An ab initio DFT Characteristics of Tautomeric Properties of Hydroxyl Radical Modified Nucleosides in Polar and Non-Polar Environments

Abstract

Tautomer / DNA Base / Free Radical / Hydroxyl Radical / DFTDFT ab initio calculations of 22 free radical derived nucleosides analogs were performed in gas phase and water solution. Most of studied compounds exist mainly in expected amino-and keto-forms. However, there were found few important exceptions: enolamino tautomer of 2-OH-adenosine is dominant in apolar environment, while in polar solution keto-amino isomer become more probable; 8-oxo-guanosine is to be represented as a mixture of two tautomers: 6,8-diketo and 6-enol-8-keto with disfavoring of the latter in polar conditions, 5-OH-cytidine adopts imino-keto form in non-polar surroundings but water stabilizes amino-keto isomer reverting order of these tautomers, cytidine glycol in apolar and polar conditions is represented mainly by keto-imino form, but more polar environment increase percentage of amino-keto tautomer not reverting their order, 6-hydroxy-5,6-dihydroxycytidine in both polar and non-polar conditions adopts keto-imino form, which dominates over keto-amino one, 5-hydroxy-5,6-dihydro-cytosine in non-polar conditions exists as keto-imino tautomer while polar conditions favors keto-amino form.

Molecular Perspective Review of Biochemical Role of Nucleobases Modified by Oxidative Stress

“…Thus, despite the presence of hydroxyl group attached to C 2 atom no changes in succession of basicities of N 1 and N 3 centers are observed. The same conclusion may be drawn taking into account the results for 8-oxoadenosine and fapy-adenosine [62,63] since protonation takes place predominantly at N 3 position. The gas phase basicities of adenosine analogues were presented in Table 2.…”

“…energetic degeneracy of these enantiomers can be destroyed and energetic degeneracy may disappear. As it was previously reported [62], not all stereoisomers are equally probable. The results presented in Fig.…”

“…As it is documented in Fig. 3 and 4, all derivatives exist exclusively in 2,4-diketo forms [62] irrespectively of the environmental polarity. Although, some of these compounds may exist as a mixture of different isomers, but their structures result from either chirality conformations or side group rotation rather than from tautomeric equilibriums.…”

“…If nucleosides were considered the simplified model was implemented, which instead of the whole 2'-deoxy-ribose ring, comprised only the methylmethoxy group (-CH 2 -O-CH 3 ) mimicking the N-glycosidic bond. Such model was documented as reliable [60][61][62][63][64][65] for it provides all important features of nucleosides with significant reduction of the size of the studied systems. The results of thermodynamic calculations were critically checked against imaginary frequencies ensuring that the obtained geometries correspond to global minima.…”

“…The GA1 tautomer is more polar both in the gas phase and in water solution than GA2 isomer. Xanthosine (GB) exists predominantly as 2,6-diketo form irrespectively of the environment polarity [26,62]. Fapy guanosine (AC) adopts predominantly the ketoamino form (GC1) in both gas phase and water solution.…”