本研究結合原子轉移自由基聚合(ATRP)、開環聚合(ROP)與點擊化學反應(click chemistry)合成出一個新型含乙二醇聚胜肽雙嵌段共聚物聚苯乙烯-b-聚[(丙炔基谷氨酸)-g-(甲氧基乙氧基乙烷基)] [polystyrene-b-poly(γ-propargyl-L -glutamate-g-2-(2-methoxyethoxy)ethyl)]。首先利用傅立葉紅外線光譜儀、廣角度X光射線繞射儀測定側鏈含乙二醇聚胜肽雙嵌段共聚物於固態下之二級結構的α螺旋構型，再藉由圓二色光譜儀測定於液態下之二級結構的轉變。接著再使用小角度X光射線散射儀與穿透式電子顯微鏡可觀察到聚苯乙烯-b-聚[(丙炔基谷氨酸)-g-(甲氧基乙氧基乙烷基)]於固態下的層板結構，而層板中聚胜肽鏈段又以α螺旋構型，自組裝成圓柱狀六角堆積結構，其方向垂直於層板，形成多層次自組裝行為。本研究亦於二甲基甲醯氨與沉澱劑(水、乙腈)之混合溶液裡可觀測到一系列微胞結構，由於聚苯乙烯與沉澱劑之交互作用參數不同，於二甲基甲醯氨與乙腈系統裡只能觀測到球型微胞，然而於二甲基甲醯氨與水混合溶液系統裡，隨著水比例增加，可觀測到微胞結構型態改變，從球型到蠕蟲狀、囊泡與大型複合微胞。

In this study, we used a combination of atom transfer radical polymerization, ring opening polymerization, and click chemistry to synthesize new PEGylated polypeptide block copolymers of polystyrene-b-poly(γ-propargyl-L-glutamate-g- 2-(2-methoxyethoxy)ethyl) [PS-b-(PPLG-g-MEO2)]. We employed FTIR and WAXD to determine the secondary structures of the α-helical conformations of these PEGylated polypeptide block copolymers in the solid state, and circular dichroism spectroscopy to characterize them in solution. Hierarchical self-assembly of the PS-b-(PPLG-g-MEO2) diblock copolymers in the bulk state (characterized using WAXD, SAXS, and TEM) led to the formation of lamellar structures as a result of microphase separation of the diblock copolymers; the hexagonal cylinder packing nanostructure featured α-helical conformations of PEGylated polypeptide segments, which were oriented perpendicular to the director of the lamellar structure formed by the diblock copolymers. We obtained a range of micellar structures from the PS-b-(PPLG-g-MEO2) diblock copolymer in DMF (common solvent) upon the addition of selective solvents (H2O or MeCN). We observed only spherical micelles from the PS-b- (PPLG-g-MEO2) diblock copolymer in DMF/MeCN systems at all MeCN compositions. The micelle structures changed, however, from spherical structures to long wormlike, vesicle, and large compound micelles in the DMF/H2O system upon increasing the content of water. These different morphology transformations arose as a result of very different PS–solvent (H2O or MeCN) interaction parameters.

