臺灣博碩士論文加值系統

本論文包括兩部份，第一部份本文係先利用diphenylamine與4-fluoronitrobenzene合成4-amino triphenylamine (ATPA)，然後ATPA再與acryloyl chloride行乙烯化反應形成4-acrylamido triphenylamine(AATPA)後再與N-isoproopyl acrylamide (NIPAAm)單體共聚合製備一系列膠體。
本文主要探討AATPA單體含量對膠體的膨潤度，機械強度及藥物釋放行為的影響。結果顯示，膠體中具有苯環基團的AATPA含量，比例由1至5mol%增加，膨潤度會由8倍降到2倍，而在不同溫度下的熱應答效應也跟著不明顯，機械強度及交聯密度則會隨著在乙醇中時AATPA的量增加，而跟著下降2到3倍以上。另外在不同溶劑下的膠體澎潤度也會隨著AATPA的量增加而有所改變。此外在本研究中將NIPAAm/AATPA做成共聚體並且溶於不同極性大小的溶劑中分別使用UV和PL分別測量最大吸收波長，及發光強度，但出現在不可見光區。
第二部份，本研究先利用diphenylamine與4-fluorobenzonitrile合成4-cyano triphenylamine，然後將4-cyano triphenylamine水解之後再利用HCl酸化得4-carboxy triphenylamine再與oxalyl Chloride進行醯氯化反應，最後在和HEMA進行脫氯化氫反應得到methacryloyloxy ethylene oxycarbonyl triphenylamine (METPA)。所得之METPA再與N-isopropyl acrylamide (NIPAAm) 單體共聚合製備成一系列膠體。
本文主要探討METPA單體含量對膠體的膨潤度，機械強度，及藥物釋放行為的影響。結果顯示，膠體中具有苯環基團的METPA含量，比例由1至5倍增加，膨潤度會由8倍降到7倍，機械強度及交聯密度則會隨著在乙醇中時METPA的量增加，而跟著增加2到3倍以上。而對咖啡因的釋放量由60%下降到30%，對indomethacin的釋放量由40%提升到90%。孔徑大小隨著METPA含量增加而 增加。並且使用UV和PL分別測量最大吸收波長，及放光強度。在光致發光行為上，結果顯示膠體的發光強度隨METPA含量增加而亮度增強。另一方面對應的膠體組成的共聚體，其在各種溶劑的發光特性以UV及PL分別測得最大吸收波長及放光強度。由其結果顯示，該單體在波長 365nm附近有良好的螢光特性

The thesis includes two parts. In first part, 4-Amino triphenylamine (ATPA) was firstly synthesized by nucleophilic substitution of 4-fluoronitrobenzene and diphenylamine in this study, and then acylation of ATPA was carried out via acryloyl chloride to obtain 4-acrylamido triphenylamine (AATPA). Then, a series of thermosensitive hydrogels were prepared by copolymerization of AATPA and N-isopropyl acrylamide (NIPAAm) by UV irradiation. The effect of AATPA content in the copolymeric gels on the swelling ratio, mechanical properties, and drug release behaviors of the gels was investigated. Results showed that the swelling ratios of the copolymeric gels decreased from 8 (g/g) to 2 (g/g) when the hydrophobic monomer AATPA content in the copolymeric gel increased from 1 mol% to 5 mol% due to the decreasing hydrophilicity. In addition, the thermosensitive behavior obviously decreased with increasing of AATPA content in the gels, but the mechanical properties and crosslinking density of the gel swelling in the ethanol solution increased with increasing of AATPA content. The swelling ratios of hydrogels were changed by increasing AATPA content in the different solvents. In addition, the corresponding copolymers of NIPAAm/AATPA copolymeric gels, were synthesized. The UV absorption and PL emission were measured. The results showed that the maximum UV absorption wavelength and PL intensity of the copolymers and the AATPA homopolymer appeared in the invisible region.
In second part, 4-Cyano triphenylamine was firstly synthesized by nucleophilic substitution of 4-fluorobenzonitrile and diphenylamine in this study. Then, the hydrolysis and acidification to obtain 4-cyano triphenylamine, and then further to carried out acylation via oxalyl chloride, and finally react with HEMA to obtain methacryloyloxy ethylene oxycarbonyl triphenylamine (METPA). Then, a series of thermosensitive hydrogels were prepared by copolymerization of METPA and N-isopropyl acrylamide (NIPAAm) by UV irradiation. The effects of METPA contents on the swelling ratio, mechanical properties of the gels were investigated. Results showed that when the hydrophobic monomer METPA content in the copolymeric gel increased from 1 mol% to 5 mol%, the swelling ratios of the copolymeric gels decreased from 8 (g/g) to 7 (g/g); the gel strength and crosslinking density increase 2 and 3 times, respectively, in the 95% ethanol solutions; the caffeine drug release ratio also decrease from 60% to 30%, but the indomethacin release ratio increased from 40% to 90%; the pore size diameter also increase with METPA contents. In photoluminescent behavior, the intensity of photoluminescent increased with an increase of the content of METPA in the copolymeric hydrogel. On the other hand, the copolymers with corresponding copolymeric hydrogels were prepared by the free radical polymerization. Their photoluminescent in various solvent (10-5M) were measured by UV and PL techniques. Their results showed that the maximum absorption wavelength is independent of the METPA content, but the intensity of photoluminescence is dependent on the content of METPA.

