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研究生： 陳怡惠
Chen, Yi-Hui
論文名稱： 綠色螢光蛋白類似物的合成、光物理及光異構化反應之探討
Synthesis, Photophysics and Photoisomerization of GFP Analogues
指導教授： 宋光生
Sung, Kuang-Sen
學位類別： 博士
Doctor
系所名稱： 理學院 - 化學系
Department of Chemistry
論文出版年： 2012
畢業學年度： 100
語文別： 中文
論文頁數： 181
中文關鍵詞： 綠色螢光蛋白 、激發態分子內氫轉移 、扭轉分子內電荷轉移 、光異構化反應
外文關鍵詞： GFP, ESIPT, TICT, photoisomerization
相關次數： 點閱：139  下載：11 
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    • 將綠色螢光蛋白主要發光團p-HBDI 置換成鄰位或對位的胺基修飾之類似物，包含下圖示所列之化合物，藉由測量各化合物的吸收及螢光放射光譜來探討其光物理性質，並以化合物的X-ray單晶結構與酸度常數理論計算來佐證。其中發現化合物o-TsABDI經由激發態分子內氫轉移現象，產生一個兩性離子異構物的螢光放射；化合物p-TsABDI則經由激發態分子間氫轉移現象，顯示一異構物的螢光放射；o-ABDI、o-DMABDI和p-DMABDI三個化合物皆產生扭轉的分子內電荷轉移的現象，但無發現激發態氫轉移的過程；化合物o-AABDI、o-PUBDI和o-AABDI皆無產生激發態氫轉移的現象，亦無扭轉的分子內電荷轉移的過程。而上述化合物皆會發生Z→E的光異構化反應，造就低的量子產率。另外，欲合成鄰位胺基修飾的綠色螢光蛋白主要發光團類似物中，意外合成出化合物3和4。

    We displaced green fluorescent protein (GFP) major chromophore p-HBDI to ortho or para-amino modified group analogues, involved those compounds that showed in a following fiqure. By measuring absorption and fluorescence emission spectra to research their photophysics, and proved by X-ray single crystals of compounds and theoretical calculations of acidity constant. We could discover that o-TsABDI displays a zwitterionic tautomer fluorescent emission through excited-state intramolecular proton thansfer (ESIPT); p-TsABDI displays a tautomer fluorescent emission through excited-state intermolecular proton thansfer (intermolecular ESPT); o-ABDI, o-DMABDI and p-DMABDI show the character of twisted intramolecular charge-thansfer (TICT), but display no tautomer emission through excited-state proton thansfer (ESPT); o-AABDI, o-PUBDI and p-AABDI display no tautomer emission through ESPT and no character of TICT. All of the above-mentioned compounds could occur Z→E photoisomerizations to produce low quantum yields. In addition, we desired to synthesize ortho-amino modified group GFP major chromophore analoques, but unexpected to synthesize compound 3 and 4.

    中 文 摘 要...............................................iii Abstract..................................................v 誌謝.....................................................vii 目錄....................................................viii 表目錄...................................................xii 圖目錄..................................................xiii 第I部份....................................................1 第I-1章 序論...............................................1 I-1-1 綠色螢光蛋白的由來及重要性.............................1 I-1-2 綠色螢光蛋白發色團的主要結構與生物合成機制...............2 I-1-3 水母之綠色螢光蛋白的發光機制...........................4 I-1-4 水母之綠色螢光蛋白的光譜特性...........................4 I-1-5 綠色螢光蛋白主要發色團的有機合成機制....................7 I-1-6 有機合成綠色螢光蛋白主要發光團的光譜分析.................8 I-1-7 鄰位取代的綠色螢光蛋白主要發色團之合成與光譜效應.........12 I-1-8 綠色螢光蛋白主要發色團和其類似物的光異構化反應..........17 I-1-9 扭轉的分子內電荷轉移 (Twisted Intramolecular Charge-Transfer, TICT)...........................................21 I-1-10 激發態分子內氫轉移 (Excited-state intramolecular proton transfer, ESIPT) 其他模型實例.......................26 I-1-11 激發態氫轉移反應之酸度常數pKa*值的測定................32 I-1-12 化合物之立體效應與溶劑效應對分子光譜影響的探討.........35 第I-2章 實驗結果與討論.....................................38 I-2-1 合成鄰位和對位胺基衍生基團的綠色螢光蛋白主要發色團類似物及其合成機構之探討.............................................38 