Kinetic isotope effects as a valid measure of structure-reactivity relations.  Isotope effects and nonclassical theory

Scheppele, Stuart E.

doi:10.1021/cr60279a004

Cited by 93 publications

(46 citation statements)

References 12 publications

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“…90 In subsequent years, the kinetics of proton-electron coupling was inferred from free energy relations and kinetic isotope effects of reactant to product conversions of enzymatic, 91,92 organic 93–95 and inorganic substrates. 96,97 Notwithstanding, a predictable framework for PCET, at least to the extent that exists by way of Marcus theory, was absent because the electron and proton had not been isolated in a PCET event.…”

Section: A Chemist’s Toolbox For Catalysis Of Consequence To Renewmentioning

confidence: 99%

Chemistry of Personalized Solar Energy

2009

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Personalized energy (PE) is a transformative idea that provides a new modality for the planet’s energy future. By providing solar energy to the individual, an energy supply becomes secure and available to people of both legacy and non-legacy worlds, and minimally contributes to increasing the anthropogenic level of carbon dioxide. Because PE will be possible only if solar energy is available 24 hours a day, 7 day a week, the key enabler for solar PE is an inexpensive storage mechanism. HX (X = halide or OH−) splitting is a fuel-forming reaction of sufficient energy density for large scale solar storage but the reaction relies on chemical transformations that are not understood at the most basic science level. Critical among these are multielectron transfers that are proton-coupled and involve the activation of bonds in energy poor substrates. The chemistry of these three italicized areas is developed, and from this platform, discovery paths leading to new HX and H2O splitting catalysts are delineated. For the case of the water splitting catalyst, it captures many of the functional elements of photosynthesis. In doing so, a highly manufacturable and inexpensive method has been discovered for solar PE storage.

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Section: A Chemist’s Toolbox For Catalysis Of Consequence To Renewmentioning

confidence: 99%

Chemistry of Personalized Solar Energy

2009

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“…Solvent Kinetic Isotope Effects on the Reduction of Thioredoxin by Dithiothreitol-Kinetic isotope measurements provide one of the most sensitive experimental monitors of proton transfer mechanisms (23,24). Unfortunately, enzyme reactions rarely allow for the systematic variation of both substrates and catalytic groups often necessary to obtain unambiguous mechanistic interpretations.…”

Section: Kinetics Of Reduction Of Wild Type and D26n E Colimentioning

confidence: 99%

The Role of the Buried Aspartate of Escherichia coliThioredoxin in the Activation of the Mixed Disulfide Intermediate

LeMaster

Springer

Ünkefer

1997

Journal of Biological Chemistry

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The structurally homologous protein disulfide isomerases and thioredoxins exhibit a 10 5 variation of redox equilibria. It is demonstrated that the kinetic distinction among these protein family members lies primarily in the rate of breakdown of the mixed disulfide intermediate. The conserved buried acid group serves as a proton transfer catalyst for the buried active site cysteine in the formation and breakdown of the mixed disulfide. The reduction rate of Escherichia coli thioredoxin by dithiothreitol is directly proportional to the fraction of Asp-26 in the protonated form over the pH range of 6 -9. The kinetic role of Asp-26 is further probed via differential solvent kinetic isotope effect measurements versus a D26N variant. The differential solvent isotope effect of 0.6 is consistent with a direct proton donation to the thiolate leaving group (Cys-35) via an enforced general acid catalysis by trapping mechanism. Such a donation necessitates a structural rearrangement as these two buried side chains are separated by 6 Å in both the oxidized and reduced forms of the protein.Despite substantial sequence variability, the mammalian and bacterial protein disulfide isomerases, as well as the ubiquitous thioredoxins, appear to share a common structural motif (1) and are generally assumed to utilize a common enzymatic mechanism to achieve their accelerated reactivities in both dithiol oxidation and disulfide reduction (Fig. 1). Although the conformation of the active sites are markedly similar (2, 3), there is a 10 5 -fold variation in redox equilibria between Escherichia coli thioredoxin (EЈ 0 ϭ Ϫ260 mV (4)) and the E. coli protein disulfide isomerase protein DsbA (EЈ 0 ϭ Ϫ0.1 mV (5)). Within the thioredoxin/protein disulfide isomerase family the active site disulfide (-CXXC-) sequence spans the top of the first turn of an a-helix (the a 2 helix in E. coli thioredoxin) with the sulfur of the first cysteine exposed for reaction with exogenous thiols and disulfides while the second cysteine is buried within the protein interior. Much of the research into the mechanism has focused on the reactions of the solvent exposed thiol (Cys-32 in E. coli thioredoxin). Particularly noteworthy is the quantitative correlation between the redox potential and the pK of this solvent exposed thiol observed for a series of protein disulfide isomerase variants (6). This correlation is also proposed to extend to the E. coli thioredoxin (7).Since K eq equals (k 1 /k Ϫ1 )⅐(k 2 /k Ϫ2 ) for Fig. 1, the large differences in redox equilibria between the protein disulfide isomerases and the thioredoxins must be manifested in the individual rate constants. E. coli thioredoxin exhibits a k 1 reaction rate of 120 M Ϫ1 s Ϫ1 with oxidized glutathione under the conditions reported for human PDI 1 ␣ domain in Fig. 1 (8). Given the similarity in the rate constants observed for this step, the major difference in kinetics exhibited by these two enzymes does not lie primarily in the reaction of the protein thiol with the target disulfide substrate. Hence,...

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“…reactions are associated with decrease in the positive charge on the carbonyl carbon in rehybridization from sp2 to sp3 (3,5,6). The relationship between the magnitude of the P-deuterium isotope effect and the amount of positive charge at the adjacent carbon is well demonstrated by three examples taken from the literature.…”

Section: Resultsmentioning

confidence: 82%

Secondary β-Hydrogen Isotope Effects in Ketal Formation Equilibria

Stoute¹,

Winnik²

1975

Can. J. Chem.

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Can. J. Chem. 53,3503 (1975). An n.m.r. technique was used to measure KH/KD of ketal formation in methylene chloride solution for acetone and phenylacetone. For acetone, KH/KD = 0.95 per D for methyl ketal formation. ,3,,1,1,3,, were examined for both dimethyl and ethylene ketal formation. For both ketals, KH/KD = 0.91 per D, for each ketone. Liquid scintillation counting was used to examine KH/KT for ketal formation in methylene chloride. An extraordinarily large isotope effect was found for ethylene ketal formation in 1,3-diphenylacetone. Here KH/KT = 0.67 for one tritium atom. This isotope effect is too large to arise from hyperconjugative effects alone. It must have a substantial steric component. [Traduit par le journal]

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Kinetic isotope effects as a valid measure of structure-reactivity relations. Isotope effects and nonclassical theory

Cited by 93 publications

References 12 publications

Chemistry of Personalized Solar Energy

Chemistry of Personalized Solar Energy

The Role of the Buried Aspartate of Escherichia coliThioredoxin in the Activation of the Mixed Disulfide Intermediate

Secondary β-Hydrogen Isotope Effects in Ketal Formation Equilibria

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