Institute of Molecular Functional Materials and Department of Biology and Chemistry, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P. R. China.
Chemistry. 2012 Oct 15;18(42):13342-54. doi: 10.1002/chem.201200979. Epub 2012 Sep 3.
A new class of phosphorescent cyclometalated iridium(III)-polyamine complexes {Ir(N^C)(2)}(n)(bPEI)(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) (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.
一种新的磷光铱（III）-聚胺配合物[{Ir（N^C）（2）}（n）（bPEI）]（PF（6））（n）（bPEI=支化聚（亚乙基亚胺），平均 M（w=25 kDa，n=15.6-27.4；HN^C=2-苯基吡啶 Hppy（1a），2-（1,1'-联苯）-4-基）吡啶 Hpppy（2a），2-苯基喹啉 Hpq（3a），2-苯基苯并噻唑 Hbt（4a），2-（1-萘基）苯并噻唑 Hbsn（5a））和[Ir（N^C）（2）（en）]（PF（6））（en=乙二胺；HN^C=Hppy（1b），Hpppy（2b），Hpq（3b），Hbt（4b），Hbsn（5b））已被合成并表征。复合物 5b 的 X 射线晶体结构也已确定。所有这些配合物在+1.01 至+1.26 V 处均显示出可逆的铱（IV/III）氧化对，在-1.54 至-2.08 V（相对于 SCE）处显示出准可逆的配体还原对。在光激发下，配合物在室温下的流体溶液中和低温玻璃中显示出强烈且长寿命的绿色到橙红色发射。亲脂性测量表明 bPEI 在复合物 1a-5a 的极性中起主要作用，从而使它们在水溶液中非常可溶。电感耦合等离子体质谱（ICP-MS）和共聚焦激光扫描显微镜（CLSM）数据表明，所有配合物的细胞摄取都涉及到能量需求的过程，如内吞作用。此外，通过 3-（4,5-二甲基-2-噻唑基）-2,5-二苯基四唑溴盐（MTT）测定评估了复合物对人宫颈上皮样癌细胞（HeLa）和人胚肾 293T（HEK293T）细胞系的细胞毒性。通过凝胶阻滞实验研究了复合物 5a 的 DNA 结合特性，并通过 Zeta 电位测量和粒径估计研究了该复合物与质粒 DNA（pDNA）形成的聚集体。此外，复合物 5a 被不同程度地接枝上聚乙二醇（PEG，平均 M（w）=2 kDa），从而得到磷光共聚物 PEG（12.3）-g-5a、PEG（25.4）-g-5a 和 PEG（62.1）-g-5a。有趣的是，这些共聚物在基于组织培养的荧光素酶测定的体外转染实验中显示出增强的转染活性。
