Syntheses, Structures and Anticancer Activities of Bridged Polynuclear Complexes Based on DNA Interactions
Bridged polynuclear structure exists widely in the active sites of the metalloprotein and metalloenzyme in organisms that makes a great impact on their physiology and catalysis. There is considerable interest in the design of metal polynuclear complexes, which react at specific sites along the DNA strand, as reactive models for protein-nucleic acid interactions, as probes of DNA structure, as an aid to drug design, and as tools of molecular biology. To search for anticancer complexes with broad spectrum, high activity and low toxicity, a series of polynuclear complexes with interesting structures based on the bridging dissymmetrical N,N’-bis(substituent)-oxamides were synthesized. Moreover, DNA binding activities and antitumor activities polynuclear complexes have been studied in-depthly.This thesis consists of three sections as follows:1.One novel dissymmetrical oxamide ligand, oxamido-N-hydroxypropyl-N’-benzoic acid (H3oxbpa), has been synthesized and characterized by elemental analysis, IR,1H NMR and MS.Three novle crystal structures of tetranuclear Cu(Ⅱ) complexes are carried out bridged by cis-oxbpa3- and endcapped with different terminal ligands, namely:[Cu4(oxbpa)2(bpy)2](ClO4)2·4H2O(1), [Cu4(oxbpa)2(dmbpy)2](ClO4)2·4H2O (2) and [Cu4(oxbpa)2(dmbt)2](NO3)2 (3). A promising method to design and synthesize polynuclear complexes is to use a “complex ligand” that contains a potential donor group capable of coordinating to another metal ion. Seven complexes with different structures are synthesized by chosing Na[Cu(oxbm)] as a “complex ligand”, controlling species of counter anions, solvent and terminal ligands:three tetranuclear complexes, [Cu2(oxbm)(bpy)Cl]2·2H2O (4), [Cu2(oxbm)(bpy)]2(NO3)2·2H2O (5) [Cu2(oxbm)(bpy)]2(ClO4)2 (6) and [Cu2(oxbm)(dmbt)]2(ClO4)2 (7); two binuclear complexes, [Cu2(oxbm)(phen)Cl]·2H2O (8) and [Cu2(oxbm)(dabt)(H2O)](pic)·H2O· DMF (9);one 1-D polynuclear complex, [Cu2(oxbm)(phen)(CH3OH)]n·nClO4(10). The structures are characterized by elemental analysis, IR spectra and X-ray single crystal diffraction, hydrogen bonds andπ-πstacking interactions which stabilize the crystal structure are also discussed.2.DNA binding studies of ten complexes with HS-DNA have been studied by the spectroscopic (absorption and emission spectra), electrochemical measurement and viscometry. The results show that all these complexes can interact with HS-DNA and the interaction mode is intercalation. The interactions of tetranuclear complexes (1)～(7) with DNA are strongest,1-D polynuclear complex (10) is better, and binuclear complexes (8) (9) are the worst. The results of tetranuclear complexes to DNA: complex (1)>(6)、(3)>(7), make us to gain some insight into the influence of structural variation of the bridging groups in this kind of complexes on DNA-binding properties, which perfect the structure-activity relationship furtherly.3.The cytotoxicities of complexes (1)～(10) are examined in vitro by SRB assay. The results indicate that the ten complexes showed different cytotoxic activities against SMMC-7721 and A549 cell lines.Among these complexes, complexes (5) and (9) have the strongest anticancer activities, which reach to the ng/mL level in two human tumor cell lines; complexes (1) and (3) also show prominent antitumor activity and specific selectivity.