DPT tautomerization of the long Aa™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 Aa (TM) A* base pair (C-s 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 (TM) A(-) zwitterion with the separated charge, with C-s symmetry. The nine key points, which can be considered as electron-topological "fingerprints" of the asynchronous concerted Aa (TM) A*a dagger"A*a (TM) A tautomerization process via the DPT, were detected and completely investigated along the IRC of the Aa (TM) A*a dagger"A*a (TM) A tautomerization. Based on the sweeps of the H-bond energies, it was found that intermolecular antiparallel N6Dea <-N6 (7.01 kcal mol(-1)) and N1Ha <-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 Aa (TM) A*a dagger"A*a (TM) A tautomerization is assisted by the third C2Ha <-HC2 dihydrogen bond (DHB), which, in contrast to the two others N6Ha <-N6 and N1Ha <-N1 H-bonds, exists within the IRC range from -2.92 to 2.92 . The DHB cooperatively strengthens, reaching its maximum energy 0.42 kcal mol(-1) at IRC = -0.52 and minimum energy 0.25 kcal mol(-1) at IRC = -2.92 , and is accompanied by strengthening of the two other aforementioned classical H-bonds. We established that the C2Ha <-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 /mdyn) at the TSAa (TM) A*a dagger"A*a (TM) A proves that the C2Ha <-HC2 DHB is a stabilizing interaction. NBO analysis predicts transfer of charge from sigma(C2-H) bonding orbital to sigma*(H-C2) anti-bonding orbital; at this point, the stabilization energy E-(2) is equal to 0.19 kcal mol(-1) at the TSAa (TM) A*a dagger"A*a (TM) A.