Comparative studies on the cumene hydroperoxide- and NADPH-supported N-oxidation of 4-chloroaniline by cytochrome P-450.
The present study confirms that cytochrome P-450 can act as a catalyst in the cumene hydroperoxide-supported N-oxidation of 4-chloroaniline. Analogous to the NADPH/O2-driven N-oxidation process, product dissociation is likely to limit the overall rate of cytochrome P-450 cycling also in the peroxidatic pathway. The oxy complexes involved in either metabolic route differ with respect to stability, spectral properties and need for thiolate-mediated resonance stabilization. With the organic hydroperoxide, the metabolic profile is shifted from the preponderant production of N-(4-chlorophenyl)hydroxylamine to the formation of 1-chloro-4-nitrobenzene. This finding suggests that the peroxide-sustained N-oxidation mechanism differs in several ways from that functional in the NADPH/O2-dependent oxenoid reaction. Thus one-electron oxidation, triggered by homolytic cleavage of the oxygen donor, is proposed as the mechanism of peroxidatic transformation of 4-chloroaniline.
D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D001555:Benzene Derivatives / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000494:pharmacology*; D005260:Female; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009249:NADP / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology; D011817:Rabbits; D013053:Spectrophotometry
D000814:Aniline Compounds; D001555:Benzene Derivatives; D009249:NADP; D003577:Cytochrome P-450 Enzyme System; C007164:cumene hydroperoxide; D010634:Phenobarbital; C004658:4-chloroaniline