葫芦脲与某些药物分子相互作用的研究

发布时间：2018-06-03 13:28

本文选题：喜树碱 + 甲氨蝶呤　；参考：《山西师范大学》2017年硕士论文

【摘要】：近年来,葫芦脲作为超分子化学领域中的一个主体化合物而被越来越多的人们所关注,葫芦脲因其特殊的结构,相比其它超分子主体具有更强大的功能,使之在分子识别与组装、分子催化、药物控释、传感器等很多领域得到了广泛研究。在本论文中,合成了几种葫芦脲并选取其中有一定水溶性的葫芦[7]脲作为研究的对象,运用光谱、差热分析、X-射线衍射以及核磁共振等多种手段研究其与抗癌药物分子喜树碱、甲氨蝶呤之间的相互作用,阐述了包合物的形成机理,CB[7]作为一种潜在的药物载体,能起到增强药物稳定性、改善药物毒性和提高药物溶解性等作用。以下是本论文研究的主要内容:1简要阐述了超分子化学的发展史,较全面的对葫芦脲及其衍生物的起源、合成及性质特征做了介绍,叙述了葫芦脲主体在药物分析和均相荧光传感器中的应用进展,同时结合本实验室前期工作经验,提出了本论文的主要研究内容。2通过荧光光谱,差热分析(DTA),X-射线粉末衍射(XRD)和傅立叶变换红外光谱(FT-IR)研究了喜树碱(CPT)和葫芦[7]脲(CB[7])之间的相互作用,1H NMR探讨了包合物的形成机理。用荧光光谱法证明了CPT与CB[7]形成1:2的包合物和表观稳定常数为3.95×1012 L2 mol 2。以404 nm为激发在521 nm处测量CB[7]与CPT在水溶液中的相对荧光强度,CPT在0.007到0.31?g mL-1的范围里和荧光强度呈现良好的线性,检测限为2 ng m L 1,相关系数为0.9994。然而在人体血浆中,观察到CB[7]和CPT之间没有明显的相互作用,这可能是由于喜树碱优先与人体血清白蛋白结合。基于葫芦[7]脲超分子包合的喜树碱运输载体,可将喜树碱均匀分散到水中,极大地增加了喜树碱的水溶性。3通过紫外可见吸收光谱,1H NMR,2D NOESY和理论计算研究了葫芦[7]脲(CB[7])和甲氨蝶呤(MTX)的相互作用。实验结果表明MTX和CB[7]形成1:2的包合物,并提出了一个简单的、灵敏的荧光检测MTX的方法。研究发现当加入CB[7]时,PAL、BER和COP的荧光强度逐渐增加。然而,当一定量的MTX加入CB[7]-PAL、CB[7]-BER或CB[7]-COP系统时,系统的荧光强度显著猝灭。检测MTX的线性范围分别为0.1~15μg mL 1、0.2~15μg mL 1和0.4~15μg mL 1,检测限分别为0.03μg mL 1、0.06μg mL 1和0.13μg mL 1,这种方法成功用于检测在生物流体中的MTX。葫芦[7]脲作为一种有潜力的药物载体,可以提高抗肿瘤疗效和减少正常组织的毒性。4主要研究了以葫芦[6]脲为主体修饰的磁性微球的制备方法,以及对合成材料过程中的具体条件进行了摸索,同时对其吸附能力进行了初步的探索。
[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.
【学位授予单位】：山西师范大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R914

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