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.
Keywords: QM/MM; density functional theory; elimination reaction; explicit solvation; hexachlorocyclohexanes; kinetic isotope effects; path integral.