Design of VX Stimulants for Enrichment of Bacteria That Detoxify VX

摘要

Bacterial enzymes are used to decontaminate and detoxify hazardousorganophosphorus-based compounds (pesticides and chemical warfare agents). However, there are no known bacteria that can effectively degrade VX. Because of its toxicity, instability in aqueous media, and toxic by-products, VX cannot be used as a growth component to enrich bacteria for detoxifying VX. Therefore, there is a need for identifying non-hazardous, stable VX simulants as growth substrates. Molecular modeling and computational chemistry techniques are used to analyze the interaction of organophosphorus and related compounds with x-ray crystal structures of enzymes known to breakdown such compounds. Stereochemical, electrostatic, and physicochemical parameters of the compounds and of the enzymes are evaluated; and a model for the design of novel VX simulants is developed. Several VX simulants are defined for synthesis and use in the bacterial studies. Enzymes analyzed for organophosphorus/dipeptide activity included acetylcholinesterase, organophosphorus hydrolase (phosphotriesterase), bovine lens leucine aminopeptidase, methionine aminopeptidase, and organophosphorus acid anhydrolases.