A theoretical conformational analysis of several substrates of cholinesterase having a cyclic ammonium group structure.

Conformational possibilities of pirrolidine analogues of acetylcholine beta-(N-methyl pirrolidinium)-ethyl ester of acetic acid and beta-(N-ethyl pirrolidinium)-ethyl ester of acetic acid and beta-(N-ethyl pirrolidinium)-ethyl ester of acetic acid were investigated by the method of atomic potentials. The conformational energy was considered as a sum of non-bonded and electrostatical interactions, torsional energy and distortions of bond angles. It has been shown that the replacement of the nitrogen methyl group to ethyl group results in decrease of the average barrier height between two gauche conformations of the O--C--C--N fragment. Comparison of conformational properties of some cholinesterase substrates permit to draw a suggestion that the barrier height influences the rate of the enzymatic hydrolysis.