本論文以過去常用於聚合反應之起始劑過硫酸鈉 (sodium persulfate, SPS)、偶氮二異丁腈 (azobisisobutyronitrile, AIBN)，以及結構上具有活性氫之新型起始劑巴比妥酸 (barbituric acid, BTA) 進行氮異丙基丙烯醯胺 (N-isopropylacrylamide, NIPAm) 之聚合反應。由於不同種類的起始劑適用不同溶劑環境，研究中發現聚合機制略有差異，進而影響PNIPAm分子量，且分子量對其最低臨界溶解溫度 (lower critical solution temperature, LCST) 有所影響；此外，將NIPAm分別與親水性單體2-HEA及疏水性單體2-EHA進行共聚合反應，所得到之共聚物皆降低PNIPAm之LCST行為發生溫度位置。另一方面，由於BTA為新型起始劑，因此亦以凝膠滲透層析儀 (GPC)、核磁共振光譜儀 (NMR)、電子順磁共振光譜儀 (EPR) 等儀器研究分析其在不同反應條件下所得到之PNIPAm差異，發現BTA主要以其本身結構存在於水中，並產生較高濃度自由基，可有效引發聚合反應。
最後使用示差掃描熱分析儀 (DSC)，對PNIPAm之LCST現象進行動力學分析，搭配動態光散射粒徑分析儀 (DLS) 之測量結果，探討此相變化發生機制。其中PNIPAm因升溫而發生的LCST行為牽涉到高分子鏈生成疏水核心及粒子聚集；然而，降溫程序中此相變化機制則與氫鍵的形成及水分子的擴散有關。

PNIPAm is a temperature-responsive polymer that undergoes a reversible lower critical solution temperature (LCST) phase transition from a swollen hydrated state to shrunken solid state. This work studied the effects of different initiators on the molecular weight and LCST of Poly(N-isopropylacrylamide) (PNIPAm). The common initiator azobisisobutyronitrile (AIBN) and sodium persulfate (SPS) which used in other polymerization systems were empolyed here. In addition , barbituric acid (BTA) also can initiate free radical polymerization with the reactive groups one >CH2 and two >NH groups in its structure. Thus, the polymerization and characterization of N-isopropylacrylamide (NIPAm) with novel initiator BTA was investigated. We also copolymerized hydrophilic and hydrophobic monomer with NIPAm respectively for adjusting the LCST behavior of PNIPAm, and find that both 2-hydroxyethyl acrylate (2-HEA) and 2-ethylhexyl acrylate (2-EHA) can decrease the LCST of PNIPAm. The LCST behavior of the aqueous solutions of polymers and copolymers was measured by differential scanning calorimetry (DSC). The technique of NMR, GPC and EPR were employed to study the reactivity of BTA.
Further, non-isothermal LCST phase transition kinetics of PNIPAm was investigated by the DSC technique. The advanced isoconversional method (model-free method) can be used to determine the effective activation energy of non-isothermal sol-gel behavior of PNIPAm. The sol-gel transition process of increasing temperature involved forming PNIPAm nucleation and particle growth, and then particle shrink and aggregate simultaneously；on the other hand, the sol-gel transition of cooling PNIPAm related to form the hydrogen-bonding between H2O and PNIPAm and particle swelling and dissolution in H2O. The detail of the phase transition mechanism will show in this study
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1. 黃世偉, 高分子材料與醫療器材專題報導. 科學發展月刊, 2010. 455: p. 14-19.
2. Cheng, C.C., et al., Highly efficient drug delivery systems based on functional supramolecular polymers: In vitro evaluation. Acta Biomaterialia, 2016. 33: p. 194-202.
3. Olgun Guven , et al., A review on the radiation synthesis of copolymeric hydrogels for adsorption and separation purposes. Radiation Physics and Chemistry, 1999. 56: p. 381-386.
4. C.Boutris., E.G.Chatzi., and C.Kiparissides, Characterization of the LCST behaviour of aqueous poly(N-isopropylacrylamide) solutions by thermal and cloud point techniques. Polymer, 1997. 38(10): p. 2567-2570.
5. 馬光輝, 蘇志國, 新型高分子材料. 2006: 曉園出版社.
6. 李青山, 功能与智能高分子材料. 2006: 國防工業出版社.
7. Zhang, J., et al., Dual thermo- and pH-sensitive poly(N-isopropylacrylamide-co-acrylic acid) hydrogels with rapid response behaviors. Polymer, 2007. 48(6): p. 1718-1728.
8. Haq, M.A., Y. Su, and D. Wang, Mechanical properties of PNIPAM based hydrogels: A review. Materials Science and Engineering C, 2017. 70(Pt 1): p. 842-855.
9. Jain, K., et al., Tunable LCST behavior of poly(N-isopropylacrylamide/ionic liquid) copolymers. Polymer Chemistry, 2015. 6(38): p. 6819-6825.
10. Shouei Fujishige, K. Kubota, and I. Ando, Phase transition of aqueous solutions of poly(N-isopropylacrylamide) and poly(N-isopropylmethacrylamide). The Journal of Physical Chemistry, 1989. 93(8): p. 3311-3313.
