臺灣博碩士論文加值系統

本研究主要目的在應用香豆素（coumarin）衍生物其光誘導電子轉移機制（Photoinduced Electron Transfer, PET）設計出分別對金屬離子及醣類具專一性的螢光感測器，探討導致螢光變化的機制。
如圖所示，各種不同的拉電子取代基團（1∼8）香豆素衍生物，會呈現出高低不同的螢光量子產率，此因PET性質被不同程度抑制的結果。將此機制應用於螢光分子的設計上，因螢光感測器與受測物結合前與結合後，光誘導電子轉移機制會被啟動或被抑制，即可觀測螢光的改變以了解受測物與感測器結合的強弱。
以香豆素衍生物作為訊號讀出單元，再結合二羧酸亞胺（iminodicarboxylic acid）作為金屬離子的辨識單元，設計出螢光感測器9；以2-甲苯硼酸（2-tolylboronic acid）作為醣類的辨識單元，設計出螢光感測器10與11。
由實驗結果得知，感測器9對汞離子具有專一性，不論在水中或有機溶劑中皆有相當大的螢光變化，即使有其它干擾離子的存在也不會受到影響。感測器11於水溶液中， pH值應用範圍較感測器10為寬；且經由實驗證明，兩者與醣類結合的機制應不相同。

The objective of this thesis is to use coumarin derivatives as molecular scaffold to design fluorosensors for detecting metal ions and monosaccharides based on PET (Photoinduced Electron Transfer) sensory mechanism. Evidences are also shown to reveal the origin of the fluorescence changes of these sensors.
Coumarin derivatives (1-8) containing various electron-withdrawing groups display different fluorescent intensity owing to the attenuation of PET mechanism by these substituents. Based on this concept, we designed fluorosensors, which can switch on or off PET mechanism in the presence of analytes. Iminodicarboxylic acid and 2-tolylboronic acid were chosen as the recognition units for detecting metal ions and monosaccharides in fluorosensors 9, 10 and 11, respectively. Monitoring the variation of fluorescent intensity of these fluorosensors accessed the strength of complexation between fluorosensors and analytes.
Experimental results indicate that fluorosensor 9 only selects Hg2+ and shows pronounced fluorescent enhancement either in organic solvent or water. The magnitude of the enhancement isn’t affected in the presence of other interfering metal ions. As to fluorescent sensors targeting to monosaccharides, fluorosensor 11 has broader working pH range than fluorosensor 10 in aqueous buffer. Spectroscopic results demonstrate that 10 and 11 undergo different binding mechanisms in the presence of monosaccharides.

目錄…………………………………………………………………………I
圖目錄………………………………………………………………………IV
表目錄………………………………………………………………………IX
流程圖目錄…………………………………………………………………X
簡稱用語對照表……………………………………………………………XI
中文摘要……………………………………………………………………XII
英文摘要……………………………………………………………………XIV
緒論…………………………………………………………………………1
第一章 香豆素衍生物之光誘導電子轉移的原理及探討………………4
1.1 前言……………………………………………………………………4
1.2 PET在化學感測器上的應用…………………………………………5
1.2.1感測器的組成原理……………………………………………5
1.2.2 PET螢光感測器………………………………………………7
1.3 香豆素衍生物的合成及PET 性質的探討………………………10
1.3.1 香豆素衍生物的合成………………………………………10
1.3.2 合成各種拉電子基團的香豆素衍生物……………………14
1.4 結果與討論………………………………………………………17
1.5 結論………………………………………………………………22
第二章 香豆素衍生物之PET機制應用於金屬離子感測器的開發…24
2.1 前言………………………………………………………………24
2.2 汞離子相關介紹…………………………………………………25
2.3 水溶性PET金屬離子感測器的設計與合成……………………29
2.3.1 PET金屬離子感測器的設計原理……………………………29
2.3.2 感測器的合成………………………………………………30
2.4 實驗測試與結果討論……………………………………………32
2.4.1 不同pH值緩衝溶液中的測試………………………………32
2.4.2 金屬陽離子的偵測…………………………………………36
2.4.3金屬離子的競爭實驗…………………………………………43
2.4.4氫核磁共振光譜的探討………………………………………44
2.5 結論………………………………………………………………55
第三章 香豆素衍生物之PET機制應用於醣類分子感測器的開發…57
3.1 前言………………………………………………………………57
3.2 PET機制應用於具硼酸官能基的醣類感測分子………………58
3.3香豆素衍生物的PET性質應用於醣類感測分子的設計與合成…64
3.3.1設計原理的討論………………………………………………64
3.3.2螢光感測器的合成……………………………………………67
3.4 實驗測試與結果討論……………………………………………69
3.4.1 不同pH值緩衝溶液中的滴定測試…………………………69
3.4.2 在甲醇中的醣類滴定實驗…………………………………73
3.4.3 在緩衝溶液中的醣類滴定實驗……………………………77
3.4.4 1H-NMR滴定實驗……………………………………………82
3.5 結論………………………………………………………………87
第四章 總結……………………………………………………………89
實驗部份………………………………………………………………90
一、一般敘述………………………………………………………90
二、合成步驟及光譜數據…………………………………………93
參考文獻………………………………………………………………112
附錄……………………………………………………………………118

