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.

Keywords:

• canonical and rare tautomers of the guanine
• syn- and anti-conformations
• sweeps of the energetic, electron-topological, geometric, polar and NBO parameters along the IRC
• the double proton transfer
• cooperativity of the H-bonds
• B3LYP and MP2
• QTAIM

Acknowledgements

This study was performed using computational facilities of the joint computer cluster of SSI ‘Institute for Single Crystals’ of the National Academy of Sciences of Ukraine and Institute for Scintillation Materials of the National Academy of Sciences of Ukraine incorporated into the Ukrainian National Grid.

Additional information

Funding

This work was partially supported by the State Fund for Fundamental Research (SFFR) of Ukraine within the Ukrainian–Japanese project No. F 52.2/001 for 2013–2014 and by the Science and Technology Center in Ukraine (STCU) within the project No. 5728 for 2012–2014. O.O. Brovarets’ was supported by the Grant of the President of Ukraine to support scientific research of young scientists for 2014 from the State Fund for Fundamental Research of Ukraine (project No. GP/F56/074) and by the Grant of the Cabinet of Ministers of Ukraine for collectives of young researchers for carrying out applied scientific researches, scientific and technological development in the priority areas of science and technology within the project No. 123 for 2014–2015.