Novel Tautomerisation Mechanisms of the Biologically Important Conformers of the Reverse Löwdin, Hoogsteen, and Reverse Hoogsteen G*·C* DNA Base Pairs via Proton Transfer: A Quantum-Mechanical Survey

Ol'ha O Brovarets'; Timothy A Oliynyk; Dmytro M Hovorun

doi:10.3389/fchem.2019.00597

Novel Tautomerisation Mechanisms of the Biologically Important Conformers of the Reverse Löwdin, Hoogsteen, and Reverse Hoogsteen G^·C^ DNA Base Pairs via Proton Transfer: A Quantum-Mechanical Survey

Front Chem. 2019 Sep 18:7:597. doi: 10.3389/fchem.2019.00597. eCollection 2019.

Authors

Ol'ha O Brovarets'^{1

2}, Timothy A Oliynyk¹, Dmytro M Hovorun^{1

3

4}

Affiliations

¹ Department of Molecular and Quantum Biophysics, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, Ukraine.
² Department of Pharmacology, Bohomolets National Medical University, Kyiv, Ukraine.
³ Department of Molecular Biotechnology and Bioinformatics, Institute of High Technologies, Taras Shevchenko National University of Kyiv, Kyiv, Ukraine.
⁴ Department of Pathophysiology, Bohomolets National Medical University, Kyiv, Ukraine.

Abstract

For the first time, in this study with the use of QM/QTAIM methods we have exhaustively investigated the tautomerization of the biologically-important conformers of the G^*·C^* DNA base pair-reverse Löwdin G^*·C^*(rWC), Hoogsteen G^*'·C^*(H), and reverse Hoogsteen G^*'·C^*(rH) DNA base pairs-via the single (SPT) or double (DPT) proton transfer along the neighboring intermolecular H-bonds. These tautomeric reactions finally lead to the formation of the novel G· $C_{O 2}^{*}$ (rWC), $G_{N 2}^{*} \cdot$ C(rWC), G*'_N2·C(rWC), $G_{N 7}^{*} \cdot$ C(H), and G*'_N7·C(rH) DNA base mispairs. Gibbs free energies of activation for these reactions are within the range 3.64-31.65 kcal·mol^-1 in vacuum under normal conditions. All TSs are planar structures (C_s symmetry) with a single exception-the essentially non-planar transition state TS_{G*·C*(rWC)↔G⁺·C^-(rWC)} (C₁ symmetry). Analysis of the kinetic parameters of the considered tautomerization reactions indicates that in reality only the reverse Hoogsteen G^*'·C^*(rH) base pair undergoes tautomerization. However, the population of its tautomerised state G*'_N7·C(rH) amounts to an insignificant value-2.3·10^-17. So, the G^*·C^*(rWC), G^*'·C^*(H), and G^*'·C^*(rH) base pairs possess a permanent tautomeric status, which does not depend on proton mobility along the neighboring H-bonds. The investigated tautomerization processes were analyzed in details by applying the author's unique methodology-sweeps of the main physical and chemical parameters along the intrinsic reaction coordinate (IRC). In general, the obtained data demonstrate the tautomeric mobility and diversity of the G^*·C^* DNA base pair.

Keywords: Hoogsteen; conformer; double proton transfer; quantum-mechanical calculation; reverse Hoogsteen; reverse Löwdin base pair; single proton transfer; transition state.