title: Reactivation of model cholinesterases by oximes and intermediate phosphyloximes: a computational study.
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.
authors.affiliation: Department of Chemistry, The Ohio State University, 100 W. 18th Avenue, Columbus, OH 43210 USA.
authors.forename: Shubham
authors.initials: S
authors.lastname: Vyas
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Hadad
mesh_terms: D002802:Cholinesterases / Q000378:metabolism*; D004789:Enzyme Activation; D004793:Enzyme Reactivators / Q000494:pharmacology*; D010091:Oximes / Q000494:pharmacology*; D013816:Thermodynamics
chemical_list: D004793:Enzyme Reactivators; D010091:Oximes; D002802:Cholinesterases