Solution equilibria and antitumor activities of pentamethylcyclopentadienyl rhodium complexes of picolinic acid and deferiprone

Complex formation processes of rhodium(III)-η⁵-pentamethylcyclopentadienyl cation RhCp*(H₂O)₃]²⁺ with 1,2-dimethyl-3-hydroxy-pyridin-4(1H)-one (deferiprone, dhp) and pyridine-2-carboxylic acid (pic) were studied with the aid of pH-potentiometry, ¹H NMR, and UV–Visible spectrophotometry in aqueous solution in the presence and absence of chloride ions. Stoichiometry and overall stability constants of the complexes formed were determined. Formation of mononuclear, monoligand complexes such as RhCp*(L)Z] (where L = dhp or pic; Z = Cl^? or H₂O) and mixed hydroxido species RhCp*(L)(OH)] were found. Relatively high pK_a values (9.32–11.90) were determined for the hydrolysis of the RhCp*(L)Z] complexes. RhCp*(L)Z] species predominate at physiological pH and negligible decomposition is probable only at low micromolar concentrations. More favored complex formation was found in the case of pic. Stability of the studied organorhodium complexes was compared with analogous Ru(II)(η⁶-p-cymene) compounds. In addition, the aqua/chlorido ligand replacement reaction in RhCp*(L)(H₂O)]⁺ of dhp and pic was monitored to provide equilibrium constants with which the extent of aquation at various chloride concentrations can be estimated. Single crystals of RhCp*(dhp)Cl] suitable for X-ray diffraction analysis were also obtained. The RhCp*(L)Cl] complexes of dhp and pic were tested for cytotoxicity in various human cancer cell lines where they showed activity depending on the attached ligand scaffold.