Mechanism of microsomal metabolism of benzene to phenol.

The mechanism of microsomal hydroxylation of benzene to phenol has been studied by examining the microsomal metabolism of the specifically deuterated derivative 1,3,5-[2H3]benzene. Evidence for the formation of the following four products was obtained: 2,3,5-[2H3]phenol, 3,5-[2H2]phenol, 2,4,6-[2H3]phenol, and 2,4-[2H2]phenol. The presence of 2,3,5-[2H3]phenol and 2,4-[2H2]phenol shows that, in the microsomal metabolism of benzene to phenol, a NIH shift had occurred. A deuterium isotope effect (kH/kD) of approximately 4 was detected in both the meta- and para-deuterated phenols. This finding indicates that cyclohexadienone, formed either by isomerization of the epoxide or directly from the enzyme-substrate complex, is a major intermediate in the metabolism of benzene to phenol.