Aliphatic hydroxylation by cytochrome P-450. Evidence for rapid hydrolysis of an intermediate iron-nitrene complex

Article abstract of DOI:10.1021/ja00329a049

Studies with synthetic metalloporphyrin-based hydrocarbon oxidation systems have suggested that the cytochrome P-450 class of heme-containing enzymes may be able to transfer a nitrene equivalent to a hydrocarbon substrate in direct analogy to their currently known ability to transfer an oxene equivalent. Exposure of cyclohexane to the nitrenoid reagent (N-(p-toluenesulfonyl)imino)phenyliodinane in the presence of a purified cytochrome P-450 isozyme (P-450(LM2)) did not result in any amidation of the hydrocarbon. Instead, cyclohexane was efficiently hydroxylated to cyclohexanol. Hydroxylation was also observed with two other hydrocarbons, methylcyclohexane and p-xylene. This reaction is a true catalytic activity of the P-450. Anaerobic and isotope-labeling studies demonstrated that the oxygen in cyclohexanol derived from the water of the reaction medium. These results are interpreted by a scheme whereby the nitrenoid reagent generates a transient iron(V)-nitrene complex which is rapidly hydrolyzed in the aqueous environment to the corresponding iron(V)-oxo complex, which then hydroxylates the substrate. Studies with synthetic metallporphyrin-based hydrocarbon oxidation systems have suggested that the cytochrome P-450 class of heme-containing enzymes may be able to transfer a nitrene equivalent to a hydrocarbon substrate in direct analogy to their currently known ability to transfer an oxene equivalent. Exposure of cyclohexane to the nitrenoid reagent (N-(p-toluenesulfonyl)imino) phenyliodinane in the presence of a purified cytochrome P-450 isozyme (P-450//L//M//2) did not result in any amidation of the hydrocarbon. Instead, cyclohexane was efficiently hydroxylated to cyclohexanol.