由銅離子周圍環境的不同，可將銅蛋白分為Type I、Type II及Type III三種。我們將藉由合成不同類型的配位子，模擬Type I及Type II銅離子周圍環境。設計全新含硫醇基配位子NSC2SN(1c): N1,N2-bis(2- mercapto-ethyl)-N1,N2-bis-(2-pyridinyl-methyl)-1,2-ethane- diamine與NSC4SN(1d): N1,N4-bis(2-mercaptoethyl)-N1,N4-bis(2- pyridinylmethyl)-1,4-butane-diamine，與[Cu(CH3CN)4]ClO4反應之後，分別得到銅離子化合物。
另一類型三角錐配位子，用以模擬Type II銅蛋白的銅離子周圍環境。藉由合成已知的配位子TNPA(4b): 2,2’2,”-nitrilotris(N-(pyridine- 2-yl)-acetamide)與全新的配位子TNPMA(4c): 2,2’2”-nitrilotris(N- (pyridin-2-ylmethyl)acetamide)，與[Cu(CH3CN)4]BF4進行反應，得到極為空氣敏感的全新銅離子化合物。且TNPA(4b)的純化方式有更簡易的方式。

The active center of copper proteins can divide into Type I, Type II and Type III categories according to their copper coordinated environment. The synthesis and characterization of thiol ligands, NSC2SN(1c): N1,N2-bis(2-mercaptoethyl)-N1,N2-bis-(2-pyridinylmethyl)- 1,2-ethanediamine and NSC4SN(1d): N1,N4-bis(2-mercaptoethyl)-N1,N4- bis(2-pyridinylmethyl)-1,4-butane-diamine to mimic that active center of copper proteins are described. Those new types of ligands (1c and 1d) react with [Cu(CH3CN)4]ClO4 afford the mononuclear copper complexes. On the other hand, the synthesis of the known tripodal ligand TNPA(4b): 2,2’2,”-nitrilotris(N-(pyridine-2-yl)acetamide) and new tripodal ligand TNPMA(4c): 2,2’2”-nitrilotris(N-(pyridin-2-ylmethyl)acetamide) are also characterized. The reactivity of [Cu(CH3CN)4]BF4 of two tripodal ligands are described.

中文摘要...........................................I
Abstract……………………………………………………..III
第壹章 緒論......................................1
1.1. 簡介..................................................1
1.2. 銅金屬類型和功用......................................4
1.3. 氮循環(Nitrogen cycle)……………………………………………..8
1.4. 銅蛋白模擬化合物之介紹………………………………………..11
1.4.1. Type I 銅蛋白模擬化合物............................................................11
1.4.2. Type II銅蛋白模擬化合物............................................................14
1.4.3. Type III 銅蛋白模擬化合物.........................................................18
1.5. 研究目的......................................................................................... 19
第貳章 實驗步驟.................................23
2.1. 實驗藥品…………………………………………………………..23
2.2. 實驗儀器…………………………………………………………..25
2.3. Thio ligands and complexes: NSCnSN, NNCnSN, NNCnSS(n=2 or 4)(見流程圖1、2)………………………………………………………..26
2.3.1. N2NH(1a): N, N’-bis(2-pyridylmethyl)-ethane-1,2-diamine的合成
..................................................................................................................26
2.3.2. N4NH(1b): N,N’-bis(2-pyridylmethyl)-butane-1,4-diamine的合成
..................................................................................................................26
2.3.3. NSC2SN(1c): N1,N2-bis(2-mercaptoethyl)-N1,N2-bis -(2-pyridinyl- methyl)-1,2-ethanediamine的合成.........................................................27
2.3.4. NSC4SN(1d):N1,N4-bis(2-mercaptoethyl)-N1,N4-bis(2-pyridinyl- methyl)-1,4-butane-diamine的合成.........................................................28
2.3.5. Cu和NSC2SN(1c)的反應得NSC2SNCu(1e)………............……28
2.3.6. Cu和NSC4SN(1d)的反應得NSC4SNCu(1f)................................29
2.3.7. N2NHboc(2a): tert-butyl 2-aminoethylcarbamate的合成.............29
2.3.8. N4NHboc(2b): tert-butyl 2-aminobutylcarbamate的合成............30
2.3.9. PyN2NHboc(2c): tert-butyl 2-(bis(pyridin-2-ylmethyl)amino)ethyl- carbamate的合成.....................................................................................30
2.3.10. PyN2NH(2e): bis[(2-pyridyl)methyl]ethylenediamine的合成…31
2.4. tris(3,5-bis(ethoxycarbonyl)-1H-pyrazol-1-yl)–hydroborate(bisEster- Tp)(3c) 配位子的合成(見流程圖3)………………………..………….32
2.4.1. 3,5-dicarboxylic acid-pyrazole(or 1H-pyrazole-3,5-dicarboxylic- acid)(3a)的合成………...………………………………………………32
2.4.2. diethyl 1H-pyrazole-3,5-dicarboxylate(3b)的合成………………32
2.4.3. tris(3,5-bis(ethoxycarbonyl)-1H-pyrazol-1-yl)hydroborate (3c):3,5- bisEsterTp ligand的合成.........................................................................33
2.5. 三角錐配位子TNPA和TNPMA的合成(見流程圖4)...................34
2.5.1. triethyl-2,2’,2”-nitrilotriacetate(4a)的合成....................................34
2.5.2. TNPA: 2,2',2'-nitrilotris(N-(pyridin-2-yl)acetamide)(4b)的合成..34
2.5.3. TNPMA: 2,2',2'-nitrilotris(N-(pyridin-2-ylmethyl)acetamide)(4c)
..................................................................................................................35
2.5.4. [Cu(CH3CN)4]BF4和 2,2',2'-nitrilotris(N-(pyridin-2-yl)acetamide) (4b)的反應CuTNPA(4d).........................................................................35
2.5.5. [Cu(CH3CN)4]BF4和2,2',2'-nitrilotris(N-(pyridin-2-ylmethyl)acet- amide)(4c)的反應CuTNPMA(4e)……………………………………...36
2.6. 含pyridine-amide官能基之配位子NONON的合成(見流程圖5) ..............................................................................................................37
2.6.1. pyridine-2,6-dicarboxylic acid(5a)的合成.....................................37
2.6.2. diethyl pyridine-2,6-dicarboxylate(5b)的合成………………......37
2.6.3. tert-butyl-2-(2-(2-aminoethoxy)ethoxy)-ethylcarbamate的合成...38
2.6.4. Boc-aminepyridine(5c)的合成.......................................................38
2.6.5. N2,N6-bis(2-(2-(2-aminoethoxy)ethoxy)ethyl)pyridine-2,6dicarb- oxamide(5d)Aminepyridine的合成........................................................39
2.7. 2,6-bis(mercaptomethyl)pyridine 配位子的合成(見流程圖6).......40
2.7.1. 2,6-bis(bromomethyl)pyridine(6a)的合成……………………….40
2.7.2. 2,6-bis(mercaptomethyl)pyridine(6b)的合成................................40
第參章 結果與討論...............................................................42
3.1. 長碳鏈硫醇配位子NSCnSN、NNCnSN與NNCnSS(n=2 or 4)的合成與反應(見流程圖1、2).........................................................................42
3.1.1. N2NH(1a): N,N’-bis(2-pyridylmethyl)-ethane-1,2-diamine與N4NH(1b): N,N’-bis(2-pyridylmethyl)-butane-1,4-diamine的合成.......42
3.1.2. NSC2SN(1c): N1,N2-bis(2-mercaptoethyl)-N1,N2-bis(2 pyridinyl- methyl)-1,2-ethanediamine與NSC4SN(1d): N1,N4-bis -(2-mercapto- ethyl)-N1,N4-bis(2-pyridinylmethyl)-1,4-butanediamine的合成.............46
3.1.3. [Cu(CH3CN)4]ClO4與NSC2SN(1c)以及 NSC4SN(1d)的反應…52
3.2. 三角錐配位子TNPA和TNPMA的合成(見流程圖4)….....55
3.2.1. Triethyl-2,2’,2’’-nitrilotriacetate(4a)的合成..................................55
3.2.2. TNPA(4b): 2,2’,2’’-nitrilotris(N-(pyridin-2-yl)acetamide)與
TNPMA(4c): 2,2’,2’’-nitrilotris(N-(pyridine-2-ylmethyl)acetamide)的合成..............................................................................................................55
3.2.3. [Cu(CH3CN)4]BF4 和TNPA 2,2’,2’’-nitrilotris(N-(pyridin-2- yl)acet-amide)的反應...............................................................................57
3.2.4. [Cu(CH3CN)4]BF4 和TNPMA : 2,2’,2’’-nitrilotris(N-(pyridine-2- ylmethyl)-acetamide)的反應………………………..…………………..59
第肆章 結論.....................................61
第伍章 參考文獻.................................62
第陸章 附錄.....................................65

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