Controlled stabilization of anionic forms of the uracil derivatives: A DFT study

Relative stabilities of the N1/N3/О5/О6 anions of 42 substituted uracils in gas phase and aqueous solutions have been theoretically studied using approximation IEFPCM (SMD) − TPSS/aug-cc-pVTZ. The specific solvation of uracil and its anions has been simulated with the first hydrate shell made up with 5 water molecules. The nonspecific solvation has been accounted in terms of the SMD model. We have found a series of relative stability under conditions of both specific and nonspecific hydration. The series is ranked according to the increase of the relative stability of the N3 anion. In gas phase, the N1 anion is significantly more stable than its N3 counterpart: the Δ G gas values vary in the range from 19.54 ( 5OH6СН3U ) to 83.14 ( 5NO26NH2U ) kJ/mol that is caused by a more effective delocalization of the excess charge through the uracil framework in the N1 anion. The hydration pronouncedly diminishes Δ G to the range from ‐0.02 ( 5OH6СН3U ) to 38.16 ( 5Br6NO2U ) kJ/mol due to the fact that the polar solvent is prone to stabilize more polar anionic states of uracils. Therefore, less polar uracil anions are more stable. We have defined the main factor influencing the N1/N3/О5/О6 distribution of anions, viz. the presence of the substituents in 5 and 6 positions of the pyrimidine ring. Herewith, the most favorable mechanism of the influence of 5-substituents has been previously defined as resonant whereas, as we found in this work, the inductive mechanism is more pronounced in the case of 6-substituents.