Does the G·G*syn DNA mismatch containing canonical and rare tautomers of the guanine tautomerise through the DPT? A QM/QTAIM microstructural study

Abstract

We have established that the asynchronous concerted double proton transfer (DPT), moving with a time gap and without stable intermediates, is the underlying mechanism for the tautomerisation of the G·G*syn DNA base mispair (C1 symmetry), formed by the keto and enol tautomers of the guanine in the anti- and syn-configurations, into the G*·G*syn base mispair (C1), formed by the enol and imino tautomers of the G base, using quantum-mechanical calculations and Bader's quantum theory of atoms in molecules. By constructing the sweeps of the geometric, electron-topological, energetic, polar and natural bond orbital properties along the intrinsic reaction coordinate of the G·G*syn↔G*·G*syn DPT tautomerisation, the nine key points, that are critical for the atomistic understanding of the tautomerisation reaction, were set and comprehensively analysed. It was found that the G·G*syn mismatch possesses pairing scheme with the formation of the O6···HO6 (7.01) and N1H···N7 (6.77) H-bonds, whereas the G*·G*syn mismatch – of the O6H···O6 (10.68) and N1···HN7 (9.59 kcal mol−1) H-bonds. Our results highlight that these H-bonds are significantly cooperative and mutually reinforce each other in both mismatches. The deformation energy necessary to apply for the G·G*syn base mispair to acquire the Watson–Crick sizes has been calculated. We have shown that the thermodynamically stable G*·G*syn base mispair is dynamically unstable structure with a lifetime of 4.1 × 10−15 s and any of its six low-lying intermolecular vibrations can develop during this period of time. These data exclude the possibility to change the tautomeric status of the bases under the dissociation of the G·G*syn mispair into the monomers during DNA replication. Finally, it has been made an attempt to draw from the physico-chemical properties of all four incorrect purine–purine DNA base pairs a general conclusion, which claims the role of the transversions in spontaneous point mutagenesis.