Coordination Sites for Sodium and Potassium Ions in Nucleophilic Adeninate Contact ion-Pairs: A Molecular-Wide and Electron Density-Based (MOWED) Perspective.

ABSTRACT: The adeninate anion (Ade^-) is a useful nucleophile used in the synthesis of many prodrugs (including those for HIV AIDS treatment). It exists as a contact ion-pair (CIP) with Na⁺ and K⁺ (M⁺) but the site of coordination is not obvious from spectroscopic data. Herein, a molecular-wide and electron density-based (MOWED) computational approach implemented in the implicit solvation model showed a strong preference for bidentate ion coordination at the N3 and N9 atoms. The N3N9-CIP has (i) the strongest inter-ionic interaction, by -30 kcal mol^-1, with a significant (10-15%) covalent contribution, (ii) the most stabilized bonding framework for Ade^-, and (iii) displays the largest ion-induced polarization of Ade^-, render

SUBMITTER: Buyens DMS 

PROVIDER: S-EPMC9505275 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature