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 E_CH⋯O/N on the electron density ρ was established: E_CH⋯O= 250.263∙ρ – .380/258.255∙ρ – .396 and E_CH⋯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.

Keywords:

• CH⋯O/N H-bonds
• pairs of nucleobases
• QTAIM and NBO analyses
• Bader’s criteria
• “two-molecule” Koch and Popelier’s criteria
• Grunenberg’s compliance constants
• quantum-chemical methods
• energy decomposition analysis
• QTAIM delocalization indexes

Additional information

Funding

Funding. This work was partially supported by the State Fund for Fundamental Research (SFFR) of Ukraine within the Ukrainian-Japanese project No. F 52.2/001 for 2013–2014 years and by the Science and Technology Center in Ukraine (STCU) within the project No. 5728 for 2012–2014 years. O.O.B. was supported by the Grant of the President of Ukraine to support scientific research of young scientists for 2014 year from the State Fund for Fundamental Research of Ukraine (project No. GP/F56/074) and by the Grant of the Cabinet of Ministers of Ukraine for collectives of young researchers for carrying out applied scientific researches, scientific and technological development in the priority areas of science and technology (project No.123). This work was performed using computational facilities of joint computer cluster of SSI “Institute for Single Crystals” of the National Academy of Sciences of Ukraine and Institute for Scintillation Materials of the National Academy of Sciences of Ukraine incorporated into Ukrainian National Grid.