The physico-chemical anatomy of the tautomerization through the DPT of the biologically important pairs of hypoxanthine with DNA bases: QM and QTAIM perspectives

The biologically important tautomerization of the Hyp center dot Cyt, Hyp*center dot Thy and Hyp center dot Hyp base pairs to the Hyp*center dot Cyt*, Hyp center dot Thy* and Hyp*center dot Hyp* base pairs, respectively, by the double proton transfer (DPT) was comprehensively studied in vacuo and in the continuum with a low dielectric constant (epsilon = 4) corresponding to hydrophobic interfaces of protein-nucleic acid interactions by combining theoretical investigations at the B3LYP/6-311++G(d,p) level of QM theory with QTAIM topological analysis. Based on the sweeps of the energetic, electron-topological, geometric and polar parameters, which describe the course of the tautomerization along the intrinsic reaction coordinate (IRC), it was proved that the tautomerization through the DPT is concerted and asynchronous process for the Hyp center dot Cyt and Hyp*center dot Thy base pairs, while concerted and synchronous for the Hyp center dot Hyp homodimer. The continuum with epsilon = 4 does not affect qualitatively the course of the tautomerization reaction for all studied complexes. The nine key points along the IRC of the Hyp center dot Cyta daggerHyp*center dot Cyt* and Hyp*center dot Thya daggerHyp center dot Thy* tautomerizations and the six key points of the Hyp center dot Hypa daggerHyp*center dot Hyp* tautomerization have been identified and fully characterized. These key points could be considered as electron-topological fingerprints of concerted asynchronous (for Hyp center dot Cyt and Hyp*center dot Thy) or synchronous (for Hyp center dot Hyp) tautomerization process via the DPT. It was found, that in the Hyp*center dot Cyt*, Hyp center dot Thy*, Hyp center dot Hyp and Hyp*center dot Hyp* base pairs all H-bonds are significantly cooperative and mutually reinforce each other, while the C2HaEuro broken vertical bar O2 H-bond in the Hyp center dot Cyt base pair and the O6HaEuro broken vertical bar O4 H-bond in the Hyp*center dot Thy base pair behave anti-cooperatively, i.e., they become weakened, while two others become strengthened.