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Keywords:

  • spontaneous point mutations in DNA;
  • amino and imino tautomers of cytosine;
  • keto and enol tautomers of thymine;
  • mutagenic tautomerization;
  • sweeps of the energetic, electron-topological, geometric and polar parameters along the IRC;
  • the double proton transfer;
  • cooperativity of the H-bonds;
  • van der Waals contact;
  • B3LYP and MP2 levels of QM theory;
  • QTAIM analysis ·Grunenberg's compliance constant

It was established that the cytosine·thymine (C·T) mismatched DNA base pair with cis-oriented N1H glycosidic bonds has propeller-like structure (|N3C4C4N3| = 38.4°), which is stabilized by three specific intermolecular interactions–two antiparallel N4H…O4 (5.19 kcal mol−1) and N3H…N3 (6.33 kcal mol−1) H-bonds and a van der Waals (vdW) contact O2…O2 (0.32 kcal mol−1). The C·T base mispair is thermodynamically stable structure (ΔGint = −1.54 kcal mol−1) and even slightly more stable than the A·T Watson–Crick DNA base pair (ΔGint = −1.43 kcal mol−1) at the room temperature. It was shown that the C·T [LEFT RIGHT ARROW] C*·T* tautomerization via the double proton transfer (DPT) is assisted by the O2…O2 vdW contact along the entire range of the intrinsic reaction coordinate (IRC). The positive value of the Grunenberg's compliance constants (31.186, 30.265, and 22.166 Å/mdyn for the C·T, C*·T*, and TSC·T [LEFT RIGHT ARROW] C*·T*, respectively) proves that the O2…O2 vdW contact is a stabilizing interaction. Based on the sweeps of the H-bond energies, it was found that the N4H…O4/O4H…N4, and N3H…N3 H-bonds in the C·T and C*·T* base pairs are anticooperative and weaken each other, whereas the middle N3H…N3 H-bond and the O2…O2 vdW contact are cooperative and mutually reinforce each other. It was found that the tautomerization of the C·T base mispair through the DPT is concerted and asynchronous reaction that proceeds via the TSC·T [LEFT RIGHT ARROW] C*·T* stabilized by the loosened N4[BOND]H[BOND]O4 covalent bridge, N3H…N3 H-bond (9.67 kcal mol−1) and O2…O2 vdW contact (0.41 kcal mol−1). The nine key points, describing the evolution of the C·T [LEFT RIGHT ARROW] C*·T* tautomerization via the DPT, were detected and completely investigated along the IRC. The C*·T* mispair was revealed to be the dynamically unstable structure with a lifetime 2.13·× 10−13 s. In this case, as for the A·T Watson–Crick DNA base pair, activates the mechanism of the quantum protection of the C·T DNA base mispair from its spontaneous mutagenic tautomerization through the DPT. © 2013 Wiley Periodicals, Inc.