Research On Hexaaza Macrocyclic Copper(Ⅱ)L And Nickel(Ⅱ)L Complexes Interaction With DNA

DNA is the carrier of genetic information and plays an especially important role in the course of genetic.Investigation of DNA is important in the life sciences field. DNA is the main target molecule that exists in anticancer and antiviral therapies. Interaction of DNA with small molecules,especially drug molecules affects physiological and physical chemical character of DNA and changes the transfer and copy of DNA.Hence it is meaning that interactions of small molecules with DNA are investigated to understand bind of DNA with protein,anticancer mechanism and to design and synthesize new drug.In medicament,it possible to foresee major steps forward in our understanding of the molecular basis of disease,both from attack by external pathogens and internally from variations within the human genome resulting in a plethora of new molecular therapeutic targets for drug design and discovery.Cleavage regents of nucleic acid are an active field in biochemistry and biology of molecule.It is very valuable that design and synthesize complexes as artificial cleavage regents of nucleic acid in theory and appliation.First,the study of mechanisms will help us to know the catalysis mechanisms of nucleic acid enzyme; second,it is very important that the chemical nucleic acid enzyme which identify selectively and cleave DNA in the gene cure of sickness;third,artificial cleavage regents of nucleic acid especially high selectivity may act as the important tool in biology of molecule.The first Part:General Introduction and ConclusionInvestigation of DNA is important in the life sciences field.This part mainly summarizes the structure of DNA,and its interaction with the small molecular,as well as the small molecule which have chemistry nuclease activity cleave DNA.The part of the interaction of DNA with small molecular mainly introduce the kinds of the main target molecule,the ways of interaction and the measures of study.The mechanisms cleave DNA including hydrolisis and oxidation.It is important to study DNA interaction with drug in theory and in practice. The second Part:Mechanism of DNA strand cleavage induced by hexaaza macrocyclic nickel(â…¡)complexThe hexaaza macrocyclic nickel(â…¡)complex has a octahedral structure,similar to B₁₂and hemoglobin,therefore it has the anti-oxidation,the anti-tumor and wide pharmacological action.The complex may change the duplication of DNA and hinder tumor cell growth.Through this part,we hope that we can understand the pharmacological action of the cancer medicine further and may expand to regard this kind of material pharmacological.In this part,the electrochemical character of Ni(â…¡)L was measured,and the interaction of Ni(â…¡)L with calf thymus DNA was studied using electrochemical techniques,emission and viscometry and circular dichroic spectral measurements.All of the experiments suggest that the complex interacts with DNA primarily by partial intercalation.The cyclic voltammetry(CV)showed that the currents of both the reduction peak and the oxidation peak decreased significantly in the presence of DNA compared with those in the absence of DNA,which indicates that Ni(â…¡)L could interact with DNA.The fluorescence intensity of the DNA-EB system decreases distinctly when Ni(â…¡)L is added.The results indicate that Ni(â…¡)L may be complete effectively with EB for the intercalative binding sites.The viscosity of DNA would be decreased slightly by addition of the complex.Circular dichroic spectral studies reveal that calf thymus B-DNA becomes more A-like in structure on interaction with the complex.Noticeably,the complex has been found to cleave double-strand plasmid pBR 322 by agarose gel electrophoresis and cleave CT-DNA by high-performance liquid chromatograph in the absence or presence of H₂O₂.The third Part:Potential-controlled DNA damage detected by high performance liquid chromatography with UV-Vis detectionDamage to DNA frequently involves interruption of DNA sugar-phosphate strands.Under aerobic conditions,transition metal ions cause DNA damage through production of reactive oxygen species.Formation of strand breaks induced by electrochemical method in presence of Cu(â…¡)L and Ni(â…¡)L complexes was investigated by using high-performance liquid chromatography(HPLC).By controlling the potential of the electrolyte solutions,this technique can be employed in studies formation of DNA strand breaks.CT-DNA was cleaved by adding amounts of Cu(â…¡)L or Ni(â…¡)L complex in the absence of chemical reagent when appropriate electrode potential(sufficiently negative or positive to reduce or oxidate metal ions) was applied.The results show that the cleave activity of Cu(â…¡)L is much stronger than Ni(â…¡)L.Further,their mechanisms of promoting DNA damage were explained.The results suggest that Cu(â…¡)L generate hydroxyl radical from O₂ by the Fenton reaction, and that these radicals cause DNA damage.As for Ni(â…¡)L promoting DNA breaks,oxidation may be involved in the mechanism.