Aliphatic hydroxylation by highly purified liver microsomal cytochrome P-450. Evidence for a carbon radical intermediate

The oxidation of norbornane by a reconstituted liver cytochrome P-450 system affords $\text{exo}$- and $\text{endo}$-2-norborneol in a ratio of 3.4:1. The ratio of these products was found to be 0.76:1 when $\text{exo,exo,exo,exo}$-2,3,5,6-tetradueteronorbornane was oxidized. Analysis of the mass spectra of the products from the deuterated hydrocarbon showed that 25% of the $\text{exo}$-norborneol contained four deuterium atoms whereas 9% of the $\text{endo}$-norborneol contained three deuterium atoms. These results, which indicate a very large isotope effect ($\text{k}{}_{\mathrm{H}}\text{k}{}_{\mathrm{D}}\text{= 11.5±1}$) and a significant amount of epimerization for the hydroxylation of norbornane by cytochrome P-450, suggest an initial hydrogen abstraction to give a carbon radical intermediate.