The Mixed Function Oxygenation of 4-Halogenoacetanilides in Rat Liver Microsomes and Model Systems

Abstract

The mixed function oxygenatlon of 4-halogenoacetanllldes (Hal. = F, Cl, Br) In rat liver microsomes and in model systems was Investigated. The enzymatic hydroxylation of the p-position with release of the halogen is inhibited In favor of a concomitant Increase In 0- and m -hydroxylation. From Inhibition and Induction experiments it is concluded that only 1 enzyme system is responsible for the mixed function oxygenatlon of acetanllide and its halogenated derivatives at all positions of the nucleus. The results of the enzymatic hydroxylatlons are compared qualitatively and quantitatively with the hydroxylations obtained by OH-radicals, peracids and the oxene mechanism. Mlcrosomal hydroxylatlons prove to proceed by an electrophilic substitution, mechanism. Migration of the halogens, a common feature of mlcrosomal hydroxylation, is observed in model systems only when peracids are used. A polar as well as a radical mechanism are discussed for the electrophilic attack of the "active oxygen" in microsomes.