1. Gmelin, L. Justusliebigs Ann. Chem. 1840, 34, 354.
2. O’kennedy, R. R.; Thornes, D. Coumarins: Biology. Applications and Mode of Action, Wiley & Sons, Chchester, 1997.
3. Meuly, W. C. in Kivk-Othmer Encyclopedia of Chemical Technology, ed. Wiley-Interscience, New York, 3rd ed. 1979, vol. 7, 196.
4. Smith, R. E.; Bissell, E. R.; Mitchell, A. R. and Pearson, K. W. Thromb. Res., 1980, 17, 393.
5. (a) U. S. Patent 4, 069, 228. 1978.
(b) U. S. Patent 4, 060, 531. 1977.
(c) U. S. Patent 3, 966, 755. 1976.
6. Singer, L. A.; Kong, N. P. J. Am. Chem. Soc., 1966, 88, 5213-5219.
7. (a) Gennaro, A. R. Remington’s Pharmaceutical Sciences, 1985, 90.
(b) Gupta, S. P.; Hansch, C. et al. Chem. Rev. 1999, 99, 3525-3601.
8. Berdy, J. in Hererocyclic Antibiotics; CRC. Press: Boca. Raton, 1981.
9. Chen, C-T.; Huang, W-P. J. Am. Chem. Soc., 2002, 124, 6246-6247.
10. Specht, D.P.; Martic, P.A.; Farid, S. Tetrahedron Lett. 1982, 23, 1203-1211.
11. Mattay, J.; Ed. Photoinduced electron transfer. Part I, Top. Curr. Chem. 1990, vol. 156.
12. Bäckstrøm, H. J. Trans. Faraday Soc. 1928, 24, 601.
13. Weigert, F. Z. Phys. Chem. 1923, 106, 303.
14. Baur, E. Helv. Chim. Acta. 1929, 12, 793-806.
15. Weiss, J. Trans. Faraday Soc. 1938, 34, 57-70.
16. (a) Valeur, B.; Leray, I. Coord. Chem. Rev. 2000, 205, 3-40
(b) Schemehl, R. H.; Li, C. J.; Xia, W. S.; Mague, J. T.; Luo, C. P.; Guldi, D. M. J. Phys. Chem. B. 2002, 106, 833-843.
17. (a) De Silva, A. P.; Gunaratne, H. Q. N.; Gunnlaugsson, T.; Huxley, A. J. M.; McCoy, C. P.; Rademacher, J. T.; Rice, T. E. Chem. Rev. 1997, 97, 1515-1566.
(b) De Silva, A. P.; Fox. D. B.; Huxley, A. J. M.; Moody, T. S. Coord. Chem. Rev. 2000, 205, 41-57.
18. Masilamani, D.; Lucas, M. E. in Fluorescent Chemosensors for Ion and Molecule Recognition; Czarnik, A. W., Ed.; American Chemical Society: Washinton, DC, 1992.
19. Earley, J. V.; Fryer, R. I.; Ning, R. Y. J. Pharm. Sci. 1979, 68, 845-850.
20. Holīk M.; Friedl Z.; Waisser K.; Gregor J. Collect. Czech. Chem. Commun. 1999, 64, 1709-1726.
21. Gao, J.; Feng, Y.; Kang, J. Synth. Commun. 1997, 27, 3219-3225.
22. David, R. L. CRC Handbbok of Chemistry and Physics, 81th, CRC Press, Boca Raton Lodon New York, Washington, D. C. 2000-2001.
