臺灣博碩士論文加值系統

本研究目的在設計以香豆素 (coumarin) 衍生物為訊號讀出單元，合成具有不同辨識基團的螢光感測分子4-9，並探討結構上的改變對於重金屬離子選擇性的影響。由螢光滴定實驗結果顯示，化合物4對於十五種金屬離子沒有螢光強度的改變。當間位導入冠醚分子 (15-monoazacrown-5-ether) 的化合物 5 時，則對鈣、鋇、鎘、鉛離子有很強的結合性，並使得螢光強度增強。當間、對位置換上是二甲喀胺基 (dipicolylamine) 的化合物 6、7 時，則對鋅和鎘離子有較好的選擇性，而且在鎘離子的存在下，化合物6、7分別有十二倍及二十六倍螢光強度增加。當苯胺連結二甲喀胺基為辨識的化合物8時，則對鎘、鋅、鉛離子有三十倍的螢光強度增加。最後當在對位導入環狀脂肪胺 (cyclen) 辨識的化合物9時，則對鎘離子有較好的選擇性，而且有三十倍的螢光強度增加。由紅外線吸收、核磁共振光譜和放射螢光光譜實驗可得知，香豆素上的羰基 (carbonyl group ) 對金屬離子的選擇性扮演的角色，並且由單晶繞射結構圖得知化合物6、9對鎘離子的結合模式。

The objective of this thesis is to design and synthesize fluosensors 4-9, which consist of coumarin-based signal-transducing units and various recognition units. Structure features v.s. heavy metal selectivity will be discussed in details.
Fluorosensor 4, which has no defined recognition site, displayed small fluorescence changes in the presence of 15 metal ions examined, whereas fluorosensor 5 having 15-monoazacrown-5 ether incorporated at the meta-position of benzoyl moiety showed tight binding with Ca2+, Ba2+, Cd2+, Pb2+ and displayed fluorescence enhancement. When the dipicolylamine recognition unit was introduced at the meta and para positions respectively, the corresponding fluorosensors 6, 7 bound Cd2+ and Zn2+ with high selectivity. Moreover, 12- and 26-fold fluorescence enhancement were observed for fluorosensors 6, 7 in acetonitrile upon addition of Cd2+ respectively. Selectivity towards metal ions remained the same in the case of fluorosensor 8, in which the ethylene unit intervened the benzoyl group and dipicolylamine, displaying 30-fold fluorescence enhancement for Cd2+, Zn2+ and Pb2+. Fluorosensor 9 containing the cyclen as recognition unit also bound Cd2+ with 30-fold fluorescence enhancement.
Infrared and fluorescence spectroscopies in combination of nuclear magnetic resonance spectra indicated the carbonyl groups also involved in metal ions complexation. Single crystal structures of 6.Cd2+ and 9.Cd2+ further confirmed the role of the carbonyl groups and polyamine moiety in the complex structures.

目錄
目錄‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥Ⅰ
圖目錄‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥Ⅲ
表目錄‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥Ⅶ
簡稱用語對照表‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥Ⅷ
中文摘要‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥Ⅸ
英文摘要‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥Ⅹ
緒論‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥1
第一章 金屬離子感測分子的原理與應用‥‥‥‥‥‥‥‥‥‥3
1.1前言‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥3
1.2 螢光感測分子的組成及特性‥‥‥‥‥‥‥‥‥‥‥‥‥‥4
1.3螢光感測分子的訊號傳遞機制‥‥‥‥‥‥‥‥‥‥‥‥‥6
1.3.1 光誘導電子轉移‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥6
1.3.2分子內電荷轉移‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥7
1.3.3 競爭型‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥ 10
1.3.4 激發態分子內質子轉移‥‥‥‥‥‥‥‥‥‥‥‥‥ 12
1.4 鋅、鎘、鉛離子的相關介紹‥‥‥‥‥‥‥‥‥‥‥‥‥14
1.4.1 鋅離子相關介紹及文獻‥‥‥‥‥‥‥‥‥‥‥‥‥14
1.4.2 鎘離子相關介紹及文獻‥‥‥‥‥‥‥‥‥‥‥‥‥16
1.4.3 鉛離子相關介紹及文獻‥‥‥‥‥‥‥‥‥‥‥‥‥19
第二章 金屬離子感測分子的合成‥‥‥‥‥‥‥‥‥‥‥‥22
2.1 金屬離子感測分子的逆合成分析‥‥‥‥‥‥‥‥‥‥‥22
2.2 金屬離子感測分子合成方法的探討‥‥‥‥‥‥‥‥‥‥26
第三章 結果與討論‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥33
3.1金屬離子感測分子4、5的光譜結果與討論‥‥‥‥‥‥ 33
3.2金屬離子感測分子6、7的光譜結果與討論‥‥‥‥‥‥ 48
3.3 金屬離子感測分子8的光譜結果與討論‥‥‥‥‥‥‥‥61
3.4 金屬離子感測分子9的光譜結果與討論‥‥‥‥‥‥‥‥68
第四章 結論‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥77
實驗部分‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥78
參考文獻‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥98
附錄‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥‥102

