The role of hydrophobic and electron donor properties in acetylcholinesterase inhibition by carbamates

Abstract

The abilities of seven m-substituted phenyl methylcarbamates to inhibit acetylcholinesterases from honey bee and cotton leafworm (Spodoptera littoralis, Boisd.) were explored. The extra inhibition bestowed by m-substituted phenyl methylcarbamate as compared with the unsubstituted (Δ log k i = log k i(X) k iH)) was well correlated with the calculated contribution of each substituent through its hydrophobic and electron donating properties (0.69 π – 0.95 σ + 1.19). The correlation coefficient r = 0.95 for cotton leafworm acetylcholinesterase and 0.92 for that of honey bee. Analysis of these data, in addition to those of the housefly from the literature, resulted in a direct linear relationship in spite of enzyme source, with r = 0.91. It was therefore postulated that hydrophobic interaction and electron donating properties of the substituent were involved in inhibition through complex formation with the enzyme acetylcholinesterase prior to the carbamylation step.