臺灣博碩士論文加值系統

Coumarin 在生物方面是一個很重要的分子，其具有相當好的生物活性，其衍生物已被廣泛的用於抗菌及抗癌藥物的研發。Coumarin 結構的化合物同時具有高度螢光性，且具有高量子產率，長期以來，coumarin 的主結構就被廣泛地運用於連結許多化合物。並經由置換不同的拉電子取代基或是改變供電子取代基的強度，就可微調化合物發色團的強度，改變發光波長甚至提高螢光效率。在文獻上已有多篇報導將 coumarin 修飾不同取代基以改變其吸收以及放射波長的位置。於是我們嘗試利用 Sonogashira 耦合反應將 3-acetyl-6-bromocoumarin 修飾上三鍵取代基，企圖延伸其共軛性質，將吸收與放射波長紅位移。結果發現隨著取代基電子效應的改變，其放射波長及螢光強度也有很大的不同。我們將這系列的衍生物運用到生物系統，與以往文獻相比，其細胞毒性大大的增加。結合了以上螢光及生物活性，我們希望將其應用於生物影像系統。

Many coumarin derivatives are biologically important molecules that possess antifungal, antibacterial, antimicrobial insecticidal, anti HIV and antibiotic activites. The coumarin moiety as chromophore of fluorescent ion indicators is a useful physical property for the bio-image technique in biological systems. It was expected that an extension of coumarin with conjugated multiple bonds might bring about the significant change in either red-shift of wavelength or intensity of the emission. Recently, several attempts in modification of 6-Br-coumarin with alkynes by the Sonogashira reaction were carried out. It led to the formation of several coumarin derivatives with expected red-shift of wavelength in fluorescence. It was also found that optical property was affected greatly by only slightly change the substitutents on the phenyl moiety which is linked through the triple bond. Moreover, we applied these coumarin derivatives to biological systems, especially, on the study of cytotoxicity towards HeLa cells. These newly-made compounds showed higher cytotoxicity toward cell compared with unmodified coumarin. By combining cytotoxicity with fluorescence property, we propose to the application of these compounds to bio-imageing technique.

第一章 序論
第一節 利用鈀金屬化合物進行的催化反應回顧-----------------2
第二節 香豆素 ( coumarin ) 的性質與應用------------------11
第三節 螢光原理及其應用於生物系統------------------------19
第四節 細胞死亡的機制簡介--------------------------------27
第五節 研究方向------------------------------------------33

第二章 結果與討論
第一節 利用 Sonogashira 耦合反應合成 coumarin 衍生物-----35
第二節 Coumarin 衍生物的物理性質-------------------------44
第三節 Coumarin 衍生物對人類子宮頸癌細胞 ( HeLa cell ) 之細胞毒性的影響----------------------------------------------51
第四節 Coumarin 衍生物對人類子宮頸癌細胞 ( HeLa cell ) 之細胞 週期 ( Cell cycle ) 的影響-----------------------------55
第五節 Coumarin 衍生物在細胞內的影像拍攝-----------------64

第三章 結論----------------------------------------------69

第四章 實驗部份
第一節 儀器、試劑和操作技巧------------------------------71
第二節 實驗製備與方法------------------------------------79
第三節 產物鑑定------------------------------------------87

參考文獻--------------------------------------------------96
附錄-----------------------------------------------------105

光譜數據
晶體數據

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