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研究生： 黎美清
Shella - Permatasari Santoso
論文名稱： 複合物的形成從2,3-二羥基苯甲酸，N-乙醯半胱氨酸 與二價過渡金屬離子：溶液平衡，合成，表徵及生物活性研究
Complex Formation of 2,3-Dihydroxybenzoic Acid and N-Acetylcysteine with Divalent Metal Ions: Solution Equilibrium, Synthesis, Characterization and Biological Activity Studies
指導教授： 朱義旭
Yi-Hsu Ju
口試委員: Ahmed Fazary
Ahmed Fazary
Felycia Edi Soetaredjo
Felycia Edi Soetaredjo
Jhy-Chern Liu
Jhy-Chern Liu
Meng-Jiy Wang
Meng-Jiy Wang
Alchris Woo Go
Alchris Woo Go
Tran Thi Ngoc Yen
Tran Thi Ngoc Yen
Suryadi Ismadji
Suryadi Ismadji
學位類別： 博士
Doctor
系所名稱： 工程學院 - 化學工程系
Department of Chemical Engineering
論文出版年： 2016
畢業學年度： 104
語文別： 英文
論文頁數： 114
中文關鍵詞： 複合物的形成 、二羥基苯甲酸 、乙醯半胱氨酸 、二價過渡金屬離子
外文關鍵詞： Complexation, dihydroxybenzoic acid, acetylcysteine, divalent metals.
相關次數： 點閱：200  下載：1 
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    • 本研究探討2,3-二羥基苯甲酸，N-乙醯基半胱氨酸與二價過渡金屬離子(錳-Mn2+, 鈷-Co2+, 鎳-Ni2+, 鋅-Zn2+, 銅-Cu2+)之溶液平衡。二成份與三成份複合物的溶液平衡常數 在類似於人體生理條件（37 攝氏度和 0.15mol•dm-3 氯化鈉離子強度) 下利用 電位滴定法求得。使用 Hyperquad2008 電腦程式修訂電位滴定數據。使用分光光度法確認 所求得之平衡常數值並以 HypSpec 電腦程式修訂之。結果發現 2,3-二羥基苯甲酸 之二成份錯合物比N-乙醯半胱氨酸二成份更稳定。而在三成份複合物中， 兩個配體組合因 協同作用而得到更穩定之錯合物。
    本研究更進一步合成 2,3-二羥基苯甲酸的二成份錯合物與三成份錯合物 （包括 N-乙醯半胱氨酸）並利用各種分析例如紫外-可見 (UV-Vis) 和紅外光譜法(IR)將之定性。 結果 發現合成的錯合物比原始配體有更高的抗微生物活性,特別是抗金黃色葡萄球菌 (S.aureus) 和大腸桿菌 (E.coli) 。在所有合成的金屬與配體錯合物中發現Zn2+的二成份與三成份錯合物 具有最好的抗微生物活性，所以進一步利用元素分析 (EA) 和氫固態核磁共振光譜 (1H NMR) 將之定性。從這些結果可推導出 Zn2+ 二成份與三成份錯合物的結構。 二成份複合物係透過2,3-二羥基苯甲酸的羥基來鍵結，而三成份複合物則是透過 2,3-二羥基 苯甲酸的羥基(—O)以及N-乙 醯半胱氨酸羧基的羧基(—COO)和巰基(—S)來鍵結形成。

    Solution equilibriums of 2,3-dihydroxybenzoic acid, N-acetylcysteine and divalent transition metal ions (Mn2+, Co2+, Ni2+, Zn2+, Cu2+) were investigated in this study. The equilibrium constant values of binary and ternary compounds were determined by using potentiometric method at conditions similar to that of human physiology (37°C, ionic strength = 0.15 mol•dm-3 NaCl). The refinement of potentiometric data were done by using the Hyperquad 2008 computer program. The determination of equilibrium constants was confirmed by spectrophotometric method with refinement using the HypSpec program. The binary complexes of 2,3-dihydroxybenzoic acid were found to be more stable than that of N-acetylcysteine complexes. While in ternary systems, the combination of the two ligands resulted in synergistic effect, thus producing more stable complexes.
    Furthermore, 2,3-dihydroxybenzoic acid binary and ternary complexes including N-acetylcysteine were synthesized and characterized by analyses such as UV-Vis and IR. The synthesized complexes were found to improve biological properties of the original ligand especially in antimicrobial activity against Staphylococcus aureus and Escherichia coli. In all complexes synthesized, binary and ternary complexes of Zn2+ gave the best antimicrobial activity and were characterized further by elemental analysis and 1H NMR. From the results structures of the synthesized binary complex and ternary complex of Zn2+ were suggested. The binary complex was formed through the binding of 2,3-dihydroxybenzoic acid hydroxyl (—O) groups while the ternary complex was formed through the binding of the same groups of 2,3-dihydroxybenzoic acid as in the binary complex and the N-acetylcysteine carboxylic group (—COO) and thiol group (—S).

    Recommendation Letter ii Qualification Letter iii 摘要 iv ABSTRACT v ACKNOWLEDGEMENT vi TABLE OF CONTENTS vii LIST OF TABLES ix LIST OF FIGURES x CHAPTER 1 1 1.1. Background 1 1.2. Objectives 2 CHAPTER 2 3 2.1. Metal in Biological Systems 3 2.1.1. Excessive Metal Intake 5 2.1.2. Metal Exposure Sources 6 2.2. Chelation 8 2.2.1. Stability Constant 9 2.3. Ligand 13 2.3.1. 2,3-Dihydroxybenzoic Acid 14 2.3.2. N-Acetylcysteine 15 2.4. Metal Ligand Synthesis 18 2.4.1. Biological Activities 19 2.4.2. Some Examples of Complex Synthesis 19 CHAPTER 3 21 3.1. Materials 21 3.2. Instrumentations 22 3.3. Experimental Procedures 22 3.3.1. Potentiometry and Spectrophotometry Measurements 22 3.3.2. Synthesis of Binary Complexes 25 3.3.3. Synthesis of Ternary Complexes 26 3.3.4. Antioxidant Assay by DPPH Method 26 3.3.5. Antimicrobial Assay 27 CHAPTER 4 28 4.1. Solution Equilibrium Studies 28 4.1.1. Complexation Study of 2,3-Dihydroxybenzoic Acid (DA) Binary Complexes 28 4.1.2. Complexation Study of N-Acetylcysteine (Nac) Binary Complexes 35 4.1.3. Complexation Study of DA and Nac Ternary Complexes 40 4.1.4. UV-Vis Spectra Measurements of Ternary Complexes 46 4.1.5. Solution Equilibrium with Toxic Metal Be2+ Binary and Ternary 49 4.2. Metal Ligand Complex Synthesis 51 4.2.1. Characteristic of FTIR Spectra 52 4.2.2. Electronic Spectra and Molar Conductivity 55 4.2.3. Antioxidant Activity 56 4.2.4. Microbial Growth Inhibitory Activity 56 4.3. Characterizations of Zinc Complexes 60 4.3.1. Binary Complex of Zinc 60 4.3.2. Ternary Complex of Zinc 61 4.3.3. Thermogravimetric Analyses 63 4.3.4. Effect of Temperature on Thermodynamic Parameters 65 CHAPTER 5 68 5.1. Conclusion 68 5.1.1. Solution Equilibrium Studies 68 5.1.2. Metal Ligand Complex Synthesis 69 5.2. Suggestions 69 REFERENCES 71 APPENDIX A A1 APPENDIX B B1 APPENDIX C C1 CURRICULUM VITAE

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