Relationships Between Activity of Organophosphorus Inhibitors of Acetylcholinesterase and Accessibility of Phosphorus Atom as Estimated by Molecular Mechanics Calculations

Irreversible inhibition of acetylcholinesterase (AChE) by organophosphorus compounds is believed to be due to phosphorylation of serine hydroxyl in the enzyme active center (Cohen, Oosterbaan, 1963). The attack by the hydroxyl may occur from the different faces of phosphorus atom (Berman and Decker, 1989). The efficiency of these reactions should depend on sterical accessibility of the phosphorus atom for the attacking agent. In particular, low …