Development of Organometallic Ruthenium-Arene Anticancer Drugs That Resist Hydrolysis
With a view to develop drugs that could resist hydrolysis in aq. media,organometallic arene-capped ruthenium(II) 1,3,5-triaza-7-phosphatricyclo[220.127.116.11]decane (RAPTA) complexes bearing chelating carboxylate ligands have been prepd. and studied. The new complexes, Ru(η6-cymene)(PTA)(C2O4) (1) and Ru(η6-cymene)(PTA)(C6H6O4) (2), were found to be highly sol. and kinetically more stable than their RAPTA precursor that contains two chloride ligands in place of the carboxylate ligands. They were also able to resist hydrolysis in water and exhibited significantly lower pKa values. Importantly, they showed a similar order of activity in inhibiting cancer cell-growth proliferation (as detd. by in vitro assays) and exhibited oligonucleotide binding characteristics (as evidenced by matrix-assisted laser desorption ionization mass spectrometry) similar to those of the RAPTA precursor, hence realizing a strategy for developing a new generation of stable and highly water-sol. RAPTA adducts.