Solution Equilibrium Studies of Anticancer Ruthenium(II)--p-cymene Complexes of Pyridinecarboxylic Acids

Stoichiometry and stability of antitumor ruthenium(II)-η-p-cymene complexes of picolinic acid and its 6-methyl and 6-carboxylic acid derivatives were determined by pHpotentiometry, H NMR spectroscopy and UV/Vis spectrophotometry in aqueous solution in the presence or absence of coordinating chloride ions. The picolinates form exclusively monoligand complexes in which they can coordinate via the bidentate (O,N) mode and a chloride or a water molecule is found at the third binding site of the ruthenium(II)-η-p-cymene moiety depending on the conditions. [Ru(η-p-cymene)(L)(H2O/Cl)] species are predominant at physiological pH in all studied cases. Hydrolysis of the aqua complex or the chlorido/hydroxido co-ligand exchange results in the formation of the mixed-hydroxido species [Ru(η-p-cymene)(L)(OH)] in the basic pH range. There is no indication for the decomposition of the mono-ligand complexes during 24 h in the ruthenium(II)-η-pcymene−picolinic acid system between pH 3 and 11; however, a slight dissociation with a low reaction rate was found in the other two systems leading to the appearance of the dinuclear trihydroxido-bridged species [Ru2(η -p-cymene)2(OH)3] + and free ligands at pH > 10. The replacement of the chlorido by an aqua ligand in [Ru(η-p-cymene)(L)Cl] was also monitored and equilibrium constants for the exchange process were determined. * Corresponding author. Tel.: +36 62 544334; fax: +36 62 420505. E-mail address: [email protected] (É. A. Enyedy).