Enzymic hydroxylation of aromatic compounds: III. Studies on the mechanism of microsomal hydroxylation

Abstract

The rabbit liver microsomal system has been used to study the mechanism of aromatic hydroxylation. Evidence that dihydrodiols and phenols are not interconvertible is presented. In accord with in vivo findings, benzenoid compounds have been shown to yield only phenols, whereas naphthalene and quinoline have been shown to yield a dihydrodiol and a dihydrodiol-like compound, respectively, as well as phenols. 1,2-Dihydronaphthalene and 1,2-dihydro-1-hydroxynaphthalene (or the 2-hydroxy isomer) do not appear to be intermediates in the conversion of naphthalene to 1,2-dihydronaphthalene-1, 2-diol. Using isotopes to study the conversion of acetanilide to 4-hydroxyacetanilide, it has been shown that molecular oxygen (O 2) is utilized in the hydroxylation reaction rather than the oxygen of water. It has also been shown that the hydrogen of tritiated water is not incorporated into the hydroxylated product. No evidence could be found for the utilization of free hydrogen peroxide in the hydroxylation of naphthalene. In accord with the above, several mechanisms proposed for aromatic hydroxylation now appear to be nonoperable, at least in the system under study. It has been proposed that phenols and dihydrodiols are formed from a common intermediate.