Synthesis And Interaction With BSA And DNA Of Arene Ruthenium Complexes Containing Rmantadine Or Rimantadine

Nowadays,cancer is one of the most important human health concerns in the world,which claims numerous deaths each year and is on the increase worldwide.A majority of drugs used for the treatment of cancer today are not "cancer cell specific"and are also potently toxic against normal cells.This has opened up a new and active area of research in bioinorganic medicinal chemistry.Organometallic compounds play a unique role in medicinal chemistry because of their physicochemical properties that include chemical stability and structural diversity combined with relevant photo-and electrochemical properties.So far,cisplatin is well-known metal-based drugs and are widely used to treat tumors.However,they have some limitations due to resistance over a period of time and severe side effects in causing nausea and the failure of kidney and liver,which are typical of heavy metal toxicity.At this juncture,a rare transitionmetal ruthenium has emerged as an attractive alternative due to several favorable properties suited to rational anticancer drug design and biological applications.In general,people first study the interaction mechanism between the ruthenium complexes and DNA through theory,the purpose is that it can guide the synthesis and preliminarily judgment that the complexes synthesized whether has the possibility of cancer.Serum albumin,which is the most abundant protein of plasma,can combine with numbers of endogenous and exogenous substances,and is an important carrier and target for drugs to take dffect.When entering the blood,drugs will generally bind to serum albumin with varying degrees,which will affect the absorbance,metabolism,efficiency effects of drugs.DNA is often referred to as the molecule of heredity,and the genetic information is determined by the sequence of specific base pairs along its length.The research show that ruthenium complexes of different ligand form different way of interaction,so metal drug development is directly relate to the choice of ligand.The amino derivative of adamantane�amantadine and rimantadine is the drugs against influenza A virus in the cinical application.The existence of amino give them to ability that they can coordination with metal through nitrogen atom.For this purpose,a series of ruthenium complexes:[{RuCl2(?6-p-PriC6H4Me)}2(1),[C10H15NH2RuCl2(?6-p-PriC6H4Me)](2)and[C12H19NH2RuCl2(?6-p-PriC6H4Me)](3)were designed,synthesized and characterized by studying their interaction with DNAand BSA.In Chapter two,two different complexes of ruthenium are synthesized and the interaction with BSA is discussed.The complex and BSA interaction is studied through fluorescence spectroscopy,fitting calculation of binding constant,and researching with electronic absorption spectra.The results show that the complexes 2,3 have an effect on BSA microenvironment and complexe 2 has stronger binding affinity than complexe 3.At the same time,the fluorescence quenching of the complexes 2,3 to BSA is a static quenching.In Chapter three,the interaction mechanism two different complexes of ruthenium and DNA are explored through electronic absorption spectra,fluorescence quenching spectroscopy and CD spectra.The results show that all of two compounds with DNA should be intercalation,the interaction of the Ru(II)complexes 2 with DNA is stronger than that of the Ru(II)complexes 3.Complexes 3 may be make the double helix of DNA have open.