Understanding the Modes of Action of β-Ketoiminato Iridium(III) Complexes in Cancer Cells

Four new charged iridium(III) 1,2,3,4,5-pentamethylcyclopentadienyl (Cp*) complexes, <b>1-4</b>, of the type [Cp*Ir(<b>L1-4</b>)(PTA)](PF₆) (where <b>L1-4</b> = functionalized β-ketoiminate ligands and PTA = 1,3,5-triaza-7-phosphaadamantane), have been successfully synthesized and characterized. Single crystal X-ray crystallographic data have been obtained for all compounds and confirm a typical <i>pseudo</i>-octahedral half-sandwich geometry. Cytotoxicity values have been determined against a range of cancerous and noncancerous cell lines and highlight high cytotoxicity and selectivity toward breast cancers. Among these compounds, the unfunctionalized β-ketoiminate Ir(III) complex (<b>1</b>) emerged as the most promising candidate, demonstrating activity that was comparable to or exceeded that of cisplatin, especially after 24 h against the triple-negative MDA-MB-231 cell line. Morphological and molecular analyses confirmed that <b>1</b> triggers apoptotic cell death, involving caspase activation and PARP cleavage, which is consistent with its DNA-damaging characteristics, highlighting the future anticancer potential of compound <b>1</b>.