The reduction of ruthenium(III) complexes with triazolopyrimidine ligands by ascorbic acid and mechanistic insight into their action in anticancer therapy

Abstract

Kinetic studies of the reduction of two ruthenium(III) complexes, mer-[RuCl3(dmso)(H2O)(tmtp)]·2H2O (1) and mer,cis-[RuCl3(dbtp)2(dmso)] (2) (where dmso – dimethylsulfoxide, tmtp – 5,6,7-trimethyl-1,2,4-triazolo[1,5-a]pyrimidine and dbtp – 5,7-ditertbutyl-1,2,4-triazolo[1,5-a]pyrimidine), by ascorbic acid were performed as a function of antioxidant concentration in acetate buffer within the pH range of 2.9–5. The rapid reduction of the ruthenium(III) complexes (1) and (2) resulted in the formation of the mer-[RuCl3(dmso)(H2O)(tmtp)]− and mer,cis-[RuCl3(dbtp)2(dmso)]− ions and was followed by successive dissociation of the chloride ligands. The second-order rate constant (k1) for the reduction of the mer-[RuCl3(dmso)(H2O)(tmtp)]·2H2O complex and the first-order rate constant for the hydrolysis of its reduced form were found to be 134 ± 2 M−1 s−1 and (3.8 ± 0.9) × 10−2 s−1 at 25 °C and pH = 2.9, respectively. Similarly, the fast process assigned to the reduction of the mer,cis-[RuCl3(dbtp)2(dmso)] complex and the subsequent, slower process attributed to the hydrolysis of the cis-[RuCl3(dbtp)2(dmso)]− ion were characterized by rate constants of 145.5 ± 0.8 M−1 s−1 and (9 ± 2) × 10−3 s−1 at 25 °C and pH = 2.9, respectively. Obtained data indicated that the reduction of the ruthenium(III) complexes strongly depends on pH and accelerates with increasing pH. The kinetic data indicates that the redox process followed an inner-sphere electron-transfer mechanism at pH higher than 3.