Synthesis Of Binuclear Aryl Ruthenium Complexes And Their Reactivity With Amantadin

At present, cancer is the most difficult diseases to cure in the world, almost no possible to cure. Therefore, the treatment of cancer is a very trickiest question, which has aroused the interest of many researchers. Since the 1960’s, Rosenberg et al accidentally discovered that cisplatin compound has antibacterial and anti-tumor activity, the research on metal-based drugs has been widespread concern. So far, cisplatin and its derivatives are the most successful anticancer drugs in the world, and it is one of the most important drugs in the clinical treatment of testicular cancer, bladder cancer, head and neck cancer and ovarian cancer. But because of its high toxicity has brought many side effects, including liver and kidney damage and gastrointestinal reactions, and it is powerless to a lot of cancer cells and metastatic cancer, therefore, in the treatment of cancer, it is an urgent need to seek alternatives to platinum-based drugs. In recent years, the development of drug based on other transition metals complexes, such as Rh, Ir, Pd, Ru, Os, developed rapidly. Organometallic compound provides the ideal basis for rational drug design due to their chemical stability, structural diversity and related optical, electrochemical properties. Studies have shown that aryl ruthenium, C, N-cyclometallation Ru, Rh, Ir, Pd and other organometallic complexes show some antibacterial and anticancer activity.It is known that the anti-cancer agents of clinical application can damage DNA, and indirectly obstruct synthesis of DNA by inhibiting the biological synthesis of nucleic acid precursors or interfering hormone secretion, and finally cause the apoptosis of cancer cells. Studies have shown that ruthenium complexes with different ligands interact with DNA in different ways, so the choice of ligand may have an impact on the performance of metal-based drugs. Amantadine and rimantadine are used against influenza A virus in the clinical, they can coordinate through nitrogen atom of amino group with metal atom. The new aryl ruthenium complexes with antibacterial, anti-cancer activity are expected by introducing the amantadine and rimantadine as ligand and synergistic effect from metal center to ligand. In view of this, aryl ruthenium complexes coordinated amantadine and rimantadine [C10H15sNH2RuCl2(η6-p-PriC6H4Me)] and [C12H19NH2RuCl2 (η6-p-PriC6H4Me)] has been synthesized and studied on the interactions with DNA and BSA in our laboratory. The results show that two complexes have a certain effect on DNA and BSA.In order to further expand our research work, and investigate the effect on complexes structure and biological activity of other coordinated ligands in coordinated amantadine and rimantadine aryl ruthenium complexes, in this paper, we synthesized oxalate, azide, thiocyanate, etc. bridged binuclear aryl ruthenium complexes, studied the reactivity of them with amantadine and rimantadine. a series amantadine and rimantadine ligand aryl ruthenium complexes has been got containning oxalate, end azide and isothiocyanato groups. It laid the foundation for further study the antibacterial, anti-cancer and other biological activity of amantadine and rimantadine coordinated aryl ruthenium complexes. Details are as follow:1. we have synthesized binuclear aryl ruthenium complexes of [Ru2(μ-η4-C2O4)Cl2(η6-p-PriC6H4Me)2] (2), [Ru2(μ-η2-N3)Cl2(η6-p-PriC6H4Me)2] (3), [Ru2(μ-η2-N3)(N3)2(η6-p-PriC6H4Me)2] (4), [{Ru2(μ-η2-NCS)Cl2(η6-p-PriC6H4Me)2] (5), [Ru2(μ-η4-C2O4)(NO3)2(η6-p-PriC6H4Me)2] (6), [{Ru2Cl3(η6-p-PriC6H4Me)2+}PF6-] (7). All these complexes were characterized by IR,’H NMR spectroscopy. The molecular structures of complexes 6 and 7 were determined by X-ray crystallography.2. Mono nuclear Ru (II) complex containing the amantadine and rimantadine [C10H15NH2Ru(C2O4)(η6-p-PriC6H4Me)](8), [C12H19NH2Ru(C2O4)(η6-p-PriC6H4Me)] (9), [C12H19NH2Ru(N3)2(η6-p-PriC6H4Me)] (12), [C10H15NH2Ru(NCS)Cl (η6-p-PriC6H4Me)] (13) and [C12H19NH2Ru(NCS)Cl(η6-p-PriC6H4Me)] (14) were synthesized by reaction of complexes 2、4、5 with amantadine and rimantadine. Complexes 8,9,12,13 and 14 were characterized by IR,1H NMR. The molecular structures of complexes 12 and 13 were determined by X-ray crystallography.