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

Abstract

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 NO₂ and electron-donating NH₂ 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 (2 and 3H and 9H for X = NO₂. Furthermore, solvation enhances the effect of the nitro group; however, the enhancement strongly depends on the proximity effects. This enhancement for the NO₂ group with two repulsive N···ON contacts can be threefold higher than that for the NO₂ with one attractive NH···ON contact. The proximity effects are even more significant for the NH₂ group, as the solvation may increase or decrease its electron-donating ability, depending on the type of proximity.