Hydride Transfer Mechanism Research Articles

Substrate specificity of flavin-dependent vanillyl-alcohol oxidase from Penicillium simplicissimum. Evidence for the production of 4-hydroxycinnamyl alcohols from 4-allylphenols.

The substrate specificity of the flavoprotein vanillyl-alcohol oxidase from Penicillium simplicissimum was investigated. Vanillyl-alcohol oxidase catalyzes besides the oxidation of 4-hydroxybenzyl alcohols, the oxidative deamination of 4-hydroxybenzylamines and the oxidative demethylation of 4-(methoxymethyl)phenols. During the conversion of vanillylamine to vanillin, a transient intermediate, most probably vanillylimine, is observed. Vanillyl-alcohol oxidase weakly interacts with 4-hydroxyphenylglycols and a series of catecholamines. These compounds are converted to the corresponding ketones. Both enantiomers of (nor)epinephrine are substrates for vanillyl-alcohol oxidase, but the R isomer is preferred. Vanillyl-alcohol oxidase is most active with chavicol and eugenol. These 4-allylphenols are converted to coumaryl alcohol and coniferyl alcohol, respectively. Isotopic labeling experiments show that the oxygen atom inserted at the C gamma atom of the side chain is derived from water. The 4-hydroxycinnamyl alcohol products and the substrate analog isoeugenol are competitive inhibitors of vanillyl alcohol oxidation. The binding of isoeugenol to the oxidized enzyme perturbs the optical spectrum of protein-bound FAD. pH-dependent binding studies suggest that vanillyl-alcohol oxidase preferentially binds the phenolate form of isoeugenol (pKa < 6, 25 degrees C). From this and the high pH optimum for turnover, a hydride transfer mechanism involving a p-quinone methide intermediate is proposed for the vanillyl-alcohol-oxidase-catalyzed conversion of 4-allylphenols.

The mechanism of hydride transfer between NADH and 3-acetylpyridine adenine dinucleotide by the pyridine nucleotide transhydrogenase of Escherichia coli

The pyridine nucleotide transhydrogenase of Escherichia coli catalyzes the reversible transfer of hydride ion equivalents between NAD + and NADP + coupled to translocation of protons across the cytoplasmic membrane. Recently, transhydrogenation of 3-acetylpyridine adenine dinucleotide (AcPyAD +), an analog of NAD +, by NADH has been described using a solubilized preparation of E. coli transhydrogenase [Hutton, M., Day, J.M., Bizouarn, T., and Jackson, J.B. (1994) Eur. J. Biochem. 219, 1041–1051]. This reaction depended on the presence of NADP(H). We show that (a) this reaction did not require NADP(H) at pH 6 in contrast to pH 8; (b) the reaction occurred at pH 8 in the absence of NADP(H) in the mutant βH91K and in a mutant in which six amino acids of the carboxy-terminus of the α subunit has been deleted; (c) the mutant transhydrogenases contained bound NADP + and were in a conformation in which the β subunit was digestible by trypsin; (d) the conformation of the β subunit of the wild-type enzyme was made susceptible to trypsin digestion by NADP(H) or by placing the enzyme at pH 6 in the absence of NADP(H). It is concluded that reduction of AcPyAD + by NADH does not involve NADPH as an intermediate and that the role of NADP(H) in this reaction at pH 8 is to cause the transhydrogenase to adopt a conformation favouring transhydrogenation between NADH and AcPyAD +.

Kinetics and mechanism of the oxidation of diols by pyridinium hydrobromide perbromide

Kinetics of oxidation of five vicinal, four non-vicinal diols, and one of thier monoethers by pyridinium hydrobromide perbromide (PHPB) have been studied. The vicinal diols yield products arising out of the glycol bond fission while the other diols yield hydroxycarbonyl compounds. The reaction is first order with respect to PHPB. Michaelis-Menten type kinetics are observed with respect to the diol. There is no effect of added pyridinium bromide on the reaction. The oxidation of [1,1,2,2-2H4]ethanediol shows the absence of a primary kinetic isotope effect. The values of solvent isotope effect,k(H2O)/k(D2O), at 313K, for the oxidation of ethanediol, propane-1,3-diol and 3-methoxybutan-1-ol are 4·71, 2·17 and 2·23 respectively. A mechanism involving glycol-bond fission has been proposed for the oxidation of the vicinal diols. The other diols are oxidised by a hydride-transfer mechanism as they are monohydric alcohols.