致謝 i
摘要 ii
ABSTRACT iii
目錄 iv
表目錄 vi
圖目錄 vi
第一章 緒論 1
1-1簡介 1
1-1-1雙嵌段共聚物之自組裝 1
1-1-2聚胜肽 5
1-2 文獻回顧與研究動機 8
第二章 原理 11
2-1 原子轉移自由基聚合(ATRP) 11
2-2 點擊化學反應(click chemistry) 13
2-3 氫鍵作用力概述 14
第三章 實驗 16
3-1實驗流程 16
3-2藥品 17
3-3實驗合成 17
3-3-1 聚苯乙烯之合成(PS) 17
3-3-2 末端疊氮基聚苯乙烯之合成(PS-N3) 17
3-3-3 末端氨基聚苯乙烯之合成(PS-NH2) 18
3-3-4 丙炔基谷氨酸之合成(PLG) 18
3-3-5 丙炔基谷氨酸羧基環內酸酐之合成(PLG-NCA) 18
3-3-6 聚苯乙烯-b-聚(丙炔基谷氨酸)之合成(PS-b-PPLG) 19
3-3-7 甲氧基乙氧基乙基對甲基苯基硫醯之合成(MEO2-OTs) 19
3-3-8 疊氮基甲氧基乙氧基乙烷之合成(MEO2-N3) 19
3-3-9 聚苯乙烯-b-聚[(丙炔基谷氨酸)-g-(甲氧基乙氧基乙烷基)]之
合成[PS-b-(PPLG-g-MEO2)] 20
3-4儀器 22
3-5檢測方法 22
3-5-1 核磁共振結構分析 22
3-5-2 膠體滲透層析儀分子量量測 23
3-5-3 圓二色光譜分析 23
3-5-4 傅立葉轉換紅外線光譜分析 25
3-5-5 微差掃描式熱分析 25
3-5-6小角度X光射線散射 25
3-5-7廣角度X光射線繞射 26
3-5-8動態光散射粒徑大小分析 26
3-5-9穿透式電子顯微鏡固態與微胞結構觀察 27
第四章 結果與討論 28
4-1合成PS-b-(PPLG-g-MEO2)結構鑑定 28
4-2 PS-b-(PPLG-g-MEO2)熱性質分析 35
4-3 PS-b-(PPLG-g-MEO2)二級結構測定 36
4-4 PS-b-(PPLG-g-MEO2)雙嵌段共聚物之自組裝結構 40
4-5 PS-b-(PPLG-g-MEO2)於溶液下的自組裝行為 44
第五章 結論 53
參考文獻 54
作者簡介 57

1. M. Matsen and F. Bates, Macromolecules, 1996, 29, 1091-1098.
2. S. P. Lim, L. Luo, D. Maysinger and A. Eisenberg, Langmuir, 2002, 18, 9996-10004.
3. S. M. Harada, K. Yamauchi, A. Harada, I. Takamisawa, K. Shimokado, and K. Kataoka, Gene therapy, 2002, 9, 407-414.
4. F. Henselwood, G. Wang and G. Liu, J. Appl. Polym. Sci., 1998, 70, 397-408.
5. L. Zhang and A. Eisenberg, J. Am. Chem. Soc., 1996, 118, 3168-3181.
6. P. Bhargava, J. X. Zheng, P. Li, R. P. Quirk, F. W. Harris and S. Z. Cheng, Macromolecules, 2006, 39, 4880-4888.
7. L. Zhang and A. Eisenberg, Polym. Adv. Technol., 1998, 9, 677-699.
8. D. Y. Chen and M. Jiang, Acc. Chem. Res., 2005, 38, 494-502.
9. D. N. Bikiarisz, G. Z. Papageorgiou and D. S. Achilias, Polym. Degrad. Stab., 2006, 91, 31-43.
10. R. A. Copeland,Methods for protein analysis: a practical guide to laboratory protocols; Chapman & Hall: London, 1994.
11. H. Fu, Protein-protein interactions: methods and applications; Humana Pr Inc: New Jersey 2004; Vol. 261.
12. 劉家福 蛋白質溶液結構測定方法 黑龍江教育出版社 哈爾濱, 2010.
13. L. Pauling and R. B. Corey, J. Am.Chem. Soc., 1950, 72, 5349.
14. L. Pauling, R. B. Corey and H. R. Branson, Proceedings of the National Academy of Sciences, 1951, 37, 205-211.
15. P. Sarkar and P. Doty, Proceedings of the National Academy of Sciences of the United States of America, 1966, 55, 981.
