrophiles that boost antioxidant enzymes, and damage removal and repair systems (for proteins, lipids, and DNA), at the optimal levels consistent with good health. PMID:23747930

  4. A colorimetric detection of acrylamide in potato chips based on nucleophile-initiated thiol-ene Michael addition.

    PubMed

    Hu, Qinqin; Fu, Yingchun; Xu, Xiahong; Qiao, Zhaohui; Wang, Ronghui; Zhang, Ying; Li, Yanbin

    2016-02-07

    Acrylamide (AA), a neurotoxin and a potential carcinogen, has been found in various thermally processed foods such as potato chips, biscuits, and coffee. Simple, cost-effective, and sensitive methods for the rapid detection of AA are needed to ensure food safety. Herein, a novel colorimetric method was proposed for the visual detection of AA based on a nucleophile-initiated thiol-ene Michael addition reaction. Gold nanoparticles (AuNPs) were aggregated by glutathione (GSH) because of a ligand-replacement, accompanied by a color change from red to purple. In the presence of AA, after the thiol-ene Michael addition reaction between GSH and AA with the catalysis of a nucleophile, the sulfhydryl group of GSH was consumed by AA, which hindered the subsequent ligand-replacement and the aggregation of AuNPs. Therefore, the concentration of AA could be determined by the visible color change caused by dispersion/aggregation of AuNPs. This new method showed high sensitivity with a linear range from 0.1 μmol L(-1) to 80 μmol L(-1) and a detection limit of 28.6 nmol L(-1), and especially revealed better selectivity than the fluorescence sensing method reported previously. Moreover, this new method was used to detect AA in potato chips with a satisfactory result in comparison with the standard methods based on chromatography, which indicated that the colorimetric method can be expanded for the rapid detection of AA in thermally processed foods.

  5. Stereoselectivity of Michael Addition of P(X)-H-Type Nucleophiles to Cyclohexen-1-ylphosphine Oxide: The Case of Base-Selective Transformation.

    PubMed

    Jaklińska, Magdalena; Cordier, Marie; Stankevič, Marek

    2016-02-19

    Michael addition of phosphorus nucleophiles to the unsymmetrically substituted tert-butyl(1,4-cyclohexadien-3-yl)phosphine oxide and its derivatives has been described. The addition proceeds with the formation of the mixture of two isomeric products with good yield and diastereoselectivity. The reaction of tert-butyl(cyclohexen-1-yl)methylphosphine oxide with phosphorus nucleophiles is base sensitive and might afford two epimers which differ at one chirality center. The absolute configuration of the products has been assigned on the basis of conformational and (1)H NMR analysis, and the mechanism of the reaction has been discussed. The Michael addition of phosphorus nucleophiles is postulated to proceed with or without consecutive epimerization of two α-carbanions.

  6. Structural Insights into Intermediate Steps in the Sir2 Deacetylation Reaction

    SciTech Connect

    Hawse, William F.; Hoff, Kevin G.; Fatkins, David G.; Daines, Alison; Zubkova, Olga V.; Schramm, Vern L.; Zheng, Weiping; Wolberger, Cynthia

    2010-07-22

    Sirtuin enzymes comprise a unique class of NAD{sup +}-dependent protein deacetylases. Although structures of many sirtuin complexes have been determined, structural resolution of intermediate chemical steps are needed to understand the deacetylation mechanism. We report crystal structures of the bacterial sirtuin, Sir2Tm, in complex with an S-alkylamidate intermediate, analogous to the naturally occurring O-alkylamidate intermediate, and a Sir2Tm ternary complex containing a dissociated NAD{sup +} analog and acetylated peptide. The structures and biochemical studies reveal critical roles for the invariant active site histidine in positioning the reaction intermediate, and for a conserved phenylalanine residue in shielding reaction intermediates from base exchange with nicotinamide. The new structural and biochemical studies provide key mechanistic insight into intermediate steps of the Sir2 deacetylation reaction.

  7. A Highly Reactive Imidazolium-Bridged Dinucleotide Intermediate in Nonenzymatic RNA Primer Extension.

    PubMed

    Walton, Travis; Szostak, Jack W

    2016-09-14

    Because of its importance for the origin of life, the nonenzymatic copying of RNA templates has been the subject of intense study for several decades. Previous characterizations of template-directed primer extension using 5'-phosphoryl-2-methylimidazole-activated nucleotides (2-MeImpNs) as substrates have assumed a classical in-line nucleophilic substitution mechanism, in which the 3'-hydroxyl of the primer attacks the phosphate of the incoming monomer, displacing the 2-methylimidazole leaving group. However, we have found that the initial rate of primer extension depends on the pH and concentration at which the activated monomer is maintained prior to the primer extension reaction. These and other results suggest an alternative mechanism, in which two monomers react with each other to form an imidazolium-bridged dinucleotide intermediate, which then binds to the template. Subsequent attack of the 3'-hydroxyl of the primer displaces an activated nucleotide as the leaving group and results in extension of the primer by one nucleotide. Analysis of monomer solutions by NMR indicates formation of the proposed imidazolium-bridged dinucleotide in the expected pH-dependent manner. We have used synthetic methods to prepare material that is enriched in this proposed intermediate and show that it is a highly reactive substrate for primer extension. The formation of an imidazolium-bridged dinucleotide intermediate provides a mechanistic interpretation of previously observed catalysis by an activated nucleotide located downstream from the site of primer extension.

  8. Compact intermediates in RNA folding

    SciTech Connect

    Woodson, S.A.

    2011-12-14

    Large noncoding RNAs fold into their biologically functional structures via compact yet disordered intermediates, which couple the stable secondary structure of the RNA with the emerging tertiary fold. The specificity of the collapse transition, which coincides with the assembly of helical domains, depends on RNA sequence and counterions. It determines the specificity of the folding pathways and the magnitude of the free energy barriers to the ensuing search for the native conformation. By coupling helix assembly with nascent tertiary interactions, compact folding intermediates in RNA also play a crucial role in ligand binding and RNA-protein recognition.

  9. Intermediate and Definitive Cleft Rhinoplasty.

    PubMed

    Gary, Celeste; Sykes, Jonathan M

    2016-11-01

    Intermediate and definitive cleft rhinoplasties are a challenging part of definitive cleft care. The anatomy of the cleft nose is severely affected by the structural deficits associated with congenital orofacial clefting. A comprehensive understanding of the related anatomy is crucial for understanding how to improve the appearance and function in patients with secondary cleft nasal deformities. Timing of intermediate and definitive rhinoplasty should be carefully considered. A thorough understanding of advanced rhinoplasty techniques is an important part of providing adequate care for patients with these deformities.

  10. Intermediate tax sanctions: an overview.

    PubMed

    Peregrine, M W

    1997-07-01

    New federal tax law applies intermediate tax sanctions when tax-exempt organizations enter into so-called excess benefit transactions with corporate insiders. The sanctions take the form of a two-tiered penalty excise tax, which is assessed not on the tax-exempt organization itself but on the insider who receives the excess benefit and the organizational managers and board members who knowingly participate in an improper transaction. The intermediate tax sanctions, therefore, present tax-planning challenges for tax-exempt hospitals and integrated delivery systems as well as for 501(c)(4) HMOs. Forthcoming treasury regulations are expected to add clarity to the new law.

  11. Structure and reactivity of bis(silyl) dihydride complexes (PMe(3))(3)Ru(SiR(3))(2)(H)(2): model compounds and real intermediates in a dehydrogenative C-Si bond forming reaction.

    PubMed

    Dioumaev, Vladimir K; Yoo, Bok R; Procopio, Leo J; Carroll, Patrick J; Berry, Donald H

    2003-07-23

    A series of stable complexes, (PMe(3))(3)Ru(SiR(3))(2)(H)(2) ((SiR(3))(2) = (SiH(2)Ph)(2), 3a; (SiHPh(2))(2), 3b; (SiMe(2)CH(2)CH(2)SiMe(2)), 3c), has been synthesized by the reaction of hydridosilanes with (PMe(3))(3)Ru(SiMe(3))H(3) or (PMe(3))(4)Ru(SiMe(3))H. Compounds 3a and 3c adopt overall pentagonal bipyramidal geometries in solution and the solid state, with phosphine and silyl ligands defining trigonal bipyramids and ruthenium hydrides arranged in the equatorial plane. Compound 3a exhibits meridional phosphines, with both silyl ligands equatorial, whereas the constraints of the chelate in 3c result in both axial and equatorial silyl environments and facial phosphines. Although there is no evidence for agostic Si-H interactions in 3a and 3b, the equatorial silyl group in 3c is in close contact with one hydride (1.81(4) A) and is moderately close to the other hydride (2.15(3) A) in the solid state and solution (nu(Ru.H.Si) = 1740 cm(-)(1) and nu(RuH) = 1940 cm(-)(1)). The analogous bis(silyl) dihydride, (PMe(3))(3)Ru(SiMe(3))(2)(H)(2) (3d), is not stable at room temperature, but can be generated in situ at low temperature from the 16e(-) complex (PMe(3))(3)Ru(SiMe(3))H (1) and HSiMe(3). Complexes 3b and 3d have been characterized by multinuclear, variable temperature NMR and appear to be isostructural with 3a. All four complexes exhibit dynamic NMR spectra, but the slow exchange limit could not be observed for 3c. Treatment of 1 with HSiMe(3) at room temperature leads to formation of (PMe(3))(3)Ru(SiMe(2)CH(2)SiMe(3))H(3) (4b) via a CH functionalization process critical to catalytic dehydrocoupling of HSiMe(3) at higher temperatures. Closer inspection of this reaction between -110 and -10 degrees C by NMR reveals a plethora of silyl hydride phosphine complexes formed by ligand redistribution prior to CH activation. Above ca. 0 degrees C this mixture converts cleanly via silane dehydrogenation to the very stable tris(phosphine) trihydride carbosilyl complex 4b

  12. Enantioselective Reactions of 2-Sulfonylalkyl Phenols with Allenic Esters: Dynamic Kinetic Resolution and [4+2] Cycloaddition Involving ortho-Quinone Methide Intermediates.

    PubMed

    Chen, Ping; Wang, Kai; Guo, Wengang; Liu, Xianghui; Liu, Yan; Li, Can

    2017-03-20

    We report herein a dynamic kinetic resolution (DKR) involving ortho-quinone methide (o-QM) intermediates. In the presence of Et3 N and the cinchonine-derived nucleophilic catalyst D, the DKR of 2-sulfonylalkyl phenols with allenic esters afforded chiral benzylic sulfones in 57-79 % yield with good to excellent enantioselectivity (85-95 % ee). Furthermore, with 2-(tosylmethyl)sesamols or 2-(tosylmethyl)naphthols, from which stable o-QM substrates can be generated, a formal [4+2] cycloaddition delivered 4-aryl- or alkyl-substituted chromans with excellent enantioselectivity (88-97 % ee).

  13. An Effective Hamiltonian Molecular Orbital-Valence Bond (MOVB) Approach for Chemical Reactions Applied to the Nucleophilic Substitution Reaction of Hydrosulfide Ion and Chloromethane.

    PubMed

    Song, Lingchun; Mo, Yirong; Gao, Jiali

    2009-01-01

    An effective Hamiltonian mixed molecular orbital and valence bond (EH-MOVB) method is described to obtain an accurate potential energy surface for chemical reactions. Building upon previous results on the construction of diabatic and adiabatic potential surfaces using ab initio MOVB theory, we introduce a diabatic-coupling scaling factor to uniformly scale the ab initio off-diagonal matrix element H(12) such that the computed energy of reaction from the EH-MOVB method is in agreement with the target value. The scaling factor is very close to unity, resulting in minimal alteration of the potential energy surface of the original MOVB model. Furthermore, the relative energy between the reactant and product diabatic states in the EH-MOVB method can be improved to match the experimental energy of reaction. A key ingredient in the EH-MOVB theory is that the off-diagonal matrix elements are functions of all degrees of freedom of the system and the overlap matrix is explicitly evaluated. The EH-MOVB method has been applied to the nucleophilic substitution reaction between hydrosulfide and chloromethane to illustrate the methodology and the results were matched to reproduce the results from ab initio valence bond self-consistent valence bond (VBSCF) calculations. The diabatic coupling (the off-diagonal matrix element in the generalized secular equation) has small variations along the minimum energy reaction path in the EH-MOVB model, whereas it shows a maximum value at the transition state and has nearly zero values in the regions of the ion-dipole complexes from VBSCF calculations. The difference in the diabatic coupling stabilization is attributed to the large overlap integral in the computationally efficient MOVB method.

  14. Copper(I)- and copper(0)-promoted homocoupling and homocoupling-hydrodehalogenation reactions of dihalogenoclathrochelate precursors for C-C conjugated iron(II) bis-cage complexes.

    PubMed

    Varzatskii, Oleg A; Shul'ga, Sergey V; Belov, Alexander S; Novikov, Valentin V; Dolganov, Alexander V; Vologzhanina, Anna V; Voloshin, Yan Z

    2014-12-28

    Iron(II) dibromo- and diiodoclathrochelates undergo copper(I)-promoted reductive homocoupling in HMPA at 70-80 °C leading to C-C conjugated dibromo- and diiodo-bis-clathrochelates in high yields. Under the same conditions, their dichloroclathrochelate analog does not undergo the same homocoupling reaction, so the target dichloro-bis-cage product was obtained in high yield via dimerization of its heterodihalogenide iodochloromonomacrobicyclic precursor. The use of NMP as a solvent at 120-140 °C gave the mixture of bis-clathrochelates resulting from a tandem homocoupling-hydrodehalogenation reaction: the initial acetonitrile copper(I) solvato-complex at a high temperature underwent re-solvatation and disproportionation leading to Cu(II) ions and nano-copper, which promoted the hydrodehalogenation process even at room temperature. The most probable pathway of this reaction in situ includes hydrodehalogenation of the already formed dihalogeno-bis-clathrochelate via the formation of reduced anion radical intermediates. As a result, chemical transformations of the iron(II) dihalogenoclathrochelates in the presence of an acetonitrile copper(I) solvato-complex were found to depend both on the nature of halogen atoms in their ribbed chelate fragments and on reaction conditions (i.e. solvent and temperature). The C-C conjugated iron(II) dihalogeno-bis-clathrochelates easily undergo nucleophilic substitution with various N,S-nucleophiles giving ribbed-functionalized bis-cage species. These iron(II) complexes were characterized by elemental analysis, MALDI-TOF mass spectrometry, IR, UV-Vis, (1)H and (13)C NMR spectroscopy, and by X-ray diffraction; their electrochemical properties were studied by cyclic voltammetry. The isomeric shift values in (57)Fe Mössbauer spectra of such cage compounds allowed identifying them as low-spin iron(II) complexes, while those of the quadrupole splitting are the evidence for a significant TP distortion of their FeN6-coordination polyhedra

  15. The Identity of the Nucleophile Substitution may Influence Metal Interactions with the Cleavage Site of the Minimal Hammerhead Ribozyme

    PubMed Central

    Osborne, Edith M.; Ward, W. Luke; Ruehle, Max Z.; DeRose, Victoria J.

