我們合成出不同碳鏈長度的chelate-dithiolate-bound DNIC，從晶體結構、反應性、以及CV圖中比較，發現有著不一樣的性質。從CV圖中，[(NO)2Fe(SC2H4S)]-/2-的還原電位（E1/2 = -1.33 V）比碳鏈較長的chelate-dithiolate-bound DNIC [(κ2-S2-o-xylene)Fe(NO)2]-/2-（E1/2 = -1.65 V）還要高許多；且{Fe(NO)2}10 DNIC [K(K-18-crown-6-ether)][(κ2-S2-o-xylene)Fe(NO)2]必須在有陽離子的作用下，才能穩定的存在；但[PPN]2[(NO)2Fe(SC2H4S)]本身就能夠穩定；而從反應性來觀察，[PPN]2[(NO)2Fe(SC2H4S)]在氧化過程中，並非與其他碳鏈較長的DNIC一樣能夠得到穩定的{Fe(NO)2}9 DNIC，反而是硫原子先被氧化形成{Fe(NO)2}10-{Fe(NO)}7產物：[PPN]2[(NO)2Fe(μ-κ2-SC2H4S)2Fe(NO)]。由以上的實驗結果，我們推測chelate-dithiolate-bound DNIC的配位基碳鏈長度與bite angle改變，對於DNIC的電子結構、穩定度和反應性皆有著重大的影響。
 

Several chelate-dithiolate-bound DNICs with different backbone length were synthesized. According to single-crystal X-ray structures, reactivity, and cyclic voltammograms, these chelate-dithiolate-bound DNICs show different properties. From the electrochemistry, the {Fe(NO)2}10 DNIC [PPN]2[(NO)2Fe(SC2H4S)] bearing a shorter backbone displays a rather positive midpoint potential compared to [PPN]2[(κ2-S2-o-xylene)Fe(NO)2 bearing a longer backbone. The interaction of [K⋯S] is an important factor to stabilize the {Fe(NO)2}10 DNIC [K(K-18-crown-6-ether)][(κ2-S2-o-xylene)Fe(NO)2]. However, [(NO)2Fe(SC2H4S)]2- was stable with [PPN]+ salt. The oxidation of [PPN]2[(NO)2Fe(SC2H4S)] might occur on S atom, and form a {Fe(NO)2}10-{Fe(NO)}7 product [PPN]2[(NO)2Fe(μ-κ-SC2H4S)2Fe(NO)]. These results infer that the backbone length and bite angle of chelate-dithiolate-bound DNIC could not only modulate the electronic structure of {Fe(NO)2} core, but also influence its stability and reactivity.

第一章 緒論 1
1-1 一氧化氮的歷史與分子特性 1
1-2 人體中一氧化氮的生成 4
1-3 一氧化氮在體內的儲存、運送與作用 7
1-4 雙亞硝基鐵錯合物 10
1-5 研究方向 17
第二章 實驗部份 18
2-1 一般實驗 18
2-2 儀器 18
2-3 藥品 20
2-4 化合物的合成與反應 21
2-4-1 2-4-1 1,2-Benzenedimethanethiol 的合成 21
2-4-2 [Cation][(κ2-S2-o-xylene)Fe(NO)2] (1) 的合成 22
2-4-3 Complex 1-PPN與NO(g) 反應 23
2-4-4 [K(K-18-crown-6-ether)][(κ2-S2-o-xylene)Fe(NO)2] (2) 的合成 23
2-4-5 Complex 2 與 (TMEDA)Fe(NO)2 反應 24
2-4-6 [PPN]2[(2-SC2H4S)Fe(NO)2] 的合成 25
2-4-7 [PPN]2[(2-SC2H4S)Fe(NO)2] 與 [Cp2Fe][BF4] 反應 26