ACKNOWLEDGEMENTSi
ABSTRACT (in English)ii
ABSTRACT (in Chinese)v
CONTENTvii
LIST OF SCHEMESx
LIST OF TABLESx
LIST OF FIGURESxi

PART I
Effect of AATPA content on swelling behavior and drug release behavior of the (NIPAAm-co-AATPA) copolymeric hydrogels 1
CHAPTER 1 INTRODUCTION 2
CHAPTER 2 EXPERIMENTAL 6
1.2.1 Materials6
1.2.2 Preparation of Copolymeric Hydrogels 7
1.2.2.1 Monomer Synthesis 7
1.2.3 Preparation of the copolymeric Hydrogels8
1.2.4 Measurement of Swelling Ratio 9
1.2.5 Physical Properties measurement9
1.2.6 Drug Release Experiment10
1.2.7 Morphology10
1.2.8 Copolymerization of NIPAAm and AATPA10
1.2.9 UV/VIS and PL spectrophotometer11
CHAPTER 3 RESULTS AND DISCUSSION12
1.3.1 Synthesis of AATPA and Characterization of NIPAAm/AATPA Copolymeric Hydrogels12
1.3.2 The Effects of AATPA Monomers on Swelling Behaviors19
1.3.3 Effect of Temperature on Swelling Ratio For NIPAAm/AATPA Copolymeric Hydrogels24
1.3.4 Effect of Solvent Polarity on Swelling Ratio For NIPAAm /AATPA Copolymeric Hydrogels 28
1.3.5 The Effects of AATPA Monomers on Mechanical Properties31
1.3.6 Effect of AATPA on the Drug Release Behavior of the Present Hydrogel33
1.3.7 Morphology40
1.3.8 UV/Vis and PL spectroscopy measurements42
CHAPTER 4 CONCLUSIONS 47
REFERENCES48

