Inhibition of Human Acetylcholinesterase by Enantiomers of V-Type Chemical Warfare Nerve Agents and Analogs

Chemical warfare nerve agents are extremely toxic organophosphorus compounds that contain a chiral phosphorus center. Analytical scale methods using a supercritical fluid chromatography (SFC) system in tandem with a mass spectrometer were developed for the separation and detection of individual stereoisomers of VX, VR, and VS, and the analogs V1 thru V4. Separation was evaluated with respect to the chromatography parameter resolution (Rs) with a value of 蠅1.7 indicating complete separation. The ChiralCel OD-H column yielded Rs values >1.7 for each V-type compound with mobile phase modifier concentrations 蠄2%. Methods that provided the highest Rs values were scaled up to the semi-preparative level, allowing for isolation and analysis of individual stereoisomers at >99% purity. Ellipticity (Θ) values of each enantiomer were determined by circular dichroism (CD) spectroscopy. VX, V1, V2, and V3 all had a ΘMAX at 221nm, while VR, VS, and V4 had a ΘMAX at 226nm. For all agents, the first eluting isomer had a n...