Studies On The Syntheses And Biological Activities Of The Quinoline And Phen Complexes

In recent decades, chemical nucleases have numbers of potential applications in gene regulation, mapping of protein and DNA interactions, probing of DNA specific structures, and cancer therapeutics. The design and studies on the artificial nucleases are one of the most active domains in chemicobiology and inorganic pharmaceutical chemistry. This thesis focused on this theme, twenty-six new complexes, utilizing three ligands based on quinoline and two ligands based on Phen as main ligands, have been synthesized and characterized by element analysis, FT-IR and X-ray crystallographic methods; The nuclease activities of the complexes have been explored by spectroscopy methods, fluid dynamics method and gel electrophoresis method; Moreover, the anticancer activities and mechanisms for some complexes are investigated through MTT assay, DAPI staining assay, Cell cycle arrest, Annexin V/PI analysis, mitochondrial membrane potential and caspase-3were measured under the confocal microscope. These provide valuable information for the design and development of novel metal anticancer drugs.The main contributions in this work are as follow:1. Seven new transition metal complexes have been synthesized with three quinoline ligands. The strcutures and composition of the complexes have been determined by X-ray crystallographic methods. The complexes could interact with CT-DNA through intercalation mode, and quench the fluorescence of BSA by a static quenching mechanism. The DNA cleavage mechanism for complexes indicated that DNA cleavage activity is via a mechanistic pathway involving the formation of hydroxyl radical and singlet oxygen as the reactive species. The tumor growth inhibition test in vitro was done to test the abilities of complexes to inhibit cell growth. The results showed that complexes exhibit significant cytotoxic activities toward tumor cell lines The water-soluble copper complexes4and5exhibit significant cytotoxic activities toward MCF-7, HeLa and A549, which were significantly better than cisplatino The cell cycle arrest indicated that complexes4-5 could delay or inhibit cell cycle progression through the S phase.2. Twelve new metal complexes have been synthesized with Phen derivatives (Nip and Aip) as the main ligands and other coligands have been synthesized. The strcutures and composition of the complexes have been determined by X-ray crystallographic methods. The complex could bind to CT-DNA through partly intercalation mode, and quench the intrinsic fluorescence of BSA by a static quenching mechanism. The DNA cleavage mechanism for complexes indicated that DNA cleavage activity is via a mechanistic pathway involving the formation of hydroxyl radical and singlet oxygen as the reactive species. The tumor growth inhibition test in vitro was done to test the abilities of some complexes to inhibit cell growth. The results showed that most of the complexes exhibit significant cytotoxic activities toward some tumor cells. The zinc complex11exhibit significant cytotoxic activities toward MCF-7cells with IC50=7.935±0.409μM; the copper complex20exhibit significant cytotoxic activities toward7404cells with IC50＝3.305±0.538μM. The antitumor activities and mechanisms for some complexeswere also investigated through DAPI staining assay, Cell cycle arrest, Annexin V/7-AAD analysis by flow cytometry and mitochondrial membrane potential and caspase-3were measured under the confocal microscope. The results showed that11could delay or inhibit cell cycle progression through the G1phase;20could delay or inhibit cell cycle progression through the G2/M phase, and there might be some link between apoptosis and mitochondria-Caspase-3pathay.3. Seven rare earth complexes with Nip as the main ligands and dibenzoyl methane as the coligand have been synthesized. The strcutures and composition of the complexes have been determined by X-ray crystallographic methods. The complex could bind to CT-DNA through partly intercalation mode, and quench the intrinsic fluorescence of BSA by a static quenching mechanism. The DNA cleavage mechanism for complexes indicated that DNA cleavage activity is via a mechanistic pathway involving the formation of hydroxyl radical and singlet oxygen as the reactive species. The tumor growth inhibition test in vitro was done to test the abilities of some complexes to inhibit cell growth. The results showed that the complexes exhibit significant cytotoxic activities toward some tumor cells, which may be potential antitumor drugs. The antitumor activities and mechanisms for complex26on7404were also investigated. The results showed that26could delay or inhibit cell cycle progression through the G2/M phase and there might be some link between apoptosis and mitochondria-caspase-3pathay.In our paper, we have mainly investigated the artificial nuclease activities of metal complexes with ligands based on quinoline and Phen ligands. Some quantitative parameters are calculated. All of these will provide reference information for the design and development of novel metal anticancer drugs.