Effect of methyl groups on the oxidation of xanthine and correlation of oxidation potentials with frontier molecular orbital energies

Abstract

The effect of methyl groups on the ease of oxidation of xanthine at N₁ , N₃ , N₇ and N₉ positions has been studied at physiological <i>p</i>H<i> </i>using voltammetric and spectral studies. The electroactive species is found to be anion and the removal of proton occurs first from N₃ and then from N₇ or N₉ positions. The presence

of methyl group has been found to increase electron density at corresponding nitrogens; however, its extent is maximum at N₇ position. The <i>E_p </i>value also shifts maximum to more positive potentials in presence of methyl group at N₇ position. A poor correlation between <i>E_p</i> and HOMO is observed, most probably due to adsorption complications involved in the electrode reactions. The major product of oxidation is 5- hydroxyhydantoin derivative when methyl groups are present in the pyrimidine ring whereas allantoin derivative is also obtained if methyl groups are only in imidazole ring. A general reaction scheme for the oxidation of xanthines is also presented.