The Investigation Of Interactions Of Metal-Naph-Ring Aminopolycarboxylic Complexes To HSA And Structural Analyses Of Correlative Complexes

Tumor is a severe disease threatening human health, scientists investigate the development of novel anti-cancer drugs for years. Recently, the application of transition metals and lanthanide metals were studied in order to develop antitumor drugs because of their good biological activities. Except for central metal ions, organic ligands also play a important role for properties of coordination compounds. Synthesis multifunctional ligands is a important study for developing new complexes. Amino acid is a component unit of organism. Protein molecules have different biological activity because their different construction of amino acid. Aminopolycarboxylic acid has similar performance of amino acids and more coordination atoms as good metal chelating agent. We should note that multifunctional aminopolycarboxylic acid will increase the binding strength and photoresponse capability of complexes and label specific chemical compounds as target molecule carrier. Aminopolycarboxylic acid could be widely used as a promising candidate in many fields of science. So the research of interaction of proteins and novel complexes is meaningful in the domain of molecular biology, analytical chemistry and pharmacology areas.In this paper, two novel naph-ring aminopolycarboxylic acid compounds, H₂edta-naph and H₃dtpa-naph were synthesized. Their corresponding Cu（II） complex （Cu-edta-naph）, Eu（III） complex （Eu-dtpa-naph）, Gd（III） complex （Gd-dtpa-naph） and Tb（III） complex （Tb-dtpa-naph） were successfully prepared through heat-refluxing method. Further, we take these novel complexes as the research object and take human serum albumin （HSA） molecules as the target to perform experiment in this paper. This paper emphasizes particularly the mechanism of interaction between four complexes and HSA. Meanwhile, two novel Nd（III） complexes with H₆ttha and H₄egta ligands were synthesized and their molecule, coordination and crystal structures were analyzed, respectively.This paper mainly contains three parts as following:1. In this section, a naph-ring aminopolycarboxylic acid compound, H₂edta-naph was synthesized. Its corresponding Cu（Ⅲ） complex（Cu-edta-naph） was successfully prepared. This part mainly studies the interaction mechanism between HSA and the Cu（Ⅲ） complex（Cu-edta-naph）. According to a series of correlation coefficient, it’s safely draw a conclusion that the Cu（Ⅲ） complex for HSA molecular fluorescence quenching is static quenching mechanism. This study explore whether Cu（Ⅲ） complex binds to the Tyr and Trp residues of HSA molecules with some specificity by synchronous fluorescence spectroscopy. This study also investigate the effect of cu-edta-naph on the secondary structure of HSA by circular dichroism spectrum.2. In this section a naph-ring aminopolycarboxylic acid compound, H₃dtpa-naph was synthesized. Their corresponding Eu（Ⅲ）, Gd（Ⅲ） and Tb（Ⅲ） complexes were successfully prepared. This part mainly studies the interaction mechanism between HSA and these complexes. According to the binding constant and rate constant number, its safely draw a conclusion that the Eu（Ⅲ）, Gd（Ⅲ） and Tb（Ⅲ） complexes for HSA molecular fluorescence quenching is static quenching mechanism. When ligand is focused, we want know whether the results of interactions between these complexes with HSA have similar performance. This study also explore whether these complexes bind to the Tyr and Trp residues of HSA molecules with some specificity by synchronous fluorescence spectroscopy. Moreover, this study also investigatehe effect of fluorescence of Eu（Ⅲ）, Gd（Ⅲ） and Tb（Ⅲ） complexes with addition of various amounts of HSA by fluorescence spectrum, respectively.3. Two novel Nd（Ⅲ） complexes, （enH₂）[NdⅢ（egta）H₂O]₂·6H₂O and （enH₂）_1.5[NdⅢ（ttha）]·5H₂O have been successfully synthesized through direct heating reflux and their molecular and crystal structures were determined by FT-IR spectroscopy, thermal analysis and single crystal X-ray diffraction techniques. （enH₂）_1.5[NdⅢ（ttha）]·5H₂O takes ten-coordinated structure with a distorted bicapped square antiprismaticprism belong to triclinic crystal system with P-1 space group. However, （enH₂）[NdⅢ（egta）H₂O]₂·6H₂O has a nine-coordinate mononuclear structure with pseudo-monocapped square antiprismatic conformation and crystallizes in a monoclinic system with P2（1）/c space group. This results may attribute for their different ligands.This paper mainly studies the interaction mechanism between HSA and four novel complexes. Meanwhile, （enH₂）[NdⅢ（egta）H₂O]₂·6H₂O and （enH₂）1.5[NdⅢ（ttha）]·5H₂O have been successfully synthesized and their molecular and crystal structures were analyzed by different techniques. The paper was expected to provide some valuable information on antitumor drug and MRI contrast agent design and their interaction mechanism for HSA. In addition, the two naph-ring aminopolycarboxylic acid compounds have promising function application as fluorescent probe with high absorptivity or antitumor drug.