Ion Pairing of the Neurotransmitters Acetylcholine and Glutamate in Aqueous Solutions

Abstract

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 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.

Site Density Functional Theory and Structural Bioinformatics Analysis of the SARS-CoV Spike Protein and hACE2 Complex

“…Namely, the 3DRISM reduces the problem to numerical solution of Ornstein-Zernike integral equations similar to those for simple fluids. The model is very popular for treatment of small bio-rganic solutes [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ].…”

Acetylcholine Conformational Flexibility and Its Neutral Hydrolysis in Aqueous Solution

“…They aim to determine the reactive sites of ACh conformers, [28] the conformational changes' pathway, [29] the fluorination effect to conformational changes, [30] hydration features, [31] and the features of ACh conformers paired to ions in biological media. [32] In our previous work, we demonstrated that two groups of ACh conformers, capable of undergoing hydrolysis without being preceded by conformational changes, have an energy difference of 8 kcal/mol. [33] Therefore, to verify the nonenzymatic hydrolysis contribution towards ACh depletion, we investigate the conformational effect on ACh neutral (nonenzymatic) hydrolysis in aqueous solution.…”

“…In recent decades, computational studies on ACh conformational properties in aqueous solution have dominated. They aim to determine the reactive sites of ACh conformers, [28] the conformational changes’ pathway, [29] the fluorination effect to conformational changes, [30] hydration features, [31] and the features of ACh conformers paired to ions in biological media [32] . In our previous work, we demonstrated that two groups of ACh conformers, capable of undergoing hydrolysis without being preceded by conformational changes, have an energy difference of 8 kcal/mol [33] .…”

Diclofenac Ion Hydration: Experimental and Theoretical Search for Anion Pairs

“…Organic ions, which are readily soluble in water, are usually studied: guanidinium and arginine ions [ 1 , 2 , 3 ], protonated acridine cations [ 4 ], etc. [ 5 , 6 ]. The driving force of the aggregation of identically charged organic ions in aqueous solutions is solvation free energy arising from the adaptation of the hydrogen bond (H-bond) network of water to the solute [ 7 ].…”