I-2-2 合成的鄰位和對位胺基衍生基團之綠色螢光蛋白主要發色團類似物之光譜數據、X-ray單晶結構和氮氫的酸度常數分析及其化合物在激發態分子內氫轉移或激發態分子間氫轉移之探討..............................43 I-2-2A 合成的鄰位和對位胺基衍生基團之綠色螢光蛋白主要發色團類似物在aprotic溶劑下的光譜數據分析及其化合物在激發態分子內氫轉移或激發態分子間氫轉移之探討..........................................43 I-2-2B 合成的鄰位和對位胺衍生基團之綠色螢光蛋白主要發色團類似物在aprotic及protic混合溶劑下的光譜數據分析及其化合物在激發態分子內氫轉移或激發態分子間氫轉移之探討...............................59 I-2-2C o-TsABDI及o-AABDI兩化合物之晶體結構分析..............70 I-2-2D 合成的鄰位和對位胺基修飾基團綠色螢光蛋白主要發色團類似物之取代基氮上氫的酸性常數pKa理論計算結果分析及o-TsABDI和p-TsABDI兩化合物激發態酸度常數pKa*之探討.................................74 I-2-3 合成的鄰位和對位胺基基團之綠色螢光蛋白主要發色團類似物在不同溶劑下之光譜分析及其化合物之扭轉的分子內電荷轉移過程的探討.......82 I-2-4 合成的鄰位和對位胺基修飾基團綠色螢光蛋白主要發色團類似物在酸或鹼性溶劑下的光譜數據分析...................................96 I-2-5 光異構化反應及自發性熱的異構化反應....................112 I-2-6 第一部分總結.......................................124 第I-3章 實驗步驟.........................................125 I-3-1 合成2-methyl-4-(2-nitrobenzylidene)oxazol-5(4H)-one步驟.......................................................125 I-3-2 合成1,2-dimethyl-4-(2-nitrobenzylidene)-1H-imidazol-5(4H)-one步驟.............................................125 I-3-3 合成4-(2-aminobenzylidene)-1,2-dimethyl-1H-imidazol-5(4H)- one, o-ABDI步驟....................................126 I-3-4 合成4-(2-(acetamido)benzylidene)-1,2-dimethyl-1H-imidazol- 5(4H)-one, o-AABDI步驟.........................127 I-3-5 合成4-(2-(tosylamino)benzylidene)-1,2-dimethyl-1H-imidazol- 5(4H)-one, o-TsABDI步驟........................127 I-3-6 合成4-(2-(ditosylamino)benzylidene)-1,2-dimethyl-1H-imidazol- 5(4H)-one, o-DTsABDI步驟.......................128 I-3-7 合成4-(2-(dimethylamino)benzylidene)-1,2-dimethyl-1H- imidazol-5(4H)-one, o-DMABDI步驟........................129 I-3-8 合成1-(2-((1,2-dimethyl-5-oxo-1H-imidazol-4(5H)-ylidene) methyl)phenyl)-3-phenylurea, o-PUBDI步驟........129 I-3-9 合成2-methyl-4-(4-nitrobenzylidene)oxazol-5(4H)-one步驟.......................................................130 I-3-10 合成1,2-dimethyl-4-(4-nitrobenzylidene)-1H-imidazol-5(4H)- one步驟...........................................130 I-3-11 合成 4-(4-aminobenzylidene)-1,2-dimethyl-1H-imidazol-5(4H)- one, p-ABDI步驟..........................131 I-3-12 合成4-(4-(acetamido)benzylidene)-1,2-dimethyl-1H-imidazol- 5(4H)-one, p-AABDI步驟.........................132 I-3-13 合成4-(4-(tosylamino)benzylidene)-1,2-dimethyl-1H-imidazol- 5(4H)-one, p-TsABDI步驟........................132 I-3-14 合成2-methyl-4-(4-(dimethylamino)benzylidene)oxazol-5(4H)- one步驟...........................................133 I-3-15 合成1,2-dimethyl-4-(4-(dimethylamino)benzylidene)-1H- imidazol-5(4H)-one, p-DMABDI步驟.....................134 I-3-16 合成2-methyl-4-(4-acetoxybenzylidene)oxazol-5(4H)- one步驟..................................................134 I-3-17 合成1,2-dimethyl-4-(4-hydroxybenzylidene)-1H-imidazol- 5(4H)-one, p-HBDI步驟..........................135 第I-4章 數據分析..........................................137 [2-methyl-4-(2-nitrobenzylidene)oxazol-5(4H)-one]........137 [1,2-dimethyl-4-(2-nitrobenzylidene)-1H-imidazol-5(4H)-one].....................................................137 [4-(2-aminobenzylidene)-1,2-dimethyl-1H-imidazol-5(4H)-one, o-ABDI]..................................................137 [4-(2-(acetamido)benzylidene)-1,2-dimethyl-1H-imidazol-5(4H)-one, o-AABDI].......................................138 [4-(2-(tosylamino)benzylidene)-1,2-dimethyl-1H-imidazol-5(4H)-one, o-TsABDI]......................................138 [4-(2-(ditosylamino)benzylidene)-1,2-dimethyl-1H-imidazol-5(4H)-one, o-DTsABDI].....................................139 [4-(2-(dimethylamino)benzylidene)-1,2-dimethyl-1H-imidazol-5(4H)-one, o-DMABDI]......................................140 [1-(2-((1,2-dimethyl-5-oxo-1H-imidazol-4(5H)-ylidene)methyl)phenyl)-3-phenylurea, o-PUBDI]...........................140 [2-methyl-4-(4-nitrobenzylidene)oxazol-5(4H)-one]........141 [1,2-dimethyl-4-(4-nitrobenzylidene)-1H-imidazol-5(4H)-one].....................................................141 [4-(4-aminobenzylidene)-1,2-dimethyl-1H-imidazol-5(4H)-one, p-ABDI]..................................................141 [4-(4-(acetamido)benzylidene)-1,2-dimethyl-1H-imidazol-5(4H)-one, p-AABDI].......................................142 [4-(4-(tosylamino)benzylidene)-1,2-dimethyl-1H-imidazol-5(4H)-one, p-TsABDI]......................................142 [2-methyl-4-(4-(dimethylamino)benzylidene)oxazol-5(4H)-one] ....................................................143 [4-(4-(dimethylamino)benzylidene)-1,2-dimethyl-1H-imidazol-5(4H)-one, p-DMABDI]......................................143 [2-methyl-4-(4-acetoxybenzylidene)oxazol-5(4H)-one]......144 [4-(4-hydroxybenzylidene)-1,2-dimethyl-1H-imidazol-5(4H)-one, p-HBDI].............................................144 第II部份.................................................145 第II-1章 序論............................................145 II-1-1 合成綠色螢光蛋白主要發光團類似物之期望路徑............145 II-1-2 文獻回顧..........................................146 第II-2章 結果與討論.......................................150 II-2-1 N-取代基2-aminobenzaldehyde之合成路徑..............150 II-2-2 無預期合成化合物3-acetamido-2-quinolinone (3)和2(1H)-quinolinone (4)及其機構之探討.............................152 II-2-3 第二部分結論.......................................155 第II-3章 實驗步驟........................................156 II-3-1 合成2-(acetylamino)benzyl alcohol (1a)的步驟......156 II-3-2 合成2-(benzoylamino)benzyl alcohol (1b)的步驟.....157 II-3-3 合成2-(tosylamino)benzyl alcohol (1c)的步驟.......158 II-3-4 合成2-acetylamino-benzaldehyde (2a)的步驟.........159 II-3-5 合成2-benzamidobenzaldehyde (2b)的步驟............159 II-3-6 合成2-tosylamino-benzaldehyde (2c)的步驟..........160 II-3-7 合成3-acetamido-2-quinolinone (3)的步驟...........160 II-3-8 合成2(1H)-quinolinone (4)的步驟...................161 第II-4章 數據分析........................................162 [2-(acetylamino)benzyl alcohol, 1a]......................162 [2-(benzoylamino)benzyl alcohol, 1b].....................162 [2-(tosylamino)benzyl alcohol, 1c].......................162 [2-acetylamino-benzaldehyde, 2a].........................163 [2-benzamidobenzaldehyde, 2b]............................163 [2-tosylamino-benzaldehyde, 2c]..........................164 [3-acetamido-2-quinolinone, 3]...........................164 [2(1H)-quinolinone, 4]...................................164 參考資料..................................................166 附錄.....................................................169 o-TsABDI的X-ray晶體資料...................................169 o-AABDI的X-ray晶體資料....................................176

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