Cyclometalated Iridium(III)-Polyamine Complexes with Intense and Long-Lived Multicolor Phosphorescence: Synthesis, Crystal Structure, Photophysical Behavior, Cellular Uptake, and Transfection Properties

A new class of phosphorescent cyclometalated iridium(III)–polyamine complexes [{Ir(N^C)2}n(bPEI)](PF6)n (bPEI=branched poly(ethyleneimine), average Mw=25 kDa, n=15.6–27.4; HN^C=2‐phenylpyridine Hppy (1 a), 2‐((1,1′‐biphenyl)‐4‐yl)pyridine Hpppy (2 a), 2‐phenylquinoline Hpq (3 a), 2‐phenylbenzothiazole Hbt (4 a), 2‐(1‐naphthyl)benzothiazole Hbsn (5 a)) and [Ir(N^C)2(en)](PF6) (en=ethylenediamine; HN^C=Hppy (1 b), Hpppy (2 b), Hpq (3 b), Hbt (4 b), Hbsn (5 b)) have been synthesized and characterized. The X‐ray crystal structure of complex 5 b was also determined. All of these complexes showed a reversible iridium(IV/III) oxidation couple at +1.01 to +1.26 V and a quasi‐reversible ligand‐based reduction couple at −1.54 to −2.08 V (versus SCE). Upon photoexcitation, the complexes displayed intense and long‐lived green to orange–red emission in fluid solutions at room temperature and in low‐temperature glass. Lipophilicity measurements indicated that bPEI played a dominant role in the polar nature of complexes 1 a–5 a, thus rendering them very soluble in aqueous solutions. Inductively coupled plasma–mass spectrometry (ICP‐MS) and confocal laser scanning microscopy (CLSM) data indicated that an energy‐requiring process, such as endocytosis, was involved in the cellular uptake of all of the complexes. In addition, the cytotoxicity of the complexes toward human cervix epithelioid carcinoma (HeLa) and human embryonic kidney 293T (HEK293T) cell‐lines has been evaluated by the 3‐(4,5‐dimethyl‐2‐thiazolyl)‐2,5‐diphenyltetrazolium bromide (MTT) assay. The DNA‐binding properties of complex 5 a have been investigated by gel‐retardation assays and the polyplexes that were formed from this complex with plasmid DNA (pDNA) were studied by zeta‐potential measurements and particle‐size estimation. Furthermore, complex 5 a was grafted with poly(ethylene glycol) (PEG, average Mw=2 kDa) to different extents, thereby yielding the phosphorescent copolymers PEG12.3‐g‐5 a, PEG25.4‐g‐5 a, and PEG62.1‐g‐5 a. Interestingly, these copolymers showed enhanced transfection activity, as revealed by in vitro transfection experiments with tissue‐culture‐based luciferase assays. Bright delivery! A class of cyclometalated iridium(III)–polyamine complexes with strong phosphorescence has been designed as biological reagents. The cyclometalating ligands and polyamines both play a role in the photophysical properties, lipophilicity, cellular uptake, and cytotoxicity of the complexes. One of the bran