23. Jones II, G.; Jackson, W. R.; Choi, C. Y.; Bergmark, W. R. J. Phys. Chem. 1985, 89, 294-300.
24. Munkholm, C.; Parkinson, Don-R.; Walt, D. R. J. Am. Chem. Soc. 1990, 112, 2608-2612.
25. (a) Myers, G. J.; Davidson, P. W.; Weitzman, M.; Lanphear, P. MRDD Res. Rev. 1997, 3, 239-245.
(b) Cooney, C.; Erickson, B.; Betts, K.; Petkewich, R. Environ. Sci. Technol. A-Pages 2002, 36, 323A-326A.
26. Rurack, K.; Kollmannsberger, M.; Resch-Genger, U.; Daub, J. J. Am. Chem. Soc. 2000, 122, 968-969.
27. (a) Akkaya, E. U.; Huston, M. E.; Czarnik, A. W. J. Am. Chem. Soc. 1990, 112, 3590-3593.
(b) Alfimov, M. V.; Fedorov, Y. V.; Fedorova, O.A.; Gromov, S. S.; Hester, R. E.; Lednev, I. K.; Moore, J. N.; Oleshko, V. P.; Vedernikov, A. I. J. Chem. Soc., Perkin Trans. 2 1996, 1141-1147.
(c) Brümmer, O.; La Clair, J. J.; Janda, K. D. Org. Lett. 1999, 1, 415-418.
(d) Prodi, L.; Bargossi, C.; Marco, M.; Zaccheroni, N.; Su, N.; Bradshaw, J. S.; Izatt, R. M.; Savage, P. B. J. Am. Chem. Soc. 2000, 122, 6769-6770.
(e) Brümmer, O.; La Clair, J. J.; Janda, K. D. Bioorg. Med. Chem. 2001, 9, 1067-1071.
(f) Descalzo, A. B.; Martínez-Máñez, R.; Radeglia, R.; Rurack, K.; Soto, Juan. J. Am. Chem. Soc. 2003, 125, 3418-3419.
28. Isgor, Y. G.; Akkaya, E. U. Tetrahedron Lett. 1997, 38, 7417-7420.
29. Brzeziński, B.; Grecch, E.; Malarski, Z.; Sobczyk, L. J. Chem. Soc., Perkin Trans. 2 1991, 857-859.
30. Akkaya, E. U.; Turkyilmaz, S. Tetrahedron Lett. 1997, 38, 4513-4516.
31. Grynkiewicz, G.; Poenie, M.; Tsien, R. Y. J. Biol. Chem. 1985, 260, 3440-3450.
32. (a) Bernhardt, P. V.; Moore, E. G.; Riley, M. J. Inorg, Chem. 2001, 40, 5799-5805.
(b) Gunnlaugsson, T.; Bichell, B.; Nolan, C. Tetrahedron Lett. 2002, 43, 4989-4992.
33. Minta, A.; Kao, J. P. Y.; Tsien, R. Y. J. Biol. Chem. 1989, 264, 8171-8178.
34. Lakowicz, J. R. Principles of Fluorescence Spectroscopy, Kluwer Academic / Plenum Publishers, 1999, 185-210.
35. James, T. D.; Sandanayake, K. R. A. S.; Shinkai, S. Angew. Chem. Int. Ed. Engl. 1996, 35, 1910-1922.
36. Elsaa, L. J.; Rosenberg, L. E. J. Clin. Invest. 1969, 48, 1845.
37. De Marchi, S.; Cecchin, E.; Basil, A.; Proto, G.; Donadon, W.; Jengo, A.; schinella, D.; Jus, A.; Villata, D.; De Paoli, P.; Santini, G.; Tesio, F. Am. J. Nephrol. 1984, 4, 280.
