中性雙功能型水膠之合成、鑑定、性質探討與毒性研究

本碩士論文的研究主軸在合成及鑑定新型的[中性]雙功能型(即自癒性及電活性兩種功能)的水膠材料，並探討電活性材料在進入水膠材料之後，對水膠材料的流變行為及胚胎毒性所造成的影響效果。本研究中對水膠材料訴求中性，是為了後續研究工作在進行體外實驗(細胞培養)及體內實驗(動物模型)時能夠有較多種類的細胞/器官可供研究。首先，在電活性材料的製備方面，單端胺基苯胺寡聚體(四聚體及五聚體)是以氧化偶合法合成，單端胺基苯胺二聚體則選用商品。三種電活性材料皆利用核磁共振光譜儀(NMR)、紅外光譜儀(FTIR)及質譜儀(MS)做化學結構的鑑定。單端胺基苯胺寡聚體的電活性是利用電化學伏安儀進行鑑定，研究顯示電活性趨勢: 單端胺基苯胺五聚體  單端胺基苯胺四聚體  單端胺基苯胺二聚體。進一步使用琥珀酸酐與三種電活性材料進行化學反應，以製備一系列具末端羧酸基的苯胺二聚體、四聚體及五聚體，並進一步利用NMR、FTIR及MS做化學結構的鑑定。在中性自癒性水膠材料的製備方面，以自身合成之雙端醛基聚乙二醇與[中性]的乙二醇聚殼醣商品進行反應，以合成一系列具動態亞胺鍵(-C=N-)的自癒性水膠，進一步以FTIR 確認亞胺鍵已經成功的生成，並以流變儀探討自癒性水膠之流變行為(包含: 應變掃描、應變轉換、儲存模數、極限應變及回復率)。在中性雙功能型水膠材料的製備方面，以三種具末端羧酸基苯胺寡聚體進行化學接枝中性的乙二醇殼聚醣，所得產物稱為電活性乙二醇殼聚醣。將此具電活性之殼聚醣與雙端醛基聚乙二醇（Difunctional-polyethylene glycol 2000，DF-PEG 2000）進行動態化學交聯，以製備一系列的中性雙功能型水膠，進一步以FTIR進行材料的鑑定，並與非電活性之中性自癒性水膠進行一系列的比較。中性雙功能型水膠的電活性亦是利用電化學伏安儀進行鑑定，研究顯示: 所有的雙功能型水膠的電活性均小於對應的單端胺基苯胺寡聚體。但發現單端胺基苯胺五聚體在導入中性之自癒合水膠時，大部份會析出；另一方面，單端胺基苯胺四聚體在導入中性自癒性水膠時，少部份會析出。因此，後續在中性雙功能型水膠的流變學探討上，將聚焦在由單端胺基苯胺二聚體所衍生的中性雙功能型水膠。此中性雙功能型水膠之降解行為是利用ASTM D 6400的標準方法進行檢測，經過28天的體外降解（in-vitro Degradation）實驗證實，此中性雙功能型水膠具有穩定的可降解性（81.8%）。在中性雙功能型水膠的流變學探討方面，由研究結果發現: 具末端羧酸基苯胺二聚體的導入，會造成自癒性水膠的儲存模數下降、極限應變率下降及回復率上升。此外，具末端羧酸基苯胺二聚體導入自癒性水膠的樣品經過凍乾機處理後，由掃描式電子顯微鏡的觀察發現，其平均孔隙大小會小幅上升。最後，在中性雙功能型水膠材料的毒性測試方面，是利用斑馬魚的胚胎進行材料的毒性研究，經由實驗結果證實: 單純的自癒型水膠材料不具有斑馬魚的胚胎毒性，而中性雙功能型水膠由於電活性的結構導入，因此具有斑馬魚的胚胎毒性。但是末端具羧酸基的苯胺二聚體相較於其他的電活性寡聚物則相對的具有最低的胚胎毒性。

