Intramolecular isotope effects associated with meta-hydroxylation of biphenyl catalyzed by cytochrome P-450.
Intramolecular isotope effects and the degree of deuterium retention were determined for the meta-hydroxylation of biphenyl as catalyzed by microsomal cytochrome P-450 obtained from rats pretreated with phenobarbital. The percent deuterium retention after meta-hydroxylation of 3,5,3',5'-[2H4]-biphenyl was found to be 77.3% +/- 1.9. The intramolecular isotope effects associated with 3,3'-[2H2]-biphenyl and 3,5-[2H2]-biphenyl were found to be 0.90 +/- .05 and 1.05 +/- .06, respectively. These data demonstrate conclusively that a direct insertion or abstraction mechanism is not operable in the meta-hydroxylation of biphenyl and suggest the possibility of an addition-rearrangement mechanism as opposed to initial and direct arene oxide formation.
D000818:Animals; D001713:Biphenyl Compounds / Q000378:metabolism*; D055598:Chemical Phenomena; D002621:Chemistry; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003903:Deuterium; D006900:Hydroxylation; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D008968:Molecular Conformation; D051381:Rats; D011919:Rats, Inbred Strains
D001713:Biphenyl Compounds; D003577:Cytochrome P-450 Enzyme System; D003903:Deuterium; C010574:biphenyl