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.