A Pair of Deep Red Phosphorescent Responsive Emissive Cyclometalated Iridium (III) Complexes as Carbonic Anhydrase Inhibitor and Effective Theranostic Photosensitizer

ABSTRACT Herein, two deep red phosphorescent responsive emissive cyclometalated iridium (III) complexes with CAIX inhibition moiety was designed and synthesized; they can penetrate into living cells quickly and mainly located in the lysosome. They showed a strong binding affinity towards CAIX in vitro and effectively reduced cellular expression of CAIX. Moreover, the tethered CAIX‐inhibition moiety of benzene sulfonamide can decrease the inherent cytotoxicity of Ir(III) complex towards normal cells and improve killing selectivity towards cancer cells in dark; Ir3 and Ir4 exhibit approximately five to eight times higher killing selectivity than that of cisplatin; they exhibit satisfied photodynamic therapy effect under irradiation of 425 nm, ultimately resulting in apoptosis of cancer cell, which is accompanied with weakening of extracellular acidification, increased inhibition of cellular CAIX expression, significant loss of mitochondrial membrane potential, and elevated level of reactive oxygen. Herein, our work may demonstrate that combination of inhibition CAIX and metal photosensitizer may provide a promising strategy for constructing a novel theranostic platform.