Stereospecific reaction of isopropyl methylphosphonofluoridate (sarin) with α‐cyclodextrin: A model for enzyme inhibition

Abstract

Abstract The rates of alkaline hydrolysis of the enantiomers of isopropyl methylphosphonofluoridate (Sarin) have been determined without and with varying concentrations of α‐cyclodextrin (cyclohexaamylose) in aqueous 0.1 M /‐KCl solution at pH 9.0 and 25°. The pseudo first‐order rate constants are reported. The observed kinetics and product analysis are consistent with a reaction scheme in which complex formation precedes the nucleophilic reaction of α‐cyclodextrin with Sarin. Dissociation constants ( K diss ) of the inclusion complexes and rate constants ( k 2 ) for the nucleophilic reaction are reported. The results indicate a stereospecific formation of the inclusion complexes, ( S )‐(+)‐Sarin forming a more stable complex than ( R )‐(‐)‐Sarin, as well as a stereospecific rate of reaction, ( R )‐{‐)‐Sarin reacting faster than ( S )‐(+)‐Sarin. The α‐cyclodextrin‐Sarin system represents the first model reaction for enzyme inhibition showing typical properties as complex formation, saturation effects and stereospecificity.