The significant role of the intermolecular CH⋯O/N hydrogen bonds in governing the biologically important pairs of the DNA and RNA modified bases: a comprehensive theoretical investigation

Abstract

This paper is a logical continuation of the theoretical survey of the CH⋯O/N specific contacts in the nucleobase pairs using a wide arsenal of the modern methods, which was initiated in our previous study [J. Biomol. Struct. & Dynam., 2014, 32, 993-1022]. It was established that 34 CH⋯O and 7 CH⋯N interactions, that were detected by quantum-chemical calculations in the 39 biologically important pairs involving modified nucleobases, completely satisfy all geometrical, vibrational, electron-topological, in particular Bader's and "two-molecule" Koch and Popelier's, Grunenberg's compliance constants theory and natural bond orbital criteria indicating that they can be identified as true H-bonds. The geometrical criteria of the H-bond formation are fulfilled for all considered CH⋯O/N H-bonds without any exception. It was shown that the classical rule of the stretching vibration shifts does not work in the ~95% cases of the CH⋯O/N H-bonds. Furthermore, significant increase in the frequency of the out-of-plane deformation modes γ(CH) under the formation of CH⋯O/N H-bonds and corresponding changes of their intensities can be also considered as reliable indicators of the H-bonding. We revealed high linear mutual correlations between the electron density, Laplacian of the electron density, H-bond energy at the (3, -1) bond critical points of the CH⋯O/N H-bonds, and different physico-chemical parameters of the CH⋯O/N H-bonds. We suggested that the electron density ρ and the interaction energy E((2)) of the lone orbital pairs are the most reliable descriptors of the H-bonding. The linear dependence of the H-bond energy ECH⋯O/N on the electron density ρ was established: ECH⋯O = 250.263∙ρ - .380/258.255∙ρ - .396 and ECH⋯N = 196.800∙ρ - .172/268.559∙ρ - .703 obtained at the density functional theory (DFT)/Møller-Plesset (MP2) levels of theory, respectively. The studies of the interaction energies show that the contribution of the CH⋯O and CH⋯N H-bonds into the base pairs stability varies from 3.0/4.2 to 35.1/31.2% and from 3.0/4.3 to 44.4/46.5% at the DFT/MP2 levels of theory, accordingly. Energy decomposition analysis performed for all base pairs involving canonical and modified nucleobases defines the electrostatic attraction and Pauli repulsion as dominant stabilizing forces in all complexes. This observation was additionally confirmed by the results of the QTAIM delocalization indexes analysis. The studies reported here advance our understanding of the biological role of the weak CH⋯O/N H-bonds, that dictates the requirements for the structural and dynamical similarity of the canonical and mismatched pairs with Watson-Crick (WC) geometry, which facilitates their enzymatic incorporation into the DNA double helix during DNA replication. Thus, these H-bonds in the base pairs with WC geometry may be also considered as "the last drop" at the transmission of the electronic signal that launches the chemical incorporation of the incoming nucleoside triphosphate into DNA.

Structural significance of modified nucleoside 5-taurinomethyl-2-thiouridine, τm5s2U, found at ‘wobble’ position in anticodon loop of human mitochondrial tRNALys

“…5i) maintained throughout the 5-ns MD simulation. Such bifurcated interactions have been found useful in many biological processes [44,[71][72][73][74][75][76].These intramolecular interactions within the 5-taurinomethyl side chain and phosphate backbone resulted in keeping the Watson-crick base pairing sites free during the translation process. The hydrogen bonding interaction between O4 0 …HC(6) has been vanished throughout the 5-ns MD simulation (Fig.…”

How many tautomerization pathways connect Watson–Crick-like G*·T DNA base mispair and wobble mismatches?

“…The energies of the weak CH···O H-bonds [69,70] were calculated by the empirical Espinosa-Molins-Lecomte (EML) formula [71,72], which has been first successfully applied by C.F. Matta [73] for the estimation of the individual energetic contributions of the separate H-bonds in the two Watson-Crick DNA base pairs:…”

“…were considered as criteria for the H-bond formation [69,70]. Wave functions were obtained at the level of theory used for geometry optimisation.…”

X-ray structure and conformational study of tris(2-(dimethylamino)phenyl)methanol salt derivatives: Roles of anions and hydrogen bond

“…This demonstrates that the free ligand would like to accept two protons from strong acids and to form a crystal-like divalent cation of C3 symmetry in water, despite that the symmetry and the valence of the counter anions are nonmatching with the [LH 2 ] 2þ cation (see TsOH salt. mol [28,29], which were observed in the crystal structure (Fig. 2).…”