Model studies for enzyme inhibition. Part III: Kinetics and thermodynamics of the reaction of diisopropyl phosphorofluoridate with α‐cyclodextrin in aqueous alkaline media

The temperature‐dependency of the reaction rate of diisopropyl phosphorofluoridate with α‐cyclodextrin has been determined in aqueous alkaline media. The dissociation constant (Kdiss) of the prereaction I : I inclusion complex increases from 0.078 at 5° to 0.46 M at 45°. The changes in enthalpy and entropy involved in the dissociation are 7.3 kcal · mole−1 and 21 e.u., respectively. The rate constant for the nucleophilic reaction (k2) increases from 0.109 at 5° to 1.65 min−1 at 45°; the activation energy involved is 11.6 kcal · mole−1. The thermodynamic data are discussed in relation to similar data from the literature for the inhibition of acetylcholinesterase by diisopropyl phosphorofluoridate. The results suggest that polar interactions are important in the formation of an inclusion complex between the organophosphorus compound and the cyclodextrin. The α‐cyclodextrin mimics an enzyme in certain aspects: however, its simple molecular structure limits its value as an enzyme model.