For the first time, at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory, a comprehensive quantum-mechanical investigation of the physico-chemical mechanism of the tautomeric wobblization of the four biologically-important G·C nucleobase pairs by the participation of the monomers in rare, in particular mutagenic, tautomeric forms (marked with an asterisk) was provided. These novel tautomeric transformations (wobblization or shifting of the bases within the pair) are intrinsically inherent properties of the G·C nucleobase pairs. In this study, we have obtained intriguing results, lying far beyond the existing representations. Thus, it was shown that Löwdin's G*·C*(WC) base pair does not tautomerize according to the wobblization mechanism. Tautomeric wobblization of the G*·C*(rWC) (relative Gibbs free energy ΔG = 0.00/relative electronic energy ΔE = 0.00 kcal·mol−1) (“r”—means the configuration of the base pair in reverse position; “WC”—the classic Watson-Crick configuration) and G*t·C*(H) (ΔG = −0.19/ΔE = 0.29 kcal·mol−1) (“H”—Hoogsteen configuration;”t” denotes the O6H hydroxyl group in the trans position) base pairs are preceded by the stages of the base pairs tautomerization by the single proton transfer (SPT). It was established that the G*t·C*(rH) (ΔG = 2.21/ΔE = 2.81 kcal·mol−1) base pair can be wobbled through two different pathways via the traditional one-stage mechanism through the TSs, which are tight G+·C− ion pairs, stabilized by the participation of only two intermolecular H-bonds. It was found out that the G·C base pair is most likely incorporated into the DNA/RNA double helix with parallel strands in the G*·C*(rWC), G·C*(rwwc), and G*·C(rwwc) (“w”—wobble configuration of the pair) tautomeric forms, which are in rapid tautomeric equilibrium with each other. It was proven that the G*·C*(rWC) nucleobase pair is also in rapid tautomeric equilibrium with the eight tautomeric forms of the so-called Levitt base pair. It was revealed that a few cases of tautomerization via the DPT of the nucleobase pairs by the participation of the C8H group of the guanine had occurred. The biological role of the obtained results was also made apparent.
It was established conformational transformations of the G·C nucleobase pairs, occurring via the mutual rotation of the G and C bases around the intermolecular H-bonds.
In this study at the MP2/6-311++G(d,p)//B3LYP/6-311++G(d,p) level of theory in the isolated state it was revealed 14 novel physico-chemical mechanisms of the tautomerization of the G·C nucleotide base pairs in the Watson-Crick G·C(WC) / G*·C*(WC), reverse Watson-Crick G*·C*(rWC) / G·C*O2(rWC), Hoogsteen G*t·C*(H) / G*N7·C(H) or reverse Hoogsteen G*t·C*(rH) / G*tN7·C(rH) configurations into the wobble (wWC, wH) and reverse wobble (rwWC, rwН) base pairs: 1. G·C(WC)↔G·C*(rwWC), 2./3. G*·C*(WC)↔G·C*(rwWC)/G*N2·C*(rwWC), 4. G*·C*(rWC)↔G*·C(wWC), 5. G·C*O2(rWC)↔G·C*(wWC); 6./7./8./9. G*t·C*(H)↔G*t·C(rwН)/G*t·C*O2(wH)/G*t·C*O2(rwН)/G*tN7·C*(rwН)↔G*t·C*O2(rwН), 10. G*N7·C(H)↔G*t·C(wH) amino, 11./12. G*t·C*(rH)↔G*N7·C*(wН)/G*t·C(wН), 13. G*tN7·C(rH)↔G*tN7·C*(wН)↔G*t·C(wН) and 14. G*N7·C*(rwH)↔G*N7·C*(rwH) perp↔G-·C+(wH)↔G*t·C(rwН) reaction pathways. It was established that the presence in the base pair of the two anti-parallel neighboring H-bonds is a necessary and sufficient condition for the implementation of such transformations, since it enables intermolecular proton transfer between the bases inside the base pair. It was found out that these tautomeric transitions are controlled by the TSs with quasi-orthogonal structure, which are tight G+·C-/G-·C+ ion pairs, joined by at least two parallel intermolecular H-bonds, connected on a common negatively charged endocyclic N-/C- atoms – proton acceptor. All reaction pathways have been reliably confirmed. These transitions are accompanied by the changing of the mutual cis-orientation of the N9H and N1H glycosidic bonds of the bases on the trans-orientation and vice versa. These data complement the reported earlier mechanisms of the tautomerisations of the classical A·T and G·C DNA base pairs. Experimental verification of the novel G·C nucleobase pairs is looking as an attractive task for the future research.
