Solution equilibrium studies on anticancer ruthenium(II)–η6-p-cymene complexes of 3-hydroxy-2(1H)-pyridones

RuII(η6-p-cymene) complexes of bidentate (O,O) alkoxycarbonylmethyl-3-hydroxy-2(1H)-pyridone ligands exhibit in vitro antitumor activity. We determined the stoichiometry and stability in aqueous solution of two examples by pH-potentiometry, 1H NMR spectroscopy and UV–vis spectrophotometry and also characterized the proton dissociation processes of the ligands. Formation of mono-ligand complexes with moderate stability was found to predominate in the physiological pH range. Moreover, the chlorido/aqua co-ligand exchange processes of the [RuII(η6-p-cymene)(L)(H2O)]+ species were also monitored and 55–65% of the aqua ligand was found to be replaced by chloride in 0.2 M KCl-containing aqueous solutions. Under basic conditions, the complexes decompose to dinuclear tri-hydroxido-bridged [Ru2(η6-p-cymene)2(OH)3]+ and metal-free ligand and also a hydroxido species [RuII(η6-p-cymene)(L)(OH)] was found. Furthermore, the ligands contain an ester functional group, which may hydrolyze at basic pH, which is however negligible at acidic or neutral pH.

Graphical abstractAnticancer RuII(η6-p-cymene) complexes of alkoxycarbonylmethyl-3-hydroxy-2(1H)-pyridones were investigated on their stoichiometry and stability in aqueous solution using pH-potentiometry, 1H NMR spectroscopy and UV–vis spectrophotometry. Mono-ligand complexes predominate in the physiological pH range and are present as a mixture of aqua and chlorido complexes.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Stoichiometry and stability of anticancer RuII(η6-p-cymene) complexes were determined. ► Proton dissociation processes of pyridones were investigated. ► Mono-ligand complexes with moderate stability predominate in the physiological pH range. ► In [RuII(η6-p-cymene)(L)(H2O)]+ 55–65% of aqua ligands are replaced by chlorido in 0.2 M KCl. ► Decomposition of the complexes under basic conditions yields [Ru2(η6-p-cymene)2(OH)3]+.