A series of ferrocene-appended half-sandwiched iridium­(III) phenylpyridine complexes have been designed and synthesized. These complexes show better anticancer activity than cisplatin widely used in clinic under the same conditions. Meanwhile, complexes could effectively inhibit cell migration and colony formation. Complexes could interact with protein and transport through serum protein, effectively catalyzing the oxidation of nicotinamide–adenine dinucleotid and inducing the accumulation of reactive oxygen species (ROS, 1O2), which confirmed the anticancer mechanism of oxidation. Furthermore, laser scanning confocal detection indicates that these complexes can enter cells followed by a non-energy-dependent cellular uptake mechanism, effectively accumulating in the lysosome (Pearson’s colocalization coefficient: ∼0.90), leading to lysosome damage, and reducing the mitochondrial membrane potential (MMP). Taken together, ferrocene-appended iridium­(III) complexes possess the prospect of becoming a new multifunctional therapeutic platform, including lysosome-targeted imaging and anticancer drugs.

Half-sandwiched structure iridium­(III) complexes appear to be an attractive organometallic antitumor agents in recent years. Here, four triphenylamine-modified fluorescent half-sandwich iridium­(III) thiosemicarbazone (TSC) antitumor complexes were developed. Because of the “enol” configuration of the TSC ligands, these complexes formed a unique dimeric configuration. Aided by the appropriate fluorescence properties, studies found that complexes could enter tumor cells in an energy-dependent mode, accumulate in lysosomes, and result in the damage of lysosome integrity. Complexes could block the cell cycle, improve the levels of intrastitial reactive oxygen species, and lead to apoptosis, which followed an antitumor mechanism of oxidation. Compared with cisplatin, the antitumor potential in vivo and vitro confirmed that Ir4 could effectively inhibit tumor growth. Meanwhile, Ir4 could avoid detectable side effects in the experiments of safety evaluation. Above all, half-sandwich iridium­(III) TSC complexes are expected to be an encouraging candidate for the treatment of malignant tumors.

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A series of half‐sandwich structural iridium(III) phenanthroline (Phen) complexes with halide ions (Cl−, Br−, I−) and pyridine leaving groups ([(η5‐CpX)Ir(Phen)Z](PF6)n, Cpx: electron‐rich cyclopentadienyl group, Z: leaving group) have been prepared. Target complexes, especially the Cpxbiph (biphenyl‐substituted cyclopentadienyl)‐based one, showed favourable anticancer activity against human lung cancer (A549) cells; the best one (Ir8) was almost five times that of cisplatin under the same conditions. Compared with complexes involving halide ion leaving groups, the pyridine‐based one did not display hydrolysis but effectively caused lysosomal damage, leading to accumulation in the cytosol, inducing an increase in the level of intracellular reactive oxygen species and apoptosis; this indicated an anticancer mechanism of oxidation. Additionally, these complexes could bind to serum albumin through a static quenching mechanism. The data highlight the potential value of half‐sandwich iridium(III) phenanthroline complexes as anticancer drugs.

Series of configuration-controlled Fe(II)-Ir(III) heteronuclear metal complexes, including ferrocene and half-sandwich iridium(III) complex units, have been designed and prepared. These complexes show better anticancer activity than cisplatin under the same...