Syntheses, Structures And Biological Activities Of Metal Complexes Bridged By N-(2-Hydroxyphenyl)-N’-[3-(Diethyllamino)propyl]oxamide With Antitumor Activities

Investigations on metal complexes towards DNA and protein are of current interest inconnection with information about drug design and tools of molecular biology. Nucleic acid andprotein are important target spot of many drugs. Investigation of the interaction between metalcomplexes towards DNA and protein could obtain important information about the novel antitumoror anticancer drugs design and the mechanism of action of drugs. Oxamides are good candidates asthebridging ligand in forming polynuclear complexes because their coordinating ability towardtransition–metal ions can be modified and tuned by changing the nature of the amide. Comparedwith the extensively researches in symmetrical N,N′-bis(substituted)oxamide polynuclear systems,only few dissymmetrical N,N′-bis-(substituted)oxamide polynuclear complexes have been reporteddue to the difficulties in their synthesis. In order to explore new effective anticancer drugs thatcould selectively inhibit tumor cells, in this dissertation, four polynuclear complexes withN-(2-hydroxyphenyl)-N’-[3-(diethyllamino)propyl]oxamide as the ligand have been designed andsynthesized, their DNA and BSA-binding properties and antitumor activities also have been studiedsystematically. The detail contents include several aspects as follows:1. Synthesis and structures of oxamide bridging complexes: a new oxamido-bridgedbicopper(II) complex,[Cu2(pdpox)(bpy)(CH3OH)](ClO4)(1), where H3pdpox and bpy stand forN-(2-hydroxyphenyl)-N’-[3-(diethylamino)propyl]oxamide and2,2’-bipyridine, respectively, hasbeen synthesized and characterized by elemental analyses, molar conductivity measurements, IR andelectronic spectra studies, and X-ray single crystal diffraction. Two copper complexes[Cu2(pdpox)(phen)](ClO4)(2) and [Cu2(pdpox)(DABT)](ClO4)(3) also have been synthesized withthe same bridging ligand. A nickel complex [Ni2(pdpox)(bpy)](ClO4)(4) has been synthesized withthe bridging ligand H3pdpox and bpy as terminal ligand. Then the three complexes have beencharacterized by elemental analyses, molar conductivity measurements, IR and electronic spectrastudies. The influence factors of the crystal structures of these complexes, and the effects of hydrogenbonds and π-π stacking interactions on the crystal structures and supramolecular structures of thesecomplexes were also discussed.2. Interactions of complexes with DNA: the DNA-binding properties of the four complexeshave been studied by the electronic and fluorescence spectra and viscosity measurements. Besides,the influences of the types of metal ions and terminal ligands on the interactions between complexesand HS-DNA were also investigated. The results reveal that all of the four complexes interact with HS-DNA mainly via the intercalation mode, and according to the difference of the metal ions andterminal ligands, the bonding strength of these complexes with HS-DNA are different.3. Interactions of complexes with BSA: Furthermore, the protein binding ability has beenmonitored by using UV absorption and tryptophan fluorescence quenching experiment in thepresence of the four compounds using bovine serum albumin (BSA) as model protein. The resultsreveal that all of the four compounds can interact with BSA, and the metal ions and terminal ligandscould influence the binding abilities.4. In vitro cytotoxicity studies of complexes: the in vitro cytotoxicity studies of the fourcompounds against two cancer cell lines: human hepatocellular carcinoma cell line SMMC-7721and human lung adenocarcinoma cell line A549were tested by SRB method, the results indicatethat thr four compounds have a certain cytotoxicities against SMMC-7721and A549cell lines, withIC50values less than100μg/mL, respectively.The researches of this dissertation enrich the content of oxamide-bridged complexes, supplythe chemical basis to explore novel bridging polynuclear complexes with high activity, low toxicityand antitumor activities, and could be the valuable references for studying the relationship betweenstructures and properties of complexes.