Molecular Rearrangements. XIV. The Hydrogen-Deuterium Isotope Effect in the Pinacol Rearrangement of Triarylethylene Glycols<sup>1</sup>

Collins, Clair J.; Rainey, W.T.; Smith, William B.; Kaye, Irving Allan

doi:10.1021/ja01511a051

Cited by 31 publications

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“…A nonlinear transition state gives a small isotope effect because the vibrational frequencies (and hence the zero-point energies) for bending are much lower than those for stretching (Westheimer, 1961). Intrinsic tritium isotope effects for such processes are likely to be on the order of 3-5 (Hawthorne & Lewis, 1958;Winstein & Takahashi, 1958;Collins et al, 1959). Although we do not yet have a crystal structure of the mutant isomerase complexed with substrate, the structure of the wild-type enzyme-substrate complex shown in Figure 2 suggests that when Glu-165 is replaced by Asp, the carboxylate is likely to be relocated in a direction that is orthogonal to the C-H bond on C-2 of glyceraldehyde phosphate (the carbon that receives a proton to form glyceraldehyde phosphate).…”

Section: Discussionmentioning

confidence: 99%

Reaction energetics of a mutant triose phosphate isomerase in which the active-site glutamate has been changed to aspartate

Raines¹,

et al. 1986

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The essential catalytic base at the active site of the glycolytic enzyme triosephosphate isomerase is the carboxylate group of Glu-165, which directly abstracts either the 1-pro-R proton of dihydroxyacetone phosphate or the 2-proton of (R)-glyceraldehyde 3-phosphate to yield the cis-enediol intermediate. Using the methods of site-directed mutagenesis, we have replaced Glu-165 by Asp. The three enzymes chicken isomerase from chicken muscle, wild-type chicken isomerase expressed in Escherichia coli, and mutant (Glu-165 to Asp) chicken isomerase expressed in E. coli have each been purified to homogeneity. The specific catalytic activities of the two wild-type isomerases are identical, while the specific activity of the mutant enzyme is reduced by a factor of about 1000. The observed kinetic differences do not derive from a change in mechanism in which the aspartate of the mutant enzyme acts as a general base through an intervening water molecule, because the D2O solvent isotope effects and the stoichiometries of inactivation with bromohydroxyacetone phosphate are identical for the wild-type and mutant enzymes. Using the range of isotopic experiments that were used to delineate the free-energy profile of the wild-type chicken enzyme, we here derive the complete energetics of the reaction catalyzed by the mutant protein. Comparison of the reaction energetics for the wild-type and mutant isomerases shows that only the free energies of the transition states for the two enolization steps have been seriously affected. Each of the proton abstraction steps is about 1000-fold slower in the mutant enzyme. Evidently, the excision of a methylene group from the side chain of the essential glutamate has little effect on the free energies of the intermediate states but dramatically reduces the stabilities of the transition states for the chemical steps in the catalyzed reaction.

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Section: Discussionmentioning

confidence: 99%

Reaction energetics of a mutant triose phosphate isomerase in which the active-site glutamate has been changed to aspartate

Raines¹,

et al. 1986

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“…5 By the use of kinetic isotope effect arguments, it was established that the acidcatalyzed rearrangement of 1,1,2-triphenylethylene glycol could only be accommodated by an open classical carbocation mechanism shown above. However, when similar studies were extended to the rearrangement of 1,1-dimethylethylene glycol and 1,1,2-trimethylene glycol, 6 the kinetic isotope effects (ca 1.6-1.7) were interpreted as indicating hydrogen acting as a neighboring group forming a non-classical hydrogen-bridged intermediate as shown in Scheme 2.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen as a migrating group in some pinacol rearrangements: a DFT study

Smith

1999

J. Phys. Org. Chem.

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DFT calculations at the Becke3LYP/6-31G* level were employed to demonstrate that the pinacol rearrangement of ethylene glycol and the 1,1-dimethyl and 1,1,2-trimethyl analogs undergo pinacol rearrangements by a concerted hydrogen-bridged transition structure. No evidence for a bridged intermediate was found. Calculations by two methods on the ethylene glycol system were repeated with the various structures embedded in a solvent cavity with the medium dielectric constant set for water. The ratio of rates for the two methylated glycols was calculated with good agreement with the experimental value. The kinetic isotope effect for the rearrangement of 1,1,2-trimethylethylene glycol was calculated (2.8) in fair agreement with the experimental value of 1.6. Sources of error are briefly discussed.

