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論文中文名稱:新型氟陰離子光學感測探針之設計與合成 [以論文名稱查詢館藏系統]
論文英文名稱:Design and Synthesis of the Novel Optical Sensing Chemodosimeter for Detection of Fluoride [以論文名稱查詢館藏系統]
院校名稱:臺北科技大學
學院名稱:工程學院
系所名稱:化學工程與生物科技系化學工程博士班
畢業學年度:103
畢業學期:第二學期
中文姓名:古峻安
英文姓名:Jyun-An Gu
研究生學號:100739006
學位類別:博士
語文別:中文
口試日期:2015/06/17
指導教授中文名:黃聲東
指導教授英文名:Sheng-Tung Huang
口試委員中文名:高佳麟;汪昆立;郭霽慶;郭憲壽
中文關鍵詞:氟陰離子光學檢測光學探針
英文關鍵詞:Fluoride IonOptical assayAuto-inductive signal amplification
論文中文摘要:本篇論文以亞甲基醌連接鏈自發釋放(quinone-methide self-immolative elimination)的原理,設計與合成出即時偵測氟陰離子的新型隱藏式金奈米粒子聚集比色探針與高靈敏自動誘發信號增幅螢光探針,可運用於建立微量簡易辨別氟陰離子平台,即時偵測環境危害物。在此使用了對氟陰離子有良好專一性的矽醚基保護在亞甲基醌上,在分子的末端則接著隱藏住的光學信號或催化試劑,當氟陰離子脫去分子探針上的矽醚基團時,則會引發探針分子內亞甲基醌連接鏈自發脫去的1,6-重排反應,隨即放出能被隱藏住的光學信息或催化反應的試劑。我們的比色探針(5a)建構了以金奈米粒子的顏色變化來指示氟陰離子存在的檢測新方法,是利用5a能夠釋放會與金原子產生硫金鍵的雙硫基直鏈分子,導致其自發性不可逆的聚集金奈米粒子,達到比色偵測的目的;而另一種則是融入自動誘發信號增幅概念(auto-inductive signal amplification)的隱藏式螢光分子探針(DPF1)與長波長隱藏式螢光探針(DCC)串聯的雙探針自動誘發螢光檢測平台,DPF1在檢測到氟陰離子後能夠自發地釋放香豆素螢光分子(8-formyl-7-hydroxyl coumarin),同時也釋放出兩倍當量數的氟陰離子,這些氟陰離子能夠再去啟動其他未反應的探針分子並且產生更多的氟陰離子與螢光,進而形成一個指數性的信號增幅循環,或是啟動長波長隱藏式螢光探針(DCC),最後蛻去所有的探針分子保護基團並顯露出長波長螢光分子(2-benzothiazole-3-cyano-7-hydroxy coumarin),以達到超靈敏檢測的目的。探針5a的比色檢測平台能夠在15分鐘內快速、裸眼來辨識低濃度(120μM)氟陰離子的存在,並可以配合紫外線光譜儀做出0.12~1.5 mM的檢量線,而DPF1與DCC串聯的自動誘發信號增幅長波長螢光檢測平台則能夠超靈敏地偵測氟陰離子,最低的偵測極限達到了0.5pM,比已知的所有氟陰離子檢測方法還要更低,並且在長波長的範圍釋放螢光信號,在生物體的應用上可以減少許多干擾的背景值,最後,我們還在一般性水樣品以及尿液的環境下檢測了氟陰離子,標準偏差值能夠在5%以內,證明了我們新開發的超靈敏自動誘發信號增幅螢光檢測平台在實際應用上的可行性。
論文英文摘要:We reported a sensitive detection scheme for fluoride based on a quinone-methide-type of self-immolative elimination reaction to trigger color change among cloaked gold nanoparticle agglomeration probe (5a) and another off–on fluorometric probe (DPF1) via autoinductive signal amplification. Fluoride ions remove silyl moieties from phenol groups on the surface of the probes, this spontaneous and irreversible reaction occurs in aqueous medium at room temperature and accompanied by the release of optical signal. The probe 5a release dithiol and cause aggregation of the AuNPs which leads to a color change from pink-red to violet-blue that can be seen with bare eyes. The generation of color by this cascade reactions is only caused by fluoride and not interfered by any other anions. Our developed platform offers a sensitive colorimetric assay for fluoride.The limit of detection is 120 μM and the dynamic concentration range is from 120 μM to 1.5 mM. In addition, DPF1 undergoes a cascade of self-immolative reactions concomitant with unmasking fluorogenic coumarin and ejecting of two fluoride ions. These fluoride ions are continuously activate the cascade reaction and accumulate the number of coumarins, which leads to exponentially amplifying the signal with high sensitivity. The fluorescence signal generated by this cascade reaction is rapid, specific and insensitive to other anions. Its limit of detection was 0.5 pM, considerably lower than other current methods of fluoride detection. In addition, DCC, a long wavelength fluorometric probe, was prepared. Interestingly, an assay platform coupling DPF1 and DCC showed an outstanding sensing ability at higher wavelengths, suggesting that this platform is a promising method for the sensitive and selective detection of fluoride in biological samples. The practical applicability of the proposed approach was demonstrated in urine and water samples.
