Quantum chemical studies of model cytochrome P450 hydrocarbon oxidation mechanisms II. Mechanisms and relative kinetics of oxene reactions with alkenes

Abstract

The characteristics of triplet and singlet oxene models for alkene oxidations have been examined with the MNDO method and the formalism of statistical thermodynamics. Propene was selected as a prototype unsymmetrical alkene, and methane and ethylene reactions with O( 3P), which are well documented in the experimental and ab initio literature, were used to gauge the performance of MNDO. It was found that transition state geometries and activation entropies were reliably predicted, but that an empirical factor was necessary to correct overestimation of activation enthalpies. It was determined that hydroxylations and epoxidation of propene, initiated by a O( 3P) atom, must be non-concerted, while the corresponding reactions with singlet oxene are concerted. Furthermore, singlet oxenes are not expected to show any selectivity, while O( 3P) adds to the β-carbon of propene preferentially in the first step of epoxidation, this reaction being ∼10 times faster than addition to the α-carbon and orders of magnitude faster than allyl and propenyl hydrogen abstractions, which would lead to hydroxylations. It is shown that triplet oxene is a good qualitative model for the active oxygen species of cytochrome P450, and that the detailed mechanisms considered here provide consistent explanations for experimental observations on in vitro P450 epoxidation of styrenes, and for suicide inactivation of P450 by ethylene and other small alkenes.