I. 合成3-羥基黃酮雌二醇螢光探針並探討連接子對於分子光物理性質及自組裝行為的影響
II. 發展可快速偵測光氣之螢光探針

第一部分自組裝已被廣泛應用於材料科學、化學和生物學中，作為自下而上建構奈米至微米等級大小的有序且高度複雜結構的方法。基於先前研究的啟發，本論文設計並合成了由3-HF或DBD和雌二醇組成的一系列螢光探針：HF-7α-Gly-EDIOL、HF-7α-U-EDIOL、DBD-7α-Gly-EDIOL和DBD-7α-U-EDIOL，進一步探討若在連接雌二醇和螢光團的連接鏈上作修飾，對分子光物理性質和自組裝行為的影響。此外，選擇的螢光團3-HF或DBD為對環境高度敏感的螢光團，通過探測3-HF的ESIPT/ESICT螢光強度比或DBD的螢光強度變化，可以推測出超分子奈米結構的形態。透過動態光散射、表面電位和穿透式電子顯微鏡成像的實驗，可以確認這些聚集的形態。在不同比例DMSO/H2O溶劑中之螢光測試結果發現，HF-7α-Gly-EDIOL、HF-7α-U-EDIOL、DBD-7α-Gly-EDIOL和DBD-7α-U-EDIOL這四個分子均有螢光反轉的現象，初步推測分子發生了聚集。由DLS和TEM實驗結果可進一步得知，HF-7α-Gly-EDIOL聚集結構為球狀，但彼此交聯在一起，大小約70-400 nm；HF-7α-U-EDIOL只觀測到大小不一的不規則形狀 (類圓球狀)，尺寸直徑約落在80 nm左右；DBD-7α-Gly-EDIOL聚集為不規則形狀，一樣也是彼此交聯在一起，而交聯狀匯集處呈類圓球狀，大小約小於100 nm；DBD-7α-U-EDIOL聚集為完美的球狀，大小較為均一，約為135-160 nm。結果顯示在連接鏈上修飾甘胺酸 (Gly) 和尿素 (U) 這兩個基團則是影響分子在水中傾向聚集的能力。由細胞實驗結果可知，相較於連接鏈修飾上尿素基團的分子，連接鏈修飾上甘胺酸之HF-7α-Gly-EDIOL和DBD-7α-Gly-EDIOL均能進入細胞，且大多分布在細胞質當中，反映這兩個分子在生物上的應用是具有潛力的。第二部分光氣是一種無色且劇毒的氣體，暴露於光氣會造成嚴重的急性呼吸道作用，包括非心源性肺水腫，肺氣腫和死亡。鑑於其強大的殺傷力和大規模工業用途，光氣幾乎對公共衛生安全構成嚴重威脅，不僅是因為恐怖分子潛在的使用，也因工業事故造成的意外釋放。因此，為了保護公眾健康和安全不受光氣的傷害，發展能有效且快速偵測低於安全濃度之光氣的螢光探針具有重要意義。本論文中，使用乙二胺作為識別部分和7號位置有取代的DBD單元作為螢光團的部分，開發出具有低至12.2 nM的偵測極限和小於5分鐘的反應時間之新型光氣探針7-EDADBD。該探針和光氣進行加成-離去和分子內環化反應後，可得到產物7-IDBD，其最大吸收和放射波長均藍移，螢光強度有15.6倍 (在ACN溶劑中) 或5.3倍 (在DCM溶劑中) 的增強。此外，和其他類似反應性之有毒化學物質相比，7-EDADBD對於光氣具有顯著的選擇性。

關鍵字

I. 自組裝；奈米結構；雌二醇衍生物； 3-HF ； DBD II. 光氣；乙二胺基團；分子內環化； DBD ；螢光探針

並列摘要

Part I. Self-assembly has been widely used in materials science, chemistry, and biology as a bottom-up approach to create ordered structures at the nanometer to micrometer scale with high complexity. Inspired by our previous findings, this thesis would focus on the effects of linker linking the fluorophore and estradiol on the photophysical properties and self-assembly behaviors should be further investigated. Moreover, two environmentally sensitive fluorophores such as 3-hydroxyflavone (3-HF) and 4-sulfamonyl-7-aminobenzoxadiazole (DBD) having emission properties that are highly sensitive to their immediate environment were chosen to incorporated into the molecular designs respectively. Accordingly, a series of fluorescent probes HF-7α-Gly-EDIOL, HF-7α-U-EDIOL, DBD-7α-Gly-EDIOL, and DBD-7α-U-EDIOL consisting of either 3-HF or DBD and estradiol were designed and synthesized. By probing the ESIPT/ESICT fluorescence intensity ratios of 3-HF or the fluorescent intensity changes of DBD, the morphology of the supramolecular nanostructures can be speculated. In the combination of DLS, zeta potential, and TEM images, the morphologies of the aggregates can be confirmed. The fluorescence spectra of HF-7α-Gly-EDIOL, HF-7α-U-EDIOL, DBD-7α-Gly-EDIOL, and DBD-7α-U-EDIOL showed fluorescence reversal in different proportions of DMSO/H2O solvents. Based on these observation, the aggregates with the fluorophore pointed inward were speculated. DLS and TEM experiments further confirmed that the aggregates of HF-7α-Gly-EDIOL are cross-linked spheres with a diameter of 70-400 nm; the aggregates of HF-7α-U-EDIOL are irregular sphere with the size of about 80 nm; the aggregates of DBD-7α-Gly-EDIOL are irregular shapes, while cross-linked area are spherical, with the size of less than 100 nm; the aggregates of DBD-7α-U-EDIOL are perfect globular with uniform size and a diameter of about 135-160 nm. In summary, the results indicate that modifying Gly or Urea functional groups on the linker would affect the aggregate ability of molecules in the water. In the cell imaging experiments, HF-7α-Gly-EDIOL and DBD-7α-Gly-EDIOL containing Gly linker were able to enter the cells and were mostly distributed in the cytoplasm. Its reveals that the potential application of these two molecules in biology. Part II. Phosgene is a corlorless and highly toxic gas. Exposure to phosgene has severe acute respiratory effects, including noncardiogenic pulmonary edema, pulmonary emphysema, and death. In light of its strong lethality and large-scale industrial use, phosgene virtually poses a serious threat to public health safety, not only because of its potential use by terrorists, but also because of its unexpected release during industrial accidents. Therefore, developing an efficient fluorescent probe for facile and rapid detection of phosgene with concentration below the safety margin is of great significance for protecting public health and safety from the chance of exposing harmful phosgene. Herein, a new type of phosgene probe 7-EDADBD with a detection limit down to 12.2 nM and response time of less than 5 min was developed. The probe consisting of ethylenediamine as the recognition moiety and 7-substituted DBD unit as the fluorescence signaling component. It undergoes sequential phosgene-mediated addition-elimination reaction and intramolecular cyclization with fast rate, yielding a product 7-IDBD with blue-shifts in the absorbance and emission spectra as well as 15.6-fold (ACN) or 5.3-fold (DCM) fluorescence enhancement. Furthermore, 7-EDADBD displayed remarkable reactivity toward phosgene over other similarly reactive toxic chemicals.

並列關鍵字

I. self-assembly ； nanostucture ； estradiol derivative ； 3-HF ； DBD II. phosgene ； ethylenediamine group ； intramolecular cyclization ； DBD ； fluorescence probe

參考文獻

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國際替代計量

I. 合成3-羥基黃酮雌二醇螢光探針並探討連接子對於分子光物理性質及自組裝行為的影響 II. 發展可快速偵測光氣之螢光探針

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