2-5 晶體結構解析（Crystallgraphy） 26
第三章 結果與討論 32
3-1螯合配位基{Fe(NO)2}9DNIC-[PPN][(κ2-S2-o-xylene)Fe(NO)2] (1)之結構與性質 32
3-2 [PPN][(κ2-S2-o-xylene)Fe(NO)2]與NO(g)反應之結果探討 39
3-3螯合配位基{Fe(NO)2}10 DNIC [K(K-18-crown-6-ether)][(κ2-S2-o-xylene)Fe(NO)2] (2)之結構與性質 45
3-4螯合配位基{Fe(NO)2}10 DNIC-[cation]2[(κ2-SC2H4S)Fe(NO)2] 之氧化反應與結果討論 55
第四章 結論 67
References 70

 
Figure
Fig. 1-1一氧化氮分子軌域圖 2
Fig. 1-2金屬與NO之間的鍵結關係 3
Fig. 1-3 NOS將L-arginine氧化產生NO的過程 5
Fig. 1-4 NOS在體內作用機制 7
Fig. 1-5 (a) Cys-NO、GSNO的結構. (b) RSNO的生成與機制 8
Fig. 1-6利用MRP-1傳遞GS-DNIC以及NO調節機制 10
Fig. 1-7 GST P1-1 protein-bond DNIC 合成過程與晶體結構 11
Fig. 1-8 Classical LMW DNIC 分類與結構 13
Fig. 1-9 Non-classical 多配位DNIC結構 14
Fig. 1-10 RRE、RRS、reduced RRE 結構與EPR訊號 15
Fig. 1-11常見的鐵硫亞硝基錯合物 16
Fig. 1-12{Fe(NO)2}9 DNIC轉換成[2Fe-2S] clusters 之反應機制 16
Fig. 3-1 Structure of complex 1 with thermal ellipsoids at 50% probability 34
Fig. 3-2 [PPN][(κ2-S2-o-xylene)Fe(NO)2] (1)之IR光譜(KBr) 36
Fig. 3-3 complex 1之UV-vis吸收光譜(CH3CN) 36
Fig. 3-4 complex 1之EPR光譜 (a) at 298K (g = 2.030), (b) at 77K (g1 = 2.046, g2 = 2.029, g3 = 2.013) 37
Fig. 3-5 complex 1之CV圖 38
Fig. 3-6 [PPN][(NO)2Fe(SC3H6S)]與NO(g)反應 39
Fig. 3-7 Complex 1 + NO(g)與(NO2)2Fe(NO)2之液態IR光譜in THF 41
Fig. 3-8 Complex 1與NO(g) 反應之液態IR光譜 in THF 42
Fig. 3-9 Complex 1與NO(g) 反應之固態IR光譜 42
Fig. 3-10 Fe(NO)4與(NO2)2Fe(NO)2之固態IR光譜比較 43
Fig. 3-11反應副產物cyclic disulfide之1H NMR (δ7.18 (m,2H); 7.08 (m,2H); 4.07 (s,4H) ppm (CDCl3)) 44
Fig. 3-12 Structure of complex 2 with thermal ellipsoids at 50% probability 46
Fig. 3-13 Complex 1與Complex 2 之固態IR光譜 48
Fig. 3-14 Complex 2 之UV-vis吸收光譜(CH3CN) 49
Fig. 3-15 Complex 1與Complex 2之Fe-edge比較 52
Fig. 3-16 Structure of complex 3 with thermal ellipsoids at 50% probability 53
Fig. 3-17 [PPN]2[(NO)2Fe(SC2H4S)]氧化反應追蹤之IR光譜圖(CH3CN) 56
Fig. 3-18 Structure of complex 4 with thermal ellipsoids at 50% probability 57
Fig. 3-19利用低溫UV-vis光譜儀偵測[PPN]2[(NO)2Fe(SC2H4S)]氧化反應 58
Fig. 3-20 Complex 4之固態IR光譜圖(KBr) 60
Fig. 3-21 [PPN]2[(NO)2Fe(SC2H4S)]加入0.5 eq[Cp2Fe][BF4]之氧化反應 EPR光譜 61
 
Table
Table 1-1 NO之性質整理 2
Table 1-2不同類型NOS之性質與功能 6
