鋅酵素在人體生物機能扮演著重要的角色，大多鋅金屬酵素活化中心是氮及氧的配位環境，直到最近才發現有多硫配位環境之鋅酵素存在。多硫鋅蛋白所具有的生物機能是能將甲基化的去氧核酸去除甲基，使DNA回復其正常序列，避免基因的死亡、突變及基因序列配對錯誤。
本實驗室利用多硫酚膦配位基與鋅鹽來進行模擬多硫鋅蛋白甲基轉移的行為，改變不同劑量的拔氫試劑來控制三硫酚與鋅鹽的反應，我們得到三硫酚膦基鋅化物雙聚體(2)及活化二氯甲烷的鋅化合物(4)。鋅雙聚體(2)是一個具有高度活性可以活化一些鈍性物質，可以與類DNA磷酸根結構之試劑OP(OMe)3於CH3CN下進行甲基轉移反應，此為文獻外第二個在室溫下在非高極性溶劑（DMSO）中可以將OP(OMe)3的甲基轉移的例子。

The thiolate-alkylating protein (Ada protein) is a zinc protein that repairs the defective DNA by transferring methyl group on to itself. We have used the thiophenylphosphine ligand to provide sulfur-rich environment for model study. In this work, we have accidentally found that this zinc complex can activate CH2Cl2 to generate a methylenated complex (4). Carbon-halide activation is commonly used in organic synthesis. However activation of C-Cl bond is comparatively scarce compared to C-Br or C-I bonds.
Varying the degree of deprotonation on the PS3 ligand, a simple zinc dimer (2) can be obtained instead of (4). The dimer (2) can even react with much milder alkyl-reagent, methylphosphotriester. Therefore (2) serves as a successful Ada protein model in this sense. Other related alkyl-transfer reactions using different ligand or zinc complexes were discussed to give insight of the methyl-transfer action of Ada protein.

提要…………………………………………………………………………… i
目錄…………………………………………………………………………… iv
表目錄……………………………………………………………………… vii
圖目錄……………………………………………………………………… vii
附錄目錄…………………………………………………………………… ix
壹、緒論…………………………………………………………………… 1
一、前言………………………………………………………… 1
二、背景介紹與研究動機……………………………………… 2
1. Ada protein介紹……………………………………………… 2
2. 硫上烷基化之介紹…………………………………………… 4
3. 研究動機……………………………………………………… 11
貳、實驗部分………………………………………………………………… 14
一、試藥………………………………………………………… 14
二、儀器設備…………………………………………………… 17
三、合成反應…………………………………………………… 19
1. 配位基Bis(2-thiophenyl)phenylphosphine(PS2)的合成
與鑑定………………………………………………………… 19
2. 配位基Tri(2-thiophenyl)phosphine(PS3)的合成與鑑定……… 21
3. 配位基Tris(3-trimethylsilyl-2-thiophenyl)phosphine (SiPS3)
的合成與鑑定………………………………………………… 23
4. 合成Zn(PS2)(TMEDA) (1) …………………………………… 25
5. 合成[H-TMEDA]2[Zn(PS3)]2 (2)……………………………… 26
6. 合成Zn[P(C6H4S)2(C6H4SCH3)](TMEDA) (3)……………… 27
7. 合成Zn{P(C6H4S) [(C6H4S)2CH2]}2 (4)……………………… 28
8. 合成Zn(SiPS3)(TMEDA) (5)…………………… 29
9. 合成[Me-TMEDA]2[Zn(PS3)]2 (6)………………………… 30
10合成Zn[OP(C6H4S)(C6H4S)(C6H4S)]2.………………………… 30
11. 合成[(THF)3Li(ImMe)][H-ImMe][Zn(PS3)]2．THF………… 31
叁、結果與討論……………………………………………………………… 32
一、多硫酚膦基鋅化物合成反應探討及結構解析…………… 33
1. 二硫酚膦基（PS2）與鋅金屬反應研究……………………… 33
2. 三硫酚膦基（PS3）與鋅金屬反應研究………………… 36
3. 三甲基矽三硫酚膦基（SiPS3）與鋅金屬反應研究………… 47
二、甲基轉移鋅蛋白之模擬…………………………………… 48
1. 甲基轉移蛋白之鋅金屬角色探討………………………… 48
2. 甲基轉移蛋白之鹼基角色探討…………………………… 52
3. 甲基轉移蛋白之機制探討………………………………… 54
肆、結論……………………………………………………………………… 60
伍、參考文獻………………………………………………………………… 61
陸、附錄……………………………………………………………………… 63

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