Mitochondria-targeting cyclometalated iridium(III)-PEG complexes with tunable photodynamic activity

We present a new class of phosphorescent cyclometalated iridium(III) polypyridine poly(ethylene glycol) (PEG) complexes [Ir((NC)-C-boolean AND)(2)(bpy-CONH-PEG)](PF6) (bpy-CONH-PEG = 4-(N-(2-(omega-methoxypoly-(1-oxapropyl))ethyl)aminocarbonyl)-4'-methyl-2,2'-bipyridine, number average molecular weight (M-n) = 5272.23, weight average molecular weight (M-w) = 5317.38, polydispersity index (PDI) = 1.009; (HNC)-C-boolean AND = 2-phenylpyridine, Hppy (1a), 2-((1,1'-biphenyl)-4-yl)pyridine, Hpppy (2a), 2-phenylquinoline, Hpq (3a), 2-phenylbenzothiazole, Hbt (4a), 2-(1-naphthyl)benzothiazole, Hbsn (5a)). The photophysical, photochemical, and biological properties of these complexes have been compared with those of their PEG-free counterparts [Ir((NC)-C-boolean AND)2(bpy-CONH Et)](PF6) (bpy-CoNH-Et = 4-(N-ethylaminocarbonyl)-4'-methyl-2,2'-bipyridine; HNC = Hppy (1b), Hpppy (2b), Hpq (3b), Hbt (4b), Hbsn (5b)). Upon irradiation, all the complexes exhibited intense and long-lived green to orange-red emission under ambient conditions. The emission was phosphorescence in nature and can be quenched by 02 with the generation of singlet oxygen (O-1(2)). The quantum yields for O-1(2) production of the complexes in aerated DMSO (0.24-0.83) were found to be dependent on the excited-state lifetimes of the complexes, which can be altered using different cyclometalating ligands ((NC)-C-boolean AND). Cell-based assays indicated that the PEG complexes were noncytotoxic in the dark (IC50 > 300 mu M); however, most of them became significantly cytotoxic upon irradiation (IC50 = 3.4 - 23.2 mu M). Laser-scanning confocal microscopy images revealed localization of complex 3a in the mitochondrial region of HeLa cells and the induction of rapid necrotic cell death upon light activation. Additionally, the lack of dark toxicity and potential application of the PEG complexes as a visualizing reagent have been demonstrated using zebrafish (Danio rerio) as an animal model. (C) 2013 Elsevier Ltd. All rights reserved.