Predictive studies of oxygen atom transfer reactions by Compound I of cytochrome P450. Aliphatic and aromatic hydroxylation, epoxidation, and sulfoxidation.

This review overviews recent density functional theory studies accompanied by valence bond (VB) modeling of the reactivity patterns of Compound I of cytochrome P450 and taurine/α-ketoglutarate dioxygenase. These two enzymes both have a high-valent iron(IV)-oxo species as their active intermediate and are involved in oxygen atom transfer reactions to substrates including aliphatic hydroxylation, double-bond epoxidation, heteroatom oxidation (sulfoxidation), and aromatic hydroxylation. In recent years, a number of systematic studies on these four reaction mechanisms have been performed, and the barrier heights of the rate-determining steps in these reactions have been analyzed with VB models via curve-crossing diagrams. Those diagrams predict the overall mechanisms and explain the nature of the rate-determining step in the reaction through electron transfer processes. The computational models have gained insight into the fundamental factors that drive the reaction mechanisms and explain the differences between the various reaction processes. © 2012 Elsevier Inc.