Photochemical Properties of Red-Emitting Tris(cyclometalated) Iridium(111) Complexes Having Basic and Nitro Groups and Application to pH Sensing and Photoinduced Cell Death

Cyclometalated iridium(III) complexes, because of their photophysical properties, have the potential for use as luminescent probes for cellular imaging. We previously reported on a pH-activatable iridium complex that contains three N,N-diethylamino groups, namely, fac-Ir(deatpy)(3) 5, which was synthesized via a regioselective aromatic substitution reaction at the 5'-position with tolylpyridine groups of fac-Ir(tpy)(3) 2. It was found that 5 shows a considerable enhancement in emission intensity in the pH range from neutral to slightly acidic (pH 6.5-7.4) in aqueous solution and selectively stains lysosome in HeLa-S3 cells, due to the protonation of the diethylamino groups. In addition, 5 functions as a pH-dependent singlet oxygen (O-1(2)) generator and induces necrosis-like cell death. However, observing the green emission of 5 is often hampered by autofluorescence emanating from nearby tissues. To overcome this problem, we designed and synthesized a series of new pH-activatable Ir(III) complexes that contain diethylamino, guanidyl, and iminoimidazolidinyl groups on the mpiq ligand of Ir(mpiq)(3) 7 and the tfpiq ligand of Ir(tfpiq)3 8, which exhibit a red emission, namely, Ir(deampiq)(3) 13, Ir(gmpiq)(3) 14, Ir(imzmpiq)(3) 15, and Ir(imztfpiq)(3) 16. The emission intensity of these Ir complexes is enhanced substantially by protonation of their basic groups, and they induce the necrosis-like cell death of HeLa-S3 cells by photoirradiation at 465 nm. A strong orange-red emission of Ir(mpiq-NO2)(3) 9 and Ir(tfpiq-NO2)(3) 10 is also reported.