Substituted adenine quartets: interplay between substituent effect, hydrogen bonding and aromaticity

Abstract

Adenine, one of the components of DNA/RNA helices, has an ability to form self-organizing structures with cyclic hydrogen bonds (A4), similar to guanine quartets. Here, we report a computational investigation of the effect of substituents (X = NO2, Cl, F, H, Me, NH2) on electronic structure of 9H-adenine and its quartets (A4-N1, A4-N3, and A4-N7). DFT calculations were used to show the relationships between electronic nature of the substituents, strength of H-bonds in the quartets, and aromaticity of five- and six-membered rings of adenine. We demonstrated how the remote substituent X modifies the proton-donating properties of the NH2 group involved in the H-bonds within quartets and how the position of the substituent and its electronic nature affect the stability of the quartets. We also showed the possible changes in substituent electronic properties and aromaticity of both adenine rings caused by tetramer formation. The results indicate that the observed relationships depend on the A4 type. Moreover, the same substituent can both strengthen or weaken intermolecular interactions, depending on the substitution position