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Front. Chem. | 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

 Ol’ha O Brovarets1, Timothy Oliynyk1 and  Dmytro M. Hovoruna1*
  • 1Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Ukraine

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*O2(rWC), G*N2·C(rWC), G*´N2·C(rWC), G*N7·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 (Сs symmetry) with a single exception – the essentially non-planar transition state TSG*·C*(rWC)↔G+·C-(rWC) (С1 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. In general, the obtained data demonstrate the tautomeric mobility and diversity of the G*∙C* DNA base pair.

Keywords: Single proton transfer, Double proton transfer, conformer, Hoogsteen, reverse Hoogsteen, transition state, Quantum-mechanical calculation

Received: 05 Jun 2019; Accepted: 12 Aug 2019.

Copyright: © 2019 Brovarets, Oliynyk and Hovoruna. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Dmytro M. Hovoruna, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv, Ukraine,