Theoretical exploration of gas-phase conformers of proton-bound non-covalent heterodimers of guanine and cytosine rare tautomers: structures and energies

Abstract

Due to complexity arising from the presence of various rare tautomers and multiple protonation sites, little is known of the proton-bound heterodimers of guanine (G) and cytosine (C) that may exist in the gas phase. We extensively explored structures and energies of the heterodimers by density functional theory using the B3LYP functional, wherein rare tautomers of G and C that were predicted to be energetically accessible were considered in possible heterodimer structures. This extensive search found more than 90 stable structures for the proton-bound heterodimers, where various types of base-pairings were observed. For the six lowest energy structures that lie within 3 kcal/mol in energy from the most stable structure, ionic hydrogen bonding was found to be involved in base-pairing. The non-covalent complexation energies of the heterodimers were found to be quite strong at 40-50 kcal/mol. Some pairs of the heterodimers were connected by simple proton transfer in the ionic hydrogen bond as well. In addition, a Hoogsteen base pair was predicted to be the most stable conformer in the gas phase with a more than 90% population. Solvent field effects also suggested that the Hoogsteen base pair is one of the most stable conformers in an aqueous environment. Thus, we suggest that the Hoogsteen base pair is the most predominant form of the proton-bound heterodimers of G and C that may exist in the gas phase.