參考文獻
1. Specht, D. P.; Martic, P. A.; Farid, S. Tetrahedron Lett. 1982, 38, 1203-1211.
2. Chen, C. T.; Huang W. P. J. Am. Chem. Soc. 2002, 124, 6246-6247.
3. Valeur, B.; Leray, I. Coord. Chem. Rev. 2000, 205, 3-40.
4. Masilamani, D.; Lucas, M. E. In Fluorescent Chemosensors for Ion and Molecule Recognition; Czarnik, A. W., Ed.; American Chemical Society: Washington, DC, 1992.
5. Prodi, L.; Bolletta, F.; Montalti, M.; Zaccheroni, N. Coord. Chem. Rev. 2000, 205, 59-83.
6. a) McClure, D. S. J. Chem. Phys. 1952, 20, 682-686. b) Varnes, A. W.; Dodson, R. B.; Wehry, E. L. J. Am. Chem. Soc. 1972, 94, 946-950.
7. 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, 1515-1567.
8. a) Wiskur, S. L.; Ait-Haddou H.; Lavigne, J. J.; Anslyn E.V. Acc. Chem. Res. 2001, 34, 963-972. b) Niikura, K.; Metzger, A.; Anslyn, E. V. J. Am. Chem. Soc. 1998, 120, 8533-8534. c) Metzger, A.; Anslyn, E. V. Angew. Chem. Int. Ed. Engl. 1998, 37, 682-684.; Angew. Chem. Int. Ed. Engl. 1998, 37, 649-652.
9. McCleskey, S. C.; Griffin, M. J.; Schneider, S. E.; McDevitt, J. T.; Anslyn, E. V. J. Am. Chem. Soc. 2003, 125, 1114-1115.
10. Fabbrizzi, L.; Marcotte, N.; Stomeo, F.; Taglietti A., Angew. Chem. Int. Ed. Engl. 2002, 41, 3811-3814.
11. a) Purkayastha, P.;Chattopadhyay, N. Phys. Chem. Chem. Phys. 2000, 2, 203-210. b) Lavtchieva, L.; Enchev, V.; Smedarchina, Z. J. Phys. Chem. 1993, 97, 306-310.
12. Das, K.; Sarkar, N.; Ghosh, A. K.; Majumdar, D.; Nath, D. N.; Bhattacharyya, K. J. Phys. Chem. 1994, 98, 9126-9132.
13. Tanaka, K.; Kumagai, T.; Aoki, H.; Deguchi, M.; Iwata, S. J. Org. Chem. 2001, 66, 7328-7333.
14. a) Bixby, K. A.; Nanao, M. H.; Shen, N. V.; Kreusch A.; Bellamy, H.; Pfaffinger, P. J.; Choe, S. Nature Structural Biology. 1999, 6, 38-43. b) Berg, J. M.; Shi, Y. Science 1996, 271, 1081-1085. c) Bush, A. I.; Pettingel, W. H.; Multhaup, G.; Paradis, M. D.; Vonsattel, J. P,; Gusella, J. F.; Beyreuther, K.; Masters, C. L.; Tanzi, R. E. Science 1994, 265, 1464-1467.
15. Nagano, T.; Kikuchi, K.; Hirano, T.; Urano, Y. J. Am. Chem. Soc. 2002, 124, 10650-10651.
16. Nagano, T.; Kikuchi, K.; Hirano, T.; Urano, Y. J. Am. Chem. Soc. 2000, 122, 12399-12400.
17. Burdette, S. C.; Walkup, G. K.; Spingler, B；Tsien, R. Y.; Lippard. S. J. J. Am. Chem. Soc. 2001, 123, 7831-7841.
18. Burdette, S. C.; Frederickson, C. J.; Bu, W.; Lippard, S. J. J. Am. Chem. Soc. 2003, 125, 1778-1778.
19. Chaney, R. L.; Ryan, I. A.; Li, Y. M.; Brown, S. L. In Cadmium in Soil and Plants; McLaughlin, M. J.; Singh, B. R., Eds.; Kluwer: Boston, 1999; pp. 219-259.
20. Dobson, S. Cadmium-Environmental Aspect; World Health Organization: Geneva, 1992.
21. Friberg, L.; Elinger, C. G.; Kjellstrom, T. Cadmium; World Health Organization: Geneva, 1992.
22. Fusetani, N.; Matsunaga, S.; Matsumoto, H.; Takebayashi, Y. J. Am. Chem. Soc. 1990, 122, 7054-7056.
23. Hennrich, G.; Sonnenschein, H.; Genger, U. R. J. Am. Chem. Soc., 1999, 121, 5073-5074.
24. Prodi, L.; Montali, M.; Zaccheroni, N.; Bradshaw, J. S.; Izatt, R. M.; Savage, P. B. Tetrahedron Lett, 2001, 42, 2941-2944.
25. Godwin, H. A. Curr. Opin Chem. Biol. 2001, 5, 223-227.
26. Lu, Y. Chem. Eur. J. 2002, 8, 4588-4596.
27. Needlman, H. L. Human Lead Exposure; CRC Press : Boca Ratou, FL, 1992.
28. Rifai, N.; Cohen, G.; Wolf, M.; Cohen, L.; Faser, C.; Savory, J.; DePalma, L. Ther. Drug Monitor, 1993, 15, 71.
29. Lu, Y.; Liu, J. J. Am. Chem. Soc. 2003, 125, 6642-6643.
30. Specht, D. P.; Martic, P. A.; Farid, S. Tetrahedron Lett. 1982, 38,
1203-1211.
31. Safdar, H.; Atta-ur-Rahman, M. Iqbal, C.; Khalid, M. K.; Wilhelm, S.; Ernst, B.; Tetrahedron. 2001, 57, 9951-9958.
32. Mizukami, S.; Nagano, T.; Urano, Y.; Odani, A.; Kikuchi, K. J. Am. Chem. Soc. 2002, 124, 3920-3925.
33. Li, C.; Wong, W. T. Tetrahedron Lett, 2002, 43, 3217-3220.
34. Hemmert, C.; Verelst, M.; Tuchagues, J. P. Chem.Commun, 1996, 5, 617-618.
35. a) Baldwin, J.; Chothia, C. J. Mol. Biol. 1979, 129, 175-179. b) Connors, K. A. Binding Constants; John Wiley: New York, 1987.
36. Job, A. Ann. Chim. (10th series) 1928, 9, 113.