    2010-01-01

    Potential metal interactions with the cleavage site of a minimal hammerhead ribozyme (mHHRz) were probed using 31P NMR-detected Cd2+ titration studies of HHRz constructs containing a phosphorothioate (PS) modification at the cleavage site. The mHHRz nucleophile position was replaced by either a 2′-F or a 2′-NH2 in order to block cleavage activity during the study. The 2′-F/PS cleavage site mHHRz construct, in which the 2′-F should closely imitate the atom size and electronegativity of a 2′OH, demonstrates low levels of metal ion association (<1 ppm 31P chemical shift changes). This observation indicates that having an atom size and electrostatic properties that are similar to the 2′-OH are not the governing factors in allowing metal interactions with the scissile phosphate of the mHHRz. With a 2′-NH2 substitution, a large upfield change in 31P NMR chemical shift of the phosphorothioate peak (Δ~3 ppm with 6 equivalents added Cd2+) indicates observable Cd2+ interactions with the substituted site. Since a 2′-NH2, but not a 2′-F, can serve as a metal ligand, these data suggest that a metal ion interaction with the HHRz cleavage site may include both the scissile phosphate and the 2′ nucleophile. Control samples in which the 2′-NH2/PS unit is placed either next to the mHHRz cleavage site (at U16.1), in a duplex, or in a amUPSU dinucleotide, show much weaker interactions with Cd2+. Results with these control samples indicate that simply the presence of a 2′-NH2/PS unit does not create a strong metal binding site, reinforcing the possibility that the 2′-NH2-moderated Cd-PS interaction is specific to the mHHRz cleavage site. Upfield chemical shifts of both 31P and H2′ 1H resonances in amUPSU are observed with addition of Cd2+, consistent with the predicted metal coordination to both 2′-NH2 and phosphorothioate ligands. These data suggest that metal ion association with the HHRz cleavage site may include an interaction with the 2

  16. A transitional hydrolase to glycosynthase mutant by Glu to Asp substitution at the catalytic nucleophile in a retaining glycosidase.

    PubMed

    Aragunde, Hugo; Castilla, Estela; Biarnés, Xevi; Faijes, Magda; Planas, Antoni

    2014-05-07

    Glycosynthases from more than 16 glycosidase families have been developed for the efficient synthesis of oligosaccharides and glycoconjugates. β-1,3-1,4-Glucan oligo- and polysaccharides with defined sequences can be quantitatively achieved with the glycosynthases derived from Bacillus licheniformis β-1,3-1,4-glucanase. The screening of a nucleophile saturation library of this enzyme yielded the unexpected E134D mutant which has high glycosynthase efficiency (25% higher kcat than the best glycosynthase to date, E134S) but also retains some hydrolase activity (2% relative to the wild-type enzyme). Here, we report the biochemical and structural analyses of this mutant compared to E134S and wild-type enzymes. E134D shows a pH profile of general base catalysis for the glycosynthase activity, with a kinetic pKa (on kcat/KM) assigned to Glu138 of 5.8, whereas the same residue acts as a general acid in the hydrolase activity with the same pKa value. The pKa of Glu138 in the wt enzyme was 7.0, a high value due to the presence of the catalytic nucleophile Glu134 which destabilizes the conjugate base of Glu138. Thus, the pKa of Glu138 drops 1.1 pH units in the mutant relative to the wild-type enzyme meaning that the larger distance between carboxylates in positions 138 and 134 (5.6Å for wt, 7.0Å for E134D) and/or a new hydrogen bonding interaction with a third Asp residue (Asp136) in the mutant reduces the effect of the negatively charged Asp134. In consequence, the pKa of Glu138 has a similar pKa value in the E134D mutant than in the other glycosynthase mutants having a neutral residue in position 134. The behavior of the E134D mutant shows that shortening the side chain of the nucleophile, despite maintaining a carboxylate group, confers glycosynthase activity. Therefore E134D is a transitional hydrolase to glycosynthase mutation.

  17. Material Voices: Intermediality and Autism

    ERIC Educational Resources Information Center

    Trimingham, Melissa; Shaughnessy, Nicola

    2016-01-01

    Autism continues to be regarded enigmatically; a community that is difficult to access due to perceived disruptions of interpersonal connectedness. Through detailed observations of two children participating in the Arts and Humanities Research Council funded project "Imagining Autism: Drama, Performance and Intermediality as Interventions for…

  18. Learning through Literature: Geography, Intermediate.

    ERIC Educational Resources Information Center

    Sterling, Mary Ellen

    This resource book provides specific strategies and activities for integrating the intermediate geography curriculum with related children's literature selections. The book includes the following sections: (1) "World Geography Overview"; (2) "Oceans"; (3) "Polar Regions"; (4) "Islands"; (5) "Rain Forests"; (6) "Mountains"; (7) "Forests"; (8)…

  19. Intermediality and the Child Performer

    ERIC Educational Resources Information Center

    Budd, Natasha

    2016-01-01

    This report details examples of praxis in the creation and presentation of "Joy Fear and Poetry": an intermedial theatre performance in which children aged 7-12 years generated aesthetic gestures using a range of new media forms. The impetus for the work's development was a desire to make an intervention into habituated patterns of…

  20. AIDS Elementary/Intermediate Curriculum.

    ERIC Educational Resources Information Center

    Kellogg, Nancy Rader

    This Acquired Immune Deficiency Syndrome (AIDS) Curriculum was developed for intermediate elementary (5th, 6th, and 7th grade) students. It is an integrated unit that encompasses health, science, social studies, math, and language arts. The curriculum is comprised of nine class activities designed to meet the following objectives: (1) to determine…

  1. Conversation at the Intermediate Level

    ERIC Educational Resources Information Center

    Dunlop, Ian

    1975-01-01

    Discusses the use of free conversation, especially with regard to vocabulary. Recommends group discussion in the FL, using, at the intermediate level, limited, familiar vocabulary. At a higher level, words from a special technical vocabulary may be introduced, aurally and visually. A teaching example ("Traffic") is given with thorough…

  2. Crystal Structure of Biotin Carboxylase in Complex with Substrates and Implications for Its Catalytic Mechanism

    SciTech Connect

    Chou, C.; Yu, L; Tong, L

    2009-01-01

    Biotin-dependent carboxylases are widely distributed in nature and have important functions in many cellular processes. These enzymes share a conserved biotin carboxylase (BC) component, which catalyzes the ATP-dependent carboxylation of biotin using bicarbonate as the donor. Despite the availability of a large amount of biochemical and structural information on BC, the molecular basis for its catalysis is currently still poorly understood. We report here the crystal structure at 2.0 {angstrom} resolution of wild-type Escherichia coli BC in complex with its substrates biotin, bicarbonate, and Mg-ADP. The structure suggests that Glu{sup 296} is the general base that extracts the proton from bicarbonate, and Arg{sup 338} is the residue that stabilizes the enolate biotin intermediate in the carboxylation reaction. The B domain of BC is positioned closer to the active site, leading to a 2-{angstrom} shift in the bound position of the adenine nucleotide and bringing it near the bicarbonate for catalysis. One of the oxygen atoms of bicarbonate is located in the correct position to initiate the nucleophilic attack on ATP to form the carboxyphosphate intermediate. This oxygen is also located close to the N1' atom of biotin, providing strong evidence that the phosphate group, derived from decomposition of carboxyphosphate, is the general base that extracts the proton on this N1' atom. The structural observations are supported by mutagenesis and kinetic studies. Overall, this first structure of BC in complex with substrates offers unprecedented insights into the molecular mechanism for the catalysis by this family of enzymes.

  3. Iminoboronate Formation Leads to Fast and Reversible Conjugation Chemistry of α-Nucleophiles at Neutral pH.

    PubMed

    Bandyopadhyay, Anupam; Gao, Jianmin

    2015-10-12

    Bioorthogonal reactions that are fast and reversible under physiological conditions are in high demand for biological applications. Herein, it is shown that an ortho boronic acid substituent makes aryl ketones rapidly conjugate with α-nucleophiles at neutral pH. Specifically, 2-acetylphenylboronic acid and derivatives were found to conjugate with phenylhydrazine with rate constants of 10(2) to 10(3) M(-1) s(-1) , comparable to the fastest bioorthogonal conjugations known to date. (11) B NMR analysis revealed the varied extent of iminoboronate formation of the conjugates, in which the imine nitrogen forms a dative bond with boron. The iminoboronate formation activates the imines for hydrolysis and exchange, rendering these oxime/hydrazone conjugations reversible and dynamic under physiological conditions. The fast and dynamic nature of the iminoboronate chemistry should find wide applications in biology.

  4. Synthesis of enantiopure trifluoromethyl building blocks via a highly chemo- and diastereoselective nucleophilic trifluoromethylation of tartaric acid-derived diketones.

    PubMed

    Massicot, Fabien; Monnier-Benoit, Nicolas; Deka, Naba; Plantier-Royon, Richard; Portella, Charles

    2007-02-16

    A highly diastereoselective nucleophilic mono(trifluoromethylation) of a tartaric acid-based diketone, using trifluoromethyl(trimethyl)silane, afforded the corresponding gamma-keto trifluoromethylcarbinol. The scope and limitation of this reaction was studied. The acidic removal of the acetonide moiety protecting the two hydroxyl groups of the adducts was unsuccessful. Bis(O-methylation) of the aromatic derivatives under basic conditions, followed by acidic hydrolysis and oxidative cleavage, led to two different enantiopure products: an alpha-aryl-alpha-methoxy-alpha-trifluoromethyl ethanal and an alpha-aryl-alpha-methoxycarboxylic acid. The overall process is eventually an interesting way to convert one natural chiral raw material into two functionalized enantiopure building blocks including a trifluoromethyl one.

  5. 5(6)-anti-Substituted-2-azabicyclo[2.1.1]hexanes. A Nucleophilic Displacement Route

    PubMed Central

    Krow, Grant R.; Edupuganti, Ram; Gandla, Deepa; Choudhary, Amit; Lin, Guoliang; Sonnet, Philip E.; DeBrosse, Charles; Ross, Charles W.; Cannon, Kevin C.; Raines, Ronald T.

    2012-01-01

    Nucleophilic displacements of 5(6)-anti-bromo substituents in 2-azabicyclo[2.1.1]hexanes (methanopyrrolidines) have been accomplished. These displacements have produced 5-anti-X-6-anti-Y-difunctionalized-2-azabicyclo[2.1.1]hexanes containing bromo, fluoro, acetoxy, hydroxy, azido, imidazole, thiophenyl, and iodo substituents. Such displacements of anti-bromide ions require an amine nitrogen and are a function of the solvent and the choice of metal salt. Reaction rates were faster and product yields were higher in DMSO when compared to DMF and with CsOAc compared to NaOAc. Sodium or lithium salts gave products, except with NaF, where silver fluoride in nitromethane was best for substitution by fluoride. The presence of electron-withdrawing F, OAc, N3, Br, or SPh substituents in the 6-anti-position slows bromide displacements at the 5-anti-position. PMID:19799411

  6. Reaction of Hydrogen Sulfide with Disulfide and Sulfenic Acid to Form the Strongly Nucleophilic Persulfide*♦

    PubMed Central

    Cuevasanta, Ernesto; Lange, Mike; Bonanata, Jenner; Coitiño, E. Laura; Ferrer-Sueta, Gerardo; Filipovic, Milos R.; Alvarez, Beatriz

    2015-01-01

    Hydrogen sulfide (H2S) is increasingly recognized to modulate physiological processes in mammals through mechanisms that are currently under scrutiny. H2S is not able to react with reduced thiols (RSH). However, H2S, more precisely HS−, is able to react with oxidized thiol derivatives. We performed a systematic study of the reactivity of HS− toward symmetric low molecular weight disulfides (RSSR) and mixed albumin (HSA) disulfides. Correlations with thiol acidity and computational modeling showed that the reaction occurs through a concerted mechanism. Comparison with analogous reactions of thiolates indicated that the intrinsic reactivity of HS− is 1 order of magnitude lower than that of thiolates. In addition, H2S is able to react with sulfenic acids (RSOH). The rate constant of the reaction of H2S with the sulfenic acid formed in HSA was determined. Both reactions of H2S with disulfides and sulfenic acids yield persulfides (RSSH), recently identified post-translational modifications. The formation of this derivative in HSA was determined, and the rate constants of its reactions with a reporter disulfide and with peroxynitrite revealed that persulfides are better nucleophiles than thiols, which is consistent with the α effect. Experiments with cells in culture showed that treatment with hydrogen peroxide enhanced the formation of persulfides. Biological implications are discussed. Our results give light on the mechanisms of persulfide formation and provide quantitative evidence for the high nucleophilicity of these novel derivatives, setting the stage for understanding the contribution of the reactions of H2S with oxidized thiol derivatives to H2S effector processes. PMID:26269587

  7. Dechlorination of chloropicrin and 1,3-dichloropropene by hydrogen sulfide species: redox and nucleophilic substitution reactions.

