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研究生： 簡筱芳
Hsiao-Fang Chien
論文名稱： 石英壓電晶體感測器應用於有機化合物與DNA作用力的研究
The Interaction between Organic Compounds and DNA Studied by Quartz Crystal Microbalance
指導教授： 施正雄
Shih, Jeng-Shong
學位類別： 碩士
Master
系所名稱： 化學系
Department of Chemistry
論文出版年： 2001
畢業學年度： 89
語文別： 中文
論文頁數： 137
中文關鍵詞： 石英壓電晶體感測器 、DNA 、有機化合物 、作用力
英文關鍵詞： QCM, DNA, organic compounds, interaction
論文種類： 學術論文
相關次數： 點閱：267  下載：0 
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    • 本實驗是利用自組式CPS (carboxypropyl disulfide)/EDAC (1-ethyl-3(3-dimethylaminopropyl) carbodimide)/NHS (N-hydroxy- succinimde)修飾的單層膜與雙股螺旋DNA共價鍵結固定在石英晶片的銀電極上，固定化DNA的石英壓電晶體感測器設計來作為DNA與有機化合物間作用力研究之用。
    有機化合物吸附在DNA固定的石英晶片導致石英晶片上質量增加和石英壓電晶體感測器振盪頻率下降，有機分子脫附的研究用來決定DNA與有機分子間是化學吸附或物理吸附。研究發現DNA與有機酸、醛類、pyrrole、pyridine及多環芳香族碳氫化合物(PAH)間存在有化學吸附，反之DNA與醇類或酮類間只有物理吸附存在，固定化DNA石英壓電晶體對有機分子的頻率變化大小依序為：正己酸>正戊酸>正丁酸>丙酮酸>丙酸=pyridine>丙醛=pyrrole>戊二醛=乙醛>甲醛>乙酸>甲酸，而DNA每個核甘酸與有機分子反應的鍵結數大小依序為：正己酸>丙酮醛>正戊酸>正丁酸>丙醛>乙醛>丙酸>pyrrole>pyridine>甲醛>戊二醛>乙酸>甲酸，隨著有機化合物直鏈長度的增加，會增加DNA與有機化合物間反應的鍵結數，本研究亦研究單股和雙股DNA和有機分子作用，雙股DNA和有機分子作用力顯然比單股DNA大。
    本研究同時也探討了溶劑、有機化合物的濃度、溫度、pH值和不同種類的DNA對固定化DNA石英壓電晶體感測器之感應頻率變化及DNA和有機分子作用力的影響，DNA與有機酸間反應所引起的頻率變化並不會受到溶劑變化的影響，相反的，DNA與醛類反應所引起的頻率變化則會受到溶劑變化的影響，頻率變化的大小依序為：丙醇>乙醇=丙酮>甲醇>>純水中，而有機化合物的濃度與頻率變化關係的曲線發現都趨向蘭穆爾式的飽和吸附，在pH效應研究中發現當溶液pH值的增加，會加速DNA與醛類間的反應速率，可能為鹼性溶液會催化DNA鹼基N-1或胺基的反應，而當pH值小於7時，頻率變化相差不大，隨著pH值(>7)增加，會增加DNA與醛類反應的頻率變化，在溫度效應研究中發現當反應溫度升高，會大大的降低DNA與醛類的反應時間，而最好的化學吸附溫度約在37°C左右，不同種類的雙股DNA與有機酸反應時，發現頻率變化相差不大，此可能由於各種DNA的鹼基組成類似。
    利用固定化DNA石英壓電晶體感測器成功地即時研究DNA與有機化合物間作用力，不需要複雜的分離步驟就可以計算出化學鍵結之有機分子的含量及DNA每個核甘酸可與有機分子反應的鍵結數。

    Double-stranded deoxyribonucleic acid (dsDNA) was covalently immobilized onto a self assembled CPS (carboxypropyl disulfide) / EDAC (1-ethyl-3 (3-dimethylaminopropyl) carbodimide)/ NHS (N-hydroxy-succinimde) modified sliver electrodes on a piezoelectric quartz crystal. A piezoelectric quartz crystal sensor based on immobilized dsDNA was set up to study the interaction between dsDNA and various organic molecules.