This study is devoted to the investigation of the G·C*tO2(WC)↔G*NH3·C*t(WC), G·C*O2(WC)↔G*NH3·C*(WC) and G*·C*O2(WC)↔G*NH3·C(wWC)↓ tautomerization reactions occurring through the proton transfer, obtained at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory in gas phase under normal conditions (T=298.15 K). These reactions lead to the formation of the G*NH3·C*t(WC), G*NH3·C*(WC) and G*NH3·C(wWC)↓ base pairs by the participation of the G*NH3 base with NH3 group. Gibbs free energies of activation for these reactions are 6.43, 11.00 and 1.63 kcal·mol-1, respectively. All of these tautomerization reactions are dipole active. Finally, we believe that these non-dissociative processes, which are tightly connected with the tautomeric transformations of the G·C base pairs, play outstanding role in the supporting of the spatial structure of the DNA and RNA molecules with various functional purposes.
In this study for the first time at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory it was comprehensively investigated unusual conformationally-tautomeric transformations of the G*·C*(WC), G*·C*(rWC), G*·C*t(rWC), G*t·C*(rH) and G*t·C*t(rH) base pairs - G*·C*(WC)↔G*t·C(rwН)↑↔G*N7·C*(rwH)↑↔G*N7·C*(wH)↑↔G*t·C*O2(wH)↑↔ G*t·C*O2(rwH)↑, G*·C*(rWC)↔G*t·C*O2(rwWC)↓/↔G*t·C*O2(wH)↑, G*·C*t(rWC)↔G*t·C*tO2(wН)↓↔G*t·C*tO2(rwH)↓/↔G*t·C*tO2(rwWC)↓↔G*t·C*tO2(wWC)↓, G*t·C*(rH)↔G*·C*O2(wWC)↑/↔G*·C*O2(wH)↓ and G*t·C*t(rH)↔G*·C*tO2(wWC)↑/ ↔G*·C*tO2(rwH)↓↔G*·C*tO2(wH)↓. It was reliably established that they occur through the mutual rotations of the G and C bases around intermolecular H-bonds and proton transfer along the intermolecular H-bonds. These novel conformationally-tautomeric tranformations are intrinsically inherent properties of the Watson-Crick (WC) and Hoogsteen (H) G·C base pairs and lead to their transformation into the wobble (w) or reverse wobble (rw) base pairs. These conformationally-tautomeric transformations of the G·C base pairs are accompanied by the rearrangement of the intermolecular H-bonds and changing of the dipole moments.
This study is devoted to the investigation of the G•C* t O2 (WC)↔G* NH3 •C* t (WC), G•C* O2 (WC)↔G* NH3 •C* (WC) and G*•C* O2 (WC)↔G* NH3 •C(w WC ) ↓ tautomerization reactions occurring through the proton transfer, obtained at the MP2/6-311++G(2df,pd)//B3LYP/6-311++G(d,p) level of theory in gas phase under normal conditions (T=298.15 K). These reactions lead to the formation of the G* NH3 •C* t (WC), G* NH3 •C*(WC) and G* NH3 •C(w WC ) ↓ base pairs by the participation of the G* NH3 base with NH 3 group. Gibbs free energies of activation for these reactions are 6.43, 11.00 and 1.63 kcal•mol -1 , respectively. All of these tautomerization reactions are dipole active. Finally, we believe that these non-dissociative processes, which are tightly connected with the tautomeric transformations of the G•C base pairs, play outstanding role in the supporting of the spatial structure of the DNA and RNA molecules with various functional purposes.
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