几种含氮杂环过渡金属配合物的合成、表征及其抗癌活性研究

发布时间：2018-07-07 22:32

本文选题：过渡金属配位化合物 + 结构表征　；参考：《延边大学》2014年硕士论文

【摘要】：恶性肿瘤是威胁人类身体健康的主要疾病之一,目前恶性肿瘤的主要治疗方法为药物治疗(化学治疗),这其中尤以金属配位化合物(配合物)是最常用的。顺铂是目前临床上应用最为广泛的抗癌配合物,不幸的是,频发的不良反应(常见的有肾毒性、神经毒性、恶心等)限制了顺铂的临床应用,基于上述原因,刺激和产生了一些新的、相比于顺铂能更有效提高治疗效果并降低毒性的、侧重于过渡金属配位化合物的研究领域。过渡金属中的钴(Co)、镍(Ni)和锌(Zn)因其多样的配位数和丰富的配位形式,是目前配位化合物中心离子的首选。目前,研究过渡金属配位化合物的抗肿瘤活性,主要从过渡金属配位化合物与DNA和肿瘤细胞的相互作用来初步证明其抗肿瘤活性,并从分子水平和细胞水平上探讨抗肿瘤药物的作用机理,进一步研发高效低毒的抗肿瘤新药物。使用MTT法从细胞水平研究了过渡金属配位化合物的体外毒性。本文以1-氢-1,2,3-三氮唑-4,5-二羧酸(Htda)为配体,使用溶液法合成了一个钴配合物单晶,研究了配合物的分子结构和分子间弱作用；使用溶液法分别合成了镍和锌的配合物,烘干后得到配合物的粉末；通过凝胶电泳法、荧光光谱法研究了配合物与DNA的相互作用；使用MTT法研究了配合物的体外毒性。本文具体内容包括四部分：采用溶液法合成了一个钻配合物单晶和两个镍以及锌配合物的粉末,分子式分别为[Co2(Htda)2(H2O)6·5H2O](配合物1)、[Ni2(Htda)2(H20)6·5H2O](配合物2)、[Zn2(Htda)2(H2O)6·5H2O](配合物3)。 2.用X一射线单晶衍射技术测定了钴配合物的晶体结构,采用红外光谱法、元素分析法对三种配合物进行了表征,结合钴配合物X一射线单晶衍射结果,类推得出镍和锌配合物的结构。应用荧光光谱法和凝胶电泳法,研究了过渡金属配位化合物与DNA的结合能力。结果表明,三个过渡金属配位化合物均与DNA发生作用,结合能力顺序为钴配合物镍配合物锌配合物。采用MTT法研究了三个过渡金属配位化合物对Hela和KB细胞的抑制能力,并与临床药物顺铂对比。通过数理方法计算了配合物的IC50值,结果表明：三个过渡金属配位化合物对癌细胞均有一定的抑制能力,而钴配合物是比较强。因此,本文的研究结果对进一步开发过渡金属配位化合物的研究起到了一定的指导作用。
[Abstract]:Malignant tumor is one of the major diseases threatening human health. At present, the main treatment of malignant tumor is drug therapy (chemotherapy), especially metal coordination compound (complex) is the most commonly used. Cisplatin is the most widely used anticancer complex in clinical practice. Unfortunately, frequent adverse reactions (common nephrotoxicity, neurotoxicity, nausea, etc.) limit the clinical use of cisplatin. Stimulates and produces some new, more effective therapeutic effects and less toxicity than cisplatin, focusing on transition metal coordination compounds. Cobalt (Co), nickel (Ni) and zinc (Zn) in transition metals are the first choice for the central ions of coordination compounds due to their various coordination numbers and rich coordination forms. At present, the antitumor activity of transition metal coordination compounds has been preliminarily proved by the interaction of transition metal coordination compounds with DNA and tumor cells. The mechanism of antitumor drugs was discussed at the molecular and cell levels, and the new antitumor drugs with high efficiency and low toxicity were further developed. The in vitro toxicity of transition metal coordination compounds was studied by MTT method at cell level. In this paper, a single crystal of cobalt complex was synthesized by solution method with 1-hydro-1zolium 3-triazole-3-triazole-5-dicarboxylic acid (Htda) as ligand. The molecular structure and weak intermolecular interaction of the complex were studied, and the complexes of nickel and zinc were synthesized by solution method, respectively. After drying, the complex powder was obtained, the interaction between the complex and DNA was studied by gel electrophoresis and fluorescence spectrometry, and the in vitro toxicity of the complex was studied by MTT method. The main contents of this paper are as follows: one single crystal, two nickel and two zinc complexes have been synthesized by solution method. The molecular formulas are [Co _ 2 (Htda) _ 2 (H _ 2O) _ 6 5H _ 2O] (complex 1), [Ni _ 2 (Htda) _ 2 (H _ 20) _ 6 5H _ 2O] (complex 2), [Zn _ 2 (Htda) _ 2 (H _ 2O) _ 6 5H _ 2O] (complex 3). The crystal structure of cobalt complex was determined by X-ray single crystal diffraction technique. The three complexes were characterized by infrared spectroscopy and elemental analysis. The structure of nickel and zinc complexes was deduced by analogy. The binding ability of transition metal coordination compounds to DNA was studied by fluorescence spectrometry and gel electrophoresis. The results show that the three transition metal coordination compounds all interact with DNA, and the binding ability is in the order of cobalt complex nickel complex zinc complex. The inhibitory effects of three transition metal coordination compounds on Hela and KB cells were studied by MTT assay and compared with the clinical drug cisplatin. The IC50 values of the complexes were calculated by mathematical method. The results showed that the three transition metal coordination compounds had a certain inhibition on cancer cells, while the cobalt complexes were stronger. Therefore, the results of this paper play a guiding role in the further development of transition metal coordination compounds.
【学位授予单位】：延边大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R914.5;R96

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