Syntheses and antiproliferative activity studies of some ruthenium and osmium complexes


Student thesis: Doctoral Thesis

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  • Wenxiu NI


Awarding Institution
Award date15 Jul 2011


This thesis is mainly concerned with the synthesis and anti-cancer activity of some ruthenium and osmium complexes. It is divided into three main parts. In part I, some ruthenium(II/III) compounds containing polyamine ligands have been synthesized and characterized by elemental analysis, IR, UV-Vis, and electrospray ionization mass spectrometry (ESI-MS). The structures of cis-[RuIII(imcyclen)Cl2](PF6) (2.4) and fac-[RuIIICl3(tach)] (2.9) have been determined by X-ray crystallography (imcyclen = 1,4,7,10-tetraazacyclododeca-1-ene and tach = cis, cis-1,3,5-triaminocyclohexane). The cytotoxicity of six ruthenium compounds has been studied. The water-soluble compound cis-[Ru(cyclen)Cl2]Cl (cyclen = 1,4,7,10-tetraazacyclododecane) was found to possess remarkable antiproliferative activity in vitro against human cancer cell lines, HeLa, HepG2 and HL-60; with IC50 value of 39.2, 54.9 and 41.2 μM, respectively, while it is less cytotoxic to fibroblast cells. Moreover, this complex can induce S-phase arrest in HeLa cells. However, this compound is unstable in aqueous media. The cytotoxic property of some osmium(III) complexes bearing amidine ligands has also been investigated. All complexes show high cytotoxicity towards HeLa cells. The antiproliferative activity of [OsIII(salchda){N(H)C(CH3)NH2}{N(H)C(CH3)NHC4H9}]PF6 (2.10), which affects the cell cycle and induces apoptosis, was tested in three human cancer cell lines (HepG2, HeLa and MCF-7) and two non-cancerous originated human fibroblasts cell lines (RPE, AG06858). The result indicates that this complex exhibits strong anti-proliferative activity towards human cancer cell lines; however, it is also toxic to non-cancerous cell lines. In part II, we have studied the cyctotoxicity of a series of novel nitridoosmium(VI) tridentate Schiff-base complexes [OsVI(N)(5-R-spa)Cl(H2O)] (R = H, Cl, Br, MeO, Me) (sap = i-salicylidene-2-aminophenol dianions) using HeLa as model cancer cell line, and they are found to have high antiproliferative effects. The nitridoosmium(VI) compound, [OsVI(N)(sap)Cl(H2O)], has been found to be a potential anticancer drug. It inhibits both in vitro and in vivo activities in several human cancer cell lines and in nude mouse assay. DNA-binding properties with biochemical techniques suggest the binding modes involving simultaneous intercalation and coordination. Also, mechanistic studies indicate that the lability of the Os-Cl bond plays an important role in cytotoxicity. In addition, the cytotoxic activities of several related nitridoosmium(VI) complexes with substituted sap ligands have also been tested using human carcinoma cell line, and they also possess antiproliferative properties. In part III, a number of nitridoosmium(VI) complexes containing different heterocyclic ligands with formula [OsVI(N)Cl3(H2azole)2] has been prepared by treatment of [nBu4N][OsVI(N)Cl4] with H2azole (H2azole = pyrazole, indazole, imidazole, 1-methylbenzimidazole, 3,5-dimethylpyrazole, benzimidazole, 1-methylimidazole, 5-methylimidazole, 2-methylimidazole). These compounds have also been characterized by various spectroscopic methods. The structures of [Os(N)Cl3(indazole)2] (4.2), [Os(N)Cl3(1-methylbenzimidazole)2] (4.4), [Os(N)Cl3(3,5-dimethylpyrazole)2] (4.5), and [Os(N)Cl3(5-methylpyrazole)2] (4.8) have been determined by X-ray crystallography with typical Os≡N bond distances of 1.614 - 1.675 Å. Cytotoxicity tests using two human cancer cell lines (HeLa and HepG2) indicate that four out of nine compounds, i.e. [Os(N)Cl3(pyrazole)2] (4.1), [Os(N)Cl3(indazole)2] (4.2), [Os(N)Cl3(3,5-dimethylpyrazole)2] (4.5), and [Os(N)Cl3(5-methylpyrazole)2] (4.8) have antiproliferative properties.

    Research areas

  • Osmium compounds, Ruthenium compounds, Therapeutic use, Antineoplastic agents, Tumors, Chemotherapy, Synthesis