The regulatory roles of metal ions (M+/2+ = Li+, Na+, K+, Be2+, Mg2+, and Ca2+) and water molecules in stabilizing the zwitterionic form of glycine derivatives

Abstract

The regulatory roles of metal ions (M^+/2+ = Li⁺, Na⁺, K⁺, Be²⁺, Mg²⁺, and Ca²⁺) and water molecules in stabilizing the zwitterionic form of glycine derivatives are discussed in the present paper. The involved glycine conformers are (1) the glycine zwitterion (OO), which can bind an ion to form the salt-bridge-form derivative, and (2) two neutral forms (NO and OH), which can bind the ion with both the carboxyl oxygen and the amino nitrogen (NO), or both the carboxyl oxygen and the hydroxyl oxygen (OH) to form charge-solvated structures. Results show that four water molecules can make the OO-mode glycine–Li⁺/Na⁺/K⁺ derivatives more stable than each of the corresponding NO-mode counterparts. Similarly, two water molecules can make the OO-mode glycine–Be²⁺ more stable than its corresponding NO-mode counterpart, while the OO-mode glycine–Mg²⁺/Ca²⁺ are always more stable than their corresponding NO counterparts whether there is a water molecule(s) attached or not. No OH-mode glycine–Be²⁺/Mg²⁺/Ca²⁺ hydrates are observed because the large electrostatic effect of these divalent metal ions makes the OH-mode hydrates degenerate into the OO-mode ones. For the non-hydrated or monohydrated glycine–Li⁺/Na⁺ isomers, the global minimum derives from the NO-mode structure. Their (di–tetra)hydrates, however, prefer the OH-mode to the other two. For all these different glycine–K⁺ hydrates, each OH-mode structure is always the global minimum among the corresponding isomers, as for the non-hydrated reactant (glycine–K⁺). These predictions are consistent with other theoretical and experimental results. Most of the relative binding strengths, between a metal ion and its corresponding ligand, of the three modes are in good agreement with the relative stabilities, i.e., the larger the binding energy is, the more stable the structure would be. Some exceptions to the agreement are explained. A comparison of binding strengths shows that the smaller the ion radius is, the greater its binding strength would be. For instance, Li–NO·W (−50.5 kcal mol⁻¹) > Na–NO·W (−36.4 kcal mol⁻¹) > K–NO·W (−25.4 kcal mol⁻¹).