臺灣博碩士論文加值系統

本研究中使用Suzuki coupling反應合成出在3,7號位置具有不同推拉電子取代基的10H- Phenothiazine (PTZ)衍生物，並研究其在酸性以及鹼性條件的光學性質，並且將其氧化，探討氧化產物應用於光動力治療的可行性。在酸性條件下，具有aniline與dimethyl aniline取代的PTZ化合物在質子化後，螢光劇烈增強，推測原因乃因分子聚集形成螢光有機奈米粒(Fluorescent Organic Nanoparticals, FONs)。而在鹼性條件下，此類分子吸收訊號會因去質子化而紅位移且出現紅色螢光。而具有nitrobenzene和N-butyl-1,8-naphthalimide取代的化合物的吸收訊號則會因去質子化位移到800nm以上但無明顯螢光。
此外aniline與dimethyl aniline取代的PTZ化合物經氧化後都具有超過900nm的吸收訊號，並且根據DPBF和TEMPO-9-AC測試確定前者分子在照光後能產生單重態氧以及自由基 (free radical) ；並在細胞光毒性實驗中發現對於癌細胞有選擇性，其原因是因為HeLa對於化合物的攝取量較高，且分子會累積在的溶酶體當中。

A series of 10H-phenothiazine (PTZ) derivative fluorophores ,Suzuki coupling with electron donating and/or withdrawing substitution group in 3, 7-position were prepared. In acidic condition, proton accepter groups aniline and dimethylaniline substituted PTZ derivatives could be protonated and aggregated to become fluorescent organic nanoparticles (FONs) accompany with fluorescent enhancement. On the other hand, anionic forms of these derivatives exhibited strong red light emission in alkali DMSO solutions, whereas anionic nitrobenzene and naphthaleneimide substituted PTZ derivatives exhibited the near infrared absorption at 820-840 nm. Furthermore, the oxidized aniline and dimethylaniline substituted PTZ derivatives exhibited the near infrared absorption wavelength over 900nm. The DPBF and TEMPO-9-AC have been used to detect singlet oxygen and free radical formation of compounds respectively. Biologically, the unexpected selective photo-toxicity between HeLa and MRC-5 Cell lines is caused by cellular uptake and localization difference. Consequently, oxidized aniline substituted PTZ can be a selective Near-Infrared photodynamic therapy candidate.

第一章、序論 1
1.光動力治療 1
1-1光動力治療發展 1
1-2光動力作用機制 1
1-3光感物質 2
1-4光動力治療於癌症的應用 2
2. Phenothiazine 3
2-1甲基藍 (Methylene Blue) 4
3.研究動機 7
第二章、實驗方法與合成步驟 8
2-1 實驗用藥品 8
2-2儀器設備 8
2-2-1 核磁共振光譜儀 8
2-2-2 紫外光-可見光吸收光譜儀 8
2-2-3 螢光光譜儀 9
2-2-3 螢光顯微鏡 9
2-2-4 氙燈光源 9
2-3 細胞實驗 9
2-3-1 細胞株 9
2-3-2 細胞培養條件 9
2-3-3 細胞培養方法 10
2-3-4 細胞毒性 10
2-3-5 細胞局部位置的鑑定 11
2-3-6 細胞對化合物攝取量測 11
2-3 化合物合成 12
第三章、結果與討論 16
3-1基本光譜 16
3-2酸滴定 22
3-2-1螢光有機奈米粒 22
3-3鹼性環境 29
3-4 Phenothiazine衍生物的氧化 37
3-5單重態氧及反應氧化物量測 45
3-6細胞毒性 50
3-7細胞毒性選擇性探討 56
第四章、結論 60
第五章、參考資料 61

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