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研究生: 蘇于晴
Su, Yu-Ching
論文名稱: 具三條十六碳鏈之離子對雙親分子形成的陰陽離子液胞物理性質及液胞雙層膜中分子排列特性:膽固醇效應
Physical properties of catanionic vesicle and the packing characteristic of the vesicular bilayer formed of a trihexadecyl-chained ion pair amphiphile: cholesterol effect
指導教授: 張鑑祥
Chang, Chien-Hsiang
學位類別: 碩士
Master
系所名稱: 工學院 - 化學工程學系
Department of Chemical Engineering
論文出版年: 2017
畢業學年度: 105
語文別: 中文
論文頁數: 116
中文關鍵詞: 陰陽離子液胞離子對雙親分子相轉移行為膽固醇效應分子模擬液胞雙層膜
外文關鍵詞: catanionic vesicle, cholesterol effect, molecular dynamics simulation, phase transition behavior, vesicular bilayer
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  • 本研究以雙碳鏈陽離子型界面活性劑dihexadecyldimethylammonium bromide(DHDAB)及單鏈陰離子型界面活性劑sodium hexadecylsulfate (SHS)所形成之三碳鏈離子對雙親分子dihexadecyldimethylammonium-hexadecylsulfate(DHDA-HS)為主材料,添加膽固醇以強制型製程製備出陰陽離子液胞,並分析膽固醇的添加對於液胞物理特性、雙層膜的相轉移行為及流動性的影響。同時利用分子動力學模擬探討DHDA-HS/膽固醇雙層膜的結構特性及機械性質,以進一步了解膽固醇對液胞雙層膜結構中分子排列的影響機制。
    實驗結果顯示,純成分DHDA-HS可形成穩定的液胞,但液胞表面的帶電特性隨著保存時間的增加逐漸減少,靜電排斥作用不足以避免液胞彼此聚集/融合,穩定時間並不長。添加膽固醇後,所形成之液胞的界面電位沒有明顯的變化,但能有效提升液胞的物理穩定性,可見DHDA-HS液胞系統的物理穩定性除了和液胞間的靜電排斥作用有關外,液胞雙層膜內的分子排列也扮演重要的角色。螢光偏極化法及動態雷射光散射法的分析結果顯示,膽固醇的添加能抑制DHDA-HS/膽固醇液胞雙層膜的相轉移行為。而當膽固醇添加量高於30 mol%時,由螢光偏極化的結果推測雙層膜中有膽固醇結晶的產生,此時液胞雙層膜的相轉移行為幾乎已消失。添加10 mol%的膽固醇時,相轉移溫度有最大值,推測是雙層膜中分子排列較緊密所導致的。
    關於DHDA-HS/膽固醇液胞雙層膜的排列特性及流動性,由紅外光譜法、螢光偏極化法及分子模擬的分析結果得知,添加10 mol%的膽固醇時,雙層膜整體的碳鏈排列趨於規則,但靠近雙層膜中心的流動性上升,這歸因於膽固醇對DHDA-HS碳氫鏈不同區段有不同的效應。而隨著膽固醇含量的增加,雙層膜整體的排列規則性下降,靠近雙層膜中心的流動性也提升,此時由膽固醇的不規則效應主導。
    透過分析分子頭基在雙層膜法線方向的密度分布及二維徑向分布函數,發現膽固醇的添加對於頭基排列行為的影響有限,與實驗上量測到的液胞初始界面電位無顯著變化的結果有關。藉由分析雙層膜的面積壓縮模數、分子傾角模數及有效彎曲模數,可了解雙層膜的機械性質,發現添加膽固醇對雙層膜有效彎曲模數的影響與所形成之液胞大小有關。

