Ion Pairing of the Neurotransmitters Acetylcholine and Glutamate in Aqueous Solutions

Neurotransmitters (NTs) play an important role in neural communication, regulating a variety of functions such as motivation, learning, memory, and muscle contraction. Their intermolecular interactions in biological media are an important factor affecting their biological activity. However, the available information on the features of these interactions is scarce and contradictory, especially, in an estimation of possible ion binding. In this paper, we present the results of a study for two well-known NTs, acetylcholine (ACh) and glutamate (Glu), with relation to the NT-inorganic ion and the NT-NT binding in a water environment. The features of NT pairing are investigated in aqueous AChCI and NaGlu solutions over a wide concentration range using the integral equation method in 1D- and 3D- reference interaction site model (RISM) approaches. The data for ACh are given for its two bioactive TG (trans, gauche) and TT (trans, trans) conformers. As was found, for both NTs, the results indicate the NT-inorganic counterion contact pair to be the predominant associate type in the concentrated solutions. In this case, the counterions occupy the vacated water space in the hydration shell of the onium moiety (ACh) or carboxylate groups (Glu). For ACh, the unfolded TT conformer demonstrates a slightly greater possibility for counterion pairing in comparison with the folded TG conformer. For Glu, the probability of its binding with a counterion is slightly stronger for the side-chain carboxylate group than for the backbone group. The obtained results also revealed an insignificant probability of Glu(-)-Glu(-) pairing. Namely, the RISM data indicate Glu(-)-Glu(-) binding by NH3+-COO- interactions. A link between the ion binding of NTs and their biological activity is discussed. This contribution adds new knowledge to our understanding of the interactions between the NTs and their molecular environment, providing further insights into the behavior of these compounds in biological media.

Automated summary

Neurotransmitters play a crucial role in neural communication, regulating various functions and their interactions with inorganic ions and other neurotransmitters in water environments. The study revealed that in concentrated solutions, NT-inorganic counterion contact pairs are the predominant associate type, shedding light on the behavior of NTs in biological media. The findings contribute to understanding the link between ion binding of NTs and their biological activity.