本文選題：不對(duì)稱　切入點(diǎn)：N　出處：《中國海洋大學(xué)》2014年碩士論文

【摘要】：有機(jī)小分子特別是過渡金屬配合物與生物大分子相互作用的研究是配位化學(xué)和藥物化學(xué)領(lǐng)域的研究熱點(diǎn)。而DNA和BSA不僅是重要的生物大分子，也是許多藥物體內(nèi)的作用靶點(diǎn)。因此，為進(jìn)一步探索和認(rèn)識(shí)DNA和BSA的結(jié)構(gòu)和功能，了解藥物的抗癌機(jī)理，設(shè)計(jì)和合成具有DNA和BSA鍵和功能的金屬配合物具有重要意義。 本論文選擇兩種N,N'-雙取代草酰胺作為橋聯(lián)配體，以設(shè)計(jì)合成廣譜、高效、低毒的結(jié)構(gòu)新穎的抗癌金屬配合物為主線，合成了一系列具有不同端基配體的多核銅配合物，并使用X-射線單晶衍射進(jìn)行了結(jié)構(gòu)的解析，并采用了紫外熒光等多種手段研究了配體及其配合物與DNA、BSA的相互作用模式及強(qiáng)度，對(duì)體外細(xì)胞毒活性進(jìn)行了測(cè)定。本論文具體研究?jī)?nèi)容主要包括以下三部分： 1、配體及其橋聯(lián)的多核銅配合物的合成及結(jié)構(gòu)解析：N-[2-(2-羥乙基氨基)乙基]-N′-(2-羧基苯基)草酰胺(H3bhyox)和N-(3-二乙氨基丙基)-N′-(2-羧基苯基)草酰胺(H3bdpox)作為橋聯(lián)配體，改變端基配體進(jìn)行多核銅配合物的合成，并得到了一個(gè)四核銅配合物[Cu4(bhyox)2(phen)2(H2O)2](pic)2(1)單晶，一個(gè)配體H3bdpox(2)單晶，一個(gè)一維銅聚合物{[Cu2(bdpox)(dabt)]NO3·H2O}n(3)單晶，以及兩個(gè)四核銅配合物單晶[Cu4(bdpox)2(phen)2](NO3)2·2H2O (4)、[Cu4(bdpox)2(Me2bpy)2]-(ClO4)2·2C2H5OH (5)，采用元素分析、紅外光譜進(jìn)行了結(jié)構(gòu)的表征，并使用單晶X射線衍射對(duì)單晶結(jié)構(gòu)進(jìn)行了解析。在結(jié)構(gòu)部分討論了氫鍵、π-π堆積等分子間作用力在晶體超分子結(jié)構(gòu)方面的影響。 2、配體及配合物與生物大分子DNA、BSA的鍵合活性研究：采用光譜法(紫外光譜法、熒光光譜法)、粘度法等研究了配體及四個(gè)配合物與鯡魚精DNA(HS-DNA)的相互作用；采用紫外光譜法和熒光猝滅光譜法研究了上述五個(gè)化合物與牛血清蛋白(BSA)的相互作用。與DNA的研究結(jié)果表明除配體與DNA發(fā)生溝槽結(jié)合，四個(gè)配合物均與DNA發(fā)生插入作用，且由于端基配體的影響，插入作用強(qiáng)度為(4)(5)(3)(2)。與BSA的研究結(jié)果表明，，五個(gè)化合物均能與BSA發(fā)生相互作用，引起其蛋白質(zhì)構(gòu)象的改變。 3、配體及配合物抗腫瘤活性研究：采用SRB法對(duì)上述配體及配合物對(duì)兩種腫瘤細(xì)胞株—人肝癌細(xì)胞(SMMC-7721)和人肺腺癌細(xì)胞(A549)進(jìn)行了體外細(xì)胞毒活性研究，研究結(jié)果表明：上述化合物對(duì)兩種腫瘤細(xì)胞株均具有不同程度的抑制作用，且配合物的抗腫瘤活性優(yōu)于自由配體的。 本論文在前期實(shí)驗(yàn)室研究工作的基礎(chǔ)上豐富了草酰胺類配合物的研究?jī)?nèi)容，為研究配合物的構(gòu)效關(guān)系對(duì)DNA和BSA鍵合強(qiáng)度與活性的影響，設(shè)計(jì)與合成高效、低毒、廣譜的配合物提供了指導(dǎo)性信息。
[Abstract]:The interaction of organic small molecules, especially transition metal complexes, with biomolecules is a hot topic in the field of coordination chemistry and pharmaceutical chemistry. DNA and BSA are not only important biomolecules. Therefore, it is of great significance to design and synthesize metal complexes with DNA and BSA bonds and functions in order to further explore and understand the structure and function of DNA and BSA, and to understand the anticancer mechanism of drugs. In this paper, two kinds of NN-N-disubstituted oxalamide were selected as bridged ligands. A series of polynuclear copper complexes with different terminal ligands were synthesized by designing and synthesizing broad spectrum, high efficiency and low toxicity anticancer metal complexes. The structure was elucidated by X-ray single crystal diffraction, and the interaction mode and intensity of ligand and its complexes with DNA-BSA were studied by means of ultraviolet fluorescence and other methods. The cytotoxic activity in vitro was determined. The main contents of this thesis include the following three parts:. Synthesis and structural Analysis of Ligand and its bridged Polynuclear Copper complexes. The polynuclear copper complexes were synthesized by changing the terminal ligands. A tetranuclear copper complex (Cu4(bhyox)2(phen)2(H2O)2), a ligand H3bdpoxt2) single crystal, a one-dimensional copper polymer {[Cu2bdpoxnabt] NO3 H2O} N3], and two tetrachronuclear copper complexes [Cu4(bdpox)2(phen)2] no _ 3O _ 2 2H2O _ 4, [Cu4(bdpox)2(Me2bpy)2] -CIO _ 4O _ 4 2C2H5OH _ 5N _ 5 were obtained by elemental analysis. The structure of single crystal was characterized by infrared spectroscopy and analyzed by single crystal X-ray diffraction. In the structure part, the influence of intermolecular forces such as hydrogen bond, 蟺-蟺 stacking and other intermolecular forces on the crystal supramolecular structure was discussed. (2) study on the binding activity of ligand and its complexes with biomolecules DNABSA: the interaction of ligand and its four complexes with herring sperm DNA HS-DNA was studied by means of spectroscopic method (UV), fluorescence spectroscopy and viscosity method. The interaction of the above five compounds with bovine serum protein (BSA) was studied by ultraviolet spectroscopy and fluorescence quenching spectroscopy. The results of the study with DNA showed that the ligand was trenched with DNA and the four complexes were intercalated with DNA. Because of the effect of the terminal ligand, the insertion intensity was 4x4, 5, 5, 3, 2. The results of the study with BSA showed that the five compounds could interact with BSA, resulting in the conformation change of their proteins. 3, the antitumor activity of ligands and their complexes: the cytotoxic activities of these ligands and complexes against two kinds of tumor cell lines, human hepatoma cell line SMMC-7721) and human lung adenocarcinoma cell line A549, were studied by SRB assay in vitro. The results showed that these compounds had different inhibitory effects on both tumor cell lines and the antitumor activity of the complexes was superior to that of free ligands. In this paper, the research contents of oxalamide complexes were enriched on the basis of previous laboratory work. In order to study the effect of structure-activity relationship of complexes on the bond strength and activity of DNA and BSA, the design and synthesis of oxalamide complexes were highly efficient and low toxic. Broad spectrum complexes provide guidance information.
【學(xué)位授予單位】：中國海洋大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R914.5;R96

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