16. N. J. Greenfield and G. D. Fasman, Biochemistry, 1969, 8, 4108-4116.
17. X. L. Qi, C. Holt, D. McNulty, D. T. Clarke, S. Brownlow and G. R. Jones, J. Biochem., 1997, 324, 341-346.
18. A. Barth, Prog. Biophys. Mol. Biol., 2000, 74, 141-173.
19. Y. El Khoury, R. Hielscher, M. Voicescu, J. Gross and P. Hellwig, Vib. Spectrosc., 2011, 55, 258-266.
20. E. I. Ramm, V. P. Gorenburg, A. B. Klionsky and E. E. Smirnova, Biofizika, 1980, 25, 559-560.
21. E. Peggion, A. Cosani and M. Terbojevich, Macromolecules, 1974, 7, 453-459.
22. Y. S. Lu, Y. C. Lin and S. W. Kuo, Macromolecules, 2012, 45, 6547-6556.
23. S. W. Kuo and C. J. Chen, Macromolecules, 2011, 44, 7315-7326.
24. H. Bader, H. Ringsdorf and B. Schmidt, Die Angewandte Makromolekulare Chemie, 1984, 123, 457-485.
25. P. Bhargava, Y. Tu, J. X. Zheng, H. Xiong, R. P. Quirk and S. Z. J. Cheng, Am. Chem. Soc., 2007, 129, 1113-1121.
26. P. Papadopoulos, G. Floudas, H. Klok, I. Schnell and T. Pakula, Biomacromolecules, 2004, 5, 81-91.
27. X. Zhao, Z. Poon, A. C. Engler, D. K. Bonner and P. T. Hammond, Biomacromolecules, 2012, 13, 1315-1322.
28. A. C. Engler, H. i. Lee and P. T. Hammond, Angew. Chem. Int. Ed., 2009, 48, 9334-9338.
29. Y. Cheng, C. He, C. Xiao, J. Ding, X. Zhuang and X. Chen, Polym. Chem., 2011, 2, 2627-2634.
30. C. M. Chopko, E. L. Lowden, A. C. Engler, L. G. Griffith and P. T. Hammond, ACS Macro Letters, 2012, 1, 727-731.
31. Y. C. Lin and S. W. Kuo, Polym. Chem., 2012, 3, 162-171.
32. Y. C. Lin, P. I. Wang and S. W. Kuo, Soft Matter, 2012, 8, 9676-9684.
33. Y. C. Lin and S. W. Kuo, Polym. Chem., 2012, 3, 882-891.
34. J. S. Wang and K. Matyjaszewski, J. Am. Chem. Soc., 1995, 117, 5614-5615.
35. M. Kato, M. Kamigaito, M. Sawamoto and T. Higashimura, Macromolecules, 1995, 28, 1721-1723.
36. K. Matyjaszewski and N. V. Tsarevsky, Nature chemistry, 2009, 1, 276-288.
37. K. Matyjaszewski, Isr. J. Chem., 2012, 52, 206-220.
38. K. Min and K. Matyjaszewski, Central European Journal of Chemistry, 2009, 7, 657-674.
39. J. Xia and K. Matyjaszewski, Macromolecules, 1997, 30, 7692-7696.
40. J. Gromada and K. Matyjaszewski, Macromolecules, 2001, 34, 7664-7671.
41. R. Huisgen, Proc. Chem. Soc., 1961, 5, 357-396.
42. H. C. Kolb, M. Finn and K. B. Sharpless, Angew. Chem. Int. Ed., 2001, 40, 2004-2021.
43. V. O. Rodionov, S. I. Presolski, D. Díaz Díaz, V. V. Fokin and M. Finn, J. Am. Chem. Soc., 2007, 129, 12705-12712.
44. N. Purdie and H. Brittain, Analytical applications of circular dichroism; Elsevier Science Ltd, 1994; Vol. 14.
45. J. T. Yang, C. S. C. Wu and H. M. Martinez, Method Enzymol., 1986, 130, 208-269.
46. K. Watanabe, K. Muto and T. Ishii, Biospectroscopy, 1997, 3, 103-111.
47. S. Lecommandoux, F. Checot, R. Borsali, M. Schappacher, A. Deffieux, A. Brulet and J. Cotton, Macromolecules, 2002, 35, 8878-8881.
48. Y. Mai and A. Eisenberg, Chem. Soc. Rev., 2012, 41, 5969-5985.