Hydration features of the neurotransmitter acetylcholine

Acetylcholine (ACh) is one of the intercellular neurotransmitters (NT) involved in the transmission of nervous excitation in the central and peripheral nervous systems. Hydration is one of the factors that can affect the structure, functions and biological activity of NTs. In order to gain more detailed insights on NT hydration, we studied the ACh cation in aqueous AChCl solutions with the integral equation method in the framework of the 1D- and 3D-RISM (Reference Interaction Site Model) approaches. The concentration range from infinite dilution to 0.53 M was covered, and data were obtained for two bioactive conformers, namely the trans, gauche (TG) and the trans, trans (TT) species, which are both stable in water. For both conformers the results indicate the onium and carbonyl groups as the most favorable hydration sites, with well-defined hydration layers and large hydration numbers over the entire concentration range. The difference in hydration of the TG and TT conformers is connected with their spatial configurations. Due to its more folded structure, the TG conformer exhibits steric limitations for water penetration to the cation. In comparison with the unfolded TT conformer, the folded TG conformer has the decreased amount of water in the nearest environment of the onium group and the oxygen of ester group. The obtained results are discussed from the viewpoint of biological activity of TG and TT in relation to the receptors under classical description of neurotransmission and new ideas about the membrane-dependent / membrane-independent mechanism of this process. The presented results add new knowledge to understanding of the interactions between the NTs and their molecular environment. (C) 2020 Elsevier B.V. All rights reserved.