PART II
Effect of AATPA content on swelling behavior and drug release behavior of the (NIPAAm-co-METPA) copolymeric hydrogels
52
CHAPTER 1 INTRODUCTION53
CHAPTER 2 EXPERIMENTAL58
2.2.1 Materials58
2.2.2 Preparation of Copolymer Synthesis 60
2.2.2.1-4 Monomer Synthesis60
2.2.2.5 Preparation of the Copolymer Hydrogels62
2.2.3 Measurement of Swelling Ratio62
2.2.4 Physical Properties measurement 63
2.2.5 Drug Release Experiment64
2.2.6 Morphology64
2.2.7 Copolymerization of NIPAAm and AATPA64
2.2.8 UV/VIS and PL spectrophotometer 65
2.2.9 Pore diameter distribution65
CHAPTER 3 RESULTS AND DISCUSSION67
2.3.1 Synthesis of METPA and Characterization of NIPAAm/METPA Copolymeric Hydrogels67
2.3.2 The Effects of METPA content on Swelling Behaviors74
2.3.3 Effect of Temperature on Swelling Ratio For NIPAAm/METPA Copolymeric Hydrogels79
2.3.4 Effect of Solvent polarity on Swelling Ratio For NIPAAm/METPA Copolymeric Hydrogels83
2.3.5 Effects of METPA content on mechanical properties86
2.3.6 Effect of METPA on the Drug Release Behavior of the Present Hydrogels88
2.3.7 Morphology95
2.3.8 Effect of METPA content on the pore size distribution for the NIPAAm/METPA copolymeric hydrogels97
2.3.9 Photoluminescence of the copolymeric gel102
2.3.10 UV/Vis and PL spectroscopy measurements105
CHAPTER 4 CONCLUSIONS 112
REFERENCES113

LIST OF SCHEMES
PART I
Scheme 1.1. Synthesis of 4-acrylamido triphenylamine (AATPA). 14
Scheme 1.2. Preparation of NIPAAm/ AATPA copolymeric hydrogels 15

PART II
Scheme 2.1. Synthesis of Methacryloyloxy ethylene oxycarbonyl triphenylamine (METPA) 69
Scheme 2.2. Preparation of NIPAAm/ METPA copolymeric hydrogels70

LIST OF TABLES
PART I
Table 1.1. Equilibrium-swelling ratios and feed compositions of the hydrogels18
Table 1.2. Fundamental properties of the NIPAAm/AATPA copolymeric hydrogels23
Table 1.3. Mechanical Properties and Crosslinking densities of the present copolymeric gels 32
Table 1.4. The concentrations of caffeine absorption, the concentrations of caffeine release, and the relative release ratios of the NIPAAm/AATPA copolymeric hydrogels37
Table 1.5. The concentrations of Indomethacin absorption, the concentrations of Indomethacin release, and the relative release ratios of the NIPAAm/AATPA copolymeric hydrogels39
Table 1.6. The UV-Vis absorption and PL spectra of NIPAAm-co-AATPA in the different solvent46
PART II
Table 2.1. Equilibrium-swelling ratios and feed compositions of the hydrogels73
Table 2.2. Fundamental properties of the NIPAAm/METPA copolymeric hydrogels78
Table 2.3. Crosslinking densities of the present gels 87
Table 2.4. The concentrations of caffeine absorption, the concentrations of caffeine release, and the relative release ratios of the NIPAAm/METPA copolymeric hydrogels 92
Table 2.5. The concentrations of Indomethacin absorption, the concentrations of Indomethacin release, and the relative release ratios of the NIPAAm/METPA copolymeric hydrogels94
Table 2.6. The NIPAAm/METPA (1%-5%) of diameter distribution101
Table 2.7. The UV-Vis absorption and PL spectra of NIPAAm-co-METPA in the different solvent 111

