The Design of Organometallic Ruthenium Arene Anticancer Agents

Organometallic half-sandwich RuII anticancer complexes of the type [(?6-arene)Ru(YZ)X]n can exhibit interesting anticancer activity. We review the comparative aqueous solution chemistry (hydrolysis rates, pKa values of aqua complexes), cancer cell cytotoxicities, cross-resistance, reactivity towards nucleobases, DNA and important biomolecules for complexes containing various arenes, N,N- or N,O- or O,O-chelating ligands as YZ, and monodentate leaving groups X. We show that the choice of these ligands can have a dramatic effect on reactivity. The same is true for analogous OsII arene complexes. The interpretation of structure–activity relationships requires an understanding of reactions of these organometallic complexes under biological test conditions.