關鍵字

水膠；自癒性；電活性；雙功能；流變；降解；毒性

並列摘要

The research spindle of this master's thesis is to synthesize and identify the new type of dual effect (i.e., self-healing and electroactivity) hydrogel materials, and to explore the effects of electroactive materials on the rheological behavior and embryonic toxicity of hydrogel materials after entering the hydrogel materials. In this study, the hydrogel materials sought neutrality, in order to follow-up research work in in-vitro experiments (cell culture) and in-vivo experiments (animal models) can have more kinds of cells/organs available for study. 　　First of all, in the preparation of electroactive materials, aniline oligomers (i.e., tetramers and pentamers) with one terminal primary amine are synthesized by oxidative coupling reaction. All three electroactive aniline oligomers with different conjugated length ( dimer, tetramer and pentamer) are used to identify chemical structures using nuclear magnetic resonance (NMR), Fourier-Transformation infrared spectrometer (FTIR) and mass spectroscopy (MS). Electroactivity of three distinctive aniline oligomers is identified by electrochemical cyclic voltammetry, and study shows the trend of electroactivity: aniline pentamer  aniline tetramer  aniline dimer. Subsequently, the amber anhydride was further reacted with three electroactive aniline oligomers to prepare series of carboxylic acid terminated aniline oligomers, followed by NMR, FTIR and MS. 　　In the preparation of neutral self-healing hydrogel materials, the reaction of the self-synthetic end-capped aldehyde-based polyglycol and the polyglycol polychcocel commodity of the neutral, in order to synthesize a series of self-healing hydrogels with dynamic imine bonds (-C=N-), and confirmed by FTIR that the imine bonds have been successfully formed. 　　The rheological behavior of self-healing hydrogel (including: strain scanning, strain conversion, storage module, limit strain and response rate) is discussed by rheometer. In the preparation of neutral dual-function hydrogel materials, three kinds of aniline oligomers are chemically grafted neutrally glycol polysaccharides, and the resulting product is called electroactive glycol polysaccharides. This electroactive polyglycol is paired with end-capped aldehyde-based polyglycol (Difunction-polyethylene glycol 2000, DF-PEG 2000) to prepare a series of neutral dual-function hydrogels for further identification of the materials by FTIR. And a series of comparisons were made with non-electrically active psychoactive self-healing hydrogel. The electroactivity of neutral dual-function gel is also to use electrochemical cyclic voltammetry for identification, the study shows that: All dual-function hydrogel electroactive is smaller than the corresponding aniline oligomers. However, it was found that most of the aniline tetramers would be precipitated when importing neutral self-healing gels, and on the other hand, a small portion of aniline tetramers would be precipitated when importing neutral self-healing hydrogels. Therefore, the follow-up discussion on the rheological discussion of neutral dual-function hydrogel will focus on the neutral dual-function hydrogel derived from the aniline dimer. 　　The degradation behavior of this neutral dual-function gel is tested using the standard method of ASTM D 6400, and after 28 days of in-vitro degradation (in-vitro Degradation) experiments, it is proved that this neutral dual-function gel has stable degradation ability (81.8%). In the study of the rheological of neutral dual-function gel, the results of study found that: the introduction of aniline dimer will cause the storage module of self-healing gel to decrease, the limit strain rate to decrease and the recovery rate to rise. 　　In addition, the sample of self-healing hydrogel imported into the aniline polysaccharides was treated by a freeze-drying machine, and the observation of scanning electron microscopy found that the average pore size would increase slightly. Finally, in the toxicity test of neutral dual-function hydrogel material, it is the toxicity study of materials using the embryo of zebrafish, which is proved by the experimental results: the pure self-healing hydrogel materials does not have the embryo toxicity of zebrafish, and the neutral dual-function hydrogel has the embryonic toxicity of zebrafish due to the incorporation of electrically active structure. 　　However, the aniline dimer with terminated carboxylic acid had the lowest embryo toxicity compared to other incorporated electroactive oligomers with higher conjugated lengths.