DPT tautomerization of the long A∙A Watson-Crick base pair formed by the amino and imino tautomers of adenine: combined QM and QTAIM investigation.

Combining quantum-mechanical (QM) calculations with quantum theory of atoms in molecules (QTAIM) and using the methodology of sweeps of the energetic, electron-topological, geometric and polar parameters, which describe the course of the tautomerization along the intrinsic reaction coordinate (IRC), we showed for the first time that the biologically important A∙A base pair (Cs symmetry) formed by the amino and imino tautomers of adenine (A) tautomerizes via asynchronous concerted double proton transfer (DPT) through a transition state (TS), which is the A(+)∙A(-) zwitterion with the separated charge, with Cs symmetry. The nine key points, which can be considered as electron-topological "fingerprints" of the asynchronous concerted A∙A ↔A ∙A tautomerization process via the DPT, were detected and completely investigated along the IRC of the A∙A*↔A*∙A tautomerization. Based on the sweeps of the H-bond energies, it was found that intermolecular antiparallel N6Н⋯N6 (7.01 kcal mol(-1)) and N1H⋯N1 (6.88 kcal mol(-1)) H-bonds are significantly cooperative and mutually reinforce each other. It was shown for the first time that the A∙A ↔A ∙A tautomerization is assisted by the third C2H⋯HC2 dihydrogen bond (DHB), which, in contrast to the two others N6H⋯N6 and N1H⋯N1 H-bonds, exists within the IRC range from -2.92 to 2.92 Å. The DHB cooperatively strengthens, reaching its maximum energy 0.42 kcal mol(-1) at IRC = -0.52 Å and minimum energy 0.25 kcal mol(-1) at IRC = -2.92 Å, and is accompanied by strengthening of the two other aforementioned classical H-bonds. We established that the C2H⋯HC2 DHB completely satisfies the electron-topological criteria for H-bonding, in particular Bader's and all eight "two-molecule" Koch and Popelier's criteria. The positive value of the Grunenberg's compliance constant (5.203 Å/mdyn) at the TSA∙A ↔A ∙A proves that the C2H⋯HC2 DHB is a stabilizing interaction. NBO analysis predicts transfer of charge from σ(C2-H) bonding orbital to σ (H-C2) anti-bonding orbital; at this point, the stabilization energy E((2)) is equal to 0.19 kcal mol(-1) at the TSA∙A ↔A ∙A.