論文目次:目錄
摘要 I
ABSTRACT III
誌謝 V
目錄 VI
圖目錄 IX
表目錄 XI
第一章 前言 1
第二章 文獻回顧與探討 3
2.1 光學檢測 3
2.2 比色檢測法 4
2.2.1 比色染料 4
2.2.2 金奈米粒子 6
2.2.3 金奈米粒子比色探針 7
2.2.4隱藏式金奈米粒子比色探針 9
2.3 螢光檢測 10
2.3.1長波長隱藏式螢光分子探針 11
2.3.2 自發釋放脫去 13
2.3.3 自發釋放脫去概念應用 14
2.4 氟陰離子檢測 17
2.4.1 氫鍵型探針檢測氟陰離子 17
2.4.2 裂解型探針檢測氟陰離子 18
第三章 研究動機與目的 21
3.1 研究目的 21
3.2 研究動機 21
3.3 氟陰離子光學檢測探針設計概念 22
3.4 金奈米粒子比色探針檢測氟陰離子概念 23
3.5 雙探針自動誘發螢光檢測平台檢測氟陰離子概念 24
第四章 實驗方法與討論 26
4.1 儀器與試藥 26
4.1.1 實驗儀器 26
4.1.2 實驗藥品 27
4.1.3 縮寫參照 28
4.2 金奈米粒子比色探針5a, 5b合成步驟 28
4.2.1 N,N’-Bis[4-(tritylthio)phenyl]-3,6,9-trioxa undecanedicarboxamide(3)之合成步驟 29
4.2.2 N,N’- Bis{4-[tert-butyl(dimethyl)silyloxy]benzyl(4-phenyl)sulfane}- 3,6,9-trioxaundecanedicarboxamide (5a)之合成步驟 29
4.2.3 N,N’- Bis{4-[tert-butyl (diphenyl)silyloxy] benzyl(4-phenyl)sulfane} -3,6,9-trioxaundecane dicarboxamide(5b)之合成步驟 30
4.3 自動誘發隱藏式螢光探針DPF1與長波長隱藏式螢光探針DCC合成圖 31
4.3.1 7-{[4-(tert-butyldiphenylsilyloxy)benzyl]-oxy} -8-formylcoumarin (DPA1)之合成步驟 32
4.3.2 7-{[4-(tert-butyldiphenylsilyloxy)benzyl]-oxy} -8-(difluoromethyl)-coumarin (DPF1)之合成步驟 32
4.3.3 3-(benzothiazol-2-yl)-4-carbonitrile-7-{[4- (tert-butyldiphenylsilyloxy)benzyl]-oxy}couma rin (DCC)之合成步驟 33
4.4配置磷酸鹽緩衝溶液(phosphate buffer) 34
4.5 金奈米粒子比色探針檢測氟陰離子實驗步驟 34
4.6 雙探針自動誘發螢光檢測平台檢測氟陰離子實驗步驟 34
第五章 結果與討論 35
5.1 矽醚探針分子醛基氟化反應 35
5.2 以比色法檢測氟陰離子 37
5.2.1探針5a與5b檢測氟陰離子 37
5.2.2 探針5a之選擇性測試 38
5.2.3探針5a定量實驗 39
5.3以自動誘發螢光檢測平台檢測氟陰離子 40
5.3.1自動誘發隱藏式螢光探針DPF1檢測氟陰離子效果 40
5.3.2探針DPF1之選擇性測試 42
5.4以長波長自動誘發螢光檢測平台檢測氟陰離子 43
5.4.1長波長隱藏式螢光探針DCC檢測氟陰離子 43
5.4.2雙探針自動誘發螢光檢測平台信號傳遞 44
5.4.3 雙探針自動誘發螢光檢測平台檢測氟陰離子 45
第六章 結論 51
參考文獻 51
附錄 58
附圖1 化合物3之 1H – NMR 圖譜 58
附圖2 化合物5a之 1H – NMR 圖譜 59
附圖3 化合物5b之 1H – NMR 圖譜 60
附圖4化合物DPA1之 1H – NMR 圖譜 61
附圖5化合物DPF1之 1H – NMR 圖譜 62
附圖6化合物DCC之 1H – NMR 圖譜 63
附圖7 化合物3之13C – NMR 圖譜 64
附圖8 化合物5a之 13C – NMR 圖譜 65
附圖9化合物5b之 13C – NMR 圖譜 66
附圖10化合物DPA1之 13C – NMR 圖譜 67
附圖11化合物DPF1之 13C – NMR 圖譜 68
附圖12化合物DCC之 13C – NMR 圖譜 69
附圖13 化合物3 Mass - ESI- 圖譜 70
附圖14 化合物5a Mass - ESI- 圖譜 71
附圖15 化合物5b Mass – ESI- 圖譜 72
附圖16 化合物DPA1 Mass – ESI+ 圖譜 73
附圖17 化合物DPF1 Mass – ESI- 圖譜 74
附圖18 化合物DCC Mass – ESI- 圖譜 75
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