The evolution of sugar isomerases.

L-Arabinose isomerase (EC 5.3.1.4) catalyzes the isomerization of L-arabinose to L-ribulose. Here we report on the purification, kinetic mechanism and chemical mechanism of L-arabinose isomerase from Escherichia coli. The enzyme catalyzes the isomerization of L-arabinose to L-ribulose by a proton transfer mechanism, in contrast to xylose isomerase which uses a hydride transfer mechanism to perform a similar isomerization. Arabinose isomerase activity is metal dependent, although the enzyme can catalyze the exchange of the proton attached to carbon 2 of arabinose with the solvent in the absence of metal ion. Manganese(II) is the only metal ion which renders the enzyme active for the isomerization reaction. Arabinose isomerase has high substrate specificity for L-arabinose. The difference in chemical mechanism between xylose isomerase and arabinose isomerase suggests that these enzymes are not related by convergent evolution. This work also suggests that unless convergent evolution has been demonstrated, the mechanism of one enzyme may not give any insight into the mechanism of a second enzyme catalyzing the same reaction.

Conformationally biased tri- and di-basic 1,3,5-triazacyclohexyl ligands

The biased ligand cis-cis-2,4,6-trimethyl-1,3,5-triaminocyclohexane is weakly basic and may be converted into di-and tri-basic complexing agents bearing hydroxyphenyl, carboxylate or phosphinate groups; an unusual tricyclic bis-aminal intermediate hydrolyses in acidic media to yield a stable bicyclic amidine via an intramolecular hydride transfer mechanism.

Diastereoselective Synthesis of α‐Hydroxy‐ and α‐Aminoindolizidines and ‐quinolizidines. Evidence for a Novel Cyclization/Hydride Migration Mechanism in the TiCl4‐Induced Reaction of Prolinal Benzylimines by Deuterium Labeling Studies

Lewis acid‐catalyzed cyclization of prolinal and 2‐piperidine‐carbaldehyde benzylimines 11, 12 results in the diastereoselective formation of α‐amino‐β‐alkyl‐substituted indolizidines 15, 17, 19, 21 and ‐quinolizidines 16, 18, 20, respectively. Both diastereoselectivity and constitution depend on the Lewis acid. FeCl3 yields α,β‐trans‐α‐(benzylamino)‐β‐isopropenyl derivatives 15 and 16, probably by a cationic cyclization via carbenium ions 32a, b. In contrast, TiCl4 yields α,β‐cis‐α‐(benzylideneamino)‐β‐isopropyl derivatives 19 and 20 by a novel cyclization/intermolecular hydride transfer mechanism, which was supported by deuterium labeling studies. Compounds 15, 16, 19, and 20 were converted to the diastereomeric acetamides 24, 25 and 28, 29. By an analogous cyclization of the aldehydes 8 and 9 only α,β‐cis‐α‐hydroxy‐β‐isopropenylindolizidines 51 and ‐quinolizidines 52 were obtained irrespective of the Lewis acid used. The structures of 30 and 52 were elucidated by X‐ray analysis.

