有机小分子荧光探针的合成与性质研究

发布时间：2018-04-23 17:53

本文选题：荧光探针 + 小分子　；参考：《济南大学》2017年硕士论文

【摘要】：荧光探针的合成与应用作为各学科领域交叉的前沿学科,正在得到科研工作者的广泛关注。其工作原理是将肉眼无法观察到的分子间的作用以光信号的形式表现出来。荧光探针存在的典型的特点是稳定性好,操作简单易行,检测时间短,生物毒性低。将荧光探针与生物成像结合,可以用于示踪生物体内的某种物质,实现对物质的实时原位检测,甚至是监测生理过程。因此对荧光探针的研究具有十分重要的意义。本文以希夫碱类化合物设计了一种检测锌离子的探针,以花菁类染料为荧光团设计了一种检测肼的探针,以BODIPY为荧光团设计了一种检测氯磷酸二乙酯(DCP)的探针。在第一部分,基于锌离子对脑功能、基因转移、免疫功能起着非常重要的作用。实验设计合成了一种基于希夫碱的检测锌离子的荧光探针。该探针以肼为桥,将2-位醛基取代的氰基联苯酚的醛基与氨茴酸甲酯的酯基连接得到探针化合物。锌离子具有强的配位能力,会与探针形成比较稳定的配合物。探针的共轭程度变大,刚性平面更加稳定,发射波长红移。此探针的响应时间为17 s,检测限为1.3×10~(-8) mol/L。探针被成功的应用于细胞中锌离子的识别。在第二部分,由于肼的浓度过高的时候会引起人体的一些病变,像头晕眼花、恶心、昏迷肺部水肿的症状并且皮肤接长时间的暴露在肼含量高的环境中会引起皮炎等皮肤中毒现象。因此我们以花菁类染料为荧光团,以4-溴丁酸为识别基团合成了一种检测肼的荧光探针。肼的强的亲核作用会与溴发生取代反应,中间产物中游离的氨基进攻酯基,释放出荧光团中的羟基,探针的荧光恢复,是一个比率型的近红外荧光探针。其响应时间为18 min,检测限为1.19×10~(-8) mol/L。探针被成功的用于细胞和生物活体内肼的检测。在第三部分,基于DCP是一种结构与神经毒剂沙林相似的神经毒剂模拟分子,当环境中DCP的含量过高时会危及生命。我们以BODIPY为荧光团,以氰基联苯酚的羟基作为识别基团合成了一种检测DCP的荧光探针。DCP是一种强的亲电试剂,探针化合物中加入的DCP会与包含的羟基发生亲电取代反应,导致探针分子内的PET被禁阻,同时由于位阻的原因探针含有羟基的供电部分旋转受阻,探针表现出荧光。是一种荧光增强型的检测DCP的探针。探针的响应时间为9 min,检测限为1.3×10~(-8) mol/L。探针分子被成功的设计成试纸,用于环境中DCP的检测。
[Abstract]:The synthesis and application of fluorescent probes, as a frontier subject in various disciplines, are receiving extensive attention from researchers. The principle is that the interaction between molecules can not be observed by the naked eye in the form of light signals. The typical characteristics of fluorescent probe are good stability, simple operation, short detection time and low biotoxicity. The combination of fluorescent probe and biological imaging can be used to trace a certain substance in the organism and realize the real-time in-situ detection of the substance, and even monitor the physiological process. Therefore, the study of fluorescent probe is of great significance. In this paper, we designed a probe for the detection of zinc ion with Schiff base compounds, a probe for the detection of hydrazine with cyanine dyes as fluorescence group, and a probe for the detection of diethyl chlorophosphate with BODIPY as fluorescence group. In the first part, zinc ion plays a very important role in brain function, gene transfer and immune function. A fluorescence probe for zinc ion detection based on Schiff base was designed and synthesized. Using hydrazine as a bridge, the probe compound was obtained by connecting the aldehyde group of 2-position substituted cyano-biphenol with the ester group of methyl anethanilate. Zinc ions have strong coordination ability and form stable complexes with the probe. The conjugation degree of the probe becomes larger, the rigid plane is more stable, and the emission wavelength is redshift. The response time of the probe is 17 s and the detection limit is 1.3 脳 10 ~ (-8) mol / L. The probe has been successfully applied to the recognition of zinc ions in cells. In the second part, when the concentration of hydrazine is too high, it can cause some pathological changes in the human body, such as dizziness, nausea, Symptoms of pulmonary edema in coma and prolonged skin exposure to high levels of hydrazine can lead to dermatitis and other skin poisoning. Therefore, we synthesized a fluorescence probe for hydrazine with cyanine dyes as fluorescence group and 4-bromobutyric acid as recognition group. The strong nucleophilic effect of hydrazine can replace bromine. The free amino attack ester group in the intermediate product releases the hydroxyl in the fluorescence group and the fluorescence of the probe recovers. It is a ratio type near infrared fluorescence probe. The response time was 18 min and the detection limit was 1.19 脳 10 ~ (-8) mol 路L ~ (-1) 路L ~ (-1) 路L ~ (-1) 路min. The probe was successfully used for the detection of hydrazine in cells and living organisms. In the third part, DCP is a mimic molecule of nerve agent similar to the nerve agent sarin. When the content of DCP in environment is too high, it will be life-threatening. Using BODIPY as fluorescence group and hydroxyl group of cyano-biphenol as recognition group, we synthesized a fluorescent probe. DCP is a strong electrophilic reagent for the detection of DCP. The DCP added in the probe compound can take place in the electrophilic substitution reaction with the containing hydroxyl group. As a result, the PET in the probe molecule is blocked, and the probe exhibits fluorescence due to the hindrance of the rotation of the power supply part containing hydroxyl groups in the probe due to the steric resistance. It is a fluorescent enhanced probe for detecting DCP. The response time of the probe was 9 min and the detection limit was 1.3 脳 10 ~ (-8) mol 路L ~ (-1) 路L ~ (-1) 路L ~ (-1). Probe molecules were successfully designed as test papers for the detection of DCP in the environment.
【学位授予单位】：济南大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：O657.3

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