Solution equilibrium studies of anticancer ruthenium(II)-η6-p-cymene complexes of pyridinecarboxylic acids

Stoichiometry and stability of antitumor ruthenium(II)-eta(6)-p-cymene complexes of picolinic acid and its 6-methyl and 6-carboxylic acid derivatives were determined by pH-potentiometry, H-1 NMR spectroscopy and UV-Vis spectrophotometry in aqueous solution in the presence or absence of coordinating chloride ions. The picolinates form exclusively mono-ligand complexes in which they can coordinate via the bidentate (0,N) mode and a chloride or a water molecule is found at the third binding site of the ruthenium(11)-eta(6)-p-cymene moiety depending on the conditions. [Ru(eta(6)-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(eta(6)-p-cymene)(L)(OH)] in the basic pH range. There is no indication for the decomposition of the mono-ligand complexes during 24h in the ruthenium(II)-eta(6)-p-cymene-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 [Ru-2(eta(6)-p-cymene)(2)(OH)(3)](+) and free ligands at pH > 10. The replacement of the chlorido by an aqua ligand in [Ru(eta(6)-p-cymene)(L)Cl) was also monitored and equilibrium constants for the exchange process were determined. (C) 2013 Elsevier Ltd. All rights reserved.