Article

Reactivation of model cholinesterases by oximes and intermediate phosphyloximes: A computational study

Department of Chemistry, The Ohio State University, 100 W. 18th Avenue, Columbus, OH 43210 USA.
Chemico-Biological Interactions (Impact Factor: 2.98). 06/2008; 175(1-3):187-91. DOI: 10.1016/j.cbi.2008.05.006
Source: PubMed

ABSTRACT Phosphyloximes (POX) are generated upon the reactivation of organophosphorus (OP)-inhibited cholinesterases (ChEs) by pyridinium oximes. These POXs are known to be potent inhibitors of the ChEs following reactivation. However, they can also decompose to give an OP derivative and a cyano derivative of the oxime when a base abstracts the benzylic proton. Using density functional theory, thermodynamic properties were calculated for the reactivation and decomposition pathways of three different oximes (2-PAM, 3-PAM and 4-PAM) with six different OPs (cyclosarin, paraoxon, sarin, tabun, VR and VX). For reactivation purposes, 2-PAM is predicted to be more efficient than 3- and 4-PAM. Based on atomic charges and relative energies, 2-POXs were found to be more inclined towards the decomposition process.

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