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Author: 林昱辰
Lin Yu Chen
Thesis Title: 含各式4-羥基脯胺酸配位基之鎳錯合物合成及反應性探討與含鎳超氧化物歧化酶活性中心模擬之研究
Synthesis and Reactivity of Nickel Complexes with various 4-Hydroxy-L-Prolinol Ligands Relevant to the Active Site of Nickel Superoxide Dismutase
Advisor: 李位仁
Lee, Way-Zen
Degree: 碩士
Master
Department: 化學系
Department of Chemistry
Thesis Publication Year: 2013
Academic Year: 101
Language: 中文
Number of pages: 139
Keywords (in Chinese): 含鎳超氧化物歧化酶正三價鎳錯合物半抑制濃度
Keywords (in English): NiSOD, Ni(III) complex, half maximal inhibitory concentration
Thesis Type: Academic thesis/ dissertation
Reference times: Clicks: 96Downloads: 3
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  • 近年來有研究從土壤鏈黴菌及海生藍綠藻中發現含鎳超氧化物歧化酶(NiSOD),此酵素催化超氧離子的歧化反應生成過氧化氫及氧氣,藉此避免生物細胞因氧化壓力受到損壞。為了模擬NiSOD活性中心的反應性,本研究設計並合成一系列五牙配位基BMPORP (R = H, TMS, TPS)和H2BDPPOH,分別與[Ni(CH3CN)6](ClO4)2反應後,形成正二價鎳錯合物[Ni(BMPOHP)CH3CN](ClO4)2 (1)、 [Ni(BMPOTMSP)- (CH3CN)](ClO4)2 (2)、[Ni(BMPOTPSP)(CH3CN)](ClO4)2 (3) 和 Ni(BDPPOH) (4),並利用紫外可見光光譜、循環伏安法以及X光繞射解析鑑定。從循環伏安法得知,以Ag/Ag+做參考電位,發現錯合物1、2和3分別在-1.01, -1.04 and -1.09 V有不可逆的還原峰,表示[NiII(BMPORP)CH3CN](ClO4)2系列的錯合物無法形成穩定的正三價鎳錯合物。而錯合物4在0.52 V的位置有可逆的氧化還原峰,與氧化劑[CP2Fe]PF6反應後,生成正三價的鎳錯合物[NiIII(BDPPOH)]PF6(5),並可利用紫外可見光光譜、循環伏安法以及電子順磁共振光譜鑑定錯合物5的特性。錯合物5可氧化KO2產生O2,本身還原成錯合物4。在超氧化物歧化酶活性測試中,可以得到錯合物5的半抑制濃度為1.8 × 10-4 M,表示錯合物5具有NiSOD的活性。

    Nickel-containing superoxide dismutase (NiSOD) has been found in the Streptomyces species, and marine cyanobacteria in recent years. NiSOD can catalyze the disproportionation of the superoxide anion into hydrogen peroxide and dioxygen avoiding cell damage from oxidative stress. In order to mimic the active site of NiSOD, various pentadentate lignads, BMPORP (R = H, TMS, TPS) and H2BDPPOH, were designed and prepared. As these ligands reacted with [Ni(CH3CN)6](ClO4)2, four complexes, [Ni(BMPOHP)(CH3CN)](ClO4)2 (1), [Ni(BMPOTMSP)- (CH3CN)](ClO4)2 (2), [Ni(BMPOTPSP)(CH3CN)](ClO4)2 (3) and Ni(BDPPOH) (4) were formed. Complexes 1, 2, 3 and 4 were characterized by UV/vis spectroscopy, cyclic voltammetry (CV) and X-ray crystallograph. CV measurements for complex 1, 2 and 3 displayed an irreversible reduction in MeCN at -1.01, -1.04 and -1.09 V vs Ag/Ag+, respectively. It shows that [NiII(BMPORP)CH3CN](ClO4)2 cannot be oxidized to NiIII complexes. However, CV measurements of complex 4 displayed a reversible event centered at 0.52 V vs Ag/Ag+ suggesting that complex 4 could be oxidized by [CP2Fe]PF6. The NiIII complex, [Ni(BDPPOH)]PF6 (5), characterized by UV/vis spectroscopy, CV and EPR, was synthesized by oxidation of complex 4. Complex 5 could oxidize KO2 to form O2 gas and itself was reduced to complex 4. The superoxide dismutase activity, half maximal inhibitory concentration (IC50) for dismutasing superoxide anion, of complex 5 was 1.8 × 10-4 M. The IC50 reveals complex 5 possessing SOD activity.

    目 錄 中文摘要……………………………………………………………Ⅰ 英文摘要……………………………………………………………Ⅱ 圖索引………………………………………………………………Ⅲ 表索引………………………………………………………………Ⅴ 反應機構索引………………………………………………………Ⅵ 附錄索引……………………………………………………………VII 第一章 緒論 1 第一節 研究動機與目的 1 第二節 含金屬超氧化物歧化酶的相關文獻探討 2 一、銅/鋅超氧化物歧化酶,Cu/ZnSOD 3 二、含錳或鐵超氧化物歧化酶,Mn or FeSOD 4 三、含鎳超氧化物歧化酶 6 第三節 含鎳超氧化物歧化酶擬態化合物的相關文獻探討 10 一、結構性還原態NiSOD擬態化合物 10 二、結構性氧化態NiSOD擬態化合物 13 三、還原態NiSOD之活性擬態化合物 15 第二章實驗部分 18 第一節 實驗儀器及藥品 18 一、實驗儀器 18 二、實驗藥品 19 三、實驗條件 22 第二節 配位基與錯合物的合成與鑑定 24 一、配位基BMPOHP之合成 24 二、配位基BMPOTMSP之合成 27 三、配位基BMPOTPSP之合成 28 四、配位基H2BDPPOH之合成 29 五、錯合物 [NiII(BMPOHP)](ClO4)2 (1)的合成 33 六、錯合物 [NiII(BMPOTMSP)](ClO4)2 (2)的合成 34 七、錯合物 [NiII(BMPOTPSP)](ClO4)2 (3)的合成 34 八、錯合物 [NiII(BDPPOH)] (4)的合成 35 九、錯合物 [NiIII(BDPPOH)]PF6 (5)的合成 36 第三節 三價鎳擬態錯合物之反應 37 一、[NiIII(BDPPOH)]PF6 (5)與KO2之反應(用於GC偵測) 37 二、[NiIII(BDPPOH)]PF6 (5)與KO2之反應(用於UV/vis偵測) 37 第三章 結果與討論 38 第一節 配位基的合成與探討 39 一、BMPORP系列之配位基 39 二、配位基H2BDPPOH 40 第二節 鎳金屬錯合物的合成與探討 41 一、 正二價鎳錯合物之X-ray結構解析 41 二、 錯合物氧化還原電位之比較 49 三、 正三價鎳錯合物[Ni(BDPPOH)]PF6 (5)合成與探討 53 第三節 鎳金屬錯合物與超氧化物反應的探討 59 一、氧化態NiSOD之活性模擬 59 二、超氧化物歧化酶活性測試 62 第四章 結論與展望 64 參考文獻 66 附錄

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