The A·T(rWC)/A·T(H)/A·T(rH) ↔ A·T*(rwWC)/A·T*(wH)/A·T*(rwH) mutagenic tautomerization via sequential proton transfer: a QM/QTAIM study

Abstract

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$T*(rwWC), A$T*(wH) and A$T*(rwH) base mispairs by the participation of the mutagenic tautomers of the DNA bases (denoted by asterisk) and vice versa, thus complementing the physico-chemical property of the canonical A$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$T(WC) DNA base pair (10 8 to 10 7 ) leads authors to the conclusion, that only a base pair with WC architecture can be a building block of the DNA macromolecule as a genetic material, which is able for the evolutionary selfdevelopment. Among all four classical DNA base pairs, only A$T(WC) DNA base pair can ensure the proper rate of the spontaneous point errors of replication in DNA.