On the relevance of the electron density analysis for the study of micro-hydration and its impact on the formation of a peptide-like bond

The formation of a peptide bond from carboxylic acid and amine from the reactants taken separately in the gas phase with no catalytic surface constitutes an interesting process from an exobiological point of view. We investigated the reaction between acetic acid (CH3-COOH) and methylamine (CH3-NH2), alone and with the presence of one to five water molecules, at the LC-omega PBE/6-311++G(d,p) level of theory, with the GD3BJ Empirical Dispersion. Starting from the idea that the reaction begins with the formation of a non-covalent complex between the reagents, we first identified the main structures of non-covalent complexes that can be formed between both reagents without hydration, by maximizing interactions between complementary sites of both partners. This study led to the identification of a (CH3-COOH):(CH3-NH2) complex, with a stabilization energy of 14.22 kJ/mol, that may correspond to a preliminary step towards the formation of a peptide-like bond.