Cationic carboxylate and thioacetate ruthenium(ii) complexes: synthesis and cytotoxic activity against anaplastic thyroid cancer cells

Abstract

The cationic acetate ruthenium complex [Ru(η¹-OAc)(CO)(dppb)(phen)]OAc (1) is easily prepared in 83% yield from [Ru(η¹-OAc)(η²-OAc)(CO)(dppb)] (dppb = 1,4-bis(diphenylphosphino)butane) and 1,10-phenanthroline (phen) in MeOH. The derivative 1 undergoes easy substitution of the coordinated acetate by reaction with NaOPiv, KSAc, and KSCN in MeOH, affording the corresponding complexes [RuX(CO)(dppb)(phen)]X (X = OPiv, 2; SAc, 3; and NCS, 4), whereas its reaction with NaCl and NH₄PF₆ affords [RuCl(CO)(dppb)(phen)]PF₆ (5). Carboxylate complexes 1 and 2 show high solubility in water, enabling easy exchange of the coordinated carboxylate by water and other ligands (CH₃CN, glutathione). Cationic complexes 1–5, compared to Cisplatin, display a strong cell viability decrease in two human anaplastic thyroid cancer cell lines (SW1736 and 8505C), ranging from 3.10 μM to 0.09 μM EC₅₀ values. The most active compounds 1–3 show a marked increment of apoptosis and decrease of cancer cell aggressiveness, making them promising candidates for further evaluation studies.