Data_Sheet_1_Unexpected Routes of the Mutagenic Tautomerization of the T Nucleobase in the Classical A·T DNA Base Pairs: A QM/QTAIM Comprehensive View.PDF (312.53 kB)
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Data_Sheet_1_Unexpected Routes of the Mutagenic Tautomerization of the T Nucleobase in the Classical A·T DNA Base Pairs: A QM/QTAIM Comprehensive View.PDF

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posted on 27.11.2018, 04:28 by Ol'ha O. Brovarets', Kostiantyn S. Tsiupa, Andrii Dinets, Dmytro M. Hovorun

In this paper using quantum-mechanical (QM) calculations in combination with Bader's quantum theory of “Atoms in Molecules” (QTAIM) in the continuum with ε = 1, we have theoretically demonstrated for the first time that revealed recently highly-energetic conformers of the classical A·T DNA base pairs – Watson-Crick [A·T(wWC)], reverse Watson-Crick [A·T(wrWC)], Hoogsteen [A·T(wH)] and reverse Hoogsteen [A·T(wrH)] – act as intermediates of the intrapair mutagenic tautomerization of the T nucleobase owing to the novel tautomerisation pathways: A·T(wWC)↔A·T*(wWC); A·T(wrWC)↔A·TO2*(wrWC); A·T(wH)↔A·T*(wH); A·T(wrH)↔A·TO2*(wrH). All of them occur via the transition states as tight ion pairs (A+, protonated by the N6H2 amino group)·(T, deprotonated by the N3H group) with quasi-orthogonal geometry, which are stabilized by the participation of the strong (A)N6+H···O4/O2(T) and (A)N6+H···N3(T) H-bonds. Established tautomerizations proceed through a two-step mechanism of the protons moving in the opposite directions along the intermolecular H-bonds. Initially, proton moves from the N3H imino group of T to the N6H2 amino group of A and then subsequently from the protonated N6+H3 amino group of A to the O4/O2 oxygen atom of T, leading to the products – A·T*(wWC), A·TO2*(wrWC), A·T*(wH), and A·TO2*(wrH), which are substantially non-planar, conformationally-labile complexes. These mispairs are stabilized by the participation of the (A)N6H/N6H'···N3(T) and (T)O2H/O4H···N6(A) H-bonds, for which the pyramidalized amino group of A is their donor and acceptor. The Gibbs free energy of activation of these mutagenic tautomerizations lies in the range of 27.8–29.8 kcal·mol−1 at T = 298.15 K in the continuum with ε = 1.

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