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

摘要

This paper is a logical continuation of the theoretical survey of the CHMIDLINE HORIZONTAL ELLIPSISO/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 CHMIDLINE HORIZONTAL ELLIPSISO and 7 CHMIDLINE HORIZONTAL ELLIPSISN 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 CHMIDLINE HORIZONTAL ELLIPSISO/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 CHMIDLINE HORIZONTAL ELLIPSISO/N H-bonds. Furthermore, significant increase in the frequency of the out-of-plane deformation modes gamma(CH) under the formation of CHMIDLINE HORIZONTAL ELLIPSISO/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 CHMIDLINE HORIZONTAL ELLIPSISO/N H-bonds, and different physico-chemical parameters of the CHMIDLINE HORIZONTAL ELLIPSISO/N H-bonds. We suggested that the electron density rho 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 E-CHMIDLINE HORIZONTAL ELLIPSISO/N on the electron density rho was established: E-CHMIDLINE HORIZONTAL ELLIPSISO = 250.263 center dot rho - .380/258.255 center dot rho - .396 and E-CHMIDLINE HORIZONTAL ELLIPSISN = 196.800 center dot rho - .172/268.559 center dot rho - .703 obtained at the density functional theory (DFT)/Moller-Plesset (MP2) levels of theory, respectively. The studies of the interaction energies show that the contribution of the CHMIDLINE HORIZONTAL ELLIPSISO and CHMIDLINE HORIZONTAL ELLIPSISN 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 CHMIDLINE HORIZONTAL ELLIPSISO/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.