Anticancer Potential of (Pentamethylcyclopentadienyl)chloridoiridium(III) Complexes Bearing κP and κP,κS‐Coordinated Ph₂PCH₂CH₂CH₂S(O)_xPh (x=0–2) Ligands

Abstract

Abstract Iridium(III) complexes of the type [Ir(η 5 ‐C 5 Me 5 )Cl 2 {Ph 2 PCH 2 CH 2 CH 2 S(O) x Ph‐κ P }] ( x =0–2; 1 – 3 ) and [Ir(η 5 ‐C 5 Me 5 )Cl{Ph 2 PCH 2 CH 2 CH 2 S(O) x Ph‐κ P ,κ S }][PF 6 ] ( x =0–1; 4 and 5 ) with 3‐(diphenylphosphino)propyl phenyl sulfide, sulfoxide, and sulfone ligands Ph 2 PCH 2 CH 2 CH 2 S(O) x Ph were designed, synthesized, and characterized fully, including X‐ray diffraction analyses for complexes 3 and 4 . In vitro studies against human thyroid carcinoma (8505C), submandibular carcinoma (A253), breast adenocarcinoma (MCF‐7), colon adenocarcinoma (SW480), and melanoma (518A2) cell lines provided evidence for the high biological potential of the neutral and cationic iridium(III) complexes. Neutral iridium(III) complex 5 proved to be the most active, with IC 50 values up to about 0.1 μ M , representing activities of up to one order of magnitude higher than cisplatin. Using 8505C cells, apoptosis was shown to be the main mechanism through which complex 5 exerts its tumoricidal action. The described iridium(III) complexes represent potential leads in the search for novel metal‐based anticancer agents.