Oxidation of methyl- and octyl-αa- d-glucopyranoside, catalysed by high-valent ruthenium species; RuO 4, RuO −4 and Ruo 2−4

The oxidation of two alkyl glucopyranosides (OGP and MGP) by NaBrO 3, catalysed by three different high-valent ruthenium species, ruthenium tetroxide, perruthenate and ruthenate, is reported. At pH 4.5, RuO 4 appears to catalyze the oxidation of the alkyl glucopyranosides quite fast and produces alkyl glucuronic acid as the main product. Analysis of the kinetic and thermodynamic data suggests a hydride-transfer mechanism. At pH 10, perruthenate appears to catalyze the oxidation of the alkyl glucopyranoside by NaBrO 3, albeit with a lower reaction rate and a lower selectivity for the alkyl glucuronic acid. The kinetic data, activation parameters and UV—Vis spectroscopy experiments all point towards a radical mechanism. At pH 14, ruthenate seems to be unable to catalyze the oxidation of an alkyl glucopyranoside by NaBrO 3. Product inhibition of these homogeneous catalysts eventually results in the deactivation. Re-oxidation of the lower-valent ruthenium species appears to be prevented by coordination of the glucuronic acid to the lower-valent ruthenium species, as deduced from electronic absorption studies.

Kinetics and mechanism of the oxidation of diols by ethyl N-chlorocarbamate

The kinetics of oxidation of five vicinal and four non-vicinal diols, and two of their monoethers by ethyl N-chlorocarbamate (ECC) have been studied. The vicinal diols yielded products arising out of the glycol bond fission while the other diols yielded hydroxycarbonyl compounds. The reaction is first order with respect to ECC, the diol, and hydrogen ions. Addition of ethyl carbamate and acrylonitrile has no effect on the reaction. The oxidation of [1,1,2,2-2H4]ethanediol showed the absence of a primary kinetic isotope effect. The values of solvent isotope effect, k(H2O)/k(D2O), at 303 K for the oxidation of ethanediol, propane-1,3-diol and 3-methoxybutan-1-ol are 3.51, 2.21 and 1.98 respectively. An acyclic mechanism involving glycol bond fission has been proposed for the oxidation of the vicinal diols. The other diols are oxidized by a hydride-transfer mechanism as are monohydric alcohols.

Hydrolysis of 1,4,6-trioxaspiro[4.5]decanes to .delta.-lactones using 2,3-dichloro-5,6-dicyanobenzoquinone in aqueous acetone

A selective hydrolysis of 1,4,6-trioxaspiro[4.5]decane orthoesters by 2,3-dichloro-5,6-dicyanoquinone (DDQ) in aqueous acetone in the presence of other acid-sensitive ketals is suggested to involve the formation of a charge-transfer complex followed by hydrolysis. A hydride-transfer mechanism for this oxidation was excluded

ChemInform Abstract: Enantioselective Reduction of C=O and C=N Compounds with NADH Model N, N,1,2,4‐Pentamethyl‐1,4‐dihydronicotinamide.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Mechanism of gas-phase aldose-ketose isomerization: a study using tandem mass spectrometry and theoretical calculations

Fast-atom bombardment tandem mass spectrometry and the semiempirical molecular orbital method were used to investigate the mechanism of gas-phase aldose-ketose isomerization process in lithiated 1,3 linked disaccharide isomers. Both the 1,3 hydrogen shift and hydride transfer mechanisms were investigated. Our experimental and theoretical calculations support the latter. The hydride transfer mechanism in these lithium-coordinated systems is similar to the xylose isomerase catalyzed aldose-ketose isomerization.

Stereospecificity of (+)-pinoresinol and (+)-lariciresinol reductases from Forsythia intermedia.

Pinoresinol/lariciresinol reductase catalyzes the first known example of a highly unusual benzylic ether reduction in plants; its mechanism of hydride transfer is described. The enzyme was found in Forsythia intermedia and catalyzes the presumed regulatory branch-points in the pathway leading to benzylaryltetrahydrofuran, dibenzylbutane, dibenzylbutyrolactone, and aryltetrahydronaphthalene lignans. Using [7,7'-2H2]-pinoresinol and [7,7'-2H3]lariciresinol as substrates, the hydride transfers of the highly unusual reductase were demonstrated to be completely stereospecific (> 99%). The incoming hydrides were found to take up the pro-R position at C-7' (and/or C-7) in lariciresinol and secoisolariciresinol, thereby eliminating the possibility of random hydride delivery to a planar quinone methide intermediate. As might be expected, the mode of hydride abstraction from NADPH was also stereospecific: using [4R-3H] and [4S-3H]NADPH, it was found that only the 4 pro-R hydrogen was abstracted for enzymatic hydride transfer.

Enantioselective reduction of CO and CN compounds with NADH model N,N,1,2,4-pentamethyl-1,4-dihydronicotinamide

The scope and mechanism of enantioselective hydride transfer from NADH model 4 to prochiral CO and CN compounds were investigated. Efficient chirality transfer from 4 to α-keto esters and α-methoxycarbonylimino esters was achieved. The resemblance in reactivity and stereochemistry of the prochiral CO and CN-CO 2Me functionalities in the hydride transfer reaction is attributed to the intervention of a similar Mg(ClO 4) 2-mediated ternary complex.

Reaction of hydrogen peroxide with the oxochromium(IV) ion by hydride transfer

Oxidation of hydrogen peroxide by pentaaquaoxochromium(IV), (H[sub 2]O)[sub 5]CrO[sup 2+], in aqueous acidic solutions (0.10-1.0 M HClO[sub 4]) yields the superoxochromium(III) ion (H[sub 2]O)[sub 5]CrOO[sup 2+]. The same product is obtained in both the presence and the absence of oxygen. In 0.10 M HClO[sub 4] the second-order rate constant at 25[degrees]C is 190[+-]10 L mol[sup [minus]1] s[sup [minus]1] in O[sub 2]-saturated solutions and 172[+-]8 L mol[sup [minus]1] s[sup [minus]1] in Ar-saturated solutions, independent of acidity and ionic strength in the range 0.10-1.0 M (HClO[sub 4]/LiClO[sub 4]). In D[sub 2]O a solvent the rate constant is k[sub D] = 53[+-]3 L mol[sup [minus]1] s[sup [minus]1], resulting in the kinetic isotope effect k[sub H]/k[sub D] = 3.6. Experiments in the temperature range 6.8-38.4[degrees]C yielded [delta]H = 25[+-]kJ mol[sup [minus]1] and [delta]S = [minus]116[+-]8 J mol[sup [minus]1] K[sup [minus]1]. A hydride-transfer mechanism is suggested for the oxidation of H[sub 2]O[sub 2] by CrO[sup 2+]. It involves the coordination of H[sub 2]O[sub 2] to Cr(IV) prior to the hydride abstraction step. The reaction of HCrO[sub 4][sup [minus]] with H[sub 2]O[sub 2] under the same conditions also yields (H[sub 2]O)[sub 5]CrOO[sup 2+], which was identified by its characteristic UV spectrum. Possible mechanisms for these reactionsmore » are discussed.« less

An evaluation of the combined application of hammett reaction constant and primary kinetic isotope effects to hydride equivalent transfer reactions

AbstractBunting et al. have suggested that a combined application of Hammett ρ values (or Brønsted exponents) and primary kinetic isotope effects to hydride equivalent transfer reactions involving 1,4‐dihydronicotinamides and organic oxidants is capable of revealing whether this transfer occurs in a single step or follows a two step e− + H° transfer mechanism (J.W. Bunting, V.S.F. Chew, G. Chu, N.P. Fitzgerald, A. Gunasekara, and H.T.P. Oh, Bioorg. Chem., 12, 141 (1984)). We have used this approach with respect to the reduction of flavins by 1‐substituted 1,4‐dihydronicotinamides. Compelling lines of evidence are presented to demonstrate that this reaction follows the single step hydride transfer mechanism. We also present an analysis of the Brønsted exponent and the primary kinetic isotope effect data for the flavin reaction. It is shown that although a simple application of these parameters does indeed favor the two step e− + H° transfer mechanism for flavin reduction, various other empirical data provide conclusive evidence for the single step hydride transfer mechanism. We attribute this discrepancy to the occurrence of nonequilibrium solvation of the transition state. We have considered several mechanistic complexities which could produce seemingly inconsistent Hammett and primary isotope effect values, and have concluded that these complexities must be considered in interpreting the mechanism of a hydride‐equivalent transfer reaction from kinetic parameters. © John Wiley &amp; Sons, Inc.

