A theoretical approach to the mechanism of biological oxidation of organophosphorus pesticides

Organophosphorus pesticides are the most common classes involved in poisoni ngs related to pesticides. We used enzymatic activity of chloroperoxidase o n the metabolism of some phosphorothioate pesticides published previously a nd molecular mechanics methods to perform a theoretical approach of the mec hanism of biological oxidation of this class of pesticides. The molecular s tructure of eight pesticides were optimized by molecular mechanics methods using the CAChe program package for biomolecules, ver. 3.11 (Oxford Molecul ar Ltd., Campbell, CA). Total energy resulted from the structure optimizati on process and the partial charges of both phosphorus and sulfur were compu ted for every pesticide. Phosphorus partial charge and enzymatic activity w ere significantly related by linear regression analysis (r = 0.82, P < 0.05 ). Analyzing our results and using previously reported enzymatic activity o f chloroperoxidase on these pesticides, we deduced chemical events involved in activation of the active site of chloroperoxidase and proposed a novel mechanism of oxidation for this class of pesticides. This mechanism will al so help to understand the oxidation process of pesticides by cytochrome P45 0, and production of toxic metabolites. (C) 2000 Elsevier Science Ireland L td. All rights reserved.