Effect of the µ-Diphosphine Bridging Ligand on the Cytotoxic Activity of Homodinuclear Ruthenium Complexes

Herein we report the synthesis and full characterisation of Ru(II)-based homobimetallic complexes bridged by diphosphines of the type [{(p-cym)RuCl₂}₂(µ-dppx)], where p-cym = η⁶-1-isopropyl-4-methylbenzene, dppx = dppe (1,2-bis(diphenylphosphino)ethane, 1), tdppe (trans-1,2-bis(diphenylphosphino)ethylene, 2), dppa (bis(diphenylphosphino)acetylene, 3), dcpe (1,2-bis(dicyclohexylphosphino)ethane, 4), and 1,4dppb (1,4-bis(diphenylphosphino)benzene, 5). We also report the mononuclear complexes [(p-cym)RuCl₂(κ¹-dppx)], where dppx = dppe (6) and tdppe (7). Complexes 2, 4, 5, 6 and 7 were further characterised via single crystal X-ray diffraction analysis. The bimetallic complexes were synthesised in a straightforward fashion and isolated in good to excellent yields. The mononuclear complexes 6 and 7 are stable in air but exhibit reactions in solution, hindering their use as precursors for the synthesis of bimetallic complexes. The in vitro cytotoxic (anticancer) activities of complexes 1-5 were determined via cell viability studies and their IC₅₀ values were derived on HeLa and Ect1/E6E7 cell lines. All complexes displayed only low to moderate activity and selectivity. Strikingly, the cytotoxic profiles of the different complexes varied substantially, highlighting the importance of the bridging ligand itself in the cytotoxic behaviour of the complexes, further demonstrating the importance of ligand design in bimetallic complexes.