    PubMed

    Zheng, Wei; Yates, Scott R; Papiernik, Sharon K; Guo, Mingxin; Gan, Jianying

    2006-03-22

    The chlorinated fumigants chloropicrin (trichloronitromethane) and 1,3-dichloropropene (1,3-D) are extensively used in agricultural production for the control of soilborne pests. The reaction of these two fumigants with hydrogen sulfide species (H2S and HS-) was examined in well-defined anoxic aqueous solutions. Chloropicrin underwent an extremely rapid redox reaction in the hydrogen sulfide solution. Transformation products indicated reductive dechlorination of chloropicrin by hydrogen sulfide species to produce dichloro- and chloronitromethane. The transformation of chloropicrin in hydrogen sulfide solution significantly increased with increasing pH, indicating that H2S is less reactive toward chloropicrin than HS- is. For both 1,3-D isomers, kinetics and transformation products analysis revealed that the reaction between 1,3-D and hydrogen sulfide species is an S(N)2 nucleophilic substitution process, in which the chlorine at C3 of 1,3-D is substituted by the sulfur nucleophile to form corresponding mercaptans. The 50% disappearance time (DT50) of 1,3-D decreased with increasing hydrogen sulfide species concentration at a constant pH. Transformation of 1,3-D was more rapid at high pH, suggesting that the reactivity of hydrogen sulfide species in the experimental system stems primarily from HS-. Because of the relatively low smell threshold values and potential environmental persistence of organic sulfur products yielded by the reaction of 1,3-D and HS-, the effects of reduced sulfide species should be considered in the development of alternative fumigation practices, especially in the integrated application of sulfur-containing fertilizers.

  8. Dramatic effects of halogen substitution and solvent on the rates and mechanisms of nucleophilic substitution reactions of aziridines.

    PubMed

    Banks, Harold D

    2008-04-04

    In a previous study we reported that fluorine substitution at the carbon positions of aziridine results in profound enhancements of the rate of reaction with ammonia, a typical nucleophile, in the gas phase. In this study the investigation is extended to include chloro- and bromoaziridines. Because syntheses are largely performed in the condensed phase, the present computational investigation [(MP2(Full)/6-311++G(d,p)//MP2(Full)/6-31+G(d) level] was conducted with three typical solvents that cover a wide range of polarity: THF, CH3CN, and H2O. Nucleophiles can react with haloaziridines 1 by displacing a substituted amide ion by means of an SN2 mechanism (pathway a), producing 1,2-diaminohaloethanes (from the initially formed dipolar species 2). Alternatively, a rearrangement mechanism involving rate-determining departure of a halide ion (pathway b) to form an imidoyl halide, 3, is possible. Transition-state theory was used to compute relative reaction rates of these mechanistic possibilities and to assess the role of the halogen substituents and the reaction solvent. Gas-phase results provided the basis of mechanistic insights that were more apparent in the absence of intermolecular interactions. Fluoroaziridines were found to react at accelerated rates relative to aziridine exclusively by means of the a Menshutkin-type mechanism (SN2) in each solvent tested, while the reactions of the chloro- and bromoaziridines could be directed toward 2 in the highly nonpolar solvent, cyclohexane, or toward 3 in the more polar solvents. An assessment is made of the feasibility of using this chemistry of the haloazirdines in the synthetic laboratory.

  9. Reactivity of Ir(III) carbonyl complexes with water: alternative by-product formation pathways in catalytic methanol carbonylation.

    PubMed

    Elliott, Paul I P; Haak, Susanne; Meijer, Anthony J H M; Sunley, Glenn J; Haynes, Anthony

    2013-12-21

    The reactions of water with a number of iridium(III) complexes relevant to the mechanism for catalytic methanol carbonylation are reported. The iridium acetyl, [Ir(CO)2I3(COMe)](-), reacts with water under mild conditions to release CO2 and CH4, rather than the expected acetic acid. Isotopic labeling and kinetic experiments are consistent with a mechanism involving nucleophilic attack by water on a terminal CO ligand of [Ir(CO)2I3(COMe)](-) to give an (undetected) hydroxycarbonyl species. Subsequent decarboxylation and elimination of methane gives [Ir(CO)2I2](-). Similar reactions with water are observed for [Ir(CO)2I3Me](-), [Ir(CO)2(NCMe)I2(COMe)] and [Ir(CO)3I2Me] with the neutral complexes exhibiting markedly higher rates. The results demonstrate that CO2 formation during methanol carbonylation is not restricted to the conventional water gas shift mechanism mediated by [Ir(CO)2I4](-) or [Ir(CO)3I3], but can arise directly from key organo-iridium(III) intermediates in the carbonylation cycle. An alternative pathway for methane formation not involving the intermediacy of H2 is also suggested. A mechanism is proposed for the conversion MeOH + CO → CO2 + CH4, which may account for the similar rates of formation of the two gaseous by-products during iridium-catalysed methanol carbonylation.

  10. Synthesis, Structural and Spectroscopic Characterization, and Reactivities of Mononuclear Cobalt(III)-Peroxo Complexes

    PubMed Central

    Cho, Jaeheung; Sarangi, Ritimukta; Kang, Hye Yeon; Lee, Jung Yoon; Kubo, Minoru; Ogura, Takashi; Solomon, Edward I.; Nam, Wonwoo

    2010-01-01

    Metal-dioxygen adducts are key intermediates detected in the catalytic cycles of dioxygen activation by metalloenzymes and biomimetic compounds. In this study, mononuclear cobalt(III)- peroxo complexes bearing tetraazamacrocyclic ligands, [Co(12-TMC)(O2)]+ and [Co(13-TMC)(O2)]+, were synthesized by reacting [Co(12-TMC)(CH3CN)]2+ and [Co(13-TMC)(CH3CN)]2+, respectively, with H2O2 in the presence of triethylamine. The mononuclear cobalt(III)-peroxo intermediates were isolated and characterized by various spectroscopic techniques and X-ray crystallography, and the structural and spectroscopic characterization demonstrated unambiguously that the peroxo ligand is bound in a side-on η2 fashion. The O-O bond stretching frequency of [Co(12-TMC)(O2)]+ and [Co(13- TMC)(O2)]+ was determined to be 902 cm−1 by resonance Raman spectroscopy. The structural properties of the CoO2 core in both complexes are nearly identical; the O-O bond distances of [Co(12-TMC)(O2)]+ and [Co(13-TMC)(O2)]+ were 1.4389(17) Å and 1.438(6) Å, respectively. The cobalt(III)-peroxo complexes showed reactivities in the oxidation of aldehydes and O2-transfer reactions. In the aldehyde oxidation reactions, the nucleophilic reactivity of the cobalt-peroxo complexes was significantly dependent on the ring size of the macrocyclic ligands, with the reactivity of [Co(13-TMC)(O2)]+ > [Co(12-TMC)(O2)]+. In the O2-transfer reactions, the cobalt(III)-peroxo complexes transferred the bound peroxo group to a manganese(II) complex, affording the corresponding cobalt(II) and manganese(III)- peroxo complexes. The reactivity of the cobalt-peroxo complexes in O2-transfer was also significantly dependent on the ring size of tetraazamacrocycles, and the reactivity order in the O2-transfer reactions was the same as that observed in the aldehyde oxidation reactions. PMID:21062059

  11. Origin of Enhanced Reactivity of a Microsolvated Nucleophile in Ion Pair SN2 Reactions: The Cases of Sodium p-Nitrophenoxide with Halomethanes in Acetone.

    PubMed

    Li, Qiang-Gen; Xu, Ke; Ren, Yi

    2015-04-30

    In a kinetic experiment on the SN2 reaction of sodium p-nitrophenoxide with iodomethane in acetone-water mixed solvent, Humeres et al. (J. Org. Chem. 2001, 66, 1163) found that the reaction depends strongly on the medium, and the fastest rate constant was observed in pure acetone. The present work tries to explore why acetone can enhance the reactivity of the title reactions. Accordingly, we make a mechanistic study on the reactions of sodium p-nitrophenoxide with halomethanes (CH3X, X = Cl, Br, I) in acetone by using a supramolecular/continuum model at the PCM-MP2/6-311+G(d,p)//B3LYP/6-311+G(d,p) level, in which the ion pair nucleophile is microsolvated by one to three acetone molecules. We compared the reactivity of the microsolvated ion pair nucleophiles with solvent-free ion pair and anionic ones. Our results clearly reveal that the microsolvated ion pair nucleophile is favorable for the SN2 reactions; meanwhile, the origin of the enhanced reactivity induced by microsolvation of the nucleophile is discussed in terms of the geometries of transition state (TS) structures and activation strain model, suggesting that lower deformation energies and stronger interaction energies between the deformed reactants in the TS lead to the lower overall reaction barriers for the SN2 reaction of microsolvated sodium p-nitrophenoxide toward halomethanes in acetone.

  12. Synthesis of Aryl-Substituted 2,4-Dinitrophenylamines: Nucleophilic Aromatic Substitution as a Problem-Solving and Collaborative-Learning Approach

    ERIC Educational Resources Information Center

    Santos, Elvira Santos; Garcia, Irma Cruz Gavilan; Gomez, Eva Florencia Lejarazo; Vilchis-Reyes, Miguel Angel

    2010-01-01

    A series of experiments based on problem-solving and collaborative-learning pedagogies are described that encourage students to interpret results and draw conclusions from data. Different approaches including parallel library synthesis, solvent variation, and leaving group variation are used to study a nucleophilic aromatic substitution of…

  13. Oxidative photoredox-catalytic activation of aliphatic nucleophiles for C(sp(3))-C(sp(2)) cross-coupling reactions.

    PubMed

    Jahn, Emanuela; Jahn, Ullrich

    2014-12-01

    In the light you will find the road (Led Zeppelin): Visible-light photoredox catalysis leads the way in overcoming the reactivity limitations of alkyl nucleophiles in cross-coupling reactions. Iridium-triggered oxidative photoredox activation of alkyltrifluoroborate or carboxylic acids affords alkyl radicals, which undergo nickel-catalyzed cross-coupling reactions.

  14. On the formation of aliphatic polycarbonates from epoxides with chromium(III) and aluminum(III) metal-salen complexes.

    PubMed

    Luinstra, Gerrit A; Haas, Gerhard R; Molnar, Ferenc; Bernhart, Volker; Eberhardt, Robert; Rieger, Bernhard

    2005-10-21

    A DFT-based description is given of the CO2/epoxide copolymerization with a catalyst system consisting of metal (chromium, iron, titanium, aluminum)-salen complexes (salen = N,N'-bis(3,5-di-tert-butylsalicyliden-1,6-diaminophenyl) in combination with either chloride, acetate, or dimethylamino pyridine (DMAP) as external nucleophile. Calculations indicate that initiation proceeds through nucleophilic attack at a metal-coordinated epoxide, and the most likely propagation reaction is a bimolecular process in which a metal-bound nucleophile attacks a metal-bound epoxide. Carbon dioxide insertion occurs at a single metal center and is most likely the rate-determining step at low pressure. The prevalent chain terminating/degradation-the so-called backbiting, a reaction leading to formation of cyclic carbonate from the polymer chain-would involve attack of a carbonate nucleophile rather than an alkoxide at the last unit of the growing chain. The backbiting of a free carbonato chain end is particularly efficient. Anion dissociation from six-coordinate aluminum is appreciably easier than from chromium-salen complexes, indicating the reason why in the former case cyclic carbonate is the sole product. Experimental data were gathered for a series of chromium-, aluminum-, iron-, and zinc-salen complexes, which were used in combination with external nucleophiles like DMAP and mainly (tetraalkyl ammonium) chloride/acetate. Aluminum complexes transform PO (propylene oxide) and CO2 to give exclusively propylene carbonate. This is explained by rapid carbonate anion dissociation from a six-coordinate complex and cyclic formation. CO2 insertion or nucleophilic attack of an external nucleophile at a coordinated epoxide (at higher CO2 pressure) are the rate-determining steps. Catalysis with [Cr(salen)(acetate/chloride)] complexes leads to the formation of both cyclic carbonate and polypropylene carbonate with various quantities of ether linkages. The dependence of the activity and

  15. Final Report for: "Bis-pi-allylpalladium Complexes in Catalysis of Multicomponent Reactions"

    SciTech Connect

    Malinakova, H. C.; Shiota, Atsushi

    2012-06-29

    The research project involved the development of new and functionally improved Pd(II) catalyst for a three-component reaction of boronic acids, allenes and imines to afford homoallylic amines that are useful in synthesis of biologically active heterocycles. Furthermore, insights into the reaction mechanism and the structure and reactivity of the catalytically active intermediates involved in this process were sought. As a result of this work, a new type of Pd-catalysts possessing an auxiliary ligand attached to the Pd center via a C-Pd and N-Pd bonds were identified, and found to be more active than the traditional catalysts derived from Pd(OAc)2. The new catalysts provided an access to a broader range of homoallylic amine products. Although the final unequivocal evidence regarding the structure of the Pd(II) complex involved in the nucleophilic transfer of the allyl fragment from the palladium center to the imine could not be obtained, mechanistic insights into the events that are detrimental to the activity of the originally reported Pd(OAc)2-based catalytic systems were uncovered.

  16. Advanced intermediate temperature sodium copper chloride battery

    NASA Astrophysics Data System (ADS)

    Yang, Li-Ping; Liu, Xiao-Min; Zhang, Yi-Wei; Yang, Hui; Shen, Xiao-Dong

    2014-12-01

    Sodium metal chloride batteries, also called as ZEBRA batteries, possess many merits such as low cost, high energy density and high safety, but their high operation temperature (270-350 °C) may cause several issues and limit their applications. Therefore, decreasing the operation temperature is of great importance in order to broaden their usage. Using a room temperature ionic liquid (RTIL) catholyte composed of sodium chloride buffered 1-ethyl-3-methylimidazolium chloride-aluminum chloride and a dense β″-aluminates solid electrolyte film with 500 micron thickness, we report an intermediate temperature sodium copper chloride battery which can be operated at only 150 °C, therefore alleviating the corrosion issues, improving the material compatibilities and reducing the operating complexities associated with the conventional ZEBRA batteries. The RTIL presents a high ionic conductivity (0.247 S cm-1) at 150 °C and a wide electrochemical window (-2.6 to 2.18 vs. Al3+/Al). With the discharge plateau at 2.64 V toward sodium and the specific capacity of 285 mAh g-1, this intermediate temperature battery exhibits an energy density (750 mWh g-1) comparable to the conventional ZEBRA batteries (728-785 mWh g-1) and superior to commercialized Li-ion batteries (550-680 mWh g-1), making it very attractive for renewable energy integration and other grid related applications.

