title: Does substrate oxidation determine the regioselectivity of cyclohexene and propene oxidation by cytochrome p450?
abstract: DFT and QM/MM computations of allylic C-H hydroxylation versus C=C epoxidation in cyclohexene and propene by Compound I of P450cam demonstrate that the relative barriers for the oxidative processes themselves are not good predictors of the observed selectivity. However, a kinetic expression previously developed (Kozuch, S.; Shaik, S. J. Am. Chem. Soc. 2006, 128, 3355) for catalytic cycles under steady-state conditions, predicts, in accord with experiment, that propene will undergo exclusive C=C epoxidation, while cyclohexene will undergo both reactions with a small preference for epoxidation. The model expression for the effective barrier of the cycle forms a general basis for understanding and predicting the selectivity of P450 isozymes.
authors.affiliation: Department of Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, The Hebrew University of Jerusalem, 91904 Jerusalem, Israel.
authors.forename: Shimrit
authors.initials: S
authors.lastname: Cohen
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kozuch
authors.forename: Carina
authors.initials: C
authors.lastname: Hazan
authors.forename: Sason
authors.initials: S
authors.lastname: Shaik
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D053138:Cyclohexenes / Q000737:chemistry*; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry*; D010084:Oxidation-Reduction
chemical_list: D000475:Alkenes; D053138:Cyclohexenes; C052568:cyclohexene; D003577:Cytochrome P-450 Enzyme System; C013658:propylene