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.

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 * · C(rWC), G*'N2·C(rWC), G N 7 * · 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 (Cs symmetry) with a single exception-the essentially non-planar transition state TSG*·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.