Ab initio study of the energetics of molecular heteroconjugation reactions in systems modeling side chains of biomolecules

Abstract

By employing ab initio methods at the Restricted Hartree Fock (RHF) and Møller-Plesset (MP2) levels and using the 6-31 G* and 6-31+G** basis sets, calculations were performed on ten hydrogen-bond-stabilized (O⋯H⋯N) molecular heterocomplexed systems without proton transfer modeling acid–base interactions in side chains of polypeptides and proteins. Application of the polarizable continuum model (PCM) to the models involving water, acetonitrile and dimethyl sulfoxide allowed to take into account the influence of solvation effects on the acid–base interactions studied. It was found that the most stable hydrogen bonds in the heterocomplexed systems occur in systems formed by the following pairs: acetic acid (modeling the carboxylic group of aspartic and glutamic acid) and methylguanidine (modeling the guanidine group of arginine), as well as phenol (modeling the phenolic group of thyrosine) and methylguanidine (modeling the guanidine group of arginine). Furthermore, the calculated energies, Δ E hetero, and Gibbs free energies, Δ G hetero, of formation of the molecular heterocomplexes cations have been found to correlate well with the respective calculated energies and Gibbs free energies of protonation and cationic homoconjugation of the amines acting as proton acceptors in the case of acetic acid as proton donor.