LIST OF FIGURES
PART I
Figure 1.1 IR spectra of (a) 4-amino triphenylamine(b) the synthesized 4-acrylamido triphenylamine (AATPA)16
Figure 1.2 The 1H NMR spectrum of 4-acrylamido triphenylamine (AATPA) in DMSO-d617
Figure 1.3 The swelling ratio as a function of time for NIPAAm/AATPA copolymeric hydrogels in deionized water at 25℃22
Figure 1.4 Effect of temperature on equilibrium swelling ratio for the NIPAAm/AATPA copolymeric hydrogels26
Figure 1.5 Effect of temperature on ΔSR (20℃-37℃) for the NIPAAm/AATPA copolymeric hydrogels27
Figure 1.6 Effect of solvent on swelling ratio for NIPPAm/AATPA copolymeric hydrogels30
Figure 1.7 Caffeine release profile for the hydrogels containing AATPA during loading in EtOH at 25℃ and releasing in deionized water at 37℃.. 36
Figure 1.8 Indomethacin release profile for the hydrogels containing AATPA during loading in EtOH at 25℃ and releasing in deionized water at 37℃ 38
Figure 1.9 Section morphology of a series of present gels 41
Figure 1.10 UV-Vis absorption and PL spectra of poly(acrylamido triphenylamine) in THF solution (10-5M)43
Figure 1.11 UV-Vis absorption and PL spectra of NIPAAm-co-AATPA in DMSO solution (10-5M) 44
Figure 1.12 UV-Vis absorption and PL spectra of NIPAAm-co-AATPA in EtOH solution (10-5M) 44
Figure 1.13 UV-Vis absorption and PL spectra of NIPAAm-co-AATPA in DMF solution (10-5M) 45
Figure 1.14 UV-Vis absorption and PL spectra of NIPAAm-co-AATPA in THF solution (10-5M) 45

PART II
Figure 2.1 IR spectra of (a) 4-cyano triphenylamine(b) the synthesized 4-carboxy triphenylamine(c) pure HEMA (d) the synthesized Methacryloyloxy ethylene oxycarbonyl triphenylamine (METPA) 71
Figure 2.2 The 1H NMR spectrum of Methacryloyloxy ethylene oxycarbonyl triphenylamine (METPA) in DMSO-d6 72
Figure 2.3 The swelling ratio as a function of time for NIPAAm/METPA copolymeric hydrogels in deionized water at 25℃77
Figure 2.4 Effect of temperature on equilibrium swelling ratio for the NIPAAm/METPA copolymeric hydrogels
81
Figure 2.5 Effect of temperature on ΔSR (20℃-37℃) for the NIPAAm/METPA copolymeric hydrogels82
Figure 2.6 Effect of solvent on swelling ratio for NIPPAm/METPA copolymeric hydrogels 85
Figure 2.7 Caffeine release profile for the hydrogels containing METPA during loading in EtOH at 25℃ and releasing in deionized water at 37℃.. 91
Figure 2.8 Indomethacin release profile for the hydrogels containing METPA during loading in EtOH at 25℃ and releasing in deionized water at 37℃93
Figure 2.9 Section morphology of a series of present gels96
Figure 2.10 The diameter distribution of METPA-1% hydrogels 98
Figure 2.11 The diameter distribution of METPA-2% hydrogels 98
Figure 2.12 The diameter distribution of METPA-3% hydrogels 99
Figure 2.13 The diameter distribution of METPA-4% hydrogels 99
Figure 2.14 The diameter distribution of METPA-5% hydrogels 100
Figure 2.15 The Bubble point and Smallest detected pore diameter 100
Figure 2.16 Section morphology of a series of present gels in the 25℃ 103
Figure 2.17 Section morphology of a series of present gels in the 37℃ 104
Figure 2.18 PL spectra of dry gel on the glass film 106
Figure 2.19 UV-Vis absorption and PL spectra of NIPAAm-co-METPA in THF solution (10-5M)107
Figure 2.20 UV-Vis absorption and PL spectra of NIPAAm-co-METPA in DMF solution (10-5M)108
Figure 2.21 UV-Vis absorption and PL spectra of NIPAAm-co-METPA in EtOH solution (10-5M)109
Figure 2.22 UV-Vis absorption and PL spectra of NIPAAm-co-METPA in DMSO solution (10-5M)110

1.Zhiming, W.; Xiaomei, W.; Junfang, Z.; Wanli, J.; Ping, Y.; Xiangyun, F.; Maoyi, Z.; Manhuan, C.; Dyes and Pigments 2008, 79, 145-152.
2.Arregui, F. J.; Matı´as, I. R.; Lo´pez-Amo, M. Sens. Actuators A 2000, 79, 90.
3.Wang, X. M.; Yang, P, Xu GB.; Jiang, WL.; Yang, TS. Synthetic Metals. 2005, 155, 464-73.
4.Kuo, Y. C.; Tsi, X. S.; Jia, H. L.; Tsung, H. L.; Guey, S. L.; Shu, H. C. J. Electros. Chem. 2005, 575, 95-101.
5.Youtian, T. Qiang, W. Yuan, S. Chuluo, Y. Liang, A. Jingui, Q. Dongge, Ma. and Zhigang, Shuai. Chem. Commun., 2009, 77–79
6.Horie, K.; Ushiki, H.; Winnik, FM. Molecular photonics: fundamental and practical aspects. Tokyo: Kodansha-Wiley-VCH; 2000.
7.Andruleviciute, V.; Lazauskaite, R.; Grazulevicius, JV.; Designed Monomer and Polymers. 2007, 10, 105-18.
8.Hasegawa, M.; Horie, K. Prog Polym Sci 2001, 26, 259.
9.Agota, F.; Fehervari.; Lawino, C.; Kagumba.; Savvas, Hadjikyriacou.; Freeman, Chen.; Russell, A.; Gaudiana. J Appl Polym Sci, vol. 87, 1634-1645, 2003.
10.Annaka, M.; Tanaka, C.; Nakahira, T.; Sugiyama, M.; Aoyagi, T.; Okano, T. Macromolecules 2002, 35, 8179.
11.Barton, J. S.; Kilpatrick, J. M.; MacPherson, W. N.; Jones, J. D. C.; Chana, K. S.; Anderson, J. S.; Buttsworth, D. R., Jones, T. V. in: Proceedings of the 13th International Conference on Optical Fiber Sensors (OFS-13) 2000, SPIE 3746, 612.
12.Wade, S. A.; Collins, S. F.; Baxter, G. W.; Sun, T.; Zhang, Z. Y.; Grattan, K. T. V.; Palmer, A. W.; Monnom, G. in: Proceedings of the 13th International Conference on Optical Fiber Sensors (OFS-13) 2000, SPIE 3746, 200.
13.Park, S-H.; Ogino, K.; Sato, H. Polym Adv Technol 2000, 11, 349.
14.Marsitzky, D.; Blainey, P.; Carter, K. R. Polym Prepr 2001, 42, 468.
15.Sasaki, K.; Koshioka, M.; Misawa, H.; Kitamura, N.; Masuhara H. Opt. Lett. 2001, 16, 1463-1465.
16.Ishizaki, F.; Machida, S.; and Horie, K. Polymer Bulletin 2001, 46, 197-204.
17.Ishizaki, F, Machida, S, and Horie, K. Polym. J., 2000, 32, 62.
18.Ishizaki, F.; Machida, S.; and Horie, K.; Polym. Bull. 2000, 44, 417.
19.Yoshinari, E.; Furukawa, H.; Horie, K. J. polymer 2005, 46, 7741-7748.
20.Okajima, T.; Harada, I.; Nishino, K.; Hirotsu, S. Jpn J Appl Phys 2000; 39: 875.
21.Nakamoto, C.; Motonaga, T.; Shibayama, M. Macromolecules 2001; 34: 911.
22.Zhang, XZ.; Yang, YY.; Chung, TS.; Ma, KX. Langmuir 2001; 17: 6094.
23.Serizawa, T.; Wakita, K.; Akashi, M. Macromolecules 2002; 35: 10.
24.Horie, K.; Ushiki, H.; Winnik, FM. Molecular photonics: fundamental and practical aspects. Tokyo: Kodansha-Wiley-VCH; 2000.
25.Hofkens, J.; Hotta, J.; Sasaki, K.; Masuhara, H. J. Am. Chem. Soc. 1997, 119, 2741-2742.
26.Hofkens, J.; Hotta, J.; Sasaki, K.; Masuhara, H.; Iwai, K. Langmuir 1997, 13, 414-419.
27.Hasegawa, M.; Horie, K. Prog Polym Sci 2001; 26: 259.
28.Annaka, M.; Tanaka, C.; Nakahira, T.; Sugiyama, M.; Aoyagi T.; Okano T. Macromolecules 2002; 35:8179.
29.Shirota, H.; Ohkawa, K.; Kuwabara, N.; Endo, N.; Horie, K. Macromol Chem Phys 2000;201:2210.
30.Furukawa, H.; Horie, K.; Nozaki, R.; Hatano, T.; Okada, M. Phys Rev E 2003; 68:031406.
31.Chung, J.; Choi, B.; Lee, HH. Appl. Phys. Lett., 1999, 74, 3645.
32.Friedland, K. D.; Walker, R. V.; Davis, N. D.; Myers, K. W.; Boehlert, G. W.; Urawa, S.; Ueno, Y. Mar. Ecol.: Prog. Series 2001, 216, 235.
33.Hara, T.; Terashima, K.; Takashima, H.; Suzuki, H.; Nakura, Y.; Makino, Y.; Yamamoto, S.; Nakamura, Y. IEEE Trans. Power Delivery 2000, 14 (1), 23.
34.Betta, G.; Pietrosanto, A.; Scaglione, A. in: Proceedings of the IEEE Instrumentation and Measurement Technology Conference 1997, 703.
35.Wang, A.; Xiao, H.; Wang, J.; Zaho, W.; May, R. G. J. Lightwave Technol. 2001, 19 (10), 1495.
36.Shirota, H.; Ohkawa, K.; Kuwabara, N.; Endo, N.; Hoire, K. Macromol Chem Phys 2000, 201, 2210.
37.Yoshinari, E.; Furukawa, H.; Horie, K. J. Polymer. 2005, 46, 7741.
38.Ishizaki, F.; Machida, S.; Horie, K. Polymer. B. 2001, 46, 197.
39.He, J. ; Machida, S. ; Kishi, H. ; Horie, K.; Furukawa, H.; Yokota, R.; J. Polym. Sci.; Part A, Polym. Chem. 2002, 40, 2501.
40.Xu, J.; Tseng, Y.; Wirtz, D.; J. Biol. Chem. 2000, 275, 35886.
41.Zhan, C. M.; Cheng, Z. G.; Xiao, H.; Li, Z.; Yang, X.; Qin, J. G. Macromolecules 2000, 33, 5455.
42.Kulkarni, AP.; Kong, XX.; Jenekhe, SA. J Phys Chem B2004; 108(25):8689–701.
43.Wu, FI.; Shih, PI.; Chen, YH.; Chien, CH.; Shu, CF. J Phys Chem B2005; 109(29):14000–5.
44.Sun, QJ.; Hou, JH.; Yang, CH.; Li, YF. Appl Phys Lett 2006; 89(15):153–501.
45.Vamvounis, G.; Yu, JF.; Holdcroft, S. Eur Polym J 2004; 40(12):2659–64.
46.Jim, SH.; Jung, JE.; Park, DK.; Jeon, BC.; Kwon, SK.; Kim, YH. et al. Eur Polym J. 2001;37(5):921–5.
47.Hou, JH.; Fan, BH.; Huo, LJ.; He, C.; Yang, CH.; Li, YF. J Polym Sci Part A: Polym Chem 2006; 44(3):1279–90.
48.Kulkarni, AP.; Tonzola, CJ.; Babel, A.; Jenekhe, SA. et al. Chem Mater 2004; 16(23):4556–73.
49.Mikroyannidis, JA.; Spiliopoulos, IK.; Kasimis, TS.; Kulkarni, AP.; Jenekhe, SA. et al. Macromolecules 2003; 36 (25): 9295–302.
50.Sonar, P.; Zhang, J.; Grimsdale, AC.; Mullen, K.; Surin, M.; Lazzaroni, R. et al. Macromolecules 2004; 37(3):709–15.
51.Pu, YJ.; Soma, M.; Kido, JJ. ; Nishide, H. 2001; 13(11):3817–9.
52.Zhang, HQ.; Yang, B.; Zheng, Y.; Yang, GD.; Ye, L.; Ma, YG. et al. J Phys Chem B 2004 ;108 (28):9571–3