The A·T(rWC)/A·T(H)/A·T(rH) ↔ A·T*(rw WC )/A·T*(w H )/A·T*(rw H ) mutagenic tautomerization via sequential proton transfer: a QM/QTAIM study.

In this study for the first time we have revealed by QM and QTAIM calculations at the MP2/aug-cc-pVDZ//B3LYP/6-311++G(d,p) level of QM theory the novel routes of the mutagenic tautomerization of three biologically important A·T DNA base pairs - reverse Watson-Crick A·T(rWC), Hoogsteen A·T(H) and reverse Hoogsteen A·T(rH) - followed by their rebuilding into the wobble (w) A·T*(rw WC ), A·T*(w H ) and A·T*(rw H ) base mispairs by the participation of the mutagenic tautomers of the DNA bases (denoted by asterisk) and vice versa , thus complementing the physico-chemical property of the canonical A·T(WC) Watson-Crick DNA base pair reported earlier (Brovarets' et al. , RSC Adv. , 2015, 5 , 99594-99605). These non-dissociative tautomeric transformations in the classical A·T(rWC), A·T(H) and A·T(rH) DNA base pairs proceed similarly to the canonical A·T(WC) DNA base pair via the intrapair sequential proton transfer with shifting towards major or minor grooves of DNA followed by further double proton transfer along the intermolecular H-bonds and are controlled by the plane symmetric and highly stable transition states - tight ion pairs formed by the A + nucleobase, protonated by the N1/N7 nitrogen atoms, and T - nucleobase, deprotonated by the N3H imino group. Comparison of the estimated populations of the tautomerised states (10 -21 to 10 -14 ) with similar characteristics for the canonical A·T(WC) DNA base pair (10 -8 to 10 -7 ) leads authors to the conclusion, that only a base pair with WC architecture can be a building block of the DNA macromolecule as a genetic material, which is able for the evolutionary self-development. Among all four classical DNA base pairs, only A·T(WC) DNA base pair can ensure the proper rate of the spontaneous point errors of replication in DNA.