By how many tautomerisation routes the Watson–Crick-like A·C* DNA base mispair is linked with the wobble mismatches? A QM/QTAIM vision from a biological point of view

Here for the first time we present four novel routes of the tautomerisation via the sequential DPT that links biologically important A·C*(WC) DNA base mispair with Watson–Crick (WC) geometry and wobble (w) A*·C*(w), A·C*_O2(w), A*·C*(w ₁) and A·C(w _⊥) mismatches, pursuing the goal of estimation of their contribution into the transition mutations during DNA biosynthesis. These processes occur without opening of the pairs and are accompanied by the substantial changes in their geometry. A detailed analysis of these pathways leads to an identification of the A·C*(WC)?A*·C*(w) tautomerisation route as the most suitable among these processes from the point of view of the spontaneous point mutagenesis, since it proceeds via the time that is significantly less than the time used by the replicative DNA-polymerase for the incorporation of one incoming nucleotide into the synthesised DNA double helix. This non-dissociative transition occurs through the planar, highly stable, zwitterionic \( {\text{TS}}_{{{\text{A}} \cdot {\text{C*(WC)}} \leftrightarrow {\text{A}}^{ + } \cdot {\text{C}}^{\text{ - }} (w )}}^{{{\text{A}}^{ + } \cdot {\text{C}}^{\text{ - }} }} \) transition state and dynamically unstable intermediate A⁺·C^?(w) ion pair and is accompanied by the consistent rearrangement of the 10 unique patterns of the specific intermolecular interactions, among which there are from 2 to 4 AH···B H-bonds and 2 loosened A–H–B covalent bridges. Basic physico-chemical properties of this mutual tautomeric transformation, which is internally inherent to the A·C*(WC) and A*·C*(w) base mispairs, are documented, and its possible biological assignment is discussed here.     

The effect of CH<Subscript>3</Subscript>, F and NO<Subscript>2</Subscript> substituents on the individual hydrogen bond energies in the adenine–thymine and guanine–cytosine base pairs

The substituent effects on the geometrical parameters and the individual hydrogen bond (HB) energies of base pairs such as X–adenine–thymine (X–A–T), X–thymine–adenine (X–T–A), X–guanine–cytosine (X–G–C), and X–cytosine–guanine (X–C–G) have been studied by the quantum mechanical calculations at the B3LYP and MP2 levels with the 6–311++G(d,p) basis set. The electron withdrawing (EW) substituents (F and NO₂) increase the total binding energy (ΔE) of X–G–C derivatives and the electron donating (ED) substituent (CH₃) decreases it when they are introduced in the 8 and 9 positions of G. The effects of substituents are reversed when they are located in the 1, 5, and 6 positions of C, with exception of CH₃ in the 1 position and F in the 5 position, which in both cases the ΔE value decreases negligibly small. With minor exceptions (X=8–CH₃, 8–F, and 9–NO₂), both ED and EW substituents increase slightly the ΔE values of X–A–T derivatives. The individual HB energies (∆E _HBs) have been estimated using electron densities that calculated at the hydrogen bond critical points (HBCPs) by the atoms in molecules (AIM) method. Most of changes of individual HBs are in consistent with the ED/EW nature of substituents and the role of atoms entered H-bonding. The remarkable change is observed for NO₂ substituted derivative in each case.