Table 1-3 Protein bond DNIC之配位環境與EPR訊號 12
Table 2-1 Crystal data and structure refinement for Complex 1-PPN 27
Table 2-2 Crystal data and structure refinement for Complex 1-Crown 28
Table 2-3 Crystal data and structure refinement for Complex 2 29
Table 2-4 Crystal data and structure refinement for Complex 3 30
Table 2-5 Crystal data and structure refinement for Complex 4 31
Table 3-1 bidentate與monodentate含硫配位基{Fe(NO)2}9 DNIC之鍵長鍵 角比較 35
Table 3-2 Thiolate-bound DNIC之還原電位比較. 39
Table 3-3 bidentate thiolate-bound {Fe(NO)2}9與{Fe(NO)2}10 DNIC之性質比較 50
Table 3-4 complex 4與[PPN][(NO)Fe(S,S-C6H4)2Fe(NO)2]之鍵長鍵角 65

Scheme
Scheme 3-1 complex 1 的合成 33
Scheme 3-2 complex 1 與NO(g)反應 40
Scheme 3-3 complex 2 的合成. 45
Scheme 3-4 complex 2陽離子置換 48
Scheme 3-5 complex 2 與 TMEDA-DNIC反應 53
Scheme 3-6形成complex 3 之推測反應機構 54
Scheme 3-7 [PPN]2[(NO)2Fe(SC2H4S)]之氧化反應 59
Scheme 3-8 [PPN]2[(NO)2Fe(SC2H4S)]氧化反應之推測反應機構. 62
Scheme 3-9不同bidentate thiolate DNIC之互相轉換與反應性 66

1. Furchgott, R.F.; Zawadzki, J.V. Nature 1980, 288, 373.
2. (a) Ignarro, L. J.; Adams, J. B.; Horwitz, P. M.; Wood, K. S. J. Bioinorg. Chem. 1986, 261, 4997. (b) Ignarro, L. J.; Buga, G. M.; Wood, K. S.; Byrns, R. E.; Chaudhuri, G. Proc. Natl. Acad. Sci. 1987, 84, 9265.
3. (a) Stamler, J. S. Cell 1994, 78, 931. (b) Stamler J. S.; Singel, D. J.; Loscalzo, J. Science 1992, 258, 1898. (c) Ueno, T.; Suzuki, Y.; Fujii, S.; Vanin, A. F.; Yoshimura, Y. Biochem. Pharmacol. 2002, 63, 485. (d) Lee, J.; Chen, L; West, A. H.; Richter-Addo, G. B. Chem. Rev. 2002, 102, 1019. (e) Wang, P. G.; Xian, M.; Tang, X.; Wu, X.; Wen, Z.; Cai, T.; Janczuk, A. J. Chem. Rev. 2002, 102, 1091.
4. Koshland, D. E. Science 1992, 258, 1861.
5. Gary, L. M.; Donald, A. T.: Prentice Hall International, Inc. Inorganic Chemistry 2nd , 44.
6. Enemark, J. H.; Feltham, T. D. Coord. Chem. Rev. 1974, 13, 339.
7. Marletta, M. A. Cell 1994, 78, 927.
8. (a) Lundberg, J. O.; Weitzberg, E.; Gladwin, M. T. Nat. Rev. 2008, 7, 156. (b) Lundberg, J. O.; Weitzberg, E.; Cole, J. A.; Benjamin, N. Nat. Rev. 2004, 2, 593.
