This study aims to cast light on the physico-chemical nature and energetic of the non-conventional CH···O/N H-bonds in the biologically important natural nucleobase pairs using a comprehensive quan...

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

The values of the downfield chemical shift of the bridge hydrogen atom were estimated for a series of compounds containing an intramolecular hydrogen bond O–H⋯O, O–H⋯N, O–H⋯Hal, N–H⋯O, N–H⋯N, C–H⋯O, C–H⋯N and C–H⋯Hal. Based on these values, the empirical estimation of the hydrogen bond energy was obtained by using known relationships. For the compounds containing an intramolecular hydrogen bond, the DFT B3LYP/6-311++G(d,p) method was used both for geometry optimization and for QTAIM calculations of the topological parameters (electron density ρBCP and the density of potential energy V in the critical point of the hydrogen bond). The calculated geometric and topological parameters of hydrogen bonds were also used to evaluate the energy of the hydrogen bond based on the equations from the literature. Comparison of calibrating energies from the 1H NMR data with the energies predicted by calculations showed that the most reliable are the linear dependence on the topological ρBCP and V parameters. However, the correct prediction of the hydrogen bond energy is determined by proper fitting of the linear regression coefficients. To obtain them, new linear relationships were found between the calculated ρBCP and V parameters and the hydrogen bond energies obtained from empirical 1H NMR data. These relationships allow the comparison of the energies of different types of hydrogen bonds for various molecules and biological ensembles.

Estimating the energy of intramolecular hydrogen bonds from 1H NMR and QTAIM calculations

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 de...

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

This study provides the first accurate investigation of the tautomerization of the biologically important guanine*·thymine (G*·T) DNA base mispair with Watson–Crick geometry, involving the enol mutagenic tautomer of the G and the keto tautomer of the T, into the G·T* mispair (∆G = .99 kcal mol−1, population = 15.8% obtained at the MP2 level of quantum-mechanical theory in the continuum with e = 4), formed by the keto tautomer of the G and the enol mutagenic tautomer of the T base, using DFT and MP2 methods in vacuum and in the weakly polar medium (e = 4), characteristic for the hydrophobic interfaces of specific protein–nucleic acid interactions. We were first able to show that the G*·T↔G·T* tautomerization occurs through the asynchronous concerted double proton transfer along two antiparallel O6H···O4 and N1···HN3 H-bonds and is assisted by the third N2H···O2 H-bond, that exists along the entire reaction pathway. The obtained results indicate that the G·T* base mispair is stable from the thermodynamic po...

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The nature of the transition mismatches with Watson-Crick architecture: the G*·T or G·T* DNA base mispair or both? A QM/QTAIM perspective for the biological problem.

Herein, we first address the question posed in the title by establishing the tautomerization trajectory via the double proton transfer of the adenine·guanine (A·G) DNA base mispair formed by the canonical tautomers of the A and G bases into the A*·G* DNA base mispair, involving mutagenic tautomers, with the use of the quantum-mechanical calculations and quantum theory of atoms in molecules (QTAIM). It was detected that the A·G ↔ A*·G* tautomerization proceeds through the asynchronous concerted mechanism. It was revealed that the A·G base mispair is stabilized by the N6H···O6 (5.68) and N1H···N1 (6.51) hydrogen bonds (H-bonds) and the N2H···HC2 dihydrogen bond (DH-bond) (0.68 kcal·mol−1), whereas the A*·G* base mispair—by the O6H···N6 (10.88), N1H···N1 (7.01) and C2H···N2 H-bonds (0.42 kcal·mol−1). The N2H···HC2 DH-bond smoothly and without bifurcation transforms into the C2H···N2 H-bond at the IRC = −10.07 Bohr in the course of the A·G ↔ A*·G* tautomerization. Using the sweeps of the energies of the intermolecular H-bonds, it was observed that the N6H···O6 H-bond is anticooperative to the two others—N1H···N1 and N2H···HC2 in the A·G base mispair, while the latters are significantly cooperative, mutually strengthening each other. In opposite, all three O6H···N6, N1H···N1, and C2H···N2 H-bonds are cooperative in the A*·G* base mispair. All in all, we established the dynamical instability of the А*·G* base mispair with a short lifetime (4.83·10−14 s), enabling it not to be deemed feasible source of the A* and G* mutagenic tautomers of the DNA bases. The small lifetime of the А*·G* base mispair is predetermined by the negative value of the Gibbs free energy for the A*·G* → A·G transition. Moreover, all of the six low-frequency intermolecular vibrations cannot develop during this lifetime that additionally confirms the aforementioned results. Thus, the A*·G* base mispair cannot be considered as a source of the mutagenic tautomers of the DNA bases, as the A·G base mispair dissociates during DNA replication exceptionally into the A and G monomers in the canonical tautomeric form. © 2013 Wiley Periodicals, Inc.

Is the DPT tautomerization of the long A·G Watson-Crick DNA base mispair a source of the adenine and guanine mutagenic tautomers? A QM and QTAIM response to the biologically important question

A comprehensive quantum-chemical conformational analysis of two nucleoside analogues, 2′,3′-didehydro-2′,3′-dideoxyuridine (d4U) and 2′,3′-didehydro-2′,3′-dideoxycytidine (d4C), is reported. The electronic structure calculations were performed at the MP2/6-311++G(d,p)//B3LYP/6-31++G(d,p) level of theory. It was found that d4U and d4C adopt 20 conformers and 19 conformers, respectively, which correspond to local minima on the respective potential energy landscapes. QTAIM and NBO analyses show that the d4U and d4C conformers are stabilised by a complicated network of specific intramolecular interactions, which includes conventional (OH⋯O) and non-conventional (CH⋯O, CH⋯HC) H-bonds as well as closed-shell van der Waals (C⋯O) contacts. A satisfactory linear correlation was found between Grunenberg's compliance constants for closed-shell intramolecular interactions and their energy. It is shown that there are no conformational obstacles for incorporation of d4U and d4C into the double helical A and B forms of DNA. The less pronounced biological activity of d4U as compared to 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T) is most likely due to the presence of the bulky methyl group at the 5-position of d4T, which can be recognised by target enzymes.

Complete conformational space of the potential HIV-1 reverse transcriptase inhibitors d4U and d4C. A quantum chemical study.

A comprehensive quantum-chemical investigation of the conformational landscapes of two nucleoside HIV-1 reverse transcriptase inhibitors, 2′,3′-didehydro-2′,3′-dideoxyadenosine (d4A), and 2′,3′-did...

Alla G. Ponomareva

Papers

Complete conformational space of the potential HIV-1 reverse transcriptase inhibitors d4U and d4C. A quantum chemical study.

Structural and energetic properties of the potential HIV-1 reverse transcriptase inhibitors d4A and d4G: a comprehensive theoretical investigation

Conformational Landscape of the Nucleoside Reverse Transcriptase Inhibitor d4T: a Comprehensive Quantum-Chemical Approach

Prevalence of antibiotic resistance among bacterial strains isolated in chronic periodontitis and in healthy people