Multiple mechanisms and multiple oxidants in P450-catalyzed hydroxylations.
Cytochrome P450 enzymes catalyze a number of oxidations in nature including the difficult hydroxylations of unactivated positions in an alkyl group. The consensus view of the hydroxylation reaction 10 years ago was that a high valent iron-oxo species abstracts a hydrogen atom from the alkyl group to give a radical that subsequently displaces the hydroxy group from iron in a homolytic substitution reaction (hydrogen abstraction-oxygen rebound). More recent mechanistic studies, as summarized in this review, indicated that the cytochrome P450-catalyzed "hydroxylation reaction" is complex, involving multiple mechanisms and multiple oxidants. In addition to the iron-oxo species, another electrophilic oxidant apparently exists, either the hydroperoxo-iron intermediate that precedes iron-oxo or iron-complexed hydrogen peroxide formed by protonation of the hydroperoxo-iron species on the proximal oxygen. The other electrophilic oxidant appears to react by insertion of OH(+) into a C-H bond to give a protonated alcohol. Computational work has suggested that iron-oxo can react through multiple spin states, a low-spin ensemble that reacts by insertion of oxygen, and a high-spin ensemble that reacts by hydrogen atom abstraction to give a radical.
Newcomb
Martin
M
Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, 60607, USA. men@uic.edu
Hollenberg
Paul F
PF
Coon
Minor J
MJ
D001669:Biochemical Phenomena; D001671:Biochemistry; D002384:Catalysis; D002412:Cations; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000378:metabolism; D005609:Free Radicals; D006418:Heme / Q000737:chemistry; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008956:Models, Chemical; D010100:Oxygen / Q000378:metabolism
D002412:Cations; D005609:Free Radicals; D006418:Heme; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010100:Oxygen