Single-Crystal Neutron Diffraction Analysis of Anion–Cation Interactions in Perdeuteroacetylcholine Bromide at 100 K

The interaction of the neurotransmitter acetylcholine with receptor binding sites has been well studied over the years, but much is still unknown about how intermolecular forces govern the lock-and-key fit. Here we present an analysis of cation–anion hydrogen-bond interactions in a single-crystal of perdeuteroacetylcholine bromide, using pulsed neutron diffraction data to refine the X-ray crystal structure. The molecule crystallizes in space group P21/n, with a = 10.951 (4), b = 13.396 (8), c = 7.072(4) Å, β = 108.88(3)°, Z = 4. The final refinement included anisotropic temperature factors on all atoms and converged to wR(F) = 0.055 (244 parameters). The pyramidal configuration of C--DBr⁻ contacts observed in the crystal is in good agreement with ab initio molecular orbital predictions of favoured configuration and is consistent with a modest polarization of C--D bonds close to the N atom. There is evidence that close contact with Br⁻ is hindered by the repulsive influence of the ester O atoms, dependent on the conformation of the acetylcholine cation. This is the most detailed picture to date of close interatomic contacts around the cation and analogies are drawn with the bonding of acetylcholine to its receptors.