9. (a)Alderton, W. K.; Cooper, C. E.; Knowles, R. G. Biochem. J. 2001, 357, 593. (b)Nussler, A. K.; Billiar, T. R. J. Leukoc. Biol. 1993, 54, 171. (c) Wlodek, D.; Gonzales, M. J. Theor. Biol. 2003, 225, 33
10. Bogdan, C. Trends Cell Biol. 2001, 11, 66.
11. Jose Carlos Toledo Jr., Ohara Augusto, Chem. Res. Toxicol. 2012, 25, 975.
12. (a)Butler, A. R.; Megson, I. L. Chem. Rev. 2002, 102, 1155 (b) Ueno, T.; Susuki, Y.; Fujii, S.; Vanin, A. F.; Yoshimura, T. Biochem. Pharmacol. 2002, 63, 485. (c) Frederik., A. C.; Wiegant, I. Y.; Malyshev, I. Y.; Kleschyov, A. L.; van Faassen, E.; Vanin, A. F. FEBS Lett. 1999, 455, 179. (d) McCleverty, J. A. Chem. Rev. 2004, 104, 403. (e) Hayton, T. W.; Legzdins, P.; Sharp, W. B. Chem. Rev. 2002, 102, 935.
13. (a) Kharitonov, V. G.; Sundquist, A. R.; Sharma, V. S. J. Biol. Chem. 1995, 270, 2815. (b) Goldstein, S.; Czapski, G. J. Am. Chem. Soc. 1996, 118, 3419. (c) Junhui S.; Charles S.; and Elizabeth M. Antioxid Redox Signal. 2006, 8, 1693.
14. (a) Kharitonov, V. G.; Sundquist, A. R.; Sharma, V. S. J. Biol. Chem. 1995, 270, 2815. (b) Goldstein, S.; Czapski, G. J. Am. Chem. Soc. 1996, 118, 3419.
15. (a) Szacilowski, K.; Chmura, A.; Stasicka, Z. Coord. Chem. Rev. 2005, 249, 2408. (b) Boese, M.; Keese, M. A.; Becker, K.; Busse, R.; Mülsch, A. J. Biol. Chem. 1997, 272, 21767. (c) Lee, M.; Arosio, P.; Cozzi, A.; Chasteen, M. D. Biochemistry 1994, 33, 3679.
16. (a) Link, T. A. Adv. Inorg. Chem, 1999, 47, 83. (b) Hunsicker-Wang, L. M.; Heine, A.; Chen, Y.; Luna, E. P.; Todaro, T.; Zhang, Y. M.; Williams, P. A.; McRee, D. E.; Hirst, J.; Stout, C. D.; Fee, J. A. Biochemistry, 2003, 42, 7303.
17. (a) Calzolai, L.;Zhou, Z. H.; Adams, M. W. W.; La Mar G. N. J. Am. Chem. Soc. 1996, 118, 2513. (b) Kennedy, M. C.; Antholine, W. E.; Beinert, H. J. Biol. Chem. 1997, 727, 20340. (c) Meyer, J. Arch. Biochem. Biophys. 1981, 210, 246. (d) Welter, R.; Yu, L.; Yu, C. A. Arch. Biochem. Biophys. 1996, 331, 9. (e) Rogers, P. A.; Eide, L.; Klungland, A.; Ding, H. DNA Repair 2003, 2, 809. (f) Sellers, V. M.; Johnson, M. K.; Dailey, H. A. Biochemistry 1996, 35, 2699. (g) Ding, H.; Demple, B. Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 5146. (h) Yang, W.; Rogers, P. A.; Ding, H. J. Biol. Chem. 2002, 277, 12868. (i) Bouton, C.; Chauveau, M. J.; Lazereg, S.; Drapier, J. C. J. Biol. Chem. 2002, 277, 31220.
18. (a) Vanin, A. F.; Stukan, R. A.; Manukhina, E. B. Biophys. Acta 1996, 1295, 5. (b) Severina, I. S.; Bussygina, O. G.; Pyatakova, N.V.; Malenkova, I. V.; Vanin, A. F. Nitric Oxide 2003, 8, 155
19. (a) Malyshev, I. Y.; Manukhina, E. B.; Mikoyan, V. D.; Kubrina, L. N.; Vanin, A. F. FEBS Lett. 1995, 370, 159. (b) Kleschyov, I. Y.; Malugin, A. V.; Golubeva, L. Y.; Zenina, T. A.; Manukhina, E. B.; Mikoyan, V. D.; Vanin, A. F. FEBS Lett. 1996, 391, 21.
