Biological activity of neutral and cationic iridium(III) complexes with κP and κP,κS coordinated Ph₂PCH₂S(O)xPh (x = 0-2) ligands

Abstract

Neutral iridium(III) complexes of the type [Ir(η(5)-C₅Me₅)Cl₂{Ph₂PCH₂S(O)xPh-κP}] (1-3) with diphenylphosphino-functionalized methyl phenyl sulfides, sulfoxides, and sulfones Ph₂PCH₂S(O)xPh (x = 0, L1; 1, L2; 2, L3) and the cationic complex [Ir(η(5)-C₅Me₅)Cl{Ph₂PCH₂SPh-κP,κS}][PF6] (4) were synthesized and fully characterized analytically and spectroscopically. Furthermore, the structure of 2 was determined by X-ray diffraction analysis. The biological potential of the neutral and cationic iridium(III) complexes was tested in vitro against the cell lines 8505C, A253, MCF-7, SW480 and 518A2. Complex [Ir(η(5)-C₅Me₅)Cl₂{Ph₂PCH₂S(O)Ph-κP}] (2), with ligand L2 κP coordinated containing a pendent sulfinyl group, is the most active one (IC₅₀ values of about 3 μM), thus, with activities comparable to cisplatin. Complex 2 proved to have an even a higher antiproliferative activity than cisplatin against 8505C and SW480 cell lines, used as a model system of highly anaplastic cancers with low sensitivity to conventional chemotherapeutics such as cisplatin. Additional experiments demonstrated that apoptosis and autophagic cell death contribute to the drug's tumoricidal action.

Keywords: Cytotoxic activity; Iridium(III) complexes; Sulfur-functionalized phosphorus ligands.