Development of Organometallic Ruthenium−Arene Anticancer Drugs That Resist Hydrolysis

With a view to develop drugs that could resist hydrolysis in aqueous media, organometallic arene-capped ruthenium(II) 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (RAPTA) complexes bearing chelating carboxylate ligands have
been prepared and studied. The new complexes, Ru(η6-cymene)(PTA)(C2O4) (1) and Ru(η6-cymene)(PTA)(C6H6O4)
(2), were found to be highly soluble 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 determined 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-soluble RAPTA adducts.