20. Watts, R. N.; Hawkins, C.; Ponka, P.; Richardson, S. R. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 7670
21. (a) Harrop, T. C.; Song, D.; Lippard, S. J. J. Am. Chem. Soc. 2006, 128, 3528. (b) Harrop, T. C.; Tonzetich, Z. J.; Reisner, E.; Lippard, S. J. J. Am. Chem. Soc. 2008, 130, 15602.
22. Cesareo, E.; Parker, L. J.; Pedersen, J. Z.; Nuccetelli, M.; Mazzetti, A. P.; Pastore, A.; Federici, G.; Caccuri, A. M.; Ricci, G.; Adams, J. J.; Parker, M. W.; Bello, M. L. J. Biol. Chem. 2005, 280, 42172.
23. (a) Cruz-Ramos, H.; Crack, J.; Wu, G.; Hughes, M. N.; Scott, C.; Thomson, A. J.; Green, J.; Poole, R. K. EMBO J. 2002, 21, 3235. (b) Lee, M.; Arosio, P.; Cozzi, A.; Chasteen, M. D. Biochemistry 1994, 33, 3679. (c) D’Autréaux, B.; Horner, O.; Oddou, J.-L.; Jeandey, C.; Gambarelli, S.; Berthomieu, C.; Latour, J.-M.; Michaud-Soret, I. J. Am. Chem. Soc. 2004, 126, 6005. (d) Goussias, C.; Deligiannakis, Y.; Sanakis, Y.; Ioannidis, N.; Petrouleas, V. Biochemistry 2002, 41, 15212.
24. Gwost, D.; Caulton, K. D. Inorg. Chem. 1973, 12, 2095.
25. (a) Baltusis, L. M.; Karlin, K. D.; Rabinowitz, H. N.; Dewan, J. C.; Lippard, S. J. Inorg. Chem. 1980, 19, 2627. (b) Strasdeit, H.; Krebs, B.; Henkel, G. Z. Naturforsch. 1986, 41b, 1357. (c) Bryar, T. R.; Eaton, D. R. Can. J. Chem. 1992, 70, 1917. (d) Osterloh, F.; Saak, W.; Haase, D.; Pohl, S. Chem. Commun. 1997, 979. (e) Liaw, W.-F.; Chiang, C.-Y.; Lee, G..-H.; Peng, S.-M.; Lai, C.-H. Inorg. Chem. 2000, 39, 480. (f) Davies, S. C.; Evans, D. J.; Hughes, D. L.; Konkol, M.; Richards, R. L.; Sanders, J. R.; Sobota, P. J. Chem. Soc., Dalton Trans. 2002, 2473. (g) Chiang, C. Y.; Miller, M. L.; Reibenspies, J. H.; Darensbourg, M. Y. J. Am. Chem. Soc. 2004, 126, 10867. (h) Tsai, M.-L.; Chen, C.-C.; Hsu, I.-J.; Ke, S.-C.; Hsieh, C.-H.; Chiang, K.-A.; Lee, G.-H.; Wang, Y.; Liaw, W.-F. Inorg. Chem. 2004, 43, 5159. (i) Tsai, F.-T.; Chiou, S.-J.; Tsai, M.-C.; Tsai, M.-L.; Huang, H.-W.; Chiang, M.-H.; Liaw, W.-F. Inorg. Chem. 2005, 44, 5872. (j) Lu, T.-T.; Chiou, S.-J.; Chen, C.-Y.; Liaw, W.-F. Inorg. Chem. 2006, 45, 8799. (k) Tsai, M.-L.; Hsieh, C.-H.; Liaw, W.-F. Inorg. Chem. 2007, 46, 5110. (l) Huang, H.-W.; Tsou, C.-C.; Kuo, T.-S.; Liaw, W.-F. Inorg. Chem. 2008, 47, 2196. (m) Tsai, M.-C.; Tsai, F.-T.; Lu, T.-T.; Tsai, M.-L.; Wei, Y.-C.; Hsu, I.-J.; Lee, J.-F.; Liaw, W.-F. Inorg. Chem. 2009, 48, 9579. (l) Tsai, F.-T.; Chen, P.-L. ; Liaw, W.-F. J. Am. Chem. Soc. 2010, 132, 5290.
