- NAD(P)H-NAD(P)+ Models. 74. Entropy-Controlled Kinetics, Stereochemistry, and Tunneling Effect
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Kinetics have been studied for the reactions of three NAD(P)H analogs and their 4-deuteriated compounds with 2,6-dichloro- and tetrachloro-1,4-benzoquinones.It has been elucidated that the entropy term occupies 50-90 percent of the Gibbs energy of activat
- Ohno, Atsuyoshi,Goto, Mutsuo,Mikata, Yuji,Kashiwagi, Takeshi,Maruyama, Tetsushi
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- Deuterium Isotope Effects for the Nonenzymatic and Glutamate Dehydrogenase Catalyzed Reduction of an α-Imino Acid by NADH
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The mechanisms of the nonenzymatic and glutamate dehydrogenase catalyzed reduction of an α-imino acid, Δ1-pyrroline-2-carboxylic acid, by NAD(P)H have been studied by deuterium isotope effects.The partition isotope effects for the nonenzymatic reaction with 4-deuterated 1,4-dihydronicotinamides are about the same as the corresponding observed kinetic isotope effects with 4,4-dideuterio-1,4-dihydronicotinamides, suggesting that the hydrogen-transfer step is solely rate limiting.This reaction is characterized by an intrinsic primary kinetic isotope effect of 1.3 and a very product-like transition state.The enzymatic reaction has been studied by determining the second-order rate constants for the reduction of the imino acid by the enzyme-NADH complex with 4,4-dideuterio and stereospecifically labeled 4-deuterio NADH.The primary isotope effect when the in-place hydrogen is protium is 3.80, and the secondary isotope effect when the in-flight hydrogen is protium is 1.21.Deuteration at one site lowers the isotope effects at the other by 13percent.The following conclusions emerge for the reduction of the imino acid by the enzyme-NADH complex: (1) the hydrogen-transfer step is at least rate contributing, (2) the transition state for this reaction is more symmetric than that of the nonenzymatic reaction, (3) both the C-4 hydrogens of NADH participate in the reaction coordinate motion, and (4) there is some nuclear tunneling in the reaction coordinate.The kinetic isotope effect for the oxidation of proline and proline-2-d by enzyme-NADP(+) is 4.1.
- Srinivasan, R.,Fisher, Harvey F.
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p. 4301 - 4305
(2007/10/02)
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- Ferricyanide Oxidation of Dihydropyridines and Analogues
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The reaction of the N1-substituted dihydronicotinamides (1-6), N-benzyl-3-carbomyl-1,4-dihydropyridine (7), and tritiated N-methylacridan (8) with Fe(CN)63- is first order in 3-> and .The oxidations of 1
- Powell, Michael F.,Wu, James C.,Bruice, Thomas C.
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p. 3850 - 3856
(2007/10/02)
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- Hydride vs. Electron Transfer in the Reduction of Flavin and Flavin Radical by 1,4-Dihydropyridines
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Literature dealing with the existing controversy concerning the mechanism of hydride equivalent (H- or e-, H+, e-) transfer from N-alkyl-1,4-dihydronicotinamides is presented.Included are references to the dihyd
- Powell, Michael F.,Bruice, Thomas C.
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p. 1014 - 1021
(2007/10/02)
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- Kinetics of the Reduction of 3,4-Dihydroisoquinolinium Cations by 1,4-Dihydronicotinamides
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Pseudo-first-order rate constants for the reduction of 2-methyl-3,4-dihydroisoquinolinium cation (1) by 1-(X-benzyl)-1,4-dihydronicotinamides (3) display kinetic saturation at high concentrations of 1 (20percent CH3CN-80percent H2O, 25 deg C, ionic strength 1.0).Association constants for 1:1 complex formation are independent of X (1.4 +/- 0.2 M-1) and are most simply interpreted in terms of nonproductive complex formation.Pseudo-first-order rate constants for the reduction of 2-(Z-benzyl)-3,4-dihydroisoquinolinium cations (2) by 3 are linear for up to approximately 60 mM.Hammett correlations for the second-order rate constants for these reactions give ρx = -0.77 for the reduction of 2 (Z = 4-CN) by 3 and ρz = 0.83 for the reduction of 2 by 3 (X = H).Comparisons of ρx and ρz with equilibrium ρ values for closely related reactions indicate that the migrating hydrogen atom bears a charge of -0.33 and thus is clearly hydridic in character.These results are closely analogous to the conclusions of our earlier study of the 1,4-dihydronicotinamide reduction of 5-nitroisoquinolinium cations which have similar pKR+ values to those for 2.Thus similar reduction mechanisms apply to the reduction of aromatic and nonaromatic cations by 3. pKR+ values for pseudobase formation from 2 are correlated with a Hammett ρ = 1.72.The second-order rate constant for hydroxide ion attack on 2 (X = H) is fivefold larger than for the 2-benzyl-5-nitroisoquinolinium cation, although the second-order rate constant for reduction by 3 (X = H) is 23-fold greater for the latter cation than for 2 (X = H).This is interpreted in terms of a poorer "fit" between 2 and 3 in the transition state for the reduction, relative to the better "fit" between the planar 5-nitroisoquinolinium cations and 3.
- Bunting, John W.,Chew, Vivian S. F.,Chu, Gary
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p. 2308 - 2312
(2007/10/02)
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