博碩士論文 109223036 詳細資訊




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姓名 許祐瑄(Yu-Hsuan Hsu)  查詢紙本館藏   畢業系所 化學學系
論文名稱 合成含苯並噻唑及三氮唑吡啶結構單元之雙光子螢 光探針並探討其在細胞顯微成像應用上的潛能
(Synthesis of Two-photon Fluorescent Probes based on Benzothiazole and Triazolopyridine Units and Evaluation of Their Potentiality as Cell-imaging Agents under Microscopy)
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摘要(中) 在化學及生物跨領域的合作中,合成螢光探針,以及利用螢光探針可
視化生物體內的胞器狀況,是非常重要的技術。
本篇論文以合成出可標記脂滴與溶酶體的小分子雙光子螢光探針為目
標,主要設計的方向有以下三點:分子量不能過大、有良好的量子產率及
雙光子激發效率,以及對特定胞器的標記能力。
透過線性及非線性光學實驗量測,可以分析出分子之光學性質,
找出其與結構之關聯性。本篇論文合成不同的條形分子,結構分別為
Donor-π-Acceptor 及 Donor-Acceptor-Donor 兩種,透過更換不同的推拉電
子基,經過分析與探討分子結構與其光學性質,我們可以歸納得到以下幾
種結論:
(1) 對同一系列分子而言,分子的共軛特性與其雙光子激發效率間可能分
別存在著不同的關聯性。例如:分子的共軛長度增加有助於明顯提升雙光
子表現。
(2) 拉電子基也同樣會影響雙光子激發效率,例如:相較於三氮唑吡啶
(triazolopyridine),以苯並噻唑 (benzothiazole) 作為拉電子基團,可使分
子整體具有較高之雙光子激發效率。
(3) Donor-Acceptor-Donor 之結構使分子不管在何種溶劑下皆有較高的量
子產率,且也有較好之雙光子激發效率。
接著進行細胞實驗,判定各螢光探針於細胞內染色狀況,藉由染色結
果尋找適合於未來開發的雙光子螢光探針類型。
摘要(英) Interdisciplinary research at the chemistry/ biology interface, synthesizing fluorescent probes and using them to visualize organelle status in organisms are very important technology.
This paper synthesized small molecules two photon capable of labelling
lipid droplets and lysosomes. The main design directions have the following
three points: molecular weight should not be too large, have good quantum yield and two-photon excitation efficiency, and labelling capabilities of
specific organelles. Molecules can be analyzed through linear and nonlinear
optical experimental measurements of optical properties and their correlation with the structure. This paper synthesizes molecules which have two
different structures: Donor-π-Acceptor and Donor Acceptor-Donor. By replacing different push-pull electron groups after analyzing and discussing the
molecular structure and its optical properties, we can generalize the following
conclusions:
(1) The increased conjugate length helps to improve the two-photon performance significantly.
(2) The electron withdrawing group also affects the two-photon excitation
efficiency, such as: compared with triazolopyridine, benzothiazole as electron withdrawing group can give the whole molecule a higher two-photon
excitation efficiency.
(3) The structure of Donor-Acceptor-Donor makes the molecule no matter
what kind of solvent all have higher quantum yields and better two-photon
excitation efficiency.
Next, cell experiments are performed to determine the intracellular
staining of each fluorescent probe. In this case, we will search for two-photon
fluorescent probes suitable for future development based on the staining results
關鍵字(中) ★ 雙光子
★ 螢光探針
關鍵字(英)
論文目次 目 錄
頁次
中文摘要 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . i
英文摘要 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ii
目錄 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . iv
圖目錄 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vi
表目錄 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii
第 一 章、 序論 . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1-1 單光子螢光探針及其應用 . . . . . . . . . . . . . . . . 1
1-2 雙光子吸收理論 . . . . . . . . . . . . . . . . . . . . . 9
1-3 雙光子螢光探針的發展 . . . . . . . . . . . . . . . . . 10
1-3-1 雙光子螢光探針需考慮之要素 . . . . . . . . . . . . . 10
1-3-2 與單光子螢光探針相比之優點 . . . . . . . . . . . . . 11
1-3-3 標記不同目標胞器之雙光子螢光探針 . . . . . . . . . 13
1-4 時域聚焦多光子激發顯微技術 (TFMPEM) 介紹 . . . 20
1-5 研究動機與論文架構 . . . . . . . . . . . . . . . . . . 21
第 二 章、 分子設計與合成 . . . . . . . . . . . . . . . . . . . . . 23
2-1 模型分子的結構設計概念及目的 . . . . . . . . . . . . 23
2-2 合成流程及途徑規劃 . . . . . . . . . . . . . . . . . . 27
第 三 章、 模型分子在溶液態之光學性質 . . . . . . . . . . . . . 37
3-1 光學實驗及光學儀器詳述 . . . . . . . . . . . . . . . . 37
3-2 線性光學性質鑑定 . . . . . . . . . . . . . . . . . . . 39
3-3 雙光子相關光學性質量測 . . . . . . . . . . . . . . . . 49
3-4 結果與討論 . . . . . . . . . . . . . . . . . . . . . . . 58
第 四 章、 細胞實驗及攝影 . . . . . . . . . . . . . . . . . . . . . 61
第 五 章、 實驗藥品與步驟 . . . . . . . . . . . . . . . . . . . . . 64
5-1 合成模型分子所使用之藥品及溶劑 . . . . . . . . . . . 64
5-2 化合物合成詳細步驟 . . . . . . . . . . . . . . . . . . 66
5-2-1 本論文前驅物之詳細合成步驟 . . . . . . . . . . . . . 66
5-2-2 本論文模型分子之詳細合成步驟 . . . . . . . . . . . . 90
第 六 章、 結構鑑定光譜圖 . . . . . . . . . . . . . . . . . . . . . 102
索引 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
參考文獻 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 138
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指導教授 林子超(Tzu-Chau Lin) 審核日期 2022-8-29
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