臺灣博碩士論文加值系統

離子對雙親分子 (ion pair amphiphile, IPA) 是由二種帶異性電荷之界面活性劑經 等莫爾比例混合後去除對離子形成之複合物，其分子結構與磷脂質類似，在製藥與 DNA轉染等領域有良好的應用潛力。文獻指出，改變IPA的二種組成界面活性分子 之碳長鏈不對稱性以及碳長鏈總長，對IPA雙層膜的相態行為產生明顯影響。本研 究利用分子動態模擬，從微觀的角度解析長烷鏈三甲基–長烷鏈硫酸鹽 (CmTMA+ – CnS–) IPA複合分子之碳長鏈不對稱性以及碳長鏈總長，對於其所組成的雙層膜結構 之結構特性與機械性質的影響。基於硫酸鹽與三甲基結構上的差異，IPA長烷鏈的 不對稱性藉由可藉由不對稱指數ΔC = m - (n + 1)來定義。IPA的|ΔC|越大，會使得位 於雙層膜中心的碳鏈擁有較高的移動自由度而導致雙層膜之排列整齊度與機械性質 下降。而長烷鏈總長越長，則會因為凡得瓦作用力增強而導致雙層膜擁有較高序度 與較強機械性質。本研究提供了許多IPA雙層膜在分子層次上的資訊，有益於日後 新型IPA之設計。
本研究亦使用分子動態模擬，針對環糊精 (cyclodextrin, CD) 與聚胺酸雙親分子 (C16Thr20) 形成之溫度敏感型水膠進行熱力學分析，從微觀的角度分析此種水膠的成 膠機制以及成膠自由能變化。模擬結果顯示環糊精與聚胺酸雙親分子在室溫 (298 K) 以及高溫(398 K) 之下皆可形成穩定的包嵌複合體結構，代表水膠之凝膠–溶膠 轉化並非由環糊精/聚胺酸雙親分子包嵌複合體結構崩解所造成，並以此反推其轉化 機制主因是水膠結構中的氫鍵網絡破壞。另一方面，環糊精/聚胺酸雙親分子的包嵌 行為主要受到熱焓變化所驅動 (ΔH) 。而此包嵌複合體之形成為熱力學穩定且自發 性反應。同時根據2：1環糊精/長烷鏈(C16)之包嵌自由能計算，我們發現在水溶液 環境中，長烷鏈傾向於逐一與環糊精分子組裝成為包嵌複合體，而非由環糊精二聚 體與長烷鏈複合。利用包嵌自由能及熱力學特性分析有助於了解包嵌複合體的包嵌 機制，並可作為實驗結果之佐證。

Ion pair amphiphile (IPA), a lipid-like complex composed of a pair of cationic and anionic surfactants, has been suggested as an inexpensive phospholipid substitute with great potentials in various pharmaceutical applications. In this work, we utilized molecular dynamics (MD) simulation to systematically explore the effects of various alkyl chain combinations of the alkyltrimethylammonium – alkylsulfate IPAs, i.e. CmTMA+ – CnS–, on the corresponding IPA bilayer structural and mechanical properties at the molecular level. Based on the intrinsic molecular structures of the trimethylammonium and the sulfate groups and the observed transversed matching pattern, the CmTMA+ – CnS– IPA alkyl chain asymmetry can be characterized by the asymmetric index, ΔC = m - (n + 1). Larger |ΔC| gives rise to higher conformational fluctuations of the alkyl chains which reduces the overall packing order and the mechanical strength. Besides, higher total chain length leads to increased v.d.W interaction and thus improves the alkyl chain ordering and bilayer mechanical properties.
We also applied MD simulation to study the thermodynamical properties of the thermo-responsive supermolacular hydrogels comprised of β-CD and peptide amphiphiles (C16Thr20). The binding free energy of β-CD:C16Thr20 inclusion complex at 298 K and 333 K (above degelation temperature) is -29.60 and -26.33 kJ/mol, respectively. This result indicates the temperature, at which the degelation occurs, is not high enough to break apart the β-CD:C16Thr20 complex. This suggests that the degelation of C16Thr20 hydrogel is mainly due to the decreased hydrogen bonding network within the structures rather than the β-CD:C16Thr20 complex dissociation. Furthermore, the thermodynamic analysis showed that the β-CD:C16Thr20 complex formation is mainly driven by enthalpy. The free energy data of the thermodynamic cycle for the (β-CD)2:C16 inclusion complex formation illustrated that the C16 chain can form stable complex with two β-CDs, consistent with the reported experimental analysis. Based on the free energy data, the (β-CD)2:C16 complex is more likely formed via the sequentially threading of the β-CDs onto the C16 chain.

摘要...I
Abstract...II
Acknowledgment...III
Table of Contents...IV
List of Table...VI
List of Figures...VII
List of Symbols...XI
Chapter 1 Introduction...1
Chapter 2 Characterization of the Effects of Alkyl Chain Asymmetry on the Ion Pair...5
Amphiphile Bilayer Structures...5
2.1 Introduction...5
2.2 Methods...8
2.2.1 Simulation Details...8
Bilayer Structural Analysis...9
2.2.2 Transverse Density Profiles...9
2.2.3 Lateral Membrane Area...9
2.2.4 Alkyl Chain Tilt Angle...10
2.2.5 Deuterium Order Parameter...10
2.2.6 Gauche Fraction Analysis...11
Bilayer Mechanical Properties...11
2.2.7 Area Expansion Modulu...11
2.2.8 Molecular Tilt Modulus...12
2.2.9 Splay Modulus and Effective Bending Rigidity...12
2.3 Results and Discussion...14
2.3.1 Phase Behaviors of the CmTMA+-CnS- IPA Bilayers at 298K...14
2.3.2 Transverse Density Profile and Alkyl Chain Asymmetry Definition...14
2.3.3 Lateral Membrane Area...15
2.3.4 Tilt Angle Distribution...15
2.3.5 Deuterium Order Parameter...16
2.3.6 Gauche Fraction...17
2.3.7 Area Expansion Modulus...18
2.3.8 Molecular Tilt Modulus...19
2.3.9 Splay Modulus and Effective Bending Rigidity...19
2.4 Concluding Remarks...20
Chapter 3 Gelation Mechanism of β-Cyclodextrin:Peptide Amphiphiles Complex...49
3.1 Introduction...49
3.2 Methods...52
3.2.1 Simulation Details...52
3.2.2 Free Energy Calculation...53
3.2.3 Thermodynamic Integration with Constrained Molecular Dynamics...54
3.2.4 Free Energy Perturbation...55
3.3 Results and Discussion...56
3.3.1 Free energy of β-CD:C16Thr20 and β-CD:C16 Complex Formation...56
3.3.2 Formation of the (β-CD)2:C16 Inclusion Complexes...58
3.4 Concluding Remarks...59
Chapter 4 Conclusion...71
References...73

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