1. Novel pathway for mutagenic tautomerization of classical А∙Т DNA base pairs via sequential proton transfer through quasi-orthogonal transition states: A QM/QTAIM investigation.
- Author
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Brovarets’, Ol’ha O., Tsiupa, Kostiantyn S., and Hovorun, Dmytro M.
- Subjects
BASE pairs ,PROTON transfer reactions ,TRANSITION state theory (Chemistry) ,SYMMETRY (Physics) ,THERMODYNAMICS - Abstract
In this paper we have theoretically predicted a novel pathway for the mutagenic tautomerization of the classical A∙T DNA base pairs in the free state, the Watson-Crick A·Т(WC), reverse Watson-Crick A·Т(rWC), Hoogsteen A·Т(H) and reverse Hoogsteen A·Т(rH) pairs, via sequential proton transfer accompanied by a significant change in the mutual orientation of the bases. Quantum-mechanical (QM) calculations were performed at the MP2/aug-cc-pVDZ//B3LYP/6-311++G(d,p) level in vacuum phase, along with Bader’s quantum theory of Atoms in Molecules (QTAIM). These processes involve transition states (TSs) with quasi-orthogonal structures (symmetry C
1 ), which are highly polar, tight ion pairs (A- , N6H2 -deprotonated)∙(T+ , O4/O2-protonated). Gibbs free energies of activation for the A∙T(WC) / A∙T(rWC) ↔ A*∙Т(rwWC ) / A*∙Т(wWC ) tautomeric transitions (~43.5 kcal∙mol-1 ) are lower than for the A∙T(H) / A∙T(rH) ↔ A*N7 ∙Т(rwH ) / A*N7 ∙Т(wH ) tautomerisations (~53.0 kcal∙mol-1 ) (rare tautomers are marked by an asterisk; w—wobble configured tautomerisation products). The (T)N3+ H⋯N1- (A), (T)O4+ H⋯N1- (A) / (T)N3+ H⋯N1- (A) and (T)O2+ H⋯N1- (A) H-bonds are found in the transition states TSA-·T+ A·T(WC)↔A*·T(rwWC) / TSA-·T+ A·T(rWC)↔A*·T(wWC) . However, in the transition state TSA-·T+ A·Т(H)↔A*N7·T(rwH) / TSA-·T+ A·Т(rH)↔A*N7·T(wH) , the (T)N3+ H⋯N7- (A), (T)O4+ H⋯N7- (A) / (T)N3+ H⋯N7- (A) and (T)O2+ H⋯N7- (A) H-bonds are supplemented by the attractive (T)O4+ /O2+ ⋯N6- (A) van der Waals contacts. It was demonstrated that the products of the tautomerization of the classical A∙T DNA base pairs—A*∙Т(rwWC ), A*N7 ∙Т(rwH ) and A*N7 ∙Т(wH ) (symmetry Cs )–further transform via double proton transfer into the energetically favorable wobble A∙T*(rwWC ), A∙T*(rwH ) and A∙T*O2 (wH ) base mispairs (symmetry Cs ). [ABSTRACT FROM AUTHOR]- Published
- 2018
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