26. (a) Gwost, D.; Caulton, K. D. Inorg. Chem. 1973, 12, 2095. (b) Hess, J. L.; Hsieh, C.-H.; Reibenspies, J. H.; Darensbourg, M. Y. Inorg. Chem. 2011, 50, 8541. (c) Tsai, F.-T.; Kuo, T.-S.; Liaw, W.-F. J. Am. Chem. Soc. 2009, 131, 3426. (d) Tsai, M.-L.; Liaw, W.-F. Inorg. Chem. 2006, 45, 6583.
27. Hung, M.-C.; Tsai, M.-C.; Lee, G.-H.; Liaw, W.-F. Inorg. Chem. 2006, 45, 6041.
28. (a) Albano, V. G.; Areneo, A.; Bellon, P. L.; Ciani, G.; Manassero, M. J. Organomet. Chem. 1974, 67, 413. (b) Chau, C. N.; Wojcicki, A.; Calligaris, M.; Nardin, G. Inorg. Chim. Acta. 1990, 168, 105. (c) Reginato, N.; McCrory, C. T. C.; Pervitsky, D.; Li, L. J. Am. Chem. Soc. 1999, 121, 10217. (d) Yeh, S.-W.; Lin, C.-W.; Li, Y.-W.; Hsu, I-J.; Chen ,C.-H. ; Jang, L.-Y.; Lee, J.-F.; Liaw, W.-F. Inorg. Chem. 2012, 51, 4076
29. Shih, W.-C.; Lu, T.-T.; Yang, L,-B.; Tsai, F.-T.; Chiang, M.-H.; Lee, J.-F.; Chiang, Y.-W.; Liaw, W.-F. J. Inorg. Biochem. 2012, 113, 83.
30. (a) Russin, J. Ann. Chim. Phys. 1858, 52, 285. (b) Lu, T.-T.; Huang, H.-W.; Liaw, W.-F. Inorg. Chem. 2009, 48, 9027.
31. Tonzetich, Z. J.; McQuade L. E.; Lippard, S. J. Inorg. Chem. 2010, 49, 6388.
32. Tsou, T.-T.; Lin, Z.-S.; Lu, T.-T.; Liaw, W.-F. J. Am Chem. Soc. 2008, 130, 17154.
33. J. J., Mayerle; S. E. Denmark; B. V. DePamphilis; James A. Ibers; R. H. Holm. J. Am. Chem. Soc. 1975.97.1032
34. 林志威，2012，，單牙與雙牙之烷基硫配位{Fe(NO)2}10雙亞硝基鐵錯合物的合成與性質研究，碩士論文，新竹：國立清華大學化學所。
35. Lin, Z.-S.; Chiou, T.-W.; Liu, K.-Y.; Hsieh, C.-C.; Yu, J.-S.; Liaw, W.-F. Inorg. Chem. 2012, 51, 10092.
36. (a) Lee, C.-M.; Chen, C.-H.; Chen, H.-W.; Hsu, J.-L.; Lee, G.-H.; Liaw, W.-F. Inorg. Chem. 2005, 44, 6670. (b) Chen, H.-W.; Lin, C.-W.; Chen, C.-C.; Yang, L.-B.; Chiang, M.-H.; Liaw, W.-F. Inorg. Chem. 2005, 44, 3226. (c) Lu, T.-T.; Yang, L.-B.; Liaw, W.-F. J. Chin. Chem. Soc. 2010, 57, 909.