STUDIES ON OPTICALLY ACTIVE ISOMERS OF O O-DIETHYL MALATHION AND O O-DIETHYL MALAOXON

The optically active isomers of O,O-diethyl malathion and O,O-diethyl malaoxon have been prepared by two different synthetic routes. Partially purified carboxylesterase (99-fold) from rat liver has been prepared for kinetic studies involving inhibition rate constants (ki) and Michaelis constants (Km) for malaoxons and malathions respectively. The d-isomers of malathion and malaoxon always proved to be more toxic toward mice and houseflies than the corresponding l-isomers. The higher toxicity of the d-isomers is believed to be related to higher bimolecular rate constants of d-malaoxon (ki) with acetylcholinesterase and carboxylesterase. Although d-malaoxon is a better inhibitor for carboxylesterase, d-malathion proved to be the better substrate for this enzyme. In vivo, however, the inhibition reaction dominated the substrate reaction, resulting in the d-isomers being more toxic. © 1968.