Triplex RNA Binding And Stability Regulation By Functional Ruthenium (â…¡) Complexes

With the development of science and technology, the human disease treatments changed from the traditional drug therapy to the gene regulation therapy. By blocking the gene expression, transcription and its structure modification, etc., to achieve the purpose of treating diseases. The research about metal ion interaction with nucleic acids has become a hot topic. The ruthenium complexes with low toxicity, easily absorbed, high selectivity and rich physical and chemical properties and other characteristics, becoming a leader among these metal drugs. Therefore, ruthenium complexes in medical, chemical and biological fields is so valuable and promising.This paper focused on the following aspects:1. The first chapter introduced the development and the historical background of bio-inorganic chemistry, the knowledge about nucleic acids, especially the triple helix nucleic acids. The interaction modes, research methods and the selected topic significance and prospects of ruthenium(II) complexes with nucleic acid.2. In Chapter II, designed and synthesized two Ru(II) complexes [Ru(bpy)2(MPIP)]2+(1) and [Ru(phen)2(MPIP)]2+(2) which has imidazole group, tested by proton nuclear magnetic resonance spectroscopy(1H NMR), time of flight mass spectrometry(MALDI-TOF-MS) characterization, even more, using spectroscopy, viscosity test to study the modes of two ruthenium complexes with different ancillary ligand with the triple helix nucleic acids. Experimental results showed that the two complexes with nucleic acids are both by inserting binding mode of interaction, the different auxiliary ligands made different effects on the bonding strength. Both complexes can improve the triple helix stability of nucleic acid, but mainly on the third strand.3. The third chapter have synthesized two ruthenium benzophenone group(II) complexe [Ru(phen)2(PTBM)]2+(3) and [Ru(bpy)2(PTBM)] 2+(4), still using spectroscopy, thermodynamics, viscosity testing, etc., to study the modes of the complex with triple helix nucleic, comparing its strength and impact on the stability of the triple helix nucleic acid. Experimental results showed that, the two complexes and the triple helix nucleic acid combined by insert mode, and they played an important role in improving the stability of the triple helix.4. Chapter IV synthesized ruthenium(II) complexes [Ru(phen)2(NAIP)]2+(5) and [Ru(bpy)2(NAIP)] 2+(6) with a naphthalene ring group, with the same ideas and methods of the last two chapters, we compared the interaction strength of two complexes with a triple helix nucleic acid to study their modes of action and its impacts on the triple helix structure. By the comparison, two triple helix nucleic acid complex with the mode of action were still a combination by inserting mode, and these two complexes can enhance the stability of triple helix nucleic acids, but still mainly effect on the third strand.5. Judging from the horizontals and vertical comparison, the auxiliary ligand complexes phen, because of its plane characteristic, combined with the larger constant, that is more inserted into the triple helix nucleic acid portion, inserted ligand complexes of benzophenone due to its flat properties and can be rotated, more easily inserted into the triple helix nucleic acids, while ruthenium complexes with naphthalene ring plane because of its rigidity, inserted the least.