Photochemical Properties of Red-Emitting Tris(cyclometalated) Iridium(III) 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 (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.