On the conformational varieties of acetylcholine in the crystals of its halides

Abstract

Different conformations of acetylcholine are observed in the crystals of its chloride (trans-gauche, tg) and bromide (gauche-gauche, gg). Quantum-mechanical computations predict the tg conformation to be intrinsically preferred for the free molecule. Therefore there is obviously an influence of the crystalline environment upon the intramolecular conformation. The intermolecular lattice energy has been computed for the experimental crystals and a number of hypothetical ones, obtained by varying the conformation of acetylcholine or by exchanging the two anions. The computations point to two kinds of result: (a) if we modify the conformation of acetylcholine without drastically altering the lattice configuration each experimental crystal structure appears as the most stable one; (b) if, however, we allow important changes in the lattice configurations the bromide-type structure appears as the most stable, for both the CIand Br ions and, moreover, with a gg conformation for acetylcholine. The structure of the acetylcholine chloride crystal thus seems to correspond to a local minimum of the energy hypersurface. It is proposed that this situation may be explained by considering the crystallization process and the properties of microcrystals. It appears possible that: (a) the two different crystal structures associated with the chloride and the bromide could be stable for the corresponding microcrystals; and/or (b) a structure of the chloride type would be energetically preferred for microcrystals in both cases but a higher probability of crossing over the potential barrier in the case of Brwould make possible the transition to the bromide-type structure in the course of crystal growth.