Does substrate oxidation determine the regioselectivity of cyclohexene and propene oxidation by cytochrome P450?

DFT and QM/MM computations of allylic C-H hydroxylation versus C=C epoxidation in cyclohexene and propene by Compound I of P450_cam 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.