  17. Gold(III)-CO and gold(III)-CO2 complexes and their role in the water-gas shift reaction

    PubMed Central

    Roşca, Dragoş-Adrian; Fernandez-Cestau, Julio; Morris, James; Wright, Joseph A.; Bochmann, Manfred

    2015-01-01

    The water-gas shift (WGS) reaction is an important process for the generation of hydrogen. Heterogeneous gold catalysts exhibit good WGS activity, but the nature of the active site, the oxidation state, and competing reaction mechanisms are very much matters of debate. Homogeneous gold WGS systems that could shed light on the mechanism are conspicuous by their absence: gold(I)–CO is inactive and gold(III)–CO complexes were unknown. We report the synthesis of the first example of an isolable CO complex of Au(III). Its reactivity demonstrates fundamental differences between the CO adducts of the neighboring d8 ions Pt(II) and Au(III): whereas Pt(II)-CO is stable to moisture, Au(III)–CO compounds are extremely susceptible to nucleophilic attack and show WGS reactivity at low temperature. The key to understanding these dramatic differences is the donation/back-donation ratio of the M–CO bond: gold-CO shows substantially less back-bonding than Pt-CO, irrespective of closely similar ν(CO) frequencies. Key WGS intermediates include the gold-CO2 complex [(C^N^C)Au]2(μ-CO2), which reductively eliminates CO2. The species identified here are in accord with Au(III) as active species and a carboxylate WGS mechanism. PMID:26601313

  18. Mechanics of vimentin intermediate filaments

    NASA Technical Reports Server (NTRS)

    Wang, Ning; Stamenovic, Dimitrijie

    2002-01-01

    It is increasingly evident that the cytoskeleton of living cells plays important roles in mechanical and biological functions of the cells. Here we focus on the contribution of intermediate filaments (IFs) to the mechanical behaviors of living cells. Vimentin, a major structural component of IFs in many cell types, is shown to play an important role in vital mechanical and biological functions such as cell contractility, migration, stiffness, stiffening, and proliferation.

  19. Branching of keratin intermediate filaments.

    PubMed

    Nafeey, Soufi; Martin, Ines; Felder, Tatiana; Walther, Paul; Felder, Edward

    2016-06-01

    Keratin intermediate filaments (IFs) are crucial to maintain mechanical stability in epithelial cells. Since little is known about the network architecture that provides this stiffness and especially about branching properties of filaments, we addressed this question with different electron microscopic (EM) methods. Using EM tomography of high pressure frozen keratinocytes, we investigated the course of several filaments in a branching of a filament bundle. Moreover we found several putative bifurcations in individual filaments. To verify our observation we also visualized the keratin network in detergent extracted keratinocytes with scanning EM. Here bifurcations of individual filaments could unambiguously be identified additionally to bundle branchings. Interestingly, identical filament bifurcations were also found in purified keratin 8/18 filaments expressed in Escherichia coli which were reassembled in vitro. This excludes that an accessory protein contributes to the branch formation. Measurements of the filament cross sectional areas showed various ratios between the three bifurcation arms. This demonstrates that intermediate filament furcation is very different from actin furcation where an entire new filament is attached to an existing filament. Instead, the architecture of intermediate filament bifurcations is less predetermined and hence consistent with the general concept of IF formation.

  20. Probing the reactivation process of sarin-inhibited acetylcholinesterase with α-nucleophiles: hydroxylamine anion is predicted to be a better antidote with DFT calculations.

    PubMed

    Khan, Md Abdul Shafeeuulla; Lo, Rabindranath; Bandyopadhyay, Tusar; Ganguly, Bishwajit

    2011-08-01

    Inactivation of acetylcholinesterase (AChE) due to inhibition by organophosphorus (OP) compounds is a major threat to human since AChE is a key enzyme in neurotransmission process. Oximes are used as potential reactivators of OP-inhibited AChE due to their α-effect nucleophilic reactivity. In search of more effective reactivating agents, model studies have shown that α-effect is not so important for dephosphylation reactions. We report the importance of α-effect of nucleophilic reactivity towards the reactivation of OP-inhibited AChE with hydroxylamine anion. We have demonstrated with DFT [B3LYP/6-311G(d,p)] calculations that the reactivation process of sarin-serine adduct 2 with hydroxylamine anion is more efficient than the other nucleophiles reported. The superiority of hydroxylamine anion to reactivate the sarin-inhibited AChE with sarin-serine adducts 3 and 4 compared to formoximate anion was observed in the presence and absence of hydrogen bonding interactions of Gly121 and Gly122. The calculated results show that the rates of reactivation process of adduct 4 with hydroxylamine anion are 261 and 223 times faster than the formoximate anion in the absence and presence of such hydrogen bonding interactions. The DFT calculated results shed light on the importance of the adjacent carbonyl group of Glu202 for the reactivation of sarin-serine adduct, in particular with formoximate anion. The reverse reactivation reaction between hydroxylamine anion and sarin-serine adduct was found to be higher in energy compared to the other nucleophiles, which suggests that this α-nucleophile can be a good antidote agent for the reactivation process.

  1. π-Bonded dithiolene complexes: synthesis, molecular structures, electrochemical behavior, and density functional theory calculations.

    PubMed

    Damas, Aurélie; Chamoreau, Lise-Marie; Cooksy, Andrew L; Jutand, Anny; Amouri, Hani

    2013-02-04

    The synthesis and X-ray molecular structure of the first metal-stabilized o-dithiobenzoquinone [Cp*Ir-o-(η(4)-C(6)H(4)S(2))] (2) are described. The presence of the metal stabilizes this elusive intermediate by π coordination and increases the nucleophilic character of the sulfur atoms. Indeed, the π-bonded dithiolene complex 2 was found to react with the organometallic solvated species [Cp*M(acetone)(3)][OTf](2) (M = Rh, Ir) to give a unique class of binuclear dithiolene compounds [Cp*Ir(C(6)H(4)S(2))MCp*][OTf](2) [M = Rh (3), Ir (4)] in which the elusive dithiolene η-C(6)H(4)S(2) acts as a bridging ligand toward the two Cp*M moieties. The electrochemical behavior of all complexes was investigated and provided us with valuable information about their redox properties. Density functional theory (DFT) calculations on the π-bonded dithiobenzoquinone ligand and related bimetallic systems show that the presence of Cp*M at the arene system of the dithiolene ligand increases the stability compared to the known monomeric species [Cp*Ir-o-(C(6)H(4)S(2)-κ(2)-S,S)] and enables these complexes Cp*Ir(C(6)H(4)S(2))MCp*][OTf](2) (3 and 4) to act as electron reservoirs. Time-dependent DFT calculations also predict the qualitative trends in the experimental UV-vis spectra and indicate that the strongest transitions arise from ligand-metal charge transfer involving primarily the HOMO-1 and LUMO. All of these compounds were fully characterized and identified by single-crystal X-ray crystallography. These results illustrate the first examples describing the coordination chemistry of the elusive o-dithiobenzoquinone to yield bimetallic complexes with an o-benzodithiolene ligand. These compounds might have important applications in the area of molecular materials.

  2. Dopamine-derived biological reactive intermediates and protein modifications: Implications for Parkinson's disease.

    PubMed

    Jinsmaa, Yunden; Florang, Virginia R; Rees, Jennifer N; Mexas, Lydia M; Eckert, Laurie L; Allen, Erin M G; Anderson, David G; Doorn, Jonathan A

    2011-06-30

    Dopamine (DA) undergoes monoamine oxidase catalyzed oxidative deamination to 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is metabolized primarily to 3,4-dihydroxyphenylacetic acid (DOPAC) via aldehyde dehydrogenase (ALDH). Previous studies demonstrated DOPAL to be neurotoxic, more so than DA and other metabolites, and implicated the aldehyde intermediate as a factor in the pathogenesis of Parkinson's disease (PD). However, the mechanism for generation of DOPAL at aberrant levels and the pathways for toxicity are not conclusively known. Various models for DA catabolism revealed the susceptibility of DOPAL biotransformation (e.g., ALDH) to products of oxidative stress, e.g., 4-hydroxy-2-nonenal, at physiologic/pathologic levels and agents that induce oxidative stress. An elevated concentration of DOPAL correlated with increased protein modification with subsequent work demonstrating significant reactivity of the DA-derived electrophile toward protein nucleophiles compared to DA and other metabolites, e.g., DOPAC. The addition of DOPAL to proteins proceeds via reaction of the aldehyde with Lys residues, yielding a Schiff base; however, post-adduction chemistry occurs for the DOPAL-modification resulting in protein cross-linking. Preliminary work indicates enzymes in DA synthesis and catabolism to be cellular targets for DOPAL. Functional consequences for elevated levels of the DA-derived aldehyde and protein modification may include adverse cellular effects. These data implicate DOPAL as a toxic and reactive intermediate potentially serving as a "chemical trigger" for some stage of PD pathogenesis.

  3. Role of Intermediate Filaments in Vesicular Traffic

    PubMed Central

    Margiotta, Azzurra; Bucci, Cecilia

    2016-01-01

    Intermediate filaments are an important component of the cellular cytoskeleton. The first established role attributed to intermediate filaments was the mechanical support to cells. However, it is now clear that intermediate filaments have many different roles affecting a variety of other biological functions, such as the organization of microtubules and microfilaments, the regulation of nuclear structure and activity, the control of cell cycle and the regulation of signal transduction pathways. Furthermore, a number of intermediate filament proteins have been involved in the acquisition of tumorigenic properties. Over the last years, a strong involvement of intermediate filament proteins in the regulation of several aspects of intracellular trafficking has strongly emerged. Here, we review the functions of intermediate filaments proteins focusing mainly on the recent knowledge gained from the discovery that intermediate filaments associate with key proteins of the vesicular membrane transport machinery. In particular, we analyze the current understanding of the contribution of intermediate filaments to the endocytic pathway. PMID:27120621

  4. Picosecond Studies of Chemical Intermediates

    DTIC Science & Technology

    1991-05-01

    encapsulation significantly modify photoisomerization reaction rates. In the case of t-stilbene complexed to various cyclodextrins we directly observed...43 Figure 7.6 Schematic of equilibrium between tight and loose stilbene/ cyclodextrin complexes...how frictional effects due to the local (or "restricted") environment of the inner cyclodextrin cavity modifed the motion necessary for reaction

  5. Crystal structures of type I dehydroquinate dehydratase in complex with quinate and shikimate suggest a novel mechanism of Schiff base formation.

    PubMed

    Light, Samuel H; Antanasijevic, Aleksandar; Krishna, Sankar N; Caffrey, Michael; Anderson, Wayne F; Lavie, Arnon

    2014-02-11

    A component of the shikimate biosynthetic pathway, dehydroquinate dehydratase (DHQD) catalyzes the dehydration of 3-dehydroquniate (DHQ) to 3-dehydroshikimate. In the type I DHQD reaction mechanism a lysine forms a Schiff base intermediate with DHQ. The Schiff base acts as an electron sink to facilitate the catalytic dehydration. To address the mechanism of Schiff base formation, we determined structures of the Salmonella enterica wild-type DHQD in complex with the substrate analogue quinate and the product analogue shikimate. In addition, we determined the structure of the K170M mutant (Lys170 being the Schiff base forming residue) in complex with quinate. Combined with nuclear magnetic resonance and isothermal titration calorimetry data that revealed altered binding of the analogue to the K170M mutant, these structures suggest a model of Schiff base formation characterized by the dynamic interplay of opposing forces acting on either side of the substrate. On the side distant from the substrate 3-carbonyl group, closure of the enzyme's β8-α8 loop is proposed to guide DHQ into the proximity of the Schiff base-forming Lys170. On the 3-carbonyl side of the substrate, Lys170 sterically alters the position of DHQ's reactive ketone, aligning it at an angle conducive for nucleophilic attack. This study of a type I DHQD reveals the interplay between the enzyme and substrate required for the correct orientation of a functional group constrained within a cyclic substrate.

  6. Density functional theory studies on the oxidation of 5'-dGMP and 5'-dAMP by a platinum(IV) complex.

    PubMed

    Ariafard, Alireza; Tabatabaie, Elham S; Aghmasheh, Simin; Najaflo, Sahar; Yates, Brian F

    2012-08-06

    Density functional theory has been used to investigate the oxidation of a guanine nucleotide by platinum(IV), a process that can be important in the degradation of DNA. For the first time, we have provided a comprehensive mechanism for all of the steps in this process. A number of intermediates are predicted to occur but with short lifetimes that would make them difficult to observe experimentally. A key step in the mechanism is electron transfer from guanine to platinum(IV), and we show that this is driven by the loss of a chloride ligand from the platinum complex after nucleophilic attack of 5'-phosphate to C8 of guanine. We have investigated several different initial platinum(IV) guanine adducts and shown that the adduct formed from replacement of an axial chlorine ligand in the platinum(IV) complex undergoes oxidation more easily. We have studied adenine versus guanine adducts, and our results show that oxidation of the former is more difficult because of disruption of the aromatic π system that occurs during the process. Finally, our results show that the acidic hydrolysis step to form the final oxidized product occurs readily via an initial protonation of N7 of the guanine.

  7. Rapid determination of trace semicarbazide in flour products by high-performance liquid chromatography based on a nucleophilic substitution reaction.

    PubMed

    Wei, Tianfu; Li, Gongke; Zhang, Zhuomin

    2017-02-28

    Semicarbazide, a toxic food contaminant, widely exists in food products and it originates from the thermal degradation of a food additive of azodicarbonamide or a metabolite of nitrofurazone abused in meat specimens. Many previous methods for semicarbazide determination usually required expensive instruments, difficult-to-prepare monoclonal antibodies, and a long operation time. In this study, a high-performance liquid chromatography method was developed for the rapid determination of trace semicarbazide coupling with a nucleophilic substitution reaction firstly using 4-nitrobenzoyl chloride as derivatization reagent. The derivatization reaction was mild at room temperature for 1 min in neutral solution. Then, semicarbazide derivative was separated and quantified by high-performance liquid chromatography with ultraviolet detection under optimal separation conditions at λmax = 261 nm. The proposed method offered the detection limit of 1.8 μg/L and was successfully applied for the rapid determination of trace semicarbazide in flour products. Semicarbazide in positive real samples could be actually found and quantified in the range of 0.47-7.53 mg/kg. The recoveries were 76.6-119% with relative standard deviations of 0.5-9.1% (n = 3). This developed method was rapid, reliable, and convenient for the determination of trace semicarbazide in food.

  8. Theoretical estimation of kinetic parameters for nucleophilic substitution reactions in solution: an application of a solution translational entropy model.

    PubMed

    Han, Ling-Li; Li, Shi-Jun; Fang, De-Cai

    2016-02-17

    The kinetic parameters, such as activation entropy, activation enthalpy, activation free-energy, and reaction rate constant, for a series of nucleophilic substitution (SN) reactions in solution, are investigated using both a solution-phase translational entropy model and an ideal gas-phase translational entropy model. The results obtained from the solution translational entropy model are in excellent agreement with the experimental values, while the overestimation of activation free-energy from the ideal gas-phase translational entropy model is as large as 6.9 kcal mol(-1). For some of the reactions studied, such as and in methanol, and and in aqueous solution, the explicit + implicit model, namely, a cluster-continuum type model, should be employed to account for the strong solvent-solute interactions. In addition, the explicit + implicit models have also been applied to the DMSO-H2O mixtures, which would open up a door to investigate the reactions in a mixed solvent using density functional theory (DFT) methods.

  9. Preparation and characterization of poly (arylene ether isoxazole)s by fluoride ion-mediated aromatic nucleophilic displacement reactions

    NASA Technical Reports Server (NTRS)

    Herbert, C. G.; Bass, R. G.

    1994-01-01

    As part of a continuing effort to prepare novel thermally stable high-performance polymers, poly(arylene ether isoxazole)s have been prepared by fluoride ion-catalyzed aromatic nucleophilic substitution reactions with bis(trimethylsiloxyphenyl) isoxazoles and activated bisarylhalides in diphenyl sulfone. Initial investigation involving the preparation of these materials with isoxazole bisphenols and activated bisarylhalides in the presence of potassium carbonate indicated that, under reaction conditions necessary to prepare high-molecular-weight materials, the isoxazole monomer was converted to an enamino ketone. This side reaction was avoided by using fluoride as a base. However, trimethylsilyl ether derivatives of the isoxazole bisphenols were required in these polymerizations for the preparation of high-molecular-weight materials. Moderate to high inherent viscosity eta(sub inh): 0.43-0.87 dl/g) materials with good thermal stability (air: 409-477 C, helium: 435-512 C) can be prepared by the silyl ether method. Glass transition temperatures ranged from 182 to 225 C for polymers with phenyl pendants and from 170 to 214 C for those without. Molecular weight control by 2% endcapping and the incorporation of a phenyl pendant at the 4 position of the isoxazole is necessary to yield polymers soluble in polar aprotic solvents at room temperature. There is evidence, however, indicating the existence of crosslinks between the polymer chains when the silyl ether approach is utilized.

  10. Matrix isolation infrared and DFT study of the trimethyl phosphite-hydrogen chloride interaction: hydrogen bonding versus nucleophilic substitution.

    PubMed

    Ramanathan, N; Kar, Bishnu Prasad; Sundararajan, K; Viswanathan, K S

    2012-12-13

    Trimethyl phosphite (TMPhite) and hydrogen chloride (HCl), when separately codeposited in a N(2) matrix, yielded a hydrogen bonded adduct, which was evidenced by shifts in the vibrational frequencies of the TMPhite and HCl submolecules. The structure and energy of the adducts were computed at the B3LYP level using 6-31++G** and aug-cc-pVDZ basis sets. While our computations indicated four minima for the TMPhite-HCl adducts, only one adduct was experimentally identified in the matrix at low temperatures, which interestingly was not the structure corresponding to the global minimum, but was the structure corresponding to the first higher energy local minimum. The Onsager self-consistent reaction field model was used to explain this observation. In an attempt to prepare the hydrogen bonded adduct in the gas phase and then trap it in the matrix, TMPhite and HCl were premixed prior to deposition. However, in these experiments, no hydrogen bonded adduct was observed; on the contrary, TMPhite reacted with HCl to yield CH(3)Cl, following a nucleophilic substitution, a reaction that is apparently frustrated in the matrix.

  11. Theoretical Design and Calculation of a Crown Ether Phase-Transfer-Catalyst Scaffold for Nucleophilic Fluorination Merging Two Catalytic Concepts.

    PubMed

    Carvalho, Nathália F; Pliego, Josefredo R

    2016-09-16

    Fluorinated organic molecules are playing an increased role in the area of pharmaceuticals and agrochemicals. This fact demands the development of efficient catalytic fluorination processes. In this paper, we have designed a new crown ether with four hydroxyl groups strategically positioned. The catalytic activity of this basic scaffold was investigated with high levels of electronic structure theory, such as the ONIOM approach combining MP4 and MP2 methods. On the basis of the calculations, this new structure is able to solubilize potassium fluoride in toluene solution much more efficiently than 18-crown-6 (18C6). In addition, the strong interaction of the new catalyst with the SN2 transition state leads to a very important catalytic effect, with a predicted free energy barrier of 23.3 kcal mol(-1) for potassium fluoride plus ethyl bromide reaction model. Compared with experimental data and previous theoretical studies, this new catalyst is 10(4) times more efficient than 18C6 for nucleophilic fluorination of alkyl halides. The catalysis is predicted to be selective, leading to 97% of fluorination and only 3% of elimination. Catalytic fluorination of the aromatic ring has also been investigated, and although the catalyst is less efficient in this case, our analysis has indicated further development of this strategy can lead to more efficient catalysis.

  12. In situ nucleophilic substitution reaction of N,N-dialkylaminoethyl-2-chlorides monitored by gas chromatography/mass spectrometry.

    PubMed

    Lakshmi, V V S; Reddy, T Jagadeshwar; Murty, M R V S; Prabhakar, S; Vairamani, M

    2006-01-01

    The detection and identification of degradation products of scheduled chemicals, which are characteristic markers of Chemical Warfare agents (CWAs), plays a key role in verification analysis. Identification of such non-scheduled but specific markers of CWAs helps in deciphering the kind of agent that was present in the sample submitted for off-site analysis. This paper describes the stability of N,N-dialkylaminoethyl-2-chlorides, which are precursors for highly toxic chemicals like VX, in different solvents. These compounds are stable in chloroform, acetonitrile, hexane and dichloromethane but tend to undergo in situ nucleophilic substitution reaction in the presence of alcohols giving the corresponding alkyl ether. The study shows that N,N-dialkylaminoethyl alkyl ethers can be used as markers of N,N-dialkylaminoethyl-2-chlorides. A detailed degradation study of these compounds in the presence of alcohols was carried out and it was found that the reaction follows pseudo-first order kinetics. Electron ionization mass spectral data for the methyl ethers of all the compounds are briefly discussed.

  13. Additional Nucleophile-Free FeCl3-Catalyzed Green Deprotection of 2,4-Dimethoxyphenylmethyl-Protected Alcohols and Carboxylic Acids.

    PubMed

    Sawama, Yoshinari; Masuda, Masahiro; Honda, Akie; Yokoyama, Hiroki; Park, Kwihwan; Yasukawa, Naoki; Monguchi, Yasunari; Sajiki, Hironao

    2016-01-01

    The deprotection of the methoxyphenylmethyl (MPM) ether and ester derivatives can be generally achieved by the combinatorial use of a catalytic Lewis acid and stoichiometric nucleophile. The deprotections of 2,4-dimethoxyphenylmethyl (DMPM)-protected alcohols and carboxylic acids were found to be effectively catalyzed by iron(III) chloride without any additional nucleophile to form the deprotected mother alcohols and carboxylic acids in excellent yields. Since the present deprotection proceeds via the self-assembling mechanism of the 2,4-DMPM protective group itself to give the hardly-soluble resorcinarene derivative as a precipitate, the rigorous purification process by silica-gel column chromatography was unnecessary and the sufficiently-pure alcohols and carboxylic acids were easily obtained in satisfactory yields after simple filtration.

  14. Design and synthesis of a new type of ferrocene-based planar chiral DMAP analogues. A new catalyst system for asymmetric nucleophilic catalysis.

    PubMed

    Seitzberg, Jimmi Gerner; Dissing, Carsten; Søtofte, Inger; Norrby, Per-Ola; Johannsen, Mogens

    2005-10-14

    A new first-generation catalyst system for nucleophilic catalysis has been developed. It is based on a planar chiral ferrocene skeleton with either the potent nucleophile 4-(dimethylamino)pyridine (DMAP) or the related 4-nitropyridine N-oxide attached in either the 2- or the 3-position. The syntheses are short, efficient, and enantioselective and X-ray crystal structures of both DMAP-derived catalysts are presented. The DMAP-based catalysts were tested in asymmetric reactions and the 3-derivative 14 showed good activity and a moderate level of enantioselectivity. The sense of induction (selectivity) was studied using molecular modeling and the results pointed at new directions for future generations of catalysts based on this design.

  15. Use of a biosynthetic intermediate to explore the chemical diversity of pseudo-natural fungal polyketides

    NASA Astrophysics Data System (ADS)

    Asai, Teigo; Tsukada, Kento; Ise, Satomi; Shirata, Naoki; Hashimoto, Makoto; Fujii, Isao; Gomi, Katsuya; Nakagawara, Kosuke; Kodama, Eiichi N.; Oshima, Yoshiteru

    2015-09-01

    The structural complexity and diversity of natural products make them attractive sources for potential drug discovery, with their characteristics being derived from the multi-step combination of enzymatic and non-enzymatic conversions of intermediates in each biosynthetic pathway. Intermediates that exhibit multipotent behaviour have great potential for use as starting points in diversity-oriented synthesis. Inspired by the biosynthetic pathways that form complex metabolites from simple intermediates, we developed a semi-synthetic process that combines heterologous biosynthesis and artificial diversification. The heterologous biosynthesis of fungal polyketide intermediates led to the isolation of novel oligomers and provided evidence for ortho-quinonemethide equivalency in their isochromene form. The intrinsic reactivity of the isochromene polyketide enabled us to access various new chemical entities by modifying and remodelling the polyketide core and through coupling with indole molecules. We thus succeeded in generating exceptionally diverse pseudo-natural polyketides through this process and demonstrated an advanced method of using biosynthetic intermediates.

  16. A ligand field chemistry of oxygen generation by the oxygen-evolving complex and synthetic active sites.

    PubMed

    Betley, Theodore A; Surendranath, Yogesh; Childress, Montana V; Alliger, Glen E; Fu, Ross; Cummins, Christopher C; Nocera, Daniel G

    2008-03-27

    Oxygen-oxygen bond formation and O2 generation occur from the S4 state of the oxygen-evolving complex (OEC). Several mechanistic possibilities have been proposed for water oxidation, depending on the formal oxidation state of the Mn atoms. All fall under two general classifications: the AB mechanism in which nucleophilic oxygen (base, B) attacks electrophilic oxygen (acid, A) of the Mn4Ca cluster or the RC mechanism in which radical-like oxygen species couple within OEC. The critical intermediate in either mechanism involves a metal oxo, though the nature of this oxo for AB and RC mechanisms is disparate. In the case of the AB mechanism, assembly of an even-electron count, high-valent metal-oxo proximate to a hydroxide is needed whereas, in an RC mechanism, two odd-electron count, high-valent metal oxos are required. Thus the two mechanisms give rise to very different design criteria for functional models of the OEC active site. This discussion presents the electron counts and ligand geometries that support metal oxos for AB and RC O-O bond-forming reactions. The construction of architectures that bring two oxygen functionalities together under the purview of the AB and RC scenarios are described.

  17. Synthesis and Transformations of 5-Chloro-2,2′-Dipyrrins and Their Boron Complexes, 8-Chloro-BODIPYs**

    PubMed Central

    Wang, Haijun; Vicente, M. Graça H.; Fronczek, Frank R.

    2014-01-01

    Symmetric dipyrrylketones 1a,b were synthesized in two steps from the corresponding α-free pyrroles, by reaction with thiophosgene followed by oxidative hydrolysis under basic conditions. The dipyrrylketones produced the corresponding 5-chloro-dipyrrinium salts or 5-ethoxy-dipyrrins on reaction with phosgene or Meerwein’s salt, respectively. Boron complexation of the dipyrrins afforded the corresponding 8-functionalized BODIPYs (borondipyrromethenes) in high yields. The 5-chloro-dipyrrinium salts reacted with methoxide or ethoxide ions to produce monopyrrole esters, presumably via a 5,5-dialkoxy-dipyrromethane intermediate. In contrast, 8-chloro-BODIPYs underwent a variety of nucleophilic substitutions of the chloro group in the presence of alkoxide ions, Grignard reagents, and thiols. In the presence of excess alkoxide or Grignard reagent, at room temperature or above, substitution at the boron center also occurred. The 8-chloro-BODIPY was a particularly useful reagent for the preparation of 8-aryl-, 8-alkyl-, and 8-vinyl-substituted BODIPYs in very high yields, using Pd0-catalyzed Stille cross-coupling reactions. The X-ray structures of eleven BODIPYs and two pyrroles are presented, and the spectroscopic properties of the synthesized BODIPYs are discussed. PMID:24616111

  18. Displays for future intermediate UAV

    NASA Astrophysics Data System (ADS)

    Desjardins, Daniel; Metzler, James; Blakesley, David; Rister, Courtney; Nuhu, Abdul-Razak

    2008-04-01

    The Dedicated Autonomous Extended Duration Airborne Long-range Utility System (DAEDALUS) is a prototype Unmanned Aerial Vehicle (UAV) that won the 2007 AFRL Commander's Challenge. The purpose of the Commander's Challenge was to find an innovative solution to urgent warfighter needs by designing a UAV with increased persistence for tactical employment of sensors and communication systems. DAEDALUS was chosen as a winning prototype by AFRL, AFMC and SECAF. Follow-on units are intended to fill an intermediate role between currently fielded Tier I and Tier II UAV's. The UAV design discussed in this paper, including sensors and displays, will enter Phase II for Rapid Prototype Development with the intent of developing the design for eventual production. This paper will discuss the DAEDALUS UAV prototype system, with particular focus on its communications, to include the infrared sensor and electro-optical camera, but also displays, specifically man-portable.

  19. Intermediate superconductive magnetic energy storage

    SciTech Connect

    Masuda, M.; Fujino, H.; Iwamoto, M.; Murakomi, M.; Shintomi, T.; Veda, K.

    1983-05-01

    In the past decade, the superconducting magnetic energy storage (SMES) for application to peak shaving in utility has been investigated in a manner to construct the huge superconducting coil in bed rock. To confine the strong electromagnetic forces accompanied with the high magnetic field, megaton structures, no matter how they will be constructed in a liquid helium temperature, are needed. To meet such a requirement, the revolutionary idea was proposed that the superconducting coil would be constructed on the underground bed rock. Here presented is a 10 MWh unit as an intermediate SMES that is a milestone along the distant way of RandD of SMES against 1,000 - 10,000 MWh unit which advocate the replacement of the hydro-pumped station. Therefore, even if the 10 MWh unit would not function as a storage in the utility network, its design should also consider the same situation.

  20. Microleakage of intermediate restorative materials.

    PubMed

    Lim, K C

    1990-03-01

    This study compares the microleakage of a glass ionomer cement, Ketac Fil, used without cavity conditioning, with the established intermediate restorative materials, Cavit-W, and a reinforced zinc oxide-eugenol cement, Kalzinol. Microleakage was assessed using an electrochemical technique. At the end of 30 days, the materials tested, listed in decreasing order of microleakage, were Cavit-W, Ketac Fil inserted without cavity conditioning, Kalzinol, and the control group of Ketac Fil inserted into conditioned cavities. There was no significant difference in the microleakage observed in Ketac Fil restorations inserted without cavity conditioning and Kalzinol (p = 0.450), while the differences between the other groups were highly significant (p less than 0.001).

  1. INTERMEDIATE FILAMENTS IN SMOOTH MUSCLE

    PubMed Central

    Tang, Dale D.

    2008-01-01

    The intermediate filament (IF) network is one of the three cytoskeletal systems in smooth muscle. The type III IF proteins vimentin and desmin are major constituents of the network in smooth muscle cells and tissues. Lack of vimentin or desmin impairs contractile ability of various smooth muscle preparations, implying their important role for smooth muscle force development. The IF framework has long been viewed as a fixed cytostructure that solely provides mechanical integrity for the cell. However, recent studies suggest that the IF cytoskeleton is dynamic in mammalian cells in response to various external stimulation. In this review, the structure and biological properties of IF proteins in smooth muscle are summarized. The role of IF proteins in the modulation of smooth muscle force development and redistribution/translocation of signaling partners (such as p130 Crk-associated substrate, CAS) is depicted. This review also summarizes our latest understanding on how the IF network may be regulated in smooth muscle. PMID:18256275

  2. The diverse behaviour of the P-Cl bonds in the spiro-cis-ansa spermidine derivative cyclotriphosphazene towards mono-functional nucleophilic reagents

    NASA Astrophysics Data System (ADS)

    İbişoğlu, Hanife; Temur, Başak; Ün, İlker

    2009-10-01

    A number of new spiro-ansa spermidine derivative cyclotriphosphazenes ( 2- 10) is synthesized in order to provide insight into the reaction mechanism for nucleophilic substitution. The structures of the compounds were determined by elemental analysis, mass (MS), 1H, 19F (for 9) and 31P NMR spectroscopies. Compounds ( 2- 8) and 9, 10 can be formed by a proton abstraction-chloride elimination and both the SN1 and SN2 reaction mechanisms, respectively.

  3. Inorganic base-catalyzed formation of antivirally active N-substituted benzamides from α-amido sulfones and N-nucleophile

    PubMed Central

    2011-01-01

    Background Heteronucleophiles as well as carbanionic reagents can be used to react with α-amido sulfones, thus giving the opportunity to prepare a large array of amino derivatives. Since, novel 1,3,4-oxadiazole-2-thiol derivatives can serve as potent nucleophiles, we employed 5-subsititued phenyl-1,3,4-oxadiazole-2-thiols as the nucleophilic source of nitrogen in the reaction with α-amido sulfones. Results A series of N-substituted benzamides bearing 1,3,4-oxadiazol unit were prepared for the first time by the reaction of in situ generated protected imine from α-amido sulfones with 5-subsititued phenyl-1,3,4-oxadiazole-2-thiols as the source of nitrogen nucleophile. Some of the synthesized products displayed favourable antiviral activity against cucumber mosaic virus (CMV) in preliminary antiviral activity tests. The title compounds 5c, 5o and 5r revealed curative activity of 42.2%, 48.7% and 40.5%, respectively against CMV (inhibitory rate) compared to the commercial standard Ningnanmycin (53.4%) at 500 μg/mL. Conclusion A practical synthetic route to N-benzoyl-α-amido sulfones by the reaction of 5-subsititued phenyl-1,3,4-oxadiazole-2-thiols as the source of nitrogen nucleophiles with in situ generated protected imine from N-benzoyl-α-amido sulfones is presented. The reaction catalyzed by an inorganic base has considerable significance to exploit the potential of α-amido sulfones in organic synthesis. PMID:21545729

  4. Selenophene transition metal complexes

    SciTech Connect

    White, Carter James

    1994-07-27

    This research shows that selenophene transition metal complexes have a chemistry that is similar to their thiophene analogs. Selenophene coordination has been demonstrated and confirmed by molecular structure in both the η5- and the η1(Se)-coordination modes. The reaction chemistry of selenophene complexes closely resembles that of the analogous thiophene complexes. One major difference, however, is that selenophene is a better donor ligand than thiophene making the selenophene complexes more stable than the corresponding thiophene complexes. The 77Se NMR chemical shift values for selenophene complexes fall within distinct regions primarily depending on the coordination mode of the selenophene ligand. In the final paper, the C-H bond activation of η1(S)-bound thiophenes, η1(S)-benzothiophene and η1(Se)-bound selenophenes has been demonstrated. The deprotonation and rearrangement of the η1(E)-bound ligand to the carbon bound L-yl complex readily occurs in the presence of base. Reprotonation with a strong acid gives a carbene complex that is unreactive towards nucleophilic attack at the carbene carbon and is stable towards exposure to air. The molecular structure of [Cp(NO)(PPh3)Re(2-benzothioenylcarbene)]O3SCF3 was determined and contains a Re-C bond with substantial double bond character. Methyl substitution for the thienylcarbene or selenylcarbene gives a carbene that rearranges thermally to give back the η1(E)-bound complex. Based on these model reactions, a new mechanism for the H/D exchange of thiophene over the hydrodesulfurization catalyst has been proposed.

  5. Theoretical Studies on F(-) + NH2Cl Reaction: Nucleophilic Substitution at Neutral Nitrogen.

    PubMed

    Liu, Xu; Zhang, Jiaxu; Yang, Li; Sun, Rui

    2016-05-26

    The SN2 reactions at N center, denoted as SN2@N, has been recognized to play a significant role in carcinogenesis, although they are less studied and less understood. The potential energy profile for the model reaction of SN2@N, chloramine (NH2Cl) with fluorine anion (F(-)), has been characterized by extensive electronic structure calculations. The back-side SN2 channel dominates the reaction with the front-side SN2 channel becoming feasible at higher energies. The minimum energy pathway shows a resemblance to the well-known double-well potential model for SN2 reactions at carbon. However, the complexes involving nitrogen on both sides of the reaction barrier are characterized by NH---X (X = F or Cl) hydrogen bond and possess C1 symmetry, in contrast to the more symmetric ion-dipole carbon analogues. In the F(-) + NH2Cl system, the proton transfer pathway is found to become more competitive with the SN2 pathway than in the F(-) + CH3Cl system. The calculations reported here indicate that stationary point properties on the F(-) + NH2Cl potential energy surface are slightly perturbed by the theories employed. The MP2 and CAM-B3LYP, as well as M06-2X and MPW1K functionals give overall best agreement with the benchmark CCSD(T)/CBS energies for the major SN2 reaction channel, and are recommended as the preferred methods for the direct dynamics simulations to uncover the dynamic behaviors of the title reaction.

  6. Glassy carbon electrode modified with horse radish peroxidase/organic nucleophilic-functionalized carbon nanotube composite for enhanced electrocatalytic oxidation and efficient voltammetric sensing of levodopa.

    PubMed

    Shoja, Yalda; Rafati, Amir Abbas; Ghodsi, Javad

    2016-01-01

    A novel and selective enzymatic biosensor was designed and constructed for voltammetric determination of levodopa (L-Dopa) in aqueous media (phosphate buffer solution, pH=7). Biosensor development was on the basis of to physically immobilizing of horse radish peroxidase (HRP) as electrochemical catalyst by sol-gel on glassy carbon electrode modified with organic nucleophilic carbon nanotube composite which in this composite p-phenylenediamine (pPDA) as organic nucleophile chemically bonded with functionalized MWCNT (MWCNT-COOH). The results of this study suggest that prepared bioorganic nucleophilic carbon nanotube composite (HRP/MWCNT-pPDA) shows fast electron transfer rate for electro oxidation of L-Dopa because of its high electrochemical catalytic activity toward the oxidation of L-Dopa, more--NH2 reactive sites and large effective surface area. Also in this work we measured L-Dopa in the presence of folic acid and uric acid as interferences. The proposed biosensor was characterized by scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), FT-IR spectroscopy and cyclic voltammetry (CV). The differential pulse voltammetry (DPV) was used for determination of L-Dopa from 0.1 μM to 1.9 μM with a low detection limit of 40 nM (for S/N=3) and sensitivity was about 35.5 μA/μM. Also this biosensor has several advantages such as rapid response, high stability and reproducibility.

  7. Straightforward synthetic protocol for the introduction of stabilized C nucleophiles in the BODIPY core for advanced sensing and photonic applications.

    PubMed

    Gutiérrez-Ramos, Brenda D; Bañuelos, Jorge; Arbeloa, Teresa; López Arbeloa, Iñigo; González-Navarro, Paulina E; Wrobel, Kazimierz; Cerdán, Luis; García-Moreno, Inmaculada; Costela, Angel; Peña-Cabrera, Eduardo

    2015-01-19

    A straightforward synthetic protocol to directly incorporate stabilized 1,3-dicarbonyl C nucleophiles to the meso position of BODIPY (4,4-difluoro-4-bora-3a,4a-diaza-s-indacene) is reported. Soft nucleophiles generated by deprotonation of 1,3-dicarbonyl derivatives smoothly displace the 8-methylthio group from 8-(methylthio)BODIPY analogues in the presence of Cu(I) thiophenecarboxylate in stoichiometric amounts at room temperature. Seven highly fluorescent new derivatives are prepared with varying yields (20-92%) in short reaction times (5-30 min). The excellent photophysical properties of the new dyes allow focusing on applications never analyzed before for BODIPYs substituted with stabilized C nucleophiles such as pH sensors and lasers in liquid and solid state, highlighting the relevance of the synthetic protocol described in the present work. The attainment of these dyes, with strong UV absorption and highly efficient and stable laser emission in the green spectral region, concerns to one of the greatest challenges in the ongoing development of advanced photonic materials with relevant applications. In fact, organic dyes with emission in the green are the only ones that allow, by frequency-doubling processes, the generation of tunable ultraviolet (250-350 nm) radiation, with ultra-short pulses.

  8. A Redox-Nucleophilic Dual-Reactable Probe for Highly Selective and Sensitive Detection of H2S: Synthesis, Spectra and Bioimaging

    NASA Astrophysics Data System (ADS)

    Zhang, Changyu; Wang, Runyu; Cheng, Longhuai; Li, Bingjie; Xi, Zhen; Yi, Long

    2016-07-01

    Hydrogen sulfide (H2S) is an important signalling molecule with multiple biological functions. The reported H2S fluorescent probes are majorly based on redox or nucleophilic reactions. The combination usage of both redox and nucleophilic reactions could improve the probe’s selectivity, sensitivity and stability. Herein we report a new dual-reactable probe with yellow turn-on fluorescence for H2S detection. The sensing mechanism of the dual-reactable probe was based on thiolysis of NBD (7-nitro-1,2,3-benzoxadiazole) amine (a nucleophilic reaction) and reduction of azide to amine (a redox reaction). Compared with its corresponding single-reactable probes, the dual-reactable probe has higher selectivity and fluorescence turn-on fold with magnitude of multiplication from that of each single-reactable probe. The highly selective and sensitive properties enabled the dual-reactable probe as a useful tool for efficiently sensing H2S in aqueous buffer and in living cells.

  9. Tempering the reactivities of postulated α-oxo gold carbenes using bidentate ligands: implication of tricoordinated gold intermediates and the development of an expedient bimolecular assembly of 2,4-disubstituted oxazoles.

    PubMed

    Luo, Yingdong; Ji, Kegong; Li, Yuxue; Zhang, Liming

    2012-10-24

    2,4-Oxazole is an important structural motif in various natural products. An efficient modular synthesis of this structure has been achieved via a [3 + 2] annulation between a terminal alkyne and a carboxamide using a gold-catalyzed oxidation strategy. The postulated reactive intermediate, a terminal α-oxo gold carbene, previously known to be highly electrophilic and hence unlikely to be trapped by stoichiometric external nucleophiles, is coerced to react smoothly with the carboxamide en route to the oxazole ring by a P,N- or P,S-bidentate ligand such as Mor-DalPhos; in stark contrast, often-used ligands such as monodentate phosphines and N-heterocyclic carbenes are totally ineffective. The role of these bidentate phosphines in this reaction is attributed to the formation of a tricoordinated gold carbene intermediate, which is less electrophilic and hence more chemoselective when reacting with nucleophiles. The success in using bidentate phosphine ligands to temper the reactivities of in situ-generated gold carbenes is likely to open many new opportunities to apply oxidative gold catalysis to the development of novel methods, and the implication of tricoordinated gold intermediates in homogeneous gold catalysis should stimulate further advances in gold catalysis.

  10. Electron microscopic analysis of rotavirus assembly-replication intermediates

    SciTech Connect

    Boudreaux, Crystal E.; Kelly, Deborah F.; McDonald, Sarah M.

    2015-03-15

    Rotaviruses (RVs) replicate their segmented, double-stranded RNA genomes in tandem with early virion assembly. In this study, we sought to gain insight into the ultrastructure of RV assembly-replication intermediates (RIs) using transmission electron microscopy (EM). Specifically, we examined a replicase-competent, subcellular fraction that contains all known RV RIs. Three never-before-seen complexes were visualized in this fraction. Using in vitro reconstitution, we showed that ~15-nm doughnut-shaped proteins in strings were nonstructural protein 2 (NSP2) bound to viral RNA transcripts. Moreover, using immunoaffinity-capture EM, we revealed that ~20-nm pebble-shaped complexes contain the viral RNA polymerase (VP1) and RNA capping enzyme (VP3). Finally, using a gel purification method, we demonstrated that ~30–70-nm electron-dense, particle-shaped complexes represent replicase-competent core RIs, containing VP1, VP3, and NSP2 as well as capsid proteins VP2 and VP6. The results of this study raise new questions about the interactions among viral proteins and RNA during the concerted assembly–replicase process. - Highlights: • Rotaviruses replicate their genomes in tandem with early virion assembly. • Little is known about rotavirus assembly-replication intermediates. • Assembly-replication intermediates were imaged using electron microscopy.

  11. Evolution of trophic transmission in parasites: Why add intermediate hosts?

    USGS Publications Warehouse

    Choisy, Marc; Brown, Sam P.; Lafferty, Kevin D.; Thomas, Frédéric

    2003-01-01

    Although multihost complex life cycles (CLCs) are common in several distantly related groups of parasites, their evolution remains poorly understood. In this article, we argue that under particular circumstances, adding a second host to a single-host life cycle is likely to enhance transmission (i.e., reaching the target host). For instance, in several situations, the propagules of a parasite exploiting a predator species will achieve a higher host-finding success by encysting in a prey of the target predator than by other dispersal modes. In such a case, selection should favor the transition from a singleto a two-host life cycle that includes the prey species as an intermediate host. We use an optimality model to explore this idea, and we discuss it in relation to dispersal strategies known among free-living species, especially animal dispersal. The model found that selection favored a complex life cycle only if intermediate hosts were more abundant than definitive hosts. The selective value of a complex life cycle increased with predation rates by definitive hosts on intermediate hosts. In exploring trade-offs between transmission strategies, we found that more costly trade-offs made it more difficult to evolve a CLC while less costly trade-offs between traits could favor a mixed strategy.

  12. Activation of Molecular Oxygen: Kinetic Studies of the Oxidation of Hindered Phenols with Cobalt-Dioxygen Complexes.

    DTIC Science & Technology

    1981-07-25

    containing nucleophiles on coordinated substrates; (3) oxygen atom transfers from high oxidation state elements; (4) epoxidation of olefins using metal...or polymers, depending -2- on the choice of catalyst or reagent. The oxidation of hindered phenols by cobalt- salen -dioxygen complexes was first

  13. Nucleophilic addition to olefins. 19. Abnormally high intrinsic barrier in the reaction of piperidine and morpholine with benzylideneacetylacetone

    SciTech Connect

    Bernasconi, C.F.; Kanavarioti, A.

    1986-11-26

    The title reaction leads to the formation of the zwitterionic Michael adduct T/sup +/-/ (PhCH(R/sub 2/NH/sup +/)C(COCH/sub 3/)/sub 2//sup -/) which is in rapid acid-base equilibrium with its anionic form T/sup -/ (PhCH(R/sub 2/N)C(COCH/sub 3/)/sub 2//sup -/). Rate (K/sub 1/, k/sub -1/) and equilibrium constants (K/sub 1/) for nucleophilic addition and the pK/sub a/ of the T/sup +/-/-adducts were determined in 50% Me/sub 2/SO-50% water at 20/sup 0/C. From an interpolation of the rate constants to K/sub 1/ = 1 an intrinsic rate constant, log k/sub 0/ = 0.3, was determined. This value deviates negatively by approximately 2.5 log units from a correlation of log k/sub 0/ for amine addition to five olefins of the type PhCH=CXY, with log k/sub 0/ for the deprotonation of the corresponding carbon acids CH/sub 2/XY. Two major factors are believed to contribute to this depressed intrinsic rate constant or enhanced intrinsic barrier: (1) steric inhibition of resonance in T/sup +/-/ with the steric effect developing ahead of C-N bond formation (this conclusion is supported by an X-ray crystallographic study of p-methoxybenzylideneacetylacetone which shows that steric hindrance to optimal ..pi..-overlap in the adduct T/sup+/-/ is already present in the substrate); (2) intramolecular hydrogen bonding in T/sup +/-/, which is inferred from abnormally high pK/sub a/ values and whose development lags behind C-N bond formation. These effects are shown to be manifestations of the Principle of Nonperfect Synchronization.

  14. Chromospheric Activity at Intermediate Ages

    NASA Astrophysics Data System (ADS)

    Giampapa, Mark; Stauffer, John; Deliyannis, Constantine; Sherry, William

    2005-08-01

    The calibration of the empirical relation between Ca II chromospheric strength and stellar age between 0.6 Gyr (Hyades) and 4.0 - 5 Gyr (M67 and the Sun) relies on the uncertain determination of ages for individual field stars in the solar neighborhood. We therefore propose to obtain WIYN/Hydra spectra of ~ 100 solar-type dwarf stars in the 1.8 Gyr old open cluster, NGC 752. This cluster contains a sample of solar-type dwarfs that is homogeneous in age and chemical composition. Furthermore, NGC 752 is the nearest-and hence brightest- cluster at an age ~ 2 Gyr. The results will yield an improved calibration of the age-activity relation at intermediate ages. In addition, we will determine if the chromospheric Ca II strengths for the solar-type stars in NGC 752 lie in the so-called "Vaughan-Preston Gap''- an apparent discontinuity in the Ca II H& K strength-(B-V) diagram found for field stars in the solar neighborhood. Our data will yield insight on the two proposed origins for the gap, namely, that it is a result of two different modes of dynamo action or that it is actually an artifact of a discontinuity in the local star formation rate. This is a resubmission of a previously approved proposal that was allocated two nights in 2004 November. The time was lost to instrument problems (Hydra gripper malfunctions) and weather. No usable data were obtained.

  15. Experiments in intermediate energy physics

    SciTech Connect

    Dehnhard, D.

    2003-02-28

    Research in experimental nuclear physics was done from 1979 to 2002 primarily at intermediate energy facilities that provide pion, proton, and kaon beams. Particularly successful has been the work at the Los Alamos Meson Physics Facility (LAMPF) on unraveling the neutron and proton contributions to nuclear ground state and transition densities. This work was done on a wide variety of nuclei and with great detail on the carbon, oxygen, and helium isotopes. Some of the investigations involved the use of polarized targets which allowed the extraction of information on the spin-dependent part of the triangle-nucleon interaction. At the Indiana University Cyclotron Facility (IUCF) we studied proton-induced charge exchange reactions with results of importance to astrophysics and the nuclear few-body problem. During the first few years, the analysis of heavy-ion nucleus scattering data that had been taken prior to 1979 was completed. During the last few years we created hypernuclei by use of a kaon beam at Brookhaven National Laboratory (BNL) and an electron beam at Jefferson Laboratory (JLab). The data taken at BNL for a study of the non-mesonic weak decay of the A particle in a nucleus are still under analysis by our collaborators. The work at JLab resulted in the best resolution hypernuclear spectra measured thus far with magnetic spectrometers.

  16. Enhancement of entropic transport by intermediates.

    PubMed

    Mondal, Debasish

    2011-07-01

    Brownian particles confined in a two-dimensional enclosure that give rise to a bistable entropic potential are considered. With the introduction of an intermediate lobe, the mean first passage time from one lobe to another through the intermediate shows a turnover behavior with the variation of the stability of the entropic intermediate. The mean escape time shows a minimum for an optimal value of the barrier height of the intermediate state. A three-state model is proposed to explain the nonmonotonic behavior of the entropic transport.

  17. Rate control based on intermediate description

    NASA Astrophysics Data System (ADS)

    Liu, Meng; Guo, Yi; Li, Houqiang

    2010-07-01

    Video adaptation has been proved to be an efficient technique in dealing with various constraints such as bandwidth limitation and user requirement in multimedia applications. However, existing methods including Scalable Video Coding and transcoding cannot get a fine performance when bandwidth constraints exist in various scenarios particularly in realtime applications. In this paper, we propose a novel rate control scheme based on intermediate description. The proposed scheme can provide fast rate control for narrow and time-varying transmission channel in scenarios such as video streaming, video sharing and video on demand. In this scheme, Discrete Cosine Transform (DCT) coefficients distribution is modeled by generalized Gaussian distribution, meanwhile the parameter information of this model is stored as side information for rate control. With the stored parameter information, encoder and transcoder can achieve the target bit-rate with low complexity. Furthermore, an initial Quantization Parameter (QP) determination method is also presented to calculate a proper QP for the Instantaneous Decoding Refresh (IDR) picture. Experimental results show that compared with JVT-G012 in H.264, the proposed rate control scheme can save more than 85% encoding time and obtain the required bit-rate more precisely, meanwhile gains a performance improvement by 0.2dB averagely.

  18. Racah materials: role of atomic multiplets in intermediate valence systems

    PubMed Central

    Shick, A. B.; Havela, L.; Lichtenstein, A. I.; Katsnelson, M. I.

    2015-01-01

    We address the long-standing mystery of the nonmagnetic insulating state of the intermediate valence compound SmB6. Within a combination of the local density approximation (LDA) and an exact diagonalization (ED) of an effective discrete Anderson impurity model, the intermediate valence ground state with the f-shell occupation 〈n4f〉 = 5.6 is found for the Sm atom in SmB6. This ground state is a singlet, and the first excited triplet state ~3 meV higher in the energy. SmB6 is a narrow band insulator already in LDA, with the direct band gap of ~10 meV. The electron correlations increase the band gap which now becomes indirect. Thus, the many-body effects are relevant to form the indirect band gap, crucial for the idea of “topological Kondo insulator" in SmB6. Also, an actinide analog PuB6 is considered, and the intermediate valence singlet ground state is found for the Pu atom. We propose that [Sm, Pu]B6 belong to a new class of the intermediate valence materials with the multi-orbital “Kondo-like" singlet ground-state. Crucial role of complex spin-orbital f  n–f  n+1 multiplet structure differently hybridized with ligand states in such Racah materials is discussed. PMID:26490021

  19. Mechanistic studies of cyclohexanone monooxygenase: chemical properties of intermediates involved in catalysis.

    PubMed

    Sheng, D; Ballou, D P; Massey, V

    2001-09-18

    Cyclohexanone monooxygenase (CHMO), a bacterial flavoenzyme, carries out an oxygen insertion reaction on cyclohexanone to form a seven-membered cyclic product, epsilon-caprolactone. The reaction catalyzed involves the four-electron reduction of O2 at the expense of a two-electron oxidation of NADPH and a two-electron oxidation of cyclohexanone to form epsilon-caprolactone. Previous studies suggested the participation of either a flavin C4a-hydroperoxide or a flavin C4a-peroxide intermediate during the enzymatic catalysis [Ryerson, C. C., Ballou, D. P., and Walsh, C. (1982) Biochemistry 21, 2644-2655]. However, there was no kinetic or spectral evidence to distinguish between these two possibilities. In the present work we used double-mixing stopped-flow techniques to show that the C4a-flavin-oxygen adduct, which is formed rapidly from the reaction of oxygen with reduced enzyme in the presence of NADP, can exist in two states. When the reaction is carried out at pH 7.2, the first intermediate is a flavin C4a-peroxide with maximum absorbance at 366 nm; this intermediate becomes protonated at about 3 s(-1) to form what is believed to be the flavin C4a-hydroperoxide with maximum absorbance at 383 nm. These two intermediates can be interconverted by altering the pH, with a pK(a) of 8.4. Thus, at pH 9.0 the flavin C4a-peroxide persists mainly in the deprotonated form. Further kinetic studies also demonstrated that only the flavin C4a-peroxide intermediate could oxygenate the substrate, cyclohexanone. The requirement in catalysis of the deprotonated flavin C4a-peroxide, a nucleophile, is consistent with a Baeyer-Villiger rearrangement mechanism for the enzymatic oxygenation of cyclohexanone. In the course of these studies, the Kd for cyclohexanone to the C4a-peroxyflavin form of CHMO was determined to be approximately 1 microM. The rate-determining step in catalysis was shown to be the release of NADP from the oxidized enzyme.

