幾種含氮雜環(huán)過渡金屬配合物的合成、表征及其抗癌活性研究
本文選題:過渡金屬配位化合物 + 結(jié)構(gòu)表征; 參考:《延邊大學(xué)》2014年碩士論文
【摘要】:惡性腫瘤是威脅人類身體健康的主要疾病之一,目前惡性腫瘤的主要治療方法為藥物治療(化學(xué)治療),這其中尤以金屬配位化合物(配合物)是最常用的。順鉑是目前臨床上應(yīng)用最為廣泛的抗癌配合物,不幸的是,頻發(fā)的不良反應(yīng)(常見的有腎毒性、神經(jīng)毒性、惡心等)限制了順鉑的臨床應(yīng)用,基于上述原因,刺激和產(chǎn)生了一些新的、相比于順鉑能更有效提高治療效果并降低毒性的、側(cè)重于過渡金屬配位化合物的研究領(lǐng)域。 過渡金屬中的鈷(Co)、鎳(Ni)和鋅(Zn)因其多樣的配位數(shù)和豐富的配位形式,是目前配位化合物中心離子的首選。 目前,研究過渡金屬配位化合物的抗腫瘤活性,主要從過渡金屬配位化合物與DNA和腫瘤細(xì)胞的相互作用來初步證明其抗腫瘤活性,并從分子水平和細(xì)胞水平上探討抗腫瘤藥物的作用機(jī)理,進(jìn)一步研發(fā)高效低毒的抗腫瘤新藥物。使用MTT法從細(xì)胞水平研究了過渡金屬配位化合物的體外毒性。 本文以1-氫-1,2,3-三氮唑-4,5-二羧酸(Htda)為配體,使用溶液法合成了一個鈷配合物單晶,研究了配合物的分子結(jié)構(gòu)和分子間弱作用;使用溶液法分別合成了鎳和鋅的配合物,烘干后得到配合物的粉末;通過凝膠電泳法、熒光光譜法研究了配合物與DNA的相互作用;使用MTT法研究了配合物的體外毒性。本文具體內(nèi)容包括四部分: 采用溶液法合成了一個鉆配合物單晶和兩個鎳以及鋅配合物的粉末,分子式分別為[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一射線單晶衍射技術(shù)測定了鈷配合物的晶體結(jié)構(gòu),采用紅外光譜法、元素分析法對三種配合物進(jìn)行了表征,結(jié)合鈷配合物X一射線單晶衍射結(jié)果,類推得出鎳和鋅配合物的結(jié)構(gòu)。 應(yīng)用熒光光譜法和凝膠電泳法,研究了過渡金屬配位化合物與DNA的結(jié)合能力。結(jié)果表明,三個過渡金屬配位化合物均與DNA發(fā)生作用,結(jié)合能力順序為鈷配合物鎳配合物鋅配合物。 采用MTT法研究了三個過渡金屬配位化合物對Hela和KB細(xì)胞的抑制能力,并與臨床藥物順鉑對比。通過數(shù)理方法計算了配合物的IC50值,結(jié)果表明:三個過渡金屬配位化合物對癌細(xì)胞均有一定的抑制能力,而鈷配合物是比較強(qiáng)。因此,本文的研究結(jié)果對進(jìn)一步開發(fā)過渡金屬配位化合物的研究起到了一定的指導(dǎo)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.
【學(xué)位授予單位】:延邊大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2014
【分類號】:R914.5;R96
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