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

• Published in: Inorganic chemistry Vol. 54; no. 11; pp. 5342 - 5357
• Main Authors: Kando, Aya, Hisamatsu, Yosuke, Ohwada, Hiroki, Itoh, Taiki, Moromizato, Shinsuke, Kohno, Masahiro, Aoki, Shin
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.06.2015
• Subjects: Cell Death - drug effects; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Crystallography, X-Ray; HeLa Cells; Humans; Hydrogen-Ion Concentration; Iridium - chemistry; Iridium - pharmacology; Luminescence; Luminescent Measurements; Models, Molecular; Nitro Compounds - chemistry; Nitro Compounds - pharmacology; Optical Imaging; Photosensitizing Agents - chemistry; Photosensitizing Agents - pharmacology
• ISSN: 0020-1669; 1520-510X
• DOI: 10.1021/acs.inorgchem.5b00369

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 (1O2) 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.