Cationic Ru(η6-p-cymene) Complexes of 3-Hydroxy-4-pyr(id)ones – Lipophilic Triphenylphosphine as Co-Ligand Is Key to Highly Stable and Cytotoxic Anticancer Agents

Abstract

Ru(arene)[3-hydroxy-4(1H)-pyr(id)one]Cl complexes are known to be converted intodinuclear Ru(arene) compounds with three hydroxido bridges in aqueous solution. In an attempt to obtain anticancer Ru(arene) complexes of 3-hydroxy-4(1H)-pyr(id)one ligands that are stable in aqueous solution, triphenylphosphine (PPh3) and 1,3,5-triaza-7-phoshatricyclo[3.3.1.1]decane (pta) were introduced as co-ligands instead of the chlorido ligand. This led to a series of cationic complexes that were characterized by using standard methods and X-ray diffraction analysis. The pta complexes were found to be highly stable in aqueous solution for up to 120 h. While they were unreactive in the presence of l-histidine (His) and l-methionine (Met), l-cysteine (Cys) induced cleavage of the 3-hydroxy-4(1H)-pyr(id)one ligands from the Ru center. In vitro cytotoxicity assays against human cancer cell lines revealed that the complexes with the more lipophilic phosphine ligand were cytotoxic in the low-micromolar concentration range, while the analogous pta compounds did not significantly inhibit cell proliferation.