A QM/QTAIM microstructural analysis of the tautomerisation via the DPT of the hypoxanthine·adenine nucleobase pair

Abstract

We provide a pathway for the tautomerisation of the biologically important hypoxanthine·adenine (Hyp·Ade) nucleobase pair (Cs) formed by the keto tautomer of the Hyp and the amino tautomer of the Ade into the Hyp*·Ade* base pair (Cs) formed by the enol tautomer of the Hyp and the imino tautomer of the Ade by applying quantum-mechanical calculations and Bader's Quantum Theory of Atoms in Molecules analysis. It was found out that the dipole active Hyp·Ade↔Hyp*·Ade* tautomerisation occurs via the asynchronous concerted double proton transfer (DPT) through the TSHyp·Ade↔Hyp*·Ade* (Cs). Based on the sweeps of the energies of the intermolecular H-bonds along the intrinsic reaction coordinate, it was established that the N6H···O6 H-bond (5.40) is cooperative with the N1H···N1 H-bond (6.99) in the Hyp·Ade base pair, as well as the O6H···N6 H-bond (11.50) is cooperative with the N1H···N1 H-bond (7.28 kcal·mol−1) in the Hyp*·Ade* base pair, mutually strengthening each other. The Hyp*·Ade* base pair possesses an extremely short lifetime 2.68·10−14 s, which is predetermined by the negative value of the Gibbs free energy of the reverse barrier of its tautomerisation, and all of the six low-frequency intermolecular vibrations cannot develop during this period of time. Consequently, the Hyp·Ade→Hyp*·Ade* DPT tautomerisation cannot serve as a source of the rare tautomers of the bases.