近年來polymer dots發展主要是因受到堆疊產生螢光消光的影響，因此第一個研究為設計一個以quinoxaline為基底的分子及具有aggregation induced emission性質的分子來改善Pdots 這項缺點。首先A部分為設計一系列以quinoxaline為本體的分子透過接上長碳鍊與氟官能基增加立體障礙與量子效率，並比較不同官能基的quinoxaline的光學性質與改善Pdots堆疊的效率，最後選擇量子效率(47%)與單一亮度最高的PF-TC6FQ將其接上5%具COOH的PF後再修飾上streptavidin與葉酸，使其專一性標記到以修飾biotin-antibody的HeLa 細胞與具有葉酸受體的SKOV3的卵巢癌細胞，接著將其成功應用到斑馬魚體內做in vivo的影像觀察。而B部分則是利用在水溶液中會聚集發光即具aggregation induced emission (AIE) 性質的分子與易產生aggregation caused quenching (ACQ)現象的分子做不同比例的高分子化，並用再沉澱法做成Pdots探討其光學性質，期望透過接上AIE分子以改善Pdots易堆疊而產生螢光消光的缺點。第二研究則是設計一系列具有光轉換性質與光穩定性佳的azobenzene，並與具螢光性質的高分子結合做成Pdots在透過兩個特定波長(365 nm UV與450 nm藍光)照射下，使azobenzene產生順反結構的改變而產生不同的堆疊與電子傳遞，使其具有亮暗分別的作用希望達到對生物細胞有高解析度的辨識與觀測影像，並探討與其相接的分子結構是否會對azobenzene的光轉換性質產生影響，從而發現當azobenzene越裸露在高分子鍊外面與相接的分子立體障礙越小時，其光轉換的效果越明顯。雖然我們探討出許多因素與azobenzene的光轉換效果間的關係，但這僅止於吸收光譜而螢光光譜的光轉換變化效果仍極小，因此仍須往此方向研究與改善。

The first research describes the design and synthesis of quinoxaline-based semiconducting polymer dots (Pdots) that exhibit near-infrared fluorescence, ultrahigh brightness, large Stokes shifts, and excellent cellular targeting capability. We also introduced fluorine atoms and long alkyl chains into polymer backbones and systematically investigated their effect on the fluorescence quantum yields of Pdots. These new series of quinoxaline-based Pdots have a fluorescence quantum yield as high as 47% with a Stokes shift larger than 150 nm. Single-particle analysis reveals that the average per-particle brightness of the Pdots is at least 6 times higher than that of the commercially available quantum dots. We further demonstrated the use of this new class of quinoxaline-based Pdots for effective and specific cellular and subcellular labeling without any noticeable nonspecific binding. Moreover, the cytotoxicity of Pdots were evaluated on HeLa cells and zebrafish embryos to demonstrate their great biocompatibility. By taking advantage of their extreme brightness and minimal cytotoxicity, we performed, for the first time, in vivo microangiography imaging on living zebrafish embryos using Pdots. These quinoxaline-based NIR-fluorescent Pdots are anticipated to find broad use in a variety of in vitro and in vivo biological research.
The second research is to design and synthesize a series of azobenzene-based polymers for the development of photoswitchable Pdots. As for the photochromic trans-cis isomerization of azobenzenes, the strong absorption at 360 nm in the trans-state derives from the π-π* transition while this transition happens at ~320 nm in the cis-state. The very weak absorption centered at 450 nm mainly in the cis-state is attributed to the n-π* transition. We expect the isomerization can be used to modulate the fluorescence intensity of Pdots to produce ON and OFF states by the irradiation of UV or visible light and thereby can be applied in super-resolution fluorescence imaging. We systematically studied the chemical structures of azobenzene derivatives in an effort to achieve a large fluorescence on/off contrast and minimal fatigue. In the preliminary results, we found that the steric hindrance plays an important role for its photoswitchable behaviors. We will investigate more parameters to realize the fluorescence modulation of Pdots and then use these materials for biological imaging.

論文審定書 i
謝誌 ii
中文摘要 iv
Abstract v
.圖目錄 x
表目錄 xiii
化學結構縮寫表 xiv
第一章 緒論 1
1.前言 1
2.半導體高分子奈米顆粒組成與製備 4
3.Pdots 發展歷史 6
4.Pdots未來發展與改善方向 8
第二章 各實驗藥品與儀器 9
1.實驗藥品 9
2.實驗儀器 12
第三章 研究1-A 設計以Quinoxaline為基底分子改善Pdots堆疊消光之問題 16
一. 研究目標 16
二. 實驗方法 17
1.合成步驟 17
2.高分子化 - Suzuki coupling reaction 24
3.Pdots 製備方法 25
4.Bioconjugation 25
5.細胞標記 28
6.斑馬魚動物實驗 29
三.實驗結果與討論 33
1.光學性質比較 33
2.莫爾吸收係數計算 36
3.單一Pdots亮度影像 37
4.專一性標記細胞 39
5.動物實驗 - 斑馬魚血管影像觀測 43
四.結論 44
第四章　研究1-B 利用AIE分子特性改善Pdots因堆疊消光之問題 45
一. 研究目標 45
二. AIE 歷史沿革 46
三. 實驗方法 47
1. 合成步驟 47
2. 高分子化 - Suzuki coupling reaction 49
3. Pdots 製備 50
四. 實驗結果與討論 51
1.光學性質探討 51
2.傳統Pdots相比 51
五. 結論 52
第五章　研究二 - 合成偶氮苯並探討其光學性質 53
一.研究目標 53
二.實驗方法 55
Azo-A. 合成步驟 55
Azo-B. 合成步驟 56
Azo-C. 合成步驟 56
2.高分子化 - Suzuki-coupling reaction 60
3.Pdots 製備 66
三.實驗結果與討論 66
光學性質探討 66
四.結論 76
第六章-利用Anthracene修飾硼酸結構用以偵測葡萄糖分子 78
一.研究目標 78
二.緒論 78
三.合成步驟 79
四.合成機制探討 82
五.結論 83
第七章　參考資料 84
第八章 附圖 88

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