9.9 Quantum Mechanical Methods for Enzyme Modeling: Accurate Computation of Kinetic Isotope Effects

Tunneling probabilities for the reactions O + HD → OH + D and O + DH → OD + H have been calculated by semiclassical dynamical methods and compared to accurate quantal calculations for the same potential energy surface. The results are used to test the reliability of variational transition state theory with the least-action semiclassical method for tunneling probabilities for the prediction of intramolecular kinetic isotope effects.

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Phenomenological manifestations of quantum‐mechanical tunneling. III. Effect on relative tritium‐deuterium kinetic isotope effects

The Journal of Chemical Physics ◽

10.1063/1.1681449 ◽

1974 ◽

Vol 60 (7) ◽

pp. 2815-2821 ◽

Cited By ~ 10

Author(s):

Marvin J. Stern ◽

Ralph E. Weston

Keyword(s):

Isotope Effects ◽

Kinetic Isotope Effects ◽

Quantum Mechanical ◽

Quantum Mechanical Tunneling ◽

Kinetic Isotope

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Can Alkaline Hydrolysis of γ-HCH Serve as a Model Reaction to Study Its Aerobic Enzymatic Dehydrochlorination by LinA?

International Journal of Molecular Sciences ◽

10.3390/ijms20235955 ◽

2019 ◽

Vol 20 (23) ◽

pp. 5955 ◽

Cited By ~ 1

Author(s):

Suraj Kannath ◽

Paweł Adamczyk ◽

Langping Wu ◽

Hans H. Richnow ◽

Agnieszka Dybala-Defratyka

Keyword(s):

Isotope Fractionation ◽

Isotope Effects ◽

Aqueous Media ◽

Kinetic Isotope Effects ◽

Umbrella Sampling ◽

Quantum Mechanical ◽

Enzymatic Reactions ◽

Kinetic Isotope ◽

Hydroxyl Ion ◽

Fractionation Analysis

Hexachlorocyclohexane (HCH) isomers constitute a group of persistent organic pollutants. Their mass production and treatment have led to a global environmental problem that continues to this day. The characterization of modes of degradation of HCH by isotope fractionation is a current challenge. Multi isotope fractionation analysis provides a concept to characterize the nature of enzymatic and chemical transformation reactions. The understanding of the kinetic isotope effects (KIE) on bond cleavage reaction contributes to analyses of the mechanism of chemical and enzymatic reactions. Herein, carbon, chlorine, and hydrogen kinetic isotope effects are measured and predicted for the dehydrochlorination reaction of γ-HCH promoted by the hydroxyl ion in aqueous solution. Quantum mechanical (QM) microsolvation with an implicit solvation model and path integral formalism in combination with free-energy perturbation and umbrella sampling (PI-FEP/UM) and quantum mechanical/molecular mechanical QM/MM potentials for including solvent effects as well as calculating isotope effects are used and analyzed with respect to their performance in reproducing measured values. Reaction characterization is discussed based on the magnitudes of obtained isotope effects. The comparative analysis between the chemical dehydrochlorination of γ-HCH in aqueous media and catalyzed reaction by dehydrochlorinase, LinA is presented and discussed. Based on the values of isotope effects, these two processes seem to occur via the same net mechanism.

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