Effect of the Solvent and Substituent on Tautomeric Preferences of Amine-Adenine Tautomers

[Image: see text] Adenine is one of the basic molecules of life; it is also an important building block in the synthesis of new pharmaceuticals, electrochemical (bio)sensors, or self-assembling molecular materials. Therefore, it is important to know the effects of the solvent and substituent on the electronic structure of adenine tautomers and their stability. The four most stable adenine amino tautomers (9H, 7H, 3H, and 1H), modified by substitution (C2– or C8−) of electron-withdrawing NO(2) and electron-donating NH(2) groups, are studied theoretically in the gas phase and in solvents of different polarities (1 ≤ ε < 109). Solvents have been modeled using the polarizable continuum model. Comparison of the stability of substituted adenine tautomers in various solvents shows that substitution can change tautomeric preferences with respect to the unsubstituted adenine. Moreover, C8 substitution results in slight energy differences between tautomers in polar solvents (<1 kcal/mol), which suggests that in aqueous solution, C8–X-substituted adenine systems may consist of a considerable amount of two tautomers—9H and 7H for X = NH(2) and 3H and 9H for X = NO(2). Furthermore, solvation enhances the effect of the nitro group; however, the enhancement strongly depends on the proximity effects. This enhancement for the NO(2) group with two repulsive N···ON contacts can be threefold higher than that for the NO(2) with one attractive NH···ON contact. The proximity effects are even more significant for the NH(2) group, as the solvation may increase or decrease its electron-donating ability, depending on the type of proximity.