11. Howard G. Schild and D.A. Tirrell, Microcalorimetric detection of lower critical solution temperatures in aqueous polymer solutions. The Journal of Physical Chemistry, 1990. 94(10): p. 4352-4356.
12. Howard G. Schild, M. Muthukumar, and D.A. Tirrell, Cononsolvency in mixed aqueous solutions of poly(N-isopropylacrylamide). Macromolecules 1991. 24(4): p. 948–952.
13. Thomas Baltes, Frédéric Garret-Flaudy, and R. Freitag, Investigation of the LCST of polyacrylamides as a function of molecular parameters and the solvent composition. Journal of Polymer Science Part A: Polymer Chemistry, 1999. 37(15): p. 2977-2989.
14. Yanjie Zhang , et al., Specific Ion Effects on the Water Solubility of Macromolecules: PNIPAM and the Hofmeister Series. Journal of the American Chemical Society, 2005. 127(41): p. 14505-14510.
15. Mitsuhiro Shibayama , Shin-ya Mizutani , and a.S. Nomura, Thermal Properties of Copolymer Gels Containing N-Isopropylacrylamide. Macromolecules, 1996. 29(6): p. 2019-2024.
16. 薛敬和, 高分子化學. 2000: 高立圖書
17. Schirmann, J.-P. and P. Bourdauducq, Hydrazine, in Ullmann's Encyclopedia of Industrial Chemistry. 2000, Wiley-VCH Verlag GmbH & Co. KGaA.
18. Corporation, F., Persulfates Technical Information. 2001.
19. Ronco, L.I., R.J. Minari, and L.M. Gugliotta, Particle Nucleation Using Different Initiators in the Miniemulsion Polymerization of Styrene. Brazilian Journal of Chemical Engineering, 2015. 32(1): p. 191-200.
20. Haque, N., Coordination Chemistry of Barbituric Acid, Its Diethyl Derivative Benzildiimine with Transition Metals. 2009.
21. 张俊松, 贺艳丽, 王晓利, 藥物化學. 2007: 中国轻工业出版社.
22. Foye, W.O., T.L. Lemke, and D.A. Williams, Principles of medicinal chemistry. 1995: Lippincott Williams & Wilkins.
23. Norio Tsubokawa, N.S., Yasuo Sone, Radical Polymerization of Methyl Methacrylate Initiated by an Enolizable Ketone-Carbon Black System. Journal of Polymer Science Part A: Polymer Chemistry, 1983. 21(2): p. 425-433.
24. Jing-Pin Pan, et al., Effect of barbituric acid on the self-polymerization reaction of bismaleimides. Journal of Applied Polymer Science, 1992. 45(1): p. 103–109.
25. Su, H.-L., et al., Effects of solvent basicity on free radical polymerizations ofN,N'-bismaleimide-4,4'-diphenylmethane initiated by barbituric acid. Journal of Applied Polymer Science, 2010: p. NA-NA.
26. Vyazovkin, S., et al., ICTAC Kinetics Committee recommendations for performing kinetic computations on thermal analysis data. Thermochimica Acta, 2011. 520(1-2): p. 1-19.
27. AMMAR KHAWAM and D.R. FLANAGAN, Basics and applications of solid-state kinetics: a pharmaceutical perspective. Journal of Pharmaceutical Sciences, 2006. 95(3): p. 472-98.
28. Pham, Q.-T., et al., Kinetics of free radical polymerization of bisphenol A diglycidyl ether diacrylate initiated by barbituric acid. Thermochimica Acta, 2013. 573: p. 121-129.
29. Khawam, A. and D.R. Flanagan, Solid-State Kinetic Models: Basics and Mathematical Fundamentals. The Journal of Physical Chemistry B, 2006. 110(35): p. 17315–17328.
30. Sbirrazzuoli, N., Determination of pre-exponential factors and of the mathematical functions f(α) or G(α) that describe the reaction mechanism in a model-free way. Thermochimica Acta, 2013. 564: p. 59-69.
31. Jaroslav Šesták and G. Berggren, Study of the kinetics of the mechanism of solid-state reactions at increasing temperatures. Thermochimica Acta, 1971. 3(1): p. 1-12.
32. Yu, F.-E., et al., Effect of solvent proton affinity on the kinetics of michael addition polymerization ofn,n′-bismaleimide-4,4′-diphenylmethane with barbituric acid. Polymer Engineering & Science, 2014. 54(3): p. 559-568.
33. R.H.Pelton and P.Chibante, Preparation of aqueous latices with N-isopropylacrylamide. Colloids and Surfaces, 1986. 20(3): p. 247-256.
34. Zhu, M.-L., et al., Preparation and properties of controllable amphiphilic P(NIPAM-co-LMA) gel for drug delivery. Journal of Drug Delivery Science and Technology, 2015. 29: p. 245-250.
35. Chern, C.-S., Principles and Applications of Emulsion Polymerization. 2008: Wiley.
36. Shinya Nakano, et al., Thermoreversible gelation of isotactic-rich poly(N-isopropylacrylamide) in water. The Journal of Physical Chemistry, 2011. 135(11): p. 114903.