Influence of metal complexation on acidity of cytosine nucleosides: Part I, Li+, Na+ and K+ cation

Abstract

Gas-phase acidities of nucleosides, combined with the knowledge of deprotonation sites, could improve our understanding of chemical reactions to biological systems. In this paper, we mainly focus our attention on the influence of cation coordination on acidities of multiple sites in cytosine nucleosides. The acidities of multiple sites in M+-L (where L represents cytosine nucleosides and M+ is an alkali metal ion, including Li+, Na+ and K+) complexes have been investigated theoretically, employing B3LY P/6−311++G(d,p) basis sets. The geometrical characters, gas-phase acidities, sugar puckering and electronic properties of non-deprotonated and/or deprotonated complexes have been investigated. The shifted ΔHacidity values are a consequence of a combination of metal ion coordination to OH and NH groups and efficient stabilization of the deprotonated species. For instance, after complexation with Li+, Na+, and K+, the ΔHacidity of O2′H of the cytidine molecule shifts from 346.2 to 251.6, 258.0, and 275.7 kcal mol−1, respectively. Moreover, for a given coordination site, the metal ion changes the gap between the most and least acidic groups, with respect to that in neutral nucleosides. Such dependence of acidities on the coordination region of the metal ion suggests that acidities of active groups could be controlled by modulating the metal ion coordination site and the type of metal ion.