Novel Fluorescent Nanoparticles Constructed from AIEgens

本研究希望開發一系列的新分子，第一章節以Acridine為core利用Heck反應和Suzuki反應方法合成一系列2,7-位置具有不同官能基的Acridine衍生物，藉此研究Acridine衍生物的基本光學性質及在酸、鹼性環境下的影響，並著重於研究它們是否具有聚集誘導螢光增強 (Aggregation-Induced Emission, AIE) 的特性。我們將具有AIE特性並能形成FONs的化合物直接使用Stöber method包覆，形成內含自我聚集 (self-assembly) 特性分子的二氧化矽奈米粒 (silica nanoparticles)。 在第二章節我們改良了Stöber method建立一個以胺基酸檢測器所構築的新型奈米粒系統ASP @ OH和CSP @ OH。製作過程分為兩部分:首先在室溫環境下，本實驗室所設計的biosensor會與可構築內含染料的二氧化矽奈米粒 (dye-doped silica nanoparticles, DDSN) 的前驅物結合後，因為分子內電荷轉移 (Intramolecular Charge Transfer, ICT) 與光誘導電子轉移 (Photo-induced Electron Transfer, PET) 原理達到螢光第一階段增強的效果。再將此螢光生物檢測劑以Stöber method包覆成具有聚集誘導螢光 (AIE) 特性的螢光奈米粒ASP @ OH和CSP @ OH，經過這兩步驟可得到一個螢光雙重增強(double emission enhancement, DEE)的系統。這種螢光雙重增強的奈米粒其放射波長是可調控的，且具有高螢光量子產率、光學穩定性與表面易於改質。不僅可作為新型螢光材料且可應用於細胞內成像與生物標記 (biomarker)。The major goal for our research is to use simple synthesized method for various fluorescence dye derivatives containing acridine core via Heck reaction and Suzuki coupling reaction. The basic optical properties of acridine derivatives and their effects in acidic and alkaline environments were investigated. It is more important to study whether they have the characteristics of Aggregation-Induced Emission (AIE). We will molecules with AIE properties and capable of forming FONs, which are directly coated by the Stöber method to form dye-doped silica nanoparticles (DDSN). A set of amino acid fluorescence turn-on sensor-based fluorescence organic nanoparticles ASP@OH and CSP@OH were constructed by the modified stöber method. The constructed procedure can be divided into two steps. The room temperature-reacted amino acid sensors were firstly silanized with DDSN precursor in an ethanol solution. This is the first stage of emission enhancement due to intramolecular charge transfer (ICT) or photo-induced electron transfer (PET). After that, silane was further added to coat on the core to form a silica shell. The fluorescence of the obtained ASP@OH and CSP@OH is expected to increase further with AIE properties. That is, the ICT-induced fluorescence enhancement phenomenon was promoted according to the AIE effect that can be used to build-up a novel double emission enhancement (DEE) platform. Systematic investigations verify that the resulting ASP@OH and CSP@OH could display extremely conservative, solvent-independent and photo-stability optical properties in aqueous media as well as in most organic solvents. It means that these novel fluorescent nanoparticles are suitable to be a biomarker of living cells and functioned as fluorescent visualizers for intracellular imaging.1. 前言 1 1.1 核心分子 (Core) 1 1.2 Acridine 2 1.3分子內電荷轉移（Intramolecular Charge Transfer，ICT） 3 1.4光誘導電子轉移 (Photo-induced Electron Transfer, PET) 4 1.5螢光有機奈米粒 (Fluorescent organic nanoparticles, FONs) 5 1.6內含染料的二氧化矽奈米粒 (dye-doped silica nanoparticles, DDSN) 7 1.7 研究動機與流程 11 2. 實驗方法 12 2.1 材料與藥品 12 2.2 儀器與設備 12 2.3 Acridine衍生物的分子合成與鑑定 15 2.4 1,8-Naphthalic Anhydride衍生物的合成與鑑定 20 2.5包覆染料的二氧化矽奈米粒製備與合成 22 2.6細胞實驗方法 23 3. Acridine衍生物的合成與研究以及奈米化的評估 24 3.1結果與討論 24 3.1.1 基本光譜 24 3.1.2 酸鹼測試 40 3.1.3 AIE的測試 43 3.1.4細胞餵養情形 53 3.1.5螢光有機奈米粒的包覆與光學性質探討 56 3.2結論 58 4. 利用AIE特性構築螢光二次增強系統 59 4.1結果與討論 59 4.1.1分子設計 59 4.1.2基本光譜 61 4.1.3 生物感測劑 (biosensor) 與螢光增強 66 4.1.4 AIE的測試 69 4.1.5奈米粒的形成與螢光二次增強 72 4.1.6表面混層改質的奈米粒與細胞成像 79 4.2結論 84 5. 未來工作 85 6. 參考文獻 8