Organometallic iridium complexes are potent anticancer candidates which act through different mechanisms from cisplatin-based chemotherapy regimens. Here, ten phosphorescent cyclometalated iridium(III) complexes containing 2,2′-bipyridine-4,4′-dicarboxylic acid and its diester derivatives as ligands are designed and synthesized. The modification by ester group, which can be hydrolysed by esterase, facilitates the adjustment of drug-like properties. The quantum yields and emission lifetimes are influenced by variation of the ester substituents on the Ir(III) complexes. The cytotoxicity of these Ir(III) complexes is correlated with the length of their ester groups. Among them, 4a and 4b are found to be highly active against a panel of cancer cells screened, including cisplatin-resistant cancer cells. Mechanism studies in vitro indicate that they undergo hydrolysis of ester bonds, accumulate in mitochondria, and induce a series of cell-death related events mediated by mitochondria. Furthermore, 4a and 4b can induce pro-death autophagy and apoptosis simultaneously. Our study indicates that ester modification is a simple and feasible strategy to enhance the anticancer potency of Ir(III) complexes.

Two novel ruthenium(II) complexes coordinated with 6-chloro-5-hydroxylpyrido [3,2-a]phenazine (CQM), [Ru(L) 2 (CQM)]ClO 4 [L = 1,10-phenanthroline, (1) and 2,2'bipyridine, (2)], were investigated as potent fluorescence probes to track the dynamic changes in the nuclei of living cells. Confocal laser technology was used to observe their colocation inside the cells. Results showed that both complexes were uptaken by HepG2 cells, especially for 1, which was localized in the cell nuclei, whereas 2 was distributed in the cell nuclei and mitochondria. Further studies by real-time fluorescence observation revealed that 1 rapidly entered the living cells, namely, HepG2, HeLa and MCF-7 cells, imagined the dynamic in the nuclei of living tumor cells, and exhibited low toxicity to cells. Results demonstrated that 1 may be developed as a novel fluorescence probe for living cell nucleus.This study facilitates the development of fluorescence chemosensors with metal complexes. IntroductionNumerous studies have been performed to develop simple, sensitive, specific, and robust fluorescence probes/sensors for biochemistry, molecular biology, and clinical diagnostics. 1 Although many organic dyes have been designed and investigated, the utilization of these organic dyes is still limited because of their poor water solubility, low photo-stability, and high toxicity. [2][3][4][5] To overcome the drawbacks of organic dyes, transition metal complexes, especially the versatile ruthenium(II) complexes, have increasingly attracted attention as potential fluorescence probes because of their wide spectral range, long-term luminescence and large Stokes shifts. 6-10 Several recent notable reviews have shown that luminescent ruthenium(II) complexes have emerged as promising candidates for wide application in chemosensors, biolabeling, in vivo tumor imaging, and live cell compartmentalization staining, such as in the nucleus, in the cytoplasm, in endosome, in mitochondria, in lysosomes and endoplasmic reticulum. [11][12][13][14][15][16] Ruthenium complexes with dipyridophenazine (dppz) ligands have been frequently investigated because of their strong DNA binding and their extraordinary photophysical properties. 17,18 In particular, these compounds have been paid much attention because of their "light switch effect". These compounds are highly luminescent when intercalated into DNA and virtually nonemissive in aqueous solution, which is advantageous for fluorescence microscopy. For example, Barton et al. explored the cellular uptake of ruthenium(II) complexes and found that the complex cation [Ru(DIP) 2 (DPPZ)] 2+ (dip=4,7-diphenyl-1,10-

An arene ruthenium(ii) complex coordinated with 2-(2-chlorophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline, [(η6-C6H6)Ru(o-ClPIP)Cl]Cl (1), has been prepared by using microwave-assisted synthesis technology. The anti-tumour activity of this complex against various tumour cells has been evaluated by MTT assay and the results show that complex 1 exhibits selective inhibitory activity against the growth of human lung adenocarcinoma A549 cells with IC50 = 31.58 μM. Further studies by flow cytometric analysis showed that apoptosis of A549 cells was observed when dealt with complex 1. Furthermore, complex 1 exhibits excellent binding affinity with DNA molecules which was confirmed by spectroscopy methods, as well viscosity and melting point experiments. As a result, the conformation of DNA molecules was disturbed by complex 1.

Two new dinuclear Ru(II) arene M2L2 metallocycle complexes [Ru2(η 6-p-cymene)2(m-bitmb)2Cl2](SbF6)2 (1) and [Ru2(η 6-p-cymene)2(m-bitmb)2Cl2](CF3COO)2 (2) (m-bitmb=1,3-bis(imidazol-1-ymethyl)-2,4,6-trimethylbenzene) were synthesized and characterized by single crystal X-ray diffraction, 1 H NMR, ESI-MS and elemental analysis. Results revealed that complex 1 and 2 are M2L2 dinuclear Ru-arene complexes with unique "chair-like" conformation. Both of complexes 1 and 2 had certain anti-cancer activity, and complex 2 performed good cytotoxic effect on HeLa cells. The results of circular dichroism and agarose gel electrophoresis experiments indicated that complexes 1 and 2 could change the conformation of CT-DNA and PRB322 DNA. Moreover, compared with 1, 2 presented much stronger interaction with DNA, which was in accordance with their anti-cancer activities.