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

Abstract

A new class of phosphorescent cyclometalated iridium(III)-polyamine complexes [{Ir(N^C)(2)}(n)(bPEI)](PF(6))(n)(bPEI=branched poly(ethyleneimine), average M(w =25 kDa, n=15.6-27.4; HN^C=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)) and [Ir(N^C)(2)(en)](PF(6)) (en=ethylenediamine; HN^C=Hppy (1b), Hpppy (2b), Hpq (3b), Hbt (4b), Hbsn (5b)) have been synthesized and characterized. The X-ray crystal structure of complex 5b 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 1a-5a, 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 5a 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 5a was grafted with poly(ethylene glycol) (PEG, average M(w)=2 kDa) to different extents, thereby yielding the phosphorescent copolymers PEG(12.3)-g-5a, PEG(25.4)-g-5a, and PEG(62.1)-g-5a. Interestingly, these copolymers showed enhanced transfection activity, as revealed by in vitro transfection experiments with tissue-culture-based luciferase assays.

Iridium(iii) complexes as therapeutic and bioimaging reagents for cellular applications

“…58 These complexes retain the luminescence properties of iridium(III) complexes and the DNA retardation ability of the PEI unit. Formation of polyplexes from the iridium(III) complexes and plasmid DNA has been confirmed by zeta-potential measurements and particle size determination.…”

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

“…BTP can be taken up into living cells without using any transfection reagents. Lo et al examined the cellular properties of iridium(III)-polyamine complexes and reported that these cationic complexes were mainly localized inside mitochondria [24,25]. Mitochondria consume the greatest amount of oxygen in cells to allow oxidative phosphorylation, which is the primary metabolic pathway for ATP production.…”

Phosphorescent Iridium(III) Complexes for Bioimaging

“…Poly(ethyleneimine) (PEI) has been commonly used as a transfection reagent to delivery DNA into cells owing to its high positive-charge density and high protonbuffer capacity over a wide pH range [76]. PEI-PEG copolymers containing iridium(III) polypyridine cores have been designed [77]. These copolymers not only retain the gene-delivery properties of PEI, but also show enhanced water solubility and biocompatibility brought about by PEG.…”