Conformations of Acetylcholine

Abstract

Canepa, Pauling and Sörum¹ have reported the single crystal structure analysis of acetylcholine bromide and pointed out a correlation between that structure and those of choline chloride and muscarine iodide. In particular the (CH₃)₃N⁺–C–C–O– groups of all three are very similar in conformation with the ether oxygen atom gauche to the nitrogen atom. This correlation has been extended by Sundaralingam², who has shown that in all molecules containing the N⁺–C–C–O– group the crystal structures of which are known (twelve) the oxygen atom is gauche to the nitrogen atom. Culvenor and Ham³ have concluded, however, on the basis of a nuclear magnetic resonance study of acetylcholine in D₂O, that although it is gauche, the conformation of the acetylcholine molecule in solution is that of a normal primary ester^4,5 in which the plane of the acetyl group is rotated about the O1–C5 bond (indicated by an arrow in Fig. 1) so as to bisect approximately the H–C5–H angle. This would give a C6–O1–C5–C4 torsion angle of approximately 180° instead of about ± 60° as observed in acetylcholine bromide. An important implication of this suggestion of Culvenor and Ham is that the spatial correlation between their proposed conformation of acetylcholine and the observed conformation of muscarine is much greater than the correlation between the conformation in acetylcholine bromide and muscarine⁶.