Intermolecular CH•••O/N H-bonds in the biologically important pairs of natural nucleobases: a thorough quantum-chemical study

This study aims to cast light on the physico-chemical nature and energetic of the non-conventional CH center dot center dot center dot O/N H-bonds in the biologically important natural nucleobase pairs using a comprehensive quantum-chemical approach. As a whole, the 36 biologically important pairs, involving canonical and rare tautomers of nucleobases, were studied by means of all available up-to-date state-of-the-art quantum-chemical techniques along with quantum theory Atoms in molecules (QTAIM), Natural Bond Orbital (NBO) analysis, Grunenberg's compliance constants theory, geometrical and vibrational analyses to identify the CH center dot center dot center dot O/N interactions, reveal their physico-chemical nature and estimate their strengths as well as contribution to the overall base-pairs stability. It was shown that all the 38 CH center dot center dot center dot O/N contacts (25 CH center dot center dot center dot O and 13 CH center dot center dot center dot N H-bonds) completely satisfy all classical geometrical, electron-topological, in particular Bader's and two-molecule Koch and Popelier's, and vibrational criteria of H-bonding. The positive values of Grunenberg's compliance constants prove that the CH center dot center dot center dot O/N contacts in nucleobase pairs are stabilizing interactions unlike electrostatic repulsion and anti-H-bonds. NBO analysis indicates the electron density transfer from the lone electron pair of the acceptor atom (O/N) to the antibonding orbital corresponding to the donor group sigma(*)(CH). Moreover, significant increase in the frequency of the out-of-plane deformation modes gamma (CH) under the formation of the CH center dot center dot center dot O (by 17.2 divided by 81.3/10.8 divided by 84.7 cm(-1)) and CH center dot center dot center dot N (by 32.7 divided by 85.9/9.0 divided by 77.9 cm(-1)) H-bonds at the density functional theory (DFT)/second-order Moller-Plesset (MP2) levels of theory, respectively, and concomitant changes of their intensities can be considered as reliable indicators of H-bonding. The strengths of the CH center dot center dot center dot O/N interactions, evaluated by means of Espinosa-Molins-Lecomte formula, lie within the range 0.45 divided by 3.89/0.62 divided by 4.10 kcal/mol for the CH center dot center dot center dot O H-bonds and 1.45 divided by 3.17/1.70 divided by 3.43 kcal/mol for the CH center dot center dot center dot N H-bonds at the DFT/MP2 levels of theory, respectively. We revealed high linear mutual correlations between the H-bond energy and different physico-chemical parameters of the CH center dot center dot center dot O/N H-bonds. Based on these observations, the authors asserted that the most reliable descriptors of the H-bonding are the electron density rho at the CH center dot center dot center dot O/N H-bond critical points and the NBO calculated stabilization energy E-(2). The linear dependence of the H-bond energy E-CH center dot center dot center dot O/N (in kcal/mol) on the electron density rho (in atomic units) was established (DFT/MP2): E-CH center dot center dot center dot O = 248.501 rho-0.367/260.518 rho-0.373 and E-CH center dot center dot center dot N = 218.125 rho-0.339/243.599 rho-0.441. Red-shifted and blue-shifted CH center dot center dot center dot O/N H-bonds behave in a similar way and can be described with the same fit parameters. It was found that the A-U HH2 and U-U-3 nucleobase pairs are stabilized solely by the CH center dot center dot center dot O/N H-bonds. At the same time, in the A-U HH1, A-U HH2, A-A(syn 1), A-A(syn 2), A-A(syn 3), A-A(4), A-G(1), A-G(2), G-U-1, G-U-2, G-U-3, G-C HH1, U-U-1, U-U-2, U-U-3 and A-C nucleobase pairs the CH center dot center dot center dot O/N H-bonds play a prominent role (>30%) in their stabilization. We suppose that unconventional CH center dot center dot center dot O/N H-bond plays the role of the third fulcrum, ensuring structurally dynamic similarity of the isomorphic base pairs of different origin, which are incorporated equally well into the structure of the DNA double helix.