本文選題：三苯胺衍生物　切入點(diǎn)：有機(jī)小分子熒光探針　出處：《安徽大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：有機(jī)小分子熒光探針因其分子量小、合成簡(jiǎn)單、易獲取等優(yōu)點(diǎn)被廣泛應(yīng)用于檢測(cè)水體、土壤、空氣、生物體中的金屬離子含量,其中應(yīng)用于活體細(xì)胞顯影的有機(jī)小分子熒光探針,為科研工作者在生物醫(yī)療和藥物研發(fā)等問(wèn)題上提供了一個(gè)不可或缺的工具。本論文以槳狀結(jié)構(gòu)的三苯胺為功能團(tuán),對(duì)其進(jìn)行結(jié)構(gòu)修飾和優(yōu)化,利用Vilsmeier-Haack、Witting等反應(yīng)合成了一系列三苯胺基衍生物�；诨衔锏慕Y(jié)構(gòu)特點(diǎn),我們系統(tǒng)地研究其識(shí)別性能,結(jié)合體外實(shí)驗(yàn)結(jié)果,進(jìn)一步探索了它們?cè)谏飳W(xué)方面的應(yīng)用。主要研究?jī)?nèi)容如下:1、以三苯胺基為給體中心,C=N及苯乙烯基為π橋,引入羥基基團(tuán),合成了三苯胺基希夫堿衍生物SASB。其中多羥基的引入不僅增加有機(jī)小分子SASB的水溶性,而且還與-C=N-構(gòu)筑半空腔的類冠醚型結(jié)構(gòu),實(shí)現(xiàn)對(duì)主族元素的響應(yīng)。實(shí)驗(yàn)結(jié)果表明,在乙醇中,SASB對(duì)主族元素鎂離子有特異性識(shí)別,且不受同主族鈣離子的干擾。SASB在生物細(xì)胞內(nèi)毒性低、光穩(wěn)定性高、細(xì)胞膜穿透性好,不僅對(duì)宮頸癌細(xì)胞的亞細(xì)胞器--溶酶體上過(guò)量鎂離子有顯色響應(yīng);而且可以穿透擬南芥幼苗的細(xì)胞壁,通過(guò)脈管傳送到植物葉片的其他部位并伴有鎂離子的濃度依賴性熒光增強(qiáng)響應(yīng)。2、在上一章基礎(chǔ)上,改變末端官能團(tuán),制備了能靶向定位細(xì)胞內(nèi)亞細(xì)胞器線粒體的席夫堿PBSB。研究結(jié)果表明,PBSB在乙腈溶液中對(duì)重金屬銅離子有比率型熒光增強(qiáng)的選擇性識(shí)別,利用熒光滴定、核磁滴定實(shí)驗(yàn)對(duì)其識(shí)別機(jī)理進(jìn)行了探究。體內(nèi)實(shí)驗(yàn)結(jié)果表明,探針能靶向性定位細(xì)胞內(nèi)亞細(xì)胞器線粒體部位,且能夠通過(guò)細(xì)胞比率顯影來(lái)反應(yīng)細(xì)胞內(nèi)銅離子的分布情況。3、考慮到席夫堿易于水解,限制了其應(yīng)用,而C-N相較于C=N易于旋轉(zhuǎn),利于結(jié)合金屬離子,進(jìn)而我們對(duì)分子結(jié)構(gòu)進(jìn)行微調(diào),合成了一種柔性的有機(jī)小分子仲胺類化合物PBSA。實(shí)驗(yàn)結(jié)果表明,PBSA具有以下優(yōu)異特性:1)在乙腈溶液中能特異性識(shí)別重金屬鎳離子;2)不受其它金屬離子的干擾;3)檢測(cè)限度低;4)時(shí)效性強(qiáng);5)可循環(huán)性檢測(cè)。利用熒光滴定、Job's曲線及核磁滴定實(shí)驗(yàn)確定了 PBSA與金屬鎳離子的作用模式。生物學(xué)研究表明,探針PBSA特異性定位HepG2細(xì)胞的線粒體部位,且能在HepG2細(xì)胞內(nèi)循環(huán)使用,有利于檢測(cè)線粒體相關(guān)的疾病。
[Abstract]:Because of its advantages of low molecular weight, simple synthesis and easy to obtain, organic small molecule fluorescent probes are widely used to detect metal ions in water, soil, air and organisms. The fluorescence probe of organic small molecules used in the development of living cells provides an indispensable tool for researchers in biomedicine and drug development. In this paper, the propeller structure of trianiline was used as functional group. A series of triphenylamino derivatives were synthesized by Vilsmeier-Haack-Witting reaction. Based on the structural characteristics of the compounds, the recognition properties of the compounds were systematically studied and combined with the results of in vitro experiments. Their biological applications were further explored. The main research contents were as follows: 1. The hydroxyl group was introduced with triphenylamino as donor center Con N and styrene as 蟺 bridge. The triphenylamino Schiff base derivative SASBs was synthesized. The introduction of polyhydroxyl groups not only increased the water solubility of small organic molecules SASB, but also constructed crown ether-like structures of semicircular cavities with Cn- to achieve the response to the main group elements. In ethanol, SASB has specific recognition for magnesium ions, and it is not interfered by calcium ions of the same group. SASB has low cytotoxicity, high photostability and good cell membrane penetration. It can not only react to the excessive magnesium ion on the lysosome of cervical cancer cells, but also penetrate the cell wall of Arabidopsis thaliana seedlings. The vasculature is transported to other parts of the plant's leaves with a concentration-dependent fluorescence enhancement response of magnesium. 2. Based on the previous chapter, the terminal functional groups are changed. Schiff base PBSBs capable of targeting intracellular suborganelle mitochondria were prepared. The results showed that PBSB had selective recognition of heavy metal copper ions in acetonitrile solution and was titrated by fluorescence. The results of in vivo experiments showed that the probe could target the mitochondria of suborganelles in cells. Moreover, the distribution of copper ions in cells can be reflected by cell ratio development. Considering that Schiff base is easy to hydrolyze, which limits its application, C-N is easier to rotate than Con N, which is favorable for the binding of metal ions. And then we fine-tune the molecular structure, A flexible small organic secondary amine compound PBSA3 was synthesized. The experimental results show that PBSA has the following excellent properties: 1) in acetonitrile solution, PBSA can specifically recognize heavy metal nickel ion 2) and is not interfered by other metal ions. The interaction mode between PBSA and nickel ion was determined by fluorescence titration curve and nuclear magnetic titration experiment. The probe PBSA can specifically locate the mitochondrial site of HepG2 cells and can be circularly used in HepG2 cells, which is helpful for the detection of mitochondrial diseases.
【學(xué)位授予單位】：安徽大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：O657.3

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相關(guān)期刊論文 前1條

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本文編號(hào)：1629703