本文選題：喜樹堿 + 甲氨蝶呤��； 參考：《山西師范大學》2017年碩士論文

【摘要】：近年來,葫蘆脲作為超分子化學領(lǐng)域中的一個主體化合物而被越來越多的人們所關(guān)注,葫蘆脲因其特殊的結(jié)構(gòu),相比其它超分子主體具有更強大的功能,使之在分子識別與組裝、分子催化、藥物控釋、傳感器等很多領(lǐng)域得到了廣泛研究。在本論文中,合成了幾種葫蘆脲并選取其中有一定水溶性的葫蘆[7]脲作為研究的對象,運用光譜、差熱分析、X-射線衍射以及核磁共振等多種手段研究其與抗癌藥物分子喜樹堿、甲氨蝶呤之間的相互作用,闡述了包合物的形成機理,CB[7]作為一種潛在的藥物載體,能起到增強藥物穩(wěn)定性、改善藥物毒性和提高藥物溶解性等作用。以下是本論文研究的主要內(nèi)容:1簡要闡述了超分子化學的發(fā)展史,較全面的對葫蘆脲及其衍生物的起源、合成及性質(zhì)特征做了介紹,敘述了葫蘆脲主體在藥物分析和均相熒光傳感器中的應(yīng)用進展,同時結(jié)合本實驗室前期工作經(jīng)驗,提出了本論文的主要研究內(nèi)容。2通過熒光光譜,差熱分析(DTA),X-射線粉末衍射(XRD)和傅立葉變換紅外光譜(FT-IR)研究了喜樹堿(CPT)和葫蘆[7]脲(CB[7])之間的相互作用,1H NMR探討了包合物的形成機理。用熒光光譜法證明了CPT與CB[7]形成1:2的包合物和表觀穩(wěn)定常數(shù)為3.95×1012 L2 mol 2。以404 nm為激發(fā)在521 nm處測量CB[7]與CPT在水溶液中的相對熒光強度,CPT在0.007到0.31?g mL-1的范圍里和熒光強度呈現(xiàn)良好的線性,檢測限為2 ng m L 1,相關(guān)系數(shù)為0.9994。然而在人體血漿中,觀察到CB[7]和CPT之間沒有明顯的相互作用,這可能是由于喜樹堿優(yōu)先與人體血清白蛋白結(jié)合�；诤J[7]脲超分子包合的喜樹堿運輸載體,可將喜樹堿均勻分散到水中,極大地增加了喜樹堿的水溶性。3通過紫外可見吸收光譜,1H NMR,2D NOESY和理論計算研究了葫蘆[7]脲(CB[7])和甲氨蝶呤(MTX)的相互作用。實驗結(jié)果表明MTX和CB[7]形成1:2的包合物,并提出了一個簡單的、靈敏的熒光檢測MTX的方法。研究發(fā)現(xiàn)當加入CB[7]時,PAL、BER和COP的熒光強度逐漸增加。然而,當一定量的MTX加入CB[7]-PAL、CB[7]-BER或CB[7]-COP系統(tǒng)時,系統(tǒng)的熒光強度顯著猝滅。檢測MTX的線性范圍分別為0.1~15μg mL 1、0.2~15μg mL 1和0.4~15μg mL 1,檢測限分別為0.03μg mL 1、0.06μg mL 1和0.13μg mL 1,這種方法成功用于檢測在生物流體中的MTX。葫蘆[7]脲作為一種有潛力的藥物載體,可以提高抗腫瘤療效和減少正常組織的毒性。4主要研究了以葫蘆[6]脲為主體修飾的磁性微球的制備方法,以及對合成材料過程中的具體條件進行了摸索,同時對其吸附能力進行了初步的探索。
[Abstract]:In recent years, as a host compound in supramolecular chemistry, cucurbituril has been paid more and more attention. Because of its special structure, cucurbituril has more powerful functions than other supramolecular agents. It has been widely studied in many fields, such as molecular recognition and assembly, molecular catalysis, drug controlled release, sensor and so on. In this paper, several kinds of cucurbituron were synthesized and some water-soluble cucurbiturides were selected as the object of study, and their relationship with anticancer drug camptothecin was studied by means of spectrum, differential thermal analysis (DTA) and X-ray diffraction (DTA) and nuclear magnetic resonance (NMR). The interaction between methotrexate and the formation mechanism of inclusion compound CB [7], as a potential drug carrier, can enhance drug stability, improve drug toxicity and improve drug solubility. The following is the main content of this thesis: 1. The history of supramolecular chemistry is briefly described. The origin, synthesis and properties of cucurbituron and its derivatives are introduced. The application progress of cucurbituron in drug analysis and homogeneous fluorescence sensor is described. Combining with the previous work experience of our laboratory, the main research content of this paper is put forward that the fluorescence spectrum is the main content of this paper. Differential thermal analysis (DTA) and Fourier transform infrared spectroscopy (FTIR) were used to study the interaction between camptothecin (CPT) and cucurbita ([7] Urea [7] Urea [7] CB [7]). The formation mechanism of the inclusion complex was discussed by 1H NMR. The inclusion complex of CPT with CB [7] and its apparent stability constant of 3.95 脳 1012 L _ 2 mol ~ (2) have been proved by fluorescence spectrometry. The relative fluorescence intensities of CB [7] and CPT in aqueous solution were measured at 521 nm by 404nm excitation. The relative fluorescence intensity of CB [7] and CPT in aqueous solution showed a good linearity in the range of 0.007 ~ 0.31 g mL-1. The detection limit was 2 ng m L ~ (-1) and the correlation coefficient was 0.9994. However, no obvious interaction between CB [7] and CPT was observed in human plasma, which may be due to the preferential binding of camptothecin to human serum albumin. Camptothecin can be uniformly dispersed in water based on the supramolecular inclusion of camptothecin with cucurbita [7] urea. The water-solubility of camptothecin was greatly increased. The interaction between [7] Urea [7] Urea-CB [7] and methotrexate (MTX) was studied by UV-Vis absorption spectra 1H NMRA 2D NOESY and theoretical calculations. The experimental results show that MTX and CB [7] form a 1:2 inclusion complex, and a simple and sensitive fluorescence detection method for MTX is proposed. It was found that the fluorescence intensity of COP and BER increased gradually when CB [7] was added. However, when a certain amount of MTX is added to CB [7] -PALX CB [7] -BER or CB [7] -cop system, the fluorescence intensity of the system is significantly quenched. The linear range of MTX was 0.1 渭 g / mL (0.1 渭 g / mL) and 0.2g / mL (0.43 渭 g / mL), respectively, and the detection limit was 0.03 渭 g / mL, 0.06 渭 g / mL ~ (-1) and 0.13 渭 g / mL ~ (-1), respectively. This method was successfully applied to the determination of MTX in biological fluids. As a potential drug carrier, gourd [7] urea can improve the antitumor effect and reduce the toxicity of normal tissue. The preparation of magnetic microspheres modified with gourd [6] urea was studied. At the same time, the specific conditions of the synthetic materials were explored, and the adsorption ability of the synthesized materials was preliminarily explored.
【學位授予單位】：山西師范大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R914

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