Mitochondria-targeted oxygen probes based on cationic iridium complexes with a 5-amino-1, 10-phenanthroline ligand

A cationic iridium(III) complex (btp)(2)Ir(phen-NH2) (btp = benzothienylpyridine; phen-NH2 = 5-amino-1,10-phenanthroline) and its analog with extended pi-electronic structures (btq)(2)Ir(phen-NH2) (btq = benzothienylquinoline), (ttph)(2)Ir(phen-NH2) (ttph = thienothiophenylphenanthridine), (btph)(2)Ir(phen-NH2) (btph = benzothienylphenanthridine) have been designed and synthesized to develop new oxygen probes for living cells. The photophysical and cellular properties of these complexes were systematically investigated by using (btp)(2)Ir(acac) and its derivatives as reference compounds. The extension of the pi-electronic systems of ligands resulted in remarkable red shifts in the absorption and phosphorescence spectra; the phosphorescence bands of (ttph)(2)Ir(phen-NH2) and (btph)(2)Ir(phen-NH2) appeared in the near-infrared region, maintaining the relatively high phosphorescence quantum yields (Phi(0)(p) = 0.14-0.24). Dimethylation and diethylation of the amino group of the phen-NH2 ligand in (btp)(2)Ir(phen-NH2) and its analog significantly enhanced the cellular uptake efficiency as compared with their neutral analog with an acetylacetonate (acac) ligand. The cationic iridium(III) complex (btp)(2')Ir(phen-NH2) and its analog internalized into living HeLa cells showed selective distribution into mitochondria. Owing to the high cellular uptake, relatively high cytotoxicity was found for the cationic iridium complexes. The phosphorescence intensity of newly developed iridium complexes exhibited oxygen response in HeLa cells, demonstrating that these complexes have potential as mitochondria-selective oxygen sensors for biological cells and tissues. (C) 2014 Elsevier B.V. All rights reserved.