臺灣博碩士論文加值系統

Carbadox (CBX)，屬於quinoxaline-1,4-dioxides類之衍生物，常添加於飼料中促進豬隻生長增加體重、保持動物健康並預防瘧疾。然而有研究指出其具有造成DNA鍵結斷裂之致癌性及遺傳毒性。當carbadox進入環境時，有一部分將被土壤吸收，其中土壤有機質及粘土礦物可能有助於吸附。二氧化錳(MnO2)為土壤/底泥中常見的天然氧化劑，具有強氧化能力並可氧化降解多種有機污染物。草酸為天然環境中廣泛存在的天然還原劑，其為生物體產生的最普遍和最常見的低分子量有機酸。有研究指出，二氧化錳在草酸存在下會溶解成三價錳，而三價錳會與草酸形成較穩定之螯合物，再與carbadox形成三元錯合物，通過三價錳作為中間電子傳遞者，電子經由草酸轉移至carbadox，並將carbadox還原降解。天然有機物(NOM)是普遍存在於環境的物質，影響污染物在環境中的傳輸、吸附和降解，本研究中，為了解天然溶解性有機質的存在是否會影響二氧化錳及草酸還原降解carbadox，初步依據有機質尺寸大小選擇pyromellitic acid、alginic acid和Aldrich humic acid作為影響降解之模型有機質，探討有機物如何影響二氧化錳及草酸還原降解carbadox。
由研究結果顯示，不論有無添加不同濃度之不同模型有機質，carbadox皆於前2小時快速降解，2小時後濃度下降逐漸趨於平緩，因此以第2小時作為分界，在第2小時之前視為前段反應，在第2小時之後則視為後段反應，將降解曲線以擬一階反應作為計算，分別計算前後兩段反應之反應速率常數。在前段反應中，受pyromellitic acid影響加速降解反應最為顯著，其次是alginic acid與humic acid，由於三價錳穩定性受羧基密度影響，其羧基密度依序為pyromellitic acid > alginic acid > humic acid，因此推測三價錳之穩定性主導前段反應速率。後段反應由於三價錳幾乎不存在，由草酸直接與carbadox反應，pyromellitic acid無顯著影響；alginic acid隨濃度降低，其抑制降解反應也越明顯；humic acid分子結構較大，會直接阻礙草酸與carbadox接觸，進而抑制降解反應的進行。此外，添加模型有機質不會改變對二氧化錳及草酸還原降解carbadox產生之降解產物之種類。而添加模型有機質對主體結構碎片離子m/z 231即穩定其結構維持；由於還原反應產物m/z 247及m/z 263僅在三價錳催化反應時產生，pyromellitic acid對m/z 247生成量有增加生成之趨勢；而alginic acid及humic acid，則對m/z 247生成有抑制之現象，其中添加humic acid之抑制現象最為顯著，再次佐證前段反應為三價錳主導之催化反應。添加入pyromellitic acid及alginic acid對還原性產物m/z 263之生成無明顯影響；添加入humic acid後，增加還原產物m/z 263之生成，且可幫助降解產物較穩定停留於還原性產物m/z 263之階段。

Carbadox is commonly used as additives in animal feeds at subtherapeutic levels for newborn piglets not only to prevent epidemic diseases but also to increase growth rate and weight. A recent study shows that MnO2 will dissolve in the presence of oxalic acid to form Mn(III), and Mn(III) will form a more stable chelate with oxalic acid. And the formation of a carbadox/ Mn(III)/ oxalate ternary complex in which Mn(III) functioned as the central complexing cation and electron conduit in which the arrangement of ligands facilitated electron transfer from oxalate to carbadox, and carbadox reduction degradation. In this study, in order to understand whether the presence of dissolved organic matters (DOM) would affect the reductive degradation of MnO2 and oxalic acid on carbadox, pyromellitic acid, alginic acid and Aldrich humic acid were selected as the model organic matters to be added to reaction.
The results show that the order of adding model compounds to accelerate the initial reaction rate is pyromellitic acid > alginic acid > humic acid, which corresponds to the order of the carboxyl group density of these added compounds. Therefore, it is speculated that in the initial reaction, the stability of Mn(III) determines the reