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General Acid (general + acid)

Distribution by Scientific Domains
Chemistry100%

Terms modified by General Acid

  • general acid catalysis
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    Selected Abstracts

    Quantum chemical study of leaving group activation in T. vivax nucleoside hydrolase

    INTERNATIONAL JOURNAL OF QUANTUM CHEMISTRY, Issue 3 2006
    Stefan Loverix
    Abstract General acid catalysis is a powerful and widely used strategy in enzymatic nucleophilic displacement reactions. However, in the nucleoside hydrolase of the parasite Trypanosoma vivax, crystallographic and mutagenesis studies failed to identify a general acid. The only groups in the vicinity of the leaving group that contribute to catalysis are (i) the indole side chain of Trp260, and (ii) the 5,-group of the substrate's ribose moiety. The x-ray structure of the slow Asp10Ala mutant of nucleoside hydrolase with the substrate inosine bound in the active site displays a face-to-face aromatic stacking interaction between Trp260 and the purine base of the substrate, as well as a peculiar C4,-endo ribose pucker that allows the 5,-OH group to accept an intramolecular hydrogen bond from the C8 of the purine. The first interaction (aromatic stacking) has been shown to raise the pKa of the leaving purine. Here, we present a DFT study showing that the 5,-OH group of ribose fulfills a similar role, rather than stabilizing the oxocarbenium-like transition state. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2006 [source]

    Kinetics and mechanism of acid-catalyzed hydrolysis of the diazo functional group of diazophenylacetamide

    JOURNAL OF PHYSICAL ORGANIC CHEMISTRY, Issue 9 2003
    J. A. Chang
    Abstract The acid-catalyzed hydrolysis of diazophenylacetamide giving mandelamide as product was found to occur with a normal (kH/kD>1) hydronium ion isotope effect and to be subject to general acid rather than specific hydronium ion catalysis. This shows that the reaction occurs by rate-determining hydron transfer from the catalyzing acid to the diazo carbon atom of the substrate, followed by rapid displacement of the diazo group by water. Comparison of the rate of this reaction with those of the same process for other diazophenylacetic acid functional derivatives, PhCN2COX, reveals that the reactivity of these substrates is controlled by the electron-releasing resonance ability of the group X. Copyright © 2003 John Wiley & Sons, Ltd. [source]

    Isomerization mechanism of aspartate to isoaspartate implied by structures of Ustilago sphaerogena ribonuclease U2 complexed with adenosine 3,-monophosphate

    ACTA CRYSTALLOGRAPHICA SECTION D, Issue 7 2010
    Shuji Noguchi
    Aspartates in proteins are isomerized non-enzymatically to isoaspartate via succinimide in vitro and in vivo. In order to elucidate the mechanism of isoaspartate formation within the Asp45-Glu46 sequence of Ustilago sphaerogena ribonuclease U2 based on three-dimensional structure, crystal structures of ribonuclease U2 complexed with adenosine 3,-monophosphate have been solved at 0.96 and 0.99,Å resolution. The crystal structures revealed that the C, atom of Asp45 is located just beside the main-chain N atom of Glu46 and that the conformation which is suitable for succinimide formation is stabilized by a hydrogen-bond network mediated by water molecules 190, 219 and 220. These water molecules are suggested to promote the formation of isoaspartate via succinimide: in the succinimide-formation reaction water 219 receives a proton from the N atom of Glu46 as a general base and waters 190 and 220 stabilize the tetrahedral intermediate, and in the succinimide-hydrolysis reaction water 219 provides a proton for the N atom of Glu46 as a general acid. The purine-base recognition scheme of ribonuclease U2 is also discussed. [source]

    Structural characterization of tartrate dehydrogenase: a versatile enzyme catalyzing multiple reactions

    ACTA CRYSTALLOGRAPHICA SECTION D, Issue 6 2010
    Radhika Malik
    The first structure of an NAD-dependent tartrate dehydrogenase (TDH) has been solved to 2,Å resolution by single anomalous diffraction (SAD) phasing as a complex with the intermediate analog oxalate, Mg2+ and NADH. This TDH structure from Pseudomonas putida has a similar overall fold and domain organization to other structurally characterized members of the hydroxy-acid dehydrogenase family. However, there are considerable differences between TDH and these functionally related enzymes in the regions connecting the core secondary structure and in the relative positioning of important loops and helices. The active site in these complexes is highly ordered, allowing the identification of the substrate-binding and cofactor-binding groups and the ligands to the metal ions. Residues from the adjacent subunit are involved in both the substrate and divalent metal ion binding sites, establishing a dimer as the functional unit and providing structural support for an alternating-site reaction mechanism. The divalent metal ion plays a prominent role in substrate binding and orientation, together with several active-site arginines. Functional groups from both subunits form the cofactor-binding site and the ammonium ion aids in the orientation of the nicotinamide ring of the cofactor. A lysyl amino group (Lys192) is the base responsible for the water-mediated proton abstraction from the C2 hydroxyl group of the substrate that begins the catalytic reaction, followed by hydride transfer to NAD. A tyrosyl hydroxyl group (Tyr141) functions as a general acid to protonate the enolate intermediate. Each substrate undergoes the initial hydride transfer, but differences in substrate orientation are proposed to account for the different reactions catalyzed by TDH. [source]

    Mechanistic Investigation of Chiral Phosphoric Acid Catalyzed Asymmetric Baeyer,Villiger Reaction of 3-Substituted Cyclobutanones with H2O2 as the Oxidant

    CHEMISTRY - A EUROPEAN JOURNAL, Issue 10 2010
    Senmiao Xu Dr.
    Abstract The mechanism of the chiral phosphoric acid catalyzed Baeyer,Villiger (B,V) reaction of cyclobutanones with hydrogen peroxide was investigated by using a combination of experimental and theoretical methods. Of the two pathways that have been proposed for the present reaction, the pathway involving a peroxyphosphate intermediate is not viable. The reaction progress kinetic analysis indicates that the reaction is partially inhibited by the ,-lactone product. Initial rate measurements suggest that the reaction follows Michaelis,Menten-type kinetics consistent with a bifunctional mechanism in which the catalyst is actively involved in both carbonyl addition and the subsequent rearrangement steps through hydrogen-bonding interactions with the reactants or the intermediate. High-level quantum chemical calculations strongly support a two-step concerted mechanism in which the phosphoric acid activates the reactants or the intermediate in a synergistic manner through partial proton transfer. The catalyst simultaneously acts as a general acid, by increasing the electrophilicity of the carbonyl carbon, increases the nucleophilicity of hydrogen peroxide as a Lewis base in the addition step, and facilitates the dissociation of the OH group from the Criegee intermediate in the rearrangement step. The overall reaction is highly exothermic, and the rearrangement of the Criegee intermediate is the rate-determining step. The observed reactivity of this catalytic B,V reaction also results, in part, from the ring strain in cyclobutanones. The sense of chiral induction is rationalized by the analysis of the relative energies of the competing diastereomeric transition states, in which the steric repulsion between the 3-substituent of the cyclobutanone and the 3- and 3,-substituents of the catalyst, as well as the entropy and solvent effects, are found to be critically important. [source]