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

【摘要】：有機小分子熒光探針因其分子量小、合成簡單、易獲取等優(yōu)點被廣泛應用于檢測水體、土壤、空氣、生物體中的金屬離子含量,其中應用于活體細胞顯影的有機小分子熒光探針,為科研工作者在生物醫(yī)療和藥物研發(fā)等問題上提供了一個不可或缺的工具。本論文以槳狀結構的三苯胺為功能團,對其進行結構修飾和優(yōu)化,利用Vilsmeier-Haack、Witting等反應合成了一系列三苯胺基衍生物�；诨衔锏慕Y構特點,我們系統(tǒng)地研究其識別性能,結合體外實驗結果,進一步探索了它們在生物學方面的應用。主要研究內容如下: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,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小分子SASB的水溶性,而且還與-C=N-構筑半空腔的類冠醚型結構,實現對主族元素的響應。實驗結果表明,在乙醇中,SASB對主族元素鎂離子有特異性識別,且不受同主族鈣離子的干擾。SASB在生物細胞內毒性低、光穩(wěn)定性高、細胞膜穿透性好,不僅對宮頸癌細胞的亞細胞器--溶酶體上過量鎂離子有顯色響應;而且可以穿透擬南芥幼苗的細胞壁,通過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響應。2、在上一章基礎上,改變末端官能團,制備了能靶向定位細胞內亞細胞器線粒體的席夫堿PBSB。研究結果表明,PBSB在乙腈溶液中對重金屬銅離子有比率型熒光增強的選擇性識別,利用熒光滴定、核磁滴定實驗對其識別機理進行了探究。體內實驗結果表明,探針能靶向性定位細胞內亞細胞器線粒體部位,且能夠通過細胞比率顯影來反應細胞內銅離子的分布情況。3、考慮到席夫堿易于水解,限制了其應用,而C-N相較于C=N易于旋轉,利于結合金屬離子,進而我們對分子結構進行微調,合成了一種柔性的有機小分子仲胺類化合物PBSA。實驗結果表明,PBSA具有以下優(yōu)異特性:1)在乙腈溶液中能特異性識別重金屬鎳離子;2)不受其它金屬離子的干擾;3)檢測限度低;4)時效性強;5)可循環(huán)性檢測。利用熒光滴定、Job's曲線及核磁滴定實驗確定了 PBSA與金屬鎳離子的作用模式。生物學研究表明,探針PBSA特異性定位HepG2細胞的線粒體部位,且能在HepG2細胞內循環(huán)使用,有利于檢測線粒體相關的疾病。
[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.
【學位授予單位】：安徽大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：O657.3

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