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

Anna Jezuita,Paweł Andrzej Wieczorkiewicz,Tadeusz Marek Krygowski,Halina Szatylowicz

doi:10.1021/acsomega.1c02118

Anna Jezuita, Paweł Andrzej Wieczorkiewicz + Show 2 more

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https://doi.org/10.1021/acsomega.1c02118

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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 (<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 = NH2 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.

Highlights

Adenine, as a part of the DNA/RNA helices,[1] in a natural environment is subject to intermolecular interactions
Selected solvents were modeled as a continuum of uniform dielectric constant, ε, using the polarizable continuum model (PCM) model,[61] starting from ε = 1 up to ε = 108.94
Nitro and amino groups were selected as substituents along with a wide range of solvent properties

Summary

Introduction

As a part of the DNA/RNA helices,[1] in a natural environment is subject to intermolecular interactions. Processes in real biological systems take place in both non-polar and polar environments.[13,14] Recently, it has been shown that the polarity of the solvent changes the equilibrium constants of the double-proton transfer in G−C and A−T Watson−Crick base pairs.[15] The solvent effect on hydrogen bonds in A−T pairs was investigated.[16,17] Experimental data on population of nucleic acid base tautomers in solution are rather rare and concern mostly uracil, thymine, and adenine. The 9H tautomer is the most stable, which was confirmed by calculations in the gas phase and water[18−23] and low-temperature matrix measurements.[24,25] Detailed analysis of the electronic spectra of adenine and 2-aminoadenine suggests that the N7H and N3H tautomers, due to phototautomerization, can be observed in aqueous solutions.[26−29] The tautomeric equilibrium between the 9H and 7H forms of adenine was studied in DMF and methanol by low-temperature 1H and 13C NMR spectrosco-

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