Analysis of the hydride transfer in the [CH 3-H-CH 3] + system in terms of valence bond structures

The character of the central hydrogen has been analysed in the [CH 3-H-CH 3] + system, both at the absolute symmetric minimum, and at the stationary points of the reduced potential energy surface defined by imposing d C-C = 3 Å. For that purpose, ab initio calculations have been performed at the SCF-MO level using several common basis sets. For each geometry of chemical interest, the molecular orbitals arising from an ab initio Hartree-Fock wave function have been localized. The molecular orbital wave function has then been projected onto a set of valence bond structures describing the various hydride-transfer mechanisms. The ratio of hydride transfer to electron + hydrogen transfer has been assessed.

Visible-light-induced photocatalysis of poly(pyridine-2,5-diyl). Photoreduction of water, carbonyl compounds and alkenes with triethylamine

Poly(pyridine-2,5-diyl)(PPy) exhibits heterogeneous and visible-light-induced photocatalysis toward the reduction of water, carbonyl compounds and alkenes in the presence of triethylamine (TEA) as a sacrifical electron donor. The water reductive H2 evolution is ehnanced by colloidal noble metals concurrently photoformed from noble metal halides, and colloidal Ru gives the highest apparent quantum yield of H2, 0.21 at 450 nm. With regard to the reduction of carbonyl compounds and electron-deficient alkenes, noble-metal-free PPy leads to the efficient and selective reduction to the corresponding alcohols and dihydro compounds, respectively. Carbonyl compounds whose reduction potentials are as negative as –1.83 V vs. SCE in acetonitrile are photoreducible. Deuterium incorporation experiments with dimethyl maleate and/or dimethyl fumarate in [O-2H]methanol have revealed that the photocatalysis of PPy should proceed through sequential two-electron transfer reduction, affording dideuteriated dimethyl succinate. Sequential electron transfer and hydride transfer mechanisms are proposed.

Visualization of the total electronic density of the inter- molecular hydride transfer mechanism

Visualization of the total electronic density of the inter- molecular hydride transfer mechanism

Transformation of butanes over ZSM-5 zeolites. Part 1.—Mechanism of cracking of butanes over H-ZSM-5

The transformations of butane and isobutane over H-ZSM-5 have been studied at 773 K with a special emphasis on the mode of activation of butanes on the acidic sites. The change in the product selectivity with the total conversion of butane (and isobutane) was examined. At low conversion levels, butane is cracked exclusively by a carbonium-ion mechanism into three combinations of products, CH4+ C3H6, C2H6+ C2H4, and H2+ C4H8. The contributions of the three pathways are 42–44%, 38–36% and 20%, respectively. The ratio does not depend on the partial pressure of butane. As the degree of conversion increases, the formation of propane increases, indicating that the activation of butane by a hydride-transfer mechanism is involved. Thus, in the conversion range 20–40%, the contribution of the carbonium-ion mechanism is reduced to 50–60%, 40–50% of butane being activated by the hydride-transfer mechanism. The contribution of the hydride-transfer mechanism increases as the partial pressure of the reactant increases.

Cracking And Aromatization Of Butanes Over ZSM-5 Zeolites

ABSTRACTThe transformation of butanes over H-ZSM-5, Zn-ZSM-5, and Ga-ZSM-5 at 773 K were studied with special emphasis on the activation mechanism of butanes. Over H-ZSM-5, butanes undergo cracking exclusively by a carbonium-ion mechanism at low conversion levels. At higher conversion levels, the activation by a hydride-transfer mechanism are involved. The loading of Zn and Ga greatly enhances the dehydrogenation of starting alkanes as well as intermediate alkenes. The loading of the metal cations promotes also the cracking, especially in the case of isobutane. The synergetic action of the metal cations and protons is proposed as a mechanism of alkane dehydrogenation.