    The adsorption of organic compounds onto DNA modified quartz crystal electrodes caused the increase in the mass of quartz crystal and resulted in the decrease in the oscillating frequency of the piezoelectric crystal sensor. The desorption study was also performed to determine whether the adsorption was chemical or physical. Among various organic molecules, organic acid, aldehyde, pyrrole, pyridine and PAH (Poly-Aromatic Hybrocarbons) such as naphthalene and pyrene seemed to exhibit the chemisorption on dsDNA, while the physical adsorption was found for alcohol or ketone. The frequency shifts of the dsDNA-immobilized piezoelectric crystal sensor for various organic molecules were in the order: n-caproic acid> n-varleric acid> n-butanoic acid> methylglyoxal> n-propionic acid» pyridine> propionldehyde» pyrrole> glutaraldehyde» acetaldehyde> formaldehyde> acetic acid> formic acid and the binding numbers of organic molecules per nucleotide of DNA were in the order: n-caproic acid> methylglyoxal > n-varleric acid> n-butanoic acid> propionaldehyde > acetaldehyde> n-propionic acid> pyrrole> pyridine> formaldehyde> glutaraldehyde> acetic acid> formic acid. Binding numbers of organic molecules per nucleotide of DNA obviously increased with the longer chain length of organic molecules. Comparison of binding abilities of single strand helix (eq. ss-STDNA) and double strand helix (eq. ds-STDNA) was also made. The frequency shift of dsDNA-immobilized piezoelectric crystal sensor was higher than that of ssDNA.
    The effects of solvent, concentration of organic compounds, pH value, temperature, and different kinds of DNA on the frequency shifts of the dsDNA-immobilized piezoelectric crystal sensor were also investigated and discussed. Obviously, solvent showed no effect on the frequency shifts of the dsDNA-immobilized piezoelectric crystal sensor for organic acid, on the contrary, solvent exhibited quite significant effect for aldehyde. The frequency shifts of dsDNA-immobilized piezoelectric crystal sensor for aldehyde in various solvents were in the order: propanol>ethanol&raquo;acetone>methanol>>pure water. The curve shape of frequency shifts for concentration of organic compounds seemed to trend to be langmuir saturated adsorption. Once pH of solution raised, the reaction rate between DNA and aldehyde speed up, presumably due to the base-catalyzed N-1 or amino group reaction. The frequency shift was essentially pH independent < pH 7, but &sup3; pH 7, the frequency shift increased with increasing pH. Once temperature of solution raised, the reaction time decreased sharply, and an optimum frequency shift was formed at 37°C. Frequency shifts of various dsDNA-immobilized piezoelectric crystal sensor for organic acid are similar which may be attributed to the similar compositions for these dsDNA.
    In conclusion, DNA-immobilized piezoelectric crystal sensor can be successfully applied for in-situ study of the interaction between organic compound and DNA without complicated isolation of reactants and adducts. The amount of organic molecules for chemical binding to DNA and the binding numbers of organic molecules per nucleotide of DNA can be obtained easily.

