Ruthenafuran Complexes Supported by the Bipyridine-Bis(diphenylphosphino)methane Ligand Set: Synthesis and Cytotoxicity Studies

作者：Yeung, Chi-Fung; Tang, Sik-Him; Yang, Zhe; Li, Tsun-Yin; Li, Ka-Kit; Chan, Yuen-Man; Shek, Hau-Lam; Io, Kai-Wa; Tam, King-Ting; Yiu, Shek-Man; Tse, Man-Kit; Wong, Chun-Yuen^*

来源：MOLECULES, 2022, 27(5): 1709.

DOI：10.3390/molecules27051709

• ruthenium
• alkyne activation
• metallafuran
• cytotoxicity

Mononuclear and dinuclear Ru(II) complexes cis-[Ru(kappa(2)-dppm)(bpy)Cl-2] (1), cis-[Ru(kappa(2)-dppe)(bpy)Cl-2] (2) and [Ru-2(bpy)(2)(mu-dpam)(2)(mu-Cl)(2)](Cl)(2) ([3](Cl)(2)) were prepared from the reactions between cis(Cl), cis(S)-[Ru(bpy)(dmso-S)(2)Cl-2] and diphosphine/diarsine ligands (bpy = 2,2 '-bipyridine; dppm = 1,1-bis(diphenylphosphino)methane; dppe = 1,2-bis(diphenylphosphino)ethane; dpam = 1,1-bis(diphenylarsino)methane). While methoxy-substituted ruthenafuran [Ru(bpy)(kappa(2)-dppe)((CO)-O-boolean AND)](+) ([7](+); (CO)-O-boolean AND = anionic bidentate [C(OMe)CHC(Ph)O](-) chelate) was obtained as the only product in the reaction between 2 and phenyl ynone HC equivalent to C(C=O)Ph in MeOH, replacing 2 with 1 led to the formation of both methoxy-substituted ruthenafuran [Ru(bpy)(kappa(2)-dppm)((CO)-O-boolean AND)](+) ([4](+)) and phosphonium-ring-fused bicyclic ruthenafuran [Ru(bpy)((PCO)-C-boolean AND-O-boolean AND)Cl](+) ([5](+); (PCO)-C-boolean AND-O-boolean AND = neutral tridentate [(Ph)(2)PCH2P(Ph)(2)CCHC(Ph)O] chelate). All of these aforementioned metallafuran complexes were derived from Ru(II)-vinylidene intermediates. The potential applications of these metallafuran complexes as anticancer agents were evaluated by in vitro cytotoxicity studies against cervical carcinoma (HeLa) cancer cell line. All the ruthenafuran complexes were found to be one order of magnitude more cytotoxic than cisplatin, which is one of the metal-based anticancer agents being widely used currently.