本文選題：N + N′-雙取代草酰胺��； 參考：《中國海洋大學(xué)》2014年碩士論文

【摘要】：目前，金屬配合物與生物大分子之間相互作用的研究已經(jīng)成為了無機(jī)藥物化學(xué)領(lǐng)域的研究熱點(diǎn)。DNA是生物體內(nèi)重要的遺傳物質(zhì)，而蛋白質(zhì)是生物功能的重要載體，二者都是生物體內(nèi)重要的生物大分子，同時(shí)也是許多藥物在體內(nèi)作用的靶向目標(biāo)。因此，合成能夠與DNA和蛋白質(zhì)鍵合的金屬配合物，對(duì)其抗癌細(xì)胞活性的研究以及設(shè)計(jì)現(xiàn)代藥物和分析藥物的抗腫瘤機(jī)理具有深遠(yuǎn)的意義�；谶@一背景，本文合成了一個(gè)單核銅配合物單晶，并合成N,N’-對(duì)稱雙取代草酰胺作為橋聯(lián)配體，設(shè)計(jì)合成了多個(gè)多核銅配合物并培養(yǎng)得到了三個(gè)配合物單晶，對(duì)其晶體結(jié)構(gòu)進(jìn)行了解析，并用一系列方法研究了其與DNA和BSA的相互作用和體外抗腫瘤活性，具體如下： 1、金屬配合物的合成與單晶結(jié)構(gòu)解析：用Cu(pic)2·4H2O和bpy為原料合成了一個(gè)單核銅配合物單晶[Cu(bpy)2(pic)](pic)(1)；選取N,N’-雙(N,N’-二乙基丙二胺)草酰胺為配體，選擇不同的銅鹽和端基配體，合成得到了三個(gè)配合物的單晶：一個(gè)一維銅聚合物單晶[Cu2(deap)(N3)2]n(2)以及兩個(gè)雙核配合物單晶[Cu2(deap)(bpy)2](ClO4)2(3)和Cu2(deap)(SCN)2(4)。 2、配合物與DNA和BSA相互作用的研究：從分子水平上運(yùn)用紫外和熒光光譜學(xué)等方法研究了配合物與HS-DNA分子之間的相互作用，研究結(jié)果表明四個(gè)配合物均能與DNA發(fā)生插入作用，并研究了他們的結(jié)合能力大��；通過光譜法測(cè)定了配合物與BSA的相互作用，結(jié)果表明合成的配合物單晶其均能與BSA發(fā)生相互作用，并且作用強(qiáng)度與配合物濃度成正比。 3、配合物體外抗腫瘤細(xì)胞的研究：從細(xì)胞水平上用SRB方法研究了上述配合物對(duì)三種腫瘤細(xì)胞株：人肝癌細(xì)胞SMMC-7721、人肺腺癌細(xì)胞A549以及人肝癌細(xì)胞株Hep G2的體外細(xì)胞毒活性，發(fā)現(xiàn)配合物對(duì)腫瘤細(xì)胞均有不同程度的抑制作用，并且IC50值均在100μg/mL以下。 4、金屬離子對(duì)卡馬西平與BSA相互作用的影響：從分子水平上，運(yùn)用熒光光譜法初步研究不同金屬離子對(duì)卡馬西平(CBZ)與牛血清白蛋白(BSA)的相互作用的影響。 本論文設(shè)計(jì)合成的單核以及草酰胺多核金屬配合物，進(jìn)一步豐富了橋聯(lián)多核配合物在生物無機(jī)化學(xué)領(lǐng)域中的作用，對(duì)配合物的結(jié)構(gòu)對(duì)其與DNA和BSA相互作用的影響進(jìn)行了探索，對(duì)研究配合物的構(gòu)效關(guān)系具有一定的參考價(jià)值，，并為毒性較低的金屬類藥物的設(shè)計(jì)與合成提供了指導(dǎo)性信息。
[Abstract]:At present, the study of the interaction between metal complexes and biomolecules has become a hot topic in the field of inorganic pharmaceutical chemistry. DNA is an important genetic material in organisms, and protein is an important carrier of biological functions. Both are important biological macromolecules in organisms, and are also the target of many drugs in vivo. Therefore, it is of great significance to synthesize metal complexes that can bond with DNA and protein, to study their anticancer activity and to design modern drugs and analyze their antitumor mechanisms. Based on this background, a single crystal of a mononuclear copper complex was synthesized, and a series of mononuclear copper complexes were designed and synthesized, and three single crystals were obtained by the synthesis of NN-N-symmetric disubstituted oxalamide as bridged ligands. Its crystal structure was elucidated, and its interaction with DNA and BSA and its antitumor activity in vitro were studied by a series of methods. The main contents are as follows: 1. Synthesis and structure analysis of metal complexes: a mononuclear copper complex [Cu (bpy) 2 (pic)] (pic) (1 was synthesized from Cu (pic) 24H 2O and bpy. Different copper salts and terminal ligands were selected, Three complexes have been synthesized: one one-dimensional copper polymer single crystal [Cu _ 2 (deap) (N _ 3) _ 2] n (2) and two binuclear complexes [Cu _ 2 (deap) (bpy) _ 2] (CLO _ 4) _ 2 (3) and Cu _ 2 (deap) (SCN) _ 2 (4). Fluorescence spectroscopy and other methods were used to study the interaction between the complexes and HS-DNA molecules. The results showed that the four complexes could intercalate with DNA and their binding ability was studied, and the interaction between the complexes and BSA was determined by spectrophotometry. The results show that the synthesized complexes can interact with BSA. And the action intensity is proportional to the concentration of the complex. The antitumor effect of the complexes was studied by SRB method at the cell level: human hepatoma cell line SMMC-7721, human lung cancer cell line SMMC-7721. In vitro cytotoxic activity of human hepatoma cell line Hep G2 and A549 cell line. It was found that the complexes had different inhibitory effects on tumor cells, and the IC50 values were below 100 渭 g / mL. 4. The effect of metal ions on the interaction between carbamazepine and BSA: at the molecular level, The effect of different metal ions on the interaction between carbamazepine (CBZ) and bovine serum albumin (BSA) was studied by fluorescence spectrometry. In this thesis, mononuclear and oxalamide polynuclear metal complexes were designed and synthesized, which further enriched the role of bridged polynuclear complexes in the field of bioinorganic chemistry, and explored the effects of the structure of the complexes on their interactions with DNA and BSA. It has some reference value for studying the structure-activity relationship of the complexes and provides guidance information for the design and synthesis of metal drugs with low toxicity.
【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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