Characterization of SWRI 80A Reactivation of Recombinant Human Acetylcholinesterase and Identification of Its Absolute Chirality Using Specific Rotation Calculations in Gaussian/16 at the Hartree-Fock Level of Theory
US Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground United States
The United States Army Medical Research Institute of Chemical Defense USAMRICD in collaboration with the Southwest Research Institute SwRI has identified an uncharged reactivator of nerve agent-inhibited recombinant human acetylcholinesterase rHuAChE that was able to reactivate rHuAChE inhibited by GF cyclosarin by 90 within 5 minutes at a concentration of 500 M during in vitro testing. The oxime reactivator SwRI80A 80A was synthesized by SwRI and tested at the USAMRICD. 80A is a racemic mixture of isomers about a chiral carbon atom in a hexyl ring. Each isomer has two E-Z enantiomers about a carbon-nitrogen double bond near the reactivating oxygen on the oxime arm of the molecule. To evaluate the reaction kinetics of each isomer, the racemic mixture was separated on a super-critical-fluid chromatography system. Two peaks were identified and named by the elution order P1 and P2. This report describes the identification of the chirality of those two peaks.