    第一章 緒論 1 1-1 DNA簡介 1 1-1-1 DNA的發現 1 1-1-2 DNA的化學組成 1 1-1-3 DNA的性質 4 1-1-3.1 DNA的物理性質 4 1-1-3.2 DNA的光譜性質 5 1-1-4 DNA的結構 6 1-1-5 DNA的變性 9 1-2 DNA的化學反應 11 1-2-1 DNA的水解反應 11 1-2-2 DNA的還原反應 11 1-2-3 DNA的氧化反應 12 1-2-4 DNA的親核性反應 13 1-2-5 DNA的親電子性反應 14 1-2-5.1 與鹵化物間的反應 14 1-2-5.2 與含氮親電子基的反應 14 1-2-5.3 與含碳親電子基的反應 15 1-2-6 DNA與致癌物間的反應 18 1-2-6.1 與芳香氮化合物的反應 18 1-2-6.2 與多環芳香族碳氫化合物的反應 20 1-3 壓電晶體特性 22 1-3-1 壓電性 22 1-3-2 壓電晶體 24 1-3-3 石英振盪器 25 1-3-4 AT-cut石英振盪器的特性 27 1-3-5 石英振盪器的線路 28 1-3-6 振盪頻率的量測 30 1-3-7 石英微量天平 32 1-4 石英壓電晶體感測器的應用 36 1-4-1 石英壓電晶體感測器在氣相偵測上的應用 36 1-4-2 石英壓電晶體感測器在液相偵測上的應用 39 1-4-3 石英壓電晶體感測器在化學感測器上的應用 43 1-4-3.1石英壓電晶體感測器在化合物化學感測器上的應用 43 1-4-3.2石英壓電晶體感測器在生物感測器上的應用 43 1-4-4 石英壓電晶體感測器在DNA研究上的應用 45 1-4-5 本研究動機、目的及進行之研究項目 48 第二章 實驗部分 50 2-1 藥品溶劑及儀器 50 2-1-1 藥品溶劑 50 2-1-2 儀器 51 2-2 石英振盪晶體的處理 51 2-3 實驗裝置 52 2-3-1 振盪線路 52 2-3-2 液體靜相系統 53 2-3-2 液體脫附系統 53 2-4 實驗流程 54 2-4-1 DNA的固定化 54 2-4-2 DNA與有機化合物間作用力的研究 55 2-5 系統校正 56 2-6 DNA與有機化合物間作用力UV-VIS光譜的研究 57 第三章 結果與討論 58 3-1 CPS的固定 58 3-1-1 石英晶片銀電極與CPS間的吸附研究 58 3-1-2 CPS吸附在石英晶片銀電極上之濃度效應 58 3-1-3 CPS吸附在石英晶片銀電極上之再現性 58 3-2 DNA的固定 63 3-2-1 DNA吸附在CPS修飾之石英晶片 63 3-2-2 DNA吸附在CPS修飾之石英晶片的脫附行為 64 3-2-3 DNA吸附在CPS修飾之石英晶片的濃度效應 64 3-3 DNA與醇類間的作用力研究 68 3-3-1 DNA與甲醇和乙醇間吸附研究 68 3-3-2 甲醇和乙醇的濃度效應 68 3-3-3 DNA與正丙醇和異丙醇間吸附研究 69 3-4 DNA與酮類間的作用力研究 71 3-4-1 DNA與丙酮和丁酮之吸附研究 71 3-5 DNA與有機酸類間的作用力研究 76 3-5-1 不同的修飾石英晶片對丙酸之感應頻率變化情形 76 3-5-2 溶劑效應 76 3-5-3 有機酸的濃度效應 79 3-5-4 不同種類DNA對有機酸作用力之研究 84 3-5-5 DNA對EDTA作用力之研究 84 3-6 DNA與醛類間的作用力研究 88 3-6-1 不同的修飾石英晶片對丙醛之感應頻率變化情形 88 3-6-2 溶劑效應 88 3-6-3 醛類的濃度效應 93 3-6-4 溶液pH值對DNA與丙醛作用的影響 98 3-6-4.1 溶液pH值對DNA和丙醛作用之影響 98 3-6-4.2 溶液pH值對DNA與丙醛反應時間的影響 98 3-6-5 反應溫度對DNA與丙醛作用的影響 99 3-6-5.1 反應溫度對DNA和丙醛作用之影響 99 3-6-5.2 反應溫度對DNA與丙醛反應時間的影響 99 3-7 DNA與pyrrole及pyridine間的作用力研究 104 3-7-1 固定化DNA石英晶片對pyrrole和pyridine之吸附研究 104 3-7-2 濃度效應 104 3-8 DNA與多環芳香族碳氫化合物間的作用力研究 109 3-8-1 固定化DNA石英晶片對naphthalene之吸附研究 109 3-8-2 固定化DNA石英晶片對pyrene之吸附研究 109 3-9 DNA與有機化合物間作用之UV光譜研究 112 3-10 DNA與有機化合物間的化學吸附能力 114 第四章 結論 116 參考資料 117 附錄 123 附錄一 123

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