Mesoionic compounds exhibit a wide spectrum of biological activity and have been utilized in various pharmacological pursuits. The combination of luminescent transition metal complexes and mesoionic ligands is a promising endeavor to develop a new class of luminescent transition metal complexes as diagnostic and therapeutic tools. The synthesis, characterization, and photophysical and photochemical properties of a series of neutral cyclometalated iridium(III) complexes containing a mesoionic N^S ligand [Ir(N^C)2(p-ttqt)] (p-Httqt = 1-phenyl-5-thioxo-5,6-dihydro-[1,2,4]triazolo[1,5-c]quinazolin-1-ium-2-thiolate; HN^C = 2-phenylpyridine (Hppy) (1), 7,8-benzoquinoline (Hbzq) (2), 2-phenylbenzothiazole (Hbt) (3), and 2-(1-naphthyl)benzothiazole (Hbsn) (4)) are reported here. The p-Httqt ligand was noncytotoxic in the dark in both HeLa and A549 at high concentrations (> 100 µM) even with incubation time of 24 h, and this property could be bestowed to all the complexes (> 25 to 50 µM, 24 h). Excitingly, all the complexes showed extremely high photocytotoxic activity in the nanomolar concentrations with unusually large photocytotoxicity index values > 361 to 34013.

We thank the Hong Kong Research Grants Council (Project No. CityU 11300019, CityU 11300318, CityU 11300017, and T42‐103/16‐N) and the Hong Kong Research Grants Council, National Natural Science Foundation of China (Project No. N_CityU113/15) for financial support.