Acetylation of some novel hemicholinium compounds by soluble choline acetyltransferase: structure-activity relationships

Four bisquaternary nitrogen analogues of 2,2'-[1,1'-biphenyl]-4, 4'- diylbis [2-hydroxy-4,4- dimethylmorpholinium ] bromide (hemicholinium 3, HC-3) have been synthesized. These analogues differ from HC-3 in that they have a number of methylene groups inserted between the two phenyl rings. This study examines the significance of the internitrogen distance in these compounds with regard to their acetylation by soluble choline acetyltransferase (ChAc) in vitro. The hemicholinium compounds were incubated with [14C] acetylcoenzyme A and any acetylated products were isolated by liquid ion exchange. Only HC-3 and the analogue with three methylene groups between the two phenyl rings, that is, 2,2'-(1,3- propanediyldi -1,4-phenylene)bis[2-hydroxy-4, 4- dimethylmorpholinium ] ( 3CHC ), were found to be significantly acetylated. The acetylation rate of both these two compounds was 28% that of choline. It is concluded that an internitrogen distance of 14 A in bisquaternary nitrogen choline analogues provides the optimum distance for acetylation by ChAc in vitro.