Kinetic isotope effects implicate the iron-oxene as the sole oxidant in P450-catalyzed N-dealkylation.
Multiple oxidants have been implicated as playing a role in cytochrome P450-mediated oxidations. Herein, we report results on N-dealkylation, one of the most facile reactions mediated by P450 enzymes. We have employed the N-oxides of a series of para-substituted 13C2H2-labeled N,N-dimethylanilines to function as both substrates and surrogate oxygen atom donors for P450cam and P4502E1. Kinetic isotope effect profiles obtained using the N-oxide system were found to closely match the profiles produced using the complete NAD(P)H/NAD(P)-P450 reductase/O2 system. The results are consistent with oxidation occurring solely through an iron-oxene species.
Dowers
Tamara S
TS
Department of Chemistry, P.O. Box 644630, Washington State University, Pullman, Washington 99164-4630, USA.
Rock
Dan A
DA
Rock
Denise A
DA
Jones
Jeffrey P
JP
D000478:Alkylation; D000814:Aniline Compounds / Q000737:chemistry / Q000378:metabolism; D019475:Camphor 5-Monooxygenase / Q000737:chemistry* / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000737:chemistry* / Q000378:metabolism; D041961:Deuterium Exchange Measurement; D004852:Epoxy Compounds / Q000737:chemistry* / Q000378:metabolism; D058085:Iron Compounds / Q000737:chemistry* / Q000378:metabolism; D007700:Kinetics; D010084:Oxidation-Reduction
D000814:Aniline Compounds; D004852:Epoxy Compounds; D058085:Iron Compounds; C012469:oxirene; C015157:N,N-dimethylaniline; D019392:Cytochrome P-450 CYP2E1; D019475:Camphor 5-Monooxygenase; C005141:dimethylaniline N-oxide