Timing of the Radical Recombination Step in Cytochrome P-450 Catalysis with Ring-Strained Probes

Article abstract of DOI:10.1021/ja00245a037

Notricyclane, methylcyclopropane, and bicyclo<2.1.0>pentane have been used to probe the catalytic mechanism of microsomal cytochrome P-450.Nortricyclane is oxidized by rat liver microsomes to nortricyclanol without the detectable formation of norborn-5-en-2-ol.Methylcyclopropane is similarly oxidized to cyclopropylmethanol without the detectable formation of 3-buten-1-ol or cyclobutanol.The radical pair in the hydroxylation reaction therefore collapses faster than the cyclopropylmethyl radical rearranges (1 x 10⁸ s^-1).In contrast, microsomal oxidation of bicyclo<2.1.0>pentane yields approximately a 7:1 mixture of endo-2-hydroxybicyclo<2.1.0>pentane and 3-cyclopenten-1-ol.Deuterium labeling studies indicate the endo hydrogen is predominantly or exclusively removed from, and the hydroxyl group is delivered to, the endo face in both the rearranged and unrearranged products.The results indicate that a radical pair is formed in P-450-catalyzed hydroxylations that collapses with stereochemical specificity at a rate in excess of 1 x 10⁹ s^-1.