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“…Generally, the acid-catalyzed hydrolysis of epoxides proceeds via the formation of a carbonium ion intermediate (A-1 mechanism, Fig. 3) through the cleavage of the carbon-oxygen bond, followed by nucleophilic attack by a water molecule and formation of the diol [4][5][6]191. The other alternative would be through nucleophilic ring opening followed by formation of the diol (A-2 mechanism, Fig.…”

Section: Mechanism Of the Reaction In Buffered Watermentioning

confidence: 99%

Hydrolysis of Chlorostilbene Oxide: I. Hydrolysis in Homogeneous Systems

Metwally¹,

Wolfe²

1989

Environ Toxicol Chem

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The hydrolysis kinetics of 4-chlorostilbene oxide (CSO) in buffered distilled water, in natural waters and in sediment-associated water are reported. The disappearance of CSO followed pseudo-first-order kinetics in buffered distilled water over the experimental pH range of 3 to 11. Below pH 5 , acid-catalyzed hydrolysis dominates, with a second-order rate constant of 11.3 (k 1.0) M-' min-' . Above pH 5 , hydrolysis is independent of pH, with a rate constant of 1.02 (t0.12) x IOW4 min-' at 25°C. In natural waters, the hydrolysis rate constant of CSO had an average value of 0.59 (k0.12) x IOW4 min-I. In sediment-associated water, the observed rate constant was 1.70 (k0.05) x 10-min-' . Sorption of CSO to the humic materials in natural waters and biotic effects in sediment-associated water appropriately explain the differences from sterile buffer solutions. Buffer catalysis was observed, but on the other hand, a negative ionic strength effect was determined. The formation of diastereoisomers of l-(4-chlorophenyl)-2-phenylethylene glycol as major products at both acidic and neutral pH values suggests that CSO undergoes acid-catalyzed as well as neutral hydrolysis reactions through an A-1 carbonium ion mechanism. The rate constant for hydrolysis of CSO at pH 14 is only 70% faster than the hydrolysis rate constant over the pH range of 5 to 11, which suggests that nucleophilic addition of hydroxide ion is not the main hydrolytic mechanism of CSO hydrolysis at high pH values.

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Molecular Rearrangements. XIV. The Hydrogen-Deuterium Isotope Effect in the Pinacol Rearrangement of Triarylethylene Glycols¹

Cited by 31 publications

References 0 publications

Reaction energetics of a mutant triose phosphate isomerase in which the active-site glutamate has been changed to aspartate

Reaction energetics of a mutant triose phosphate isomerase in which the active-site glutamate has been changed to aspartate

Hydrogen as a migrating group in some pinacol rearrangements: a DFT study

Hydrolysis of Chlorostilbene Oxide: I. Hydrolysis in Homogeneous Systems

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Molecular Rearrangements. XIV. The Hydrogen-Deuterium Isotope Effect in the Pinacol Rearrangement of Triarylethylene Glycols1

Cited by 31 publications

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Reaction energetics of a mutant triose phosphate isomerase in which the active-site glutamate has been changed to aspartate

Reaction energetics of a mutant triose phosphate isomerase in which the active-site glutamate has been changed to aspartate

Hydrogen as a migrating group in some pinacol ­rearrangements: a DFT study

Hydrolysis of Chlorostilbene Oxide: I. Hydrolysis in Homogeneous Systems

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Molecular Rearrangements. XIV. The Hydrogen-Deuterium Isotope Effect in the Pinacol Rearrangement of Triarylethylene Glycols¹

Hydrogen as a migrating group in some pinacol rearrangements: a DFT study