    In this study, an ion pair amphiphile (IPA) with trihexadecyl-chained structure, dihexadecyldimethylammonium-hexadecylsulfate (DHDA-HS), was obtained as precipitate from mixed aqueous solutions of anionic surfactant, sodium hexadecylsulfate, and cationic surfactant, dihexadecyldimethylammonium bromide. Physical properties, membrane fluidity, and bilayer structure characteristic of catanionic vesicles fabricated from the IPA and cholesterol by a forced formation approach were then investigated. DHDA-HS vesicles could be fabricated in aqueous phase with an average size of 125 nm but with poor physical stability. In order to improve physical stability of the DHDA-HS vesicles, cholesterol was used as an additive. With the addition of cholesterol into the vesicular structures, the physical stability of the DHDA-HS vesicles could be improved with no significant change in the zeta potential. Fluorescence polarization, infrared spectroscopy, and molecular dynamics simulation analyses indicated that the addition of cholesterol into the DHDA-HS vesicles could have different effects on the molecular packing characteristic and vesicular membrane fluidity in different membrane regions. The phase transition temperature of the vesicular bilayers was increased with the addition of cholesterol at a low content but seemed to be reduced with the addition of cholesterol at a high content. Simulation analyses showed that the addition of cholesterol would affect the bending modulus of the vesicular bilayers, which was consistent with the findings in the size of DHDA-HS vesicles.

    摘要 I Extended Abstract III 誌謝 XIV 總目錄 XV 表目錄 XVIII 圖目錄 XX 符號說明 XXVI 第一章 緒論 1 1-1 前言 1 1-2 研究動機與目的 4 1-3 文獻回顧 5 1-3-1 離子對雙親分子 5 1-3-2 陰陽離子液胞 6 1-3-3 帶電液胞 8 1-3-4 膽固醇效應 10 1-3-5 液胞的相轉移行為 14 1-3-6 利用三碳鏈之雙親分子製備的液胞 17 1-3-7 分子動力學模擬 18 第二章 實驗及模擬方法 19 2-1 藥品 19 2-2 實驗儀器及裝置 19 2-2-1 超音波震盪分散裝置 19 2-2-2 雷射光散射法粒徑及界面電位分析儀 20 2-2-3 元素分析儀 24 2-2-4 穿透式電子顯微鏡 25 2-2-5 傅利葉轉換紅外光譜儀 25 2-2-6 發光光譜儀 27 2-3 實驗方法 28 2-3-1 離子對雙親分子的製備 28 2-3-2 液胞分散液的製備 30 2-3-3 液胞粒徑分布及界面電位的量測 31 2-3-4 穿透式紅外光譜的分析 32 2-3-5 螢光偏極化實驗 33 2-4 分子動態模擬 34 2-4-1 模擬系統 34 2-4-2 雙層膜的結構分析 37 2-4-2-1 側向膜面積(lateral membrane area) 37 2-4-2-2 縱向密度分布(transverse density profiles) 37 2-4-2-3 氘序參數(deuterium order parameter) 37 2-4-2-4 鈍式構形比率(gauche fraction) 38 2-4-2-5 傾斜角(tilt angle) 38 2-4-2-6 徑向分布函數(radial distribution function) 39 2-4-3 雙層膜的機械性質 39 2-4-3-1 面積擴張模數(area expansion modulus) 39 2-4-3-2 分子傾斜模數(molecular tilt modulus) 40 2-4-3-3 張角模數及有效彎曲硬度(splay modulus and effective bending rigidity) 41 第三章 結果與討論 43 3-1 DHDA-HS之離子對雙親分子 43 3-1-1 元素分析 43 3-1-2 界面活性劑參數 43 3-2 DHDA-HS 系統 46 3-2-1 DHDA-HS之陰陽離子液胞的物理特性 46 3-2-2 DHDA-HS液胞雙層膜的相轉移行為 51 3-2-3 DHDA-HS雙層膜的結構性質 54 3-3 膽固醇效應 59 3-3-1 混合DHDA-HS/膽固醇之陰陽離子液胞的物理特性 59 3-3-2 混合DHDA-HS/膽固醇液胞雙層膜的相轉移行為 70 3-3-3 膽固醇對液胞雙層膜排列的影響 76 3-3-4 混合DHDA-HS/膽固醇雙層膜的結構性質 80 3-3-5 混合DHDA-HS/膽固醇雙層膜的機械性質 95 第四章 結論 97 參考文獻 99

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