G.A. Krestov Institute of Solution Chemistry, the Russian Academy of Sciences, Akademicheskaya Street 1, Ivanovo 153045, Russia.
J Phys Chem B. 2021 Oct 14;125(40):11219-11231. doi: 10.1021/acs.jpcb.1c05117. Epub 2021 Oct 1.
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 AChCl 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 NH-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.
神经递质（NTs）在神经通讯中发挥着重要作用，调节着动机、学习、记忆和肌肉收缩等多种功能。它们在生物介质中的分子间相互作用是影响其生物活性的一个重要因素。然而，关于这些相互作用特征的可用信息却很少且相互矛盾，尤其是在对可能的离子结合进行估计时。在本文中，我们介绍了对两种著名的神经递质，乙酰胆碱（ACh）和谷氨酸（Glu），在水环境中与神经递质-无机离子和神经递质-神经递质结合的研究结果。使用一维和三维参考相互作用位点模型（RISM）方法中的积分方程方法，在宽浓度范围内研究了在水合 AChCl 和 NaGlu 溶液中 NT 配对的特征。为了研究 ACh，我们给出了其两种生物活性 TG（反式， gauche）和 TT（反式，反式）构象的数据。结果表明，对于这两种 NT，结果表明 NT-无机抗衡离子接触对是在浓溶液中主要的结合类型。在这种情况下，抗衡离子占据了铵部分（ACh）或羧酸盐基团（Glu）的水合壳中腾出的“水”空间。对于 ACh，与“折叠”TG 构象相比，“展开”TT 构象显示出与抗衡离子配对的可能性稍大。对于 Glu，其与抗衡离子结合的可能性对于“侧链”羧酸盐基团略强于“主链”基团。所得结果还表明 Glu-Glu 配对的可能性较小。即，RISM 数据表明 Glu-Glu 结合是通过 NH-COO 相互作用。讨论了 NT 离子结合与其生物活性之间的联系。这项贡献增加了我们对 NT 与其分子环境相互作用的理解的新知识，为这些化合物在生物介质中的行为提供了进一步的见解。
