Novel mechanisms of the conformational transformations of the biologically important G•C nucleobase pairs in Watson-Crick, Hoogsteen and wobble configurations via the mutual rotations of the bases around the intermolecular H-bonds: a QM/QTAIM study

At the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of quantum-mechanical theory, we provide for the first time a comprehensive investigation of the physico-chemical mechanisms of the 55 conformational transformations of the biologically-important G center dot C nucleobase pairs - Watson-Crick (WC), reverse Watson-Crick (rWC), Hoogsteen (H), reverse Hoogsteen (rH), wobble (w) and reverse wobble (rw) base pairs by the participation of the G and C bases in the canonical and rare tautomeric forms (r - means reverse configuration of the base pair). It was established that all these G center dot C nucleobase pairs can conformationally transform into each other without the changing of the tautomeric status of the G and C bases. These transitions occur through significantly non-planar transition states via the mutual rotation of the G and C bases relative to each other within the G center dot C nucleobase pair around the upper, middle or lower intermolecular H-bonds: WC <-> rWC, WC <-> rw(WC), rWC <-> WC, rWC <-> w(WC), w(WC) <-> rw(WC), H <-> rH, H <-> rw(H), rH <-> H, rH <-> w(H), w(H) <-> rw(H). Gibbs free energies Delta G of activation for these conformational transformations are Delta G = 2.96-19.04/3.58-13.36 kcal mol(-1) (in vacuum under normal conditions (T = 298.15 K)), which means that these reactions proceed quite fast. Obtained conformational transformations are accompanied by the disruption and further formation of the intermolecular specific contacts in the G center dot C nucleobase pairs (H-bonds and attractive van der Waals contacts). As a result, 76 conformers of the G center dot C nucleobase pairs were established - 48 base pairs in WC, rWC, w(WC) and rw(WC) configurations and 28 base pairs in H, rH, w(H) and rw(H) configurations with relative Gibbs free Delta G/electronic Delta E energies in the range Delta G/Delta E = 0.00-44.73/0.00-46.99 and Delta G/Delta E = 0.00-37.52/0.00-38.54 kcal mol(-1), respectively (in vacuum under normal conditions). Experimental investigation and verification of the novel G center dot C nucleobase pairs are promising tasks for the future research. Based on the obtained data, biologically important conclusions were made about the importance of the conformational mobility of the G center dot C nucleobase pairs for the understanding of the functioning of the DNA and RNA molecules and their transition from the parallel into the anti-parallel duplexes and vice versa.

Automated summary

A comprehensive investigation was conducted on the physico-chemical mechanisms of 55 conformational transformations of biologically-important G·C nucleobase pairs. It was found that these pairs can transform into each other through non-planar transition states without changing the tautomeric status of the bases, with key involvement of intermolecular hydrogen bonds. The fast reactions are accompanied by disruption and formation of specific contacts between the bases.