The reaction of 5 hydroxy 6 methyluracil with peroxy radicals generated by the thermal decomposition of azodiisobutyronitrile was studied at 75°С in ethanol, propan 2 ol, and dimethyl sulfoxide. The stoichiometry of the reaction is 1 : 1. The reaction product is dihydro 6 hydroxy 6 methylpyrimidine 2,4,5 trione in an anhydrous solvent or dihydro 5,5,6 trihy droxy 6 methylpyrimidine 2,4 dione in the presence of water. The rate constant for the reac tion of 5 hydroxy 6 methyluracil with the peroxy radicals is ~10 8 L mol -1 s -1 .The reactions of pyrimidines with active forms of oxy gen are of interest for understanding the mechanism of damage and protection of DNA. One of the main factors of DNA damage is the radical oxidation of nucleic bases by the hydroxy ( • ОН) and peroxy (ROO • ) radicals. 1,2It is known that 5 hydroxy 6 methyluracil is a drug with a wide spectrum of action. 3 There are data that it is also an inhibitor of free radical oxidation. 4,5 The rate con stant of the reaction of 5 hydroxy 6 methyluracil with the ethylbenzene peroxy radicals obtained by the chemi luminescence method 4 is close to that of the reaction with the hydroxyperoxy radicals measured by the absorption of oxygen in the oxidation of isopropyl alcohol 5 and to the data for ionol 4 (2.6•10 4 L mol -1 s -1 ). Increasing number of data obtained in the recent years indicate that the deep reason for damage of living systems is the action of differ ent forms of active oxygen and, first of all, hydroxy and peroxy radicals. The rate constant of the reaction of the proposed biologically active compound with peroxy radi cals (i.e., antioxidant activity) often correlates with its wide therapeutical effect. 6 In this work, we studied the reactions of 5 hydroxy 6 methyluracil with the peroxy radicals formed upon the thermal decomposition of azodiisobutyronitrile (AIBN) in the presence of oxygen at 75 °С in ethanol, propan 2 ol, and dimethyl sulfoxide. The reaction products were identified by the 13 C NMR and GC MS methods. It was shown that 5 hydroxy 6 methyluracil is a highly efficient scavenger of peroxy radicals.
ExperimentalThe density functional theory (DFT) calculations were performed by the BB1K method. 7 The 6 31+G(d,p) 8 standard two exponential basis set was used. This method gives good coincidence with the experimental values. 9 All geometric parameters for molecules, intermediates, and transition states were optimized without symmetry constraints. The nature of the optimized structures was determined by analysis of the eigenvalues of the Hesse matrix, i.e., the matrix of the second energy derivatives with respect to coordinates that were analy tically calculated. The calculated energies were corrected with allowance for the zero point vibration energies (ZPE) for the corresponding structures calculated using a correction coefficient of 0.9561. 7All quantum chemical calculations were performed using the NWChem program package. 10 Azodiisobutyronitrile (AIBN) was two times recrystallized from alcohol. Ethanol and propan 2 ol were pu...
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