  20. Intermediate filaments in nervous tissues

    PubMed Central

    Liem, RKH; Yen, S; Salomon, GD; Shelanski, ML

    1978-01-01

    Intermediate filaments have been isolated from rabbit intradural spinal nerve roots by the axonal flotation method. This method was modified to avoid exposure of axons to low ionic strength medium. The purified filaments are morphologically 75-80 percent pure. The gel electrophoretogram shows four major bands migrating at 200,000, 145,000, 68,000, and 60,000 daltons, respectively. A similar preparation from rabbit brain shows four major polypeptides with mol wt of 200,000 145,000, 68,000, and 51,000 daltons. These results indicate that the neurofilament is composed of a triplet of polypepetides with mol wt of 200,000, 145,000, and 68,000 daltons. The 51,000-dalton band that appears in brain filament preparations as the major polypeptide seems to be of glial origin. The significance of the 60,000- dalton band in the nerve root filament preparation is unclear at this time. Antibodies raised against two of the triplet proteins isolated from calf brain localize by immunofluorescence to neurons in central and peripheral nerve. On the other hand, an antibody to the 51,000-dalton polypeptide gives only glial staining in the brain, and very weak peripheral nerve staining. Prolonged exposure of axons to low ionic strength medium solubilizes almost all of the triplet polypeptides, leaving behind only the 51,000- dalton component. This would indicate that the neurofilament is soluble at low ionic strength, whereas the glial filament is not. These results indicate that neurofilaments and glial filaments are composed of different polypeptides and have different solubility characteristics. PMID:83322

  1. A Balancing Act: Stability versus Reactivity of Mn(O) Complexes.

    PubMed

    Neu, Heather M; Baglia, Regina A; Goldberg, David P

    2015-10-20

    A large class of heme and non-heme metalloenzymes utilize O2 or its derivatives (e.g., H2O2) to generate high-valent metal-oxo intermediates for performing challenging and selective oxidations. Due to their reactive nature, these intermediates are often short-lived and very difficult to characterize. Synthetic chemists have sought to prepare analogous metal-oxo complexes with ligands that impart enough stability to allow for their characterization and an examination of their inherent reactivity. The challenge in designing these molecules is to achieve a balance between their stability, which should allow for their in situ characterization or isolation, and their reactivity, in which they can still participate in interesting chemical transformations. This Account focuses on our recent efforts to generate and stabilize high-valent manganese-oxo porphyrinoid complexes and tune their reactivity in the oxidation of organic substrates. Dioxygen can be used to generate a high-valent Mn(V)(O) corrolazine (Mn(V)(O)(TBP8Cz)) by irradiation of Mn(III)(TBP8Cz) with visible light in the presence of a C-H substrate. Quantitative formation of the Mn(V)(O) complex occurs with concomitant selective hydroxylation of the benzylic substrate hexamethylbenzene. Addition of a strong H(+) donor converted this light/O2/substrate reaction from a stoichiometric to a catalytic process with modest turnovers. The addition of H(+) likely activates a transient Mn(V)(O) complex to achieve turnover, whereas in the absence of H(+), the Mn(V)(O) complex is an unreactive "dead-end" complex. Addition of anionic donors to the Mn(V)(O) complex also leads to enhanced reactivity, with a large increase in the rate of two-electron oxygen atom transfer (OAT) to thioether substrates. Spectroscopic characterization (Mn K-edge X-ray absorption and resonance Raman spectroscopies) revealed that the anionic donors (X(-)) bind to the Mn(V) ion to form six-coordinate [Mn(V)(O)(X)](-) complexes. An unusual "V

  2. Diesel Mechanics. Performance Objectives. Intermediate Course.

    ERIC Educational Resources Information Center

    Tidwell, Joseph

    Several intermediate performance objectives and corresponding criterion measures are listed for each of six terminal objectives for an intermediate diesel mechanics course (two semesters, 3 hours daily) designed for high school students who upon completion would be ready for an on-the-job training experience in diesel service and repair. Through…

  3. 19 CFR 122.84 - Intermediate airport.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 1 2011-04-01 2011-04-01 false Intermediate airport. 122.84 Section 122.84... Intermediate airport. (a) Application. The provisions of this section apply at any U.S. airport to which an... aircraft arrives at the next airport, the aircraft commander or agent shall make entry by filing the:...

  4. 19 CFR 122.84 - Intermediate airport.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 1 2010-04-01 2010-04-01 false Intermediate airport. 122.84 Section 122.84... Intermediate airport. (a) Application. The provisions of this section apply at any U.S. airport to which an... aircraft arrives at the next airport, the aircraft commander or agent shall make entry by filing the:...

  5. Business Machine Maintenance. Performance Objectives. Intermediate Course.

    ERIC Educational Resources Information Center

    McMinn, Robert

    Several intermediate performance objectives and corresponding criterion measures are listed for each of 28 terminal objectives presented in this guide for an intermediate business machine maintenance course at the secondary level. (For the basic course guide see CE 010 949.) Titles of the 28 terminal objective sections are Career Opportunities,…

  6. Liver resection for intermediate hepatocellular carcinoma

    PubMed Central

    Yi, Peng-Sheng; Zhang, Ming; Zhao, Ji-Tong; Xu, Ming-Qing

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. The Barcelona Clinic Liver Cancer (BCLC) staging system is regarded as the gold standard staging system for HCC, classifying HCC as early, intermediate, or advanced. For intermediate HCC, trans-catheter arterial chemoembolization (TACE) is recommended as the optimal strategy by the BCLC guideline. This review investigates whether liver resection is better than TACE for intermediate HCC. Based on published studies, we compare the survival benefits and complications of liver resection and TACE for intermediate HCC. We also compare the survival benefits of liver resection in early and intermediate HCC. We find that liver resection can achieve better or at least comparable survival outcomes compared with TACE for intermediate HCC; however, we do not observe a significant difference between liver resection and TACE in terms of safety and morbidity. We conclude that liver resection may improve the short- and long-term survival of carefully selected intermediate HCC patients, and the procedure may be safely performed in the management of intermediate HCC. PMID:27190577

  7. Radio and Television Servicing. Intermediate Course.

    ERIC Educational Resources Information Center

    Campbell, Guy; And Others

    Several intermediate performance objectives and corresponding criterion measures are listed for each of 32 terminal objectives for an intermediate (second year) radio/TV servicing course. This 1-year course (3 hours daily) was designed to provide the student with the basic skills and knowledges necessary for entry level employment in the Radio/TV…

  8. Appliance Services. Intermediate Course. Career Education.

    ERIC Educational Resources Information Center

    Killough, Joseph

    Several intermediate performance objectives and corresponding criterion measures are listed for each of 16 terminal objectives for an intermediate appliance repair course. The materials were developed for a 36-week course (3 hours daily) covering the areas of refrigeration, maintenance, repair, and troubleshooting of refrigerators and air…

  9. Air Conditioning. Performance Objectives. Intermediate Course.

    ERIC Educational Resources Information Center

    Long, William

    Several intermediate performance objectives and corresponding criterion measures are listed for each of seven terminal objectives for an intermediate air conditioning course. The titles of the seven terminal objectives are Refrigeration Cycle, Job Requirement Skills, Air Conditioning, Trouble Shooting, Performance Test, Shop Management, and S.I.E.…

  10. Teaching Pronunciation in the Standard Intermediate Curriculum.

    ERIC Educational Resources Information Center

    Lunn, Patricia V.

    Rationales and approaches for teaching pronunciation in the intermediate foreign language classroom are discussed. Pronunciation should be taught regularly and overtly because perfecting pronunciation is an essential part of learning to communicate, and because intermediate students have enough vocabulary to generalize pronunciation rules to new…

  11. Marine Engine Mechanics. Performance Objectives. Intermediate Course.

    ERIC Educational Resources Information Center

    Jones, Marion

    Several intermediate performance objectives and corresponding criterion measures are presented for each of ten terminal objectives for a two-semester course (3 hours daily). This 540-hour intermediate course includes advanced troubleshooting techniques on outboard marine engines, inboard-outboard marine engines, inboard marine engines, boat…

  12. Automotive Body Repair. Performance Objectives. Intermediate Course.

    ERIC Educational Resources Information Center

    Lang, Thomas

    Several intermediate performance objectives and corresponding criterion measures are listed for each of 10 terminal objectives for an intermediate automotive body repair and refinishing course. The materials were developed for a two-semester (3 hours daily) course for specialized classrooms, shop, and practical experiences designed to enable the…

  13. Some Intermediate-Level Violin Concertos.

    ERIC Educational Resources Information Center

    Abramson, Michael

    1997-01-01

    Contends that many violin students attempt difficult concertos before they are technically or musically prepared. Identifies a variety of concertos at the intermediate and advanced intermediate-level for students to study and master before attempting the advanced works by Bach and Mozart. Includes concertos by Vivaldi, Leclair, Viotti, Haydn,…

  14. Gasoline Engine Mechanics. Performance Objectives. Intermediate Course.

    ERIC Educational Resources Information Center

    Jones, Marion

    Several intermediate performance objectives and corresponding criterion measures are listed for each of six terminal objectives presented in this curriculum guide for an intermediate gasoline engine mechanics course at the secondary level. (For the beginning course guide see CE 010 947.) The materials were developed for a two-semester (2 hour…

  15. Lipid intermediates in the biosynthesis of bacterial peptidoglycan.

    PubMed

    van Heijenoort, Jean

    2007-12-01

    This review is an attempt to bring together and critically evaluate the now-abundant but dispersed data concerning the lipid intermediates of the biosynthesis of bacterial peptidoglycan. Lipid I, lipid II, and their modified forms play a key role not only as the specific link between the intracellular synthesis of the peptidoglycan monomer unit and the extracytoplasmic polymerization reactions but also in the attachment of proteins to the bacterial cell wall and in the mechanisms of action of antibiotics with which they form specific complexes. The survey deals first with their detection, purification, structure, and preparation by chemical and enzymatic methods. The recent important advances in the study of transferases MraY and MurG, responsible for the formation of lipids I and II, are reported. Various modifications undergone by lipids I and II are described, especially those occurring in gram-positive organisms. The following section concerns the cellular location of the lipid intermediates and the translocation of lipid II across the cytoplasmic membrane. The great efforts made since 2000 in the study of the glycosyltransferases catalyzing the glycan chain formation with lipid II or analogues are analyzed in detail. Finally, examples of antibiotics forming complexes with the lipid intermediates are presented.

  16. Epithelial Intermediate Filaments: Guardians against Microbial Infection?

    PubMed Central

    Geisler, Florian; Leube, Rudolf E.

    2016-01-01

    Intermediate filaments are abundant cytoskeletal components of epithelial tissues. They have been implicated in overall stress protection. A hitherto poorly investigated area of research is the function of intermediate filaments as a barrier to microbial infection. This review summarizes the accumulating knowledge about this interaction. It first emphasizes the unique spatial organization of the keratin intermediate filament cytoskeleton in different epithelial tissues to protect the organism against microbial insults. We then present examples of direct interaction between viral, bacterial, and parasitic proteins and the intermediate filament system and describe how this affects the microbe-host interaction by modulating the epithelial cytoskeleton, the progression of infection, and host response. These observations not only provide novel insights into the dynamics and function of intermediate filaments but also indicate future avenues to combat microbial infection. PMID:27355965

  17. Rotavirus protein rearrangements in purified membrane-enveloped intermediate particles.

    PubMed Central

    Poruchynsky, M S; Atkinson, P H

    1991-01-01

    Rotavirus, a double-shelled nonenveloped member of the REoviridae family, becomes transiently membrane enveloped during its maturation process, as single-shelled particles bud from cytoplasmic viroplasm structures into the adjacent endoplasmic reticulum. The present study describes the isolation of these membrane-enveloped viral intermediates from rotavirus SA11-infected Ma104 cells. The enveloped intermediates comprised the proteins VP1, VP2, VP4, VP6, VP7, and NS28 and small amounts of NS35 and NS34. VP7 in the intermediate particles was recognized by either a polyclonal antibody to VP7, which previous studies had shown recognizes the membrane-associated form of VP7, or a monoclonal antibody which recognizes VP7 on mature virus. NS28, VP7, and VP4 could be complexed to a higher-molecular-weight form when the membrane-permeable cross-linker dithiobis(succinimidylproprionate) was used. However, when an impermeable cross-linker was used, the structural proteins, including VP7, were not accessible to cross-linking. Velocity sedimentation of cross-linked immunoisolated enveloped virus particles showed that VP7 and VP4 were located in the same fractions only when the membrane-permeable cross-linker was used, implying their heterooligomeric association during outer capsid formation. When intermediate enveloped virus particles were treated with protease, VP6 and VP7 were protected, but not in the presence of detergent. Taken together, these results support the idea that in the membrane-enveloped intermediate, VP7 is repositioned from its location in the endoplasmic reticulum lumen back across the viral membrane envelope to the inferior of the virus particle during the maturation process. Images PMID:1651404

  18. The effect of intermediate clothing targets on shotgun ballistics.

    PubMed

    Cail, Kenneth; Klatt, Edward

    2013-12-01

    The ballistic properties of shotgun shells are complex because of multiple projectiles fired simultaneously that interact and spread out to affect their energy relayed to a human target. Intermediate targets such as clothing can affect penetration into tissues. We studied the effect of common clothing fabrics as intermediate targets on penetration of shotgun shell pellets, using ordnance gelatin to simulate soft tissue and thin cowhide to simulate skin. A standard 12-gauge shotgun with modified choke was used with no. 8 shot ammunition. We found that protection afforded by fabrics to reduce penetration of shotgun pellets into tissues was greater at increasing distance from the muzzle beyond 40 yd (36.6 m). The thicker denim and cotton fabrics provided slightly greater protection than polyester. This study demonstrates that clothing modifies the potential wound patterns to victims of shotgun injuries.

  19. Monoclonal antibody aggregation intermediates visualized by atomic force microscopy.

    PubMed

    Lee, Hanjoo; Kirchmeier, Marc; Mach, Henryk

    2011-02-01

    Ubiquitous but highly variable processes of therapeutic protein aggregation remain poorly characterized, especially in the context of common infusion reactions and clinical immunogenicity. Among the numerous challenges is the characterization of intermediate steps that lead to the appearance of precipitates. Although the biophysical methods for elucidation of secondary and tertiary structures as well as overall size distribution are typically well established in the development laboratories, the use of molecular scale imaging techniques is still relatively rare due to low throughput and technical complexity. In this work, we present the use of atomic force microscopy to examine morphology of monoclonal antibody aggregates. Despite varying in primary structure as a result of different complementarity defining regions, most antibodies studied exhibited a similar aggregation intermediate consisting of several monomers. However, the manner of subsequent condensation of these oligomers appeared to differ between the antibodies, suggesting stability-dependent mechanisms.

  20. Adenovirus DNA template for late transcription is not a replicative intermediate.

    PubMed Central

    Brison, O; Kédinger, C; Chambon, P

    1979-01-01

    The relationship between adenovirus replication and late transcription has been investigated using viral replication and transcription complexes isolated from infected HeLa cell nuclei. These two types of complexes extracted from adenovirus type 2-infected cell nuclei did not sediment at the same rate on sucrose gradients. Viral replicative intermediates were quantitatively precipitated by immunoglobulins raised against purified 72,000-dalton DNA-binding protein, whereas viral transcription complexes remained in the supernatant. These results show that late transcription does not occur on active replication complexes or on 72,000-dalton DNA-binding protein-containing replicative intermediates inactive in DNA synthesis. Additional evidence is presented indicating that it is very unlikely that replicative intermediates lacking the 72,000-dalton DNA-binding protein could be the template for late transcription. PMID:232191