38. Baxter, P.; Goldhill, J.; Hardcastle, P. T. Taylor, C. J. Gut. 1990, 31, 817.
39. Yasuda, H.; Kurokawa, T.; Fuji, Y.; Yamashita, A.; Ishibashi, S. Biochim. Biophys. Acta 1990, 1021, 114.
40. Fedoak, R. N.; Gershon, M. D.; Field, M. Gastroenterology 1989, 96, 37.
41. Yamamoto, T.; Seino, Y.; Fukumoto, H.; Koh, G.; Yano, H.; Inagaki, N.; Yamada, Y.; Inoue, K.; Manabe, T.; Imura, H. Biochem. Biophys. Res. Commun. 1990, 170, 233.
42. (a) Aoyama, Y.; Tanaka, Y.; Sugahara, S. J. Am. Chem. Soc. 1989, 111, 5397-5340.
(b) Kikuchi, Y.; Tanaka, Y.; Sutarto, S.; Kobayashi, K.; Toi, H.; Aoyama, Y. J. Am. Chem. Soc. 1992, 114, 10302-10306.
(c) Greenspoon, N.; Wachtel, E. J. Am. Chem. Soc. 1991, 113, 7233-7236.
(d) Huang, C. Y.; Cabell. L. A.; Lynch, V.; Anslyn, E. V. J. Am. Chem. Soc. 1992, 114, 1900-1901.
(e) Bonar-Law, R. P.; Sanders, J. K. M. J. Am. Chem. Soc. 1995, 117, 259-271.
43. Christophe, M. Tetrahedron 1994, 50, 12521-12569.
44. Michaelis, A.; Becker, P. Ber. Dtsch. Chem. Ges.1880, 13, 58.
45. Kuivila, H. G.; Keough, A. H.; Soboczenski, E. J. J. Org. Chem. 1954, 19, 780-783.
46. Roy, G. L.; Laferriere, A. L.; Edwards, J. O. J. Inorg. Nucl. Chem. 1957, 114(4), 106.
47. Lorand, J. P.; Edwards, J. D. J. Org. Chem. 1959, 24, 769-774.
48. Hartley, J. H.; James, T. D.; Ward, C. J. J. Chem. Soc., Perkin Trans. 1 2000, 3155-3184.
49. Yoon, J.; Czarnik, A. W. J. Am. Chem. Soc. 1992, 114, 5874-5875.
50. Suenaga, H.; Mikami, M.; Sandanayake, K. R. A. S.; Shinkai, S. Tetrahedron Lett.1995, 36, 4825-4828.
51. Suenaga, H.; Yamamoto, H.; Shinkai, S. Pure Appl. Chem. 1996, 68, 2179.
52. Wulff, G. Pure Appl. Chem. 1982, 54, 2093-2102.
53. (a) James, T. D.; Sandanayake, K. R. A. S.; Shinkai, J. Chem. Soc. Chem. Commun. 1994, 477-478.
(b) James, T. D.; Sandanayake, K. R. A. S.; Shinkai, S. Angew. Chem. Int. Ed. Engl. 1994, 33, 2207-2209.
54. James, T. D.; Sandanayaje, K. R. A. S.; Iguchi, R.; Shinkai, S. J. Am. Chem. Soc. 1995, 117, 8982-8987.
55. James, T. D.; Shinmori, H.; Shinkai, S. Chem. Commun. 1997, 71-72.
56. Cooper, C. R.; James, T. D. Chem. Commun. 1997, 1419-1420.
57. Cooper, C. R.; James, T. D. J. Chem. Soc., Perkin Trans. 1 2000, 963-969.
58. Wiskur, A. L.; Lavigne, J. J.; Ati-Haddou, H.; Lynch, V.; Chiu, Y. H.; Canary, J. W.; Anslyn, E. V. Org. Lett. 2001, 3, 1311-1314.
59. Sandanayake, K. R. A. S.; Shinkai, S. J. Chem. Soc. Chem. Commun. 1994, 1083-1084.
60. Arimori, S.; Bosch, L. I.; Ward, C. J.; James, T. D. Tetrahedron. Lett. 2002, 43, 911-913.
61. Semple, J. E. Tetrahedron. Lett. 1998, 39, 6645-6648.
62. DiCesare, N.; Lakowicz, J. R. J. Phys. Chem. A 2001, 105, 6834-6840.
63. Fery-Forgues, S.; Le-Bris, M. T.; Guetté, J. P.; Valeu, B. J. Phys. Chem. 1988, 92, 6233-6237.