Structural, electronic and energetic consequences of epigenetic cytosine modifications.

The hydrogen bonding patterns of cytosine and its seven C5-modifed analogues paired with canonical guanine were studied using the first principle approach. Both global minima and biologically relevant conformations were studied. The former resulted from full gradient geometry optimizations of hydrogen bonded pairs, while the latter were obtained based on 125 d(GpC) dinucleotides found in the PDB database. The obtained energetic, electronic and structural data lead to the conclusion that the epigenetically relevant modification of cytosine may have serious consequences on hydrogen bonding with guanine. First of all, the significant substituent effects were observed for such trends as charges on sites involved in hydrogen bonding, the total intermolecular interaction energy or electron densities at bond critical points. Moreover, the molecular orbital polarization contribution resulting from energy decomposition expressed in terms of absolutely localized molecular orbitals exhibited an inverse linear correlation with frozen density contributions. A substituent effect on the amount of charge transfer from pyrimidine toward guanine was also observed. The increase of intermolecular interactions of guanine with modified cytosine is associated with the increase of the electro-donating character of the C5-substituent. However, only pairs involving 5-methylcytosine are more stable than those formed by canonical cytosine. Furthermore, the energy differences observed for global minima also remain important for a broad range of displacement and angular parameters defining pair conformations in model d(GpC) dinucleotides. Due to the sensitivities of intermolecular interactions to mutual arrangements of monomers the modification of cytosine at the C5 site can significantly alter the actual energy profiles. Consequently, it may be anticipated that the modified dinucleotides will adopt different conformations than a standard G-C pair in a B-DNA double helix.

Linear and nonlinear optical properties of azobenzene derivatives.

The results of computations of spectroscopic parameters of lowest-lying electronic excited states of azobenezene derivatives are presented. The analysis of experimentally recorded spectra was supported by quantum chemical calculations using density functional theory. The theoretically determined resonant (two-photon absorption probabilities) and non-resonant (first-order hyperpolarisability) nonlinear optical properties are also discussed, with an eye towards the performance of recently proposed long-range corrected (LRC) schemes (LC-BLYP and CAM-B3LYP functionals).

Theoretical description of the coding potential of diamino-5-formamidopyrimidines.

The results of geometry optimisation of possible Watson-Crick-like pairs of 2,6-diamino-4-oxy-5-formamidopyrimidine (fapy-adenine) or 4,6-diamino-5-formamidopyrimidine (fapy-guanine) were presented. In the absence of the external field the fapy-adenine is able to form pairs with all four canonical nucleic acid bases. However, pairs with guanine, cytosine and thymine the most stable are. Thus, the potential miscoding abilities may be observed. In contrast, in the presence of the external field the mispairing abilities of fapy-adenine become insignificant since the most stable dimers are formed with thymine. The pairing properties of fapy-guanine are complex and depend on its tatomeric form. In the absence of an external field the 4-enol-6-keto-diamino tautomer of fapyG is able to form stable dimers with thymine and cytosine, while the 4,6-diketo-diamino tautomer forms the most stable pairs with cytosine and guanine. The presence of the water solvent does not significantly alter the pairing abilities of fapy-guanine. However, pairs with thymine are at least as stable as the Watson-Crick GC pair. Thus, in polar conditions the mispairing potential of fapyG will be extended and may be enriched by potential GC-->AT transition.

Effect of 2'-deoxyguanosine oxidation at C8 position on N-glycosidic bond stability.

The influence of 2'-deoxyguanosine (dG) oxidation at the C-8 position on N-glycosidic bond stability was investigated. A kinetic analysis of dG and 8-oxo-2'-deoxyguanosine (8-oxodG) depurination reactions was carried out in water solutions at pH ranging from 2 to 7.4 and temperature of 100 degrees C. The results indicate that N-glycosidic bond of 8-oxodG is significantly more stable in comparison with dG at any pH applied. At pH 5.1 hydrolysis rate of dG is 4.5-fold higher than that for 8-oxodG. The chemical stability of the modified nucleoside in oxidatively damaged DNA is one of important factors contributing to its mutagenic potential. Results of our experiments indicate that 8-oxodG, potentially mutagenic and carcinogenic nucleoside, is hardly susceptible to spontaneous depurination and its removal from cellular DNA depends mostly on the activity of DNA repair enzymes.