Is the DPT Tautomerization of the Long A.G Watson-Crick DNA Base Mispair a Source of the Adenine and Guanine Mutagenic Tautomers? A QM and QTAIM Response to the Biologically Important Question

Herein, we first address the question posed in the title by establishing the tautomerization trajectory via the double proton transfer of the adenineguanine (AG) DNA base mispair formed by the canonical tautomers of the A and G bases into the A*G* DNA base mispair, involving mutagenic tautomers, with the use of the quantum-mechanical calculations and quantum theory of atoms in molecules (QTAIM). It was detected that the AG A*G* tautomerization proceeds through the asynchronous concerted mechanism. It was revealed that the AG base mispair is stabilized by the N6HO6 (5.68) and N1HN1 (6.51) hydrogen bonds (H-bonds) and the N2HHC2 dihydrogen bond (DH-bond) (0.68 kcalmol(-1)), whereas the A*G* base mispairby the O6HN6 (10.88), N1HN1 (7.01) and C2HN2 H-bonds (0.42 kcalmol(-1)). The N2HHC2 DH-bond smoothly and without bifurcation transforms into the C2HN2 H-bond at the IRC=-10.07 Bohr in the course of the AG A*G* tautomerization. Using the sweeps of the energies of the intermolecular H-bonds, it was observed that the N6HO6 H-bond is anticooperative to the two othersN1HN1 and N2HHC2 in the AG base mispair, while the latters are significantly cooperative, mutually strengthening each other. In opposite, all three O6HN6, N1HN1, and C2HN2 H-bonds are cooperative in the A*G* base mispair. All in all, we established the dynamical instability of the ?*G* base mispair with a short lifetime (4.8310(-14) s), enabling it not to be deemed feasible source of the A* and G* mutagenic tautomers of the DNA bases. The small lifetime of the ?*G* base mispair is predetermined by the negative value of the Gibbs free energy for the A*G* AG transition. Moreover, all of the six low-frequency intermolecular vibrations cannot develop during this lifetime that additionally confirms the aforementioned results. Thus, the A*G* base mispair cannot be considered as a source of the mutagenic tautomers of the DNA bases, as the AG base mispair dissociates during DNA replication exceptionally into the A and G monomers in the canonical tautomeric form. (c) 2013 Wiley Periodicals, Inc.