The inhibition of Acetylcholinesterase (AChE) by organophosphate compounds is a serious problem whether the cause of exposure is accidental or malicious. The reactivation of organophosphate (OP) inhibited acetylcholinesterase is dependent on the OP-conjugate and oxime reactivation therapeutic. The research presented will focus on the exploration of the physicochemical properties for a series of oximes that have been tested for their ability to reactive four well known OPs: cyclosarin, sarin, tabun and VX. An ensemble of QSAR models for each OP-conjugate pair was constructed from a trial descriptor pool of semi-empirical, traditional and molecular interaction field descriptors. A subset of models was selected based on the molecular information contained within each model and its cross-validation ability to construct consensus models. The individual and consensus models were applied to proposed and known oxime reactivation therapeutics with mixed results. Each set of models provides the important physicochemical properties and thus insight to the molecular features required to reactivate each OP-conjugate.

Predictive models to better understand the nuances for the oxime-reactivation of cyclosarin, sarin, tabun, and VX inactivated acetylcholinesterase

245th National Meeting (2013)

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