Theoretical studies on cytochrome P-450 mediated hydroxylation: a predictive model for hydrogen atom abstractions

The semiempirical quantum chemical method, AM1, was used to develop a predictive model for cytochrome P-450 hydrogen abstraction reactions. Initially, a general rank-order correlation was observed between the calculated stability of a radical and the tendency of a carbon-hydrogen bond to undergo hydrogen atom abstraction by cytochrome P-450. Of several oxygen radicals studied, the p-nitrosophenoxy radical has the most appropriate transition-state symmetry for use as a model for P-450-mediated hydrogen atom abstractions. This suggests that it may be possible to obtain an estimate at the relative ability for any carbon-hydrogen bond to undergo P-450-mediated hydrogen atom abstraction by calculating the relative stability and ionization potential of the resulting radical.