Stereoselectivity in metabolism of the optical isomers of cyanofenphos (O-p-cyanophenyl O-ethyl phenylphosphonothioate) in rats and liver microsomes.

Abstract

The racemic, (+)- and (—)-forms of cyanofenphos (O-p-cyanophenyl O-ethyl phenylphosphonothioate) were rapidly metabolized in the rat by cleavage of P-O-aryl linkage, cleavage of P-O-alkyl linkage and conjugation of p-cyanophenol with sulfuric acid. There was a marked difference in the proportion of the major urinary metabolites, p-cyanophenol and p-cyanophenyl sulfate, with three forms of cyanofenphos,The three forms of cyanofenphos were metabolized at almost equal rates in rat liver microsomes-NADPH system. (+)-Cyanofenphos underwent oxidation of P=S to P = O and cleavage of P-O-aryl linkage predominantly. In contrast, the (−)-isomer was converted to the corresponding oxon analog by mixed function oxidase, and then the oxon analog was rapidly hydrolyzed to p-cyanophenol by microsomai arylesterase-type enzyme. This microsomal enzyme had a remarkable selectivity in hydrolyzing (−)-cyanofenphos oxon versus the ( + )-isomer. Stereoselectivity in the metabolism of the cyanofenphos isomers in the rat appears l...