Regioselectivity and physical nature of the interactions between (methyl)guanine with HCl and CH3OH

A comprehensive study of the hydrogen bonding interactions between guanine ( G ) and methyl guanine derivatives ( MGs ) in the presence of HCl and MeOH is carried out at B3LYP, B3LYP-D3 and M062X/6-311 + + G(d.p) levels using molecular electrostatic potential, natural bond orbital, and symmetry adapted perturbation theory. Making use of these state-of-the-art techniques, this study attempts to elucidate the chemical bonding, regioselectivity, and physical nature of the interactions responsible for the stability of (M)G…L (L = HCl, MeOH) acid-base complexes. Our calculations reveal that 1-G , 3-MG , and 5-MG interact more strongly with MeOH than HCl due to the positive hydrogen bond cooperativity. Furthermore, the carbonyl site on G is found to be the most reactive site, while methyl substitution increases the basicity of the nucleobase, thus yielding more stable complexes. The strongest H-bond interaction in G -complexes is found when HCl and MeOH attack carbonyl in anti -position. Finally, energy decomposition analyses through the symmetry-adapted perturbation theory reveal that most complexes are mainly stabilized via electrostatic interactions. The energy difference between complex isomers shows a competition between 3-HCl-G (MG) and 4-HCl-G (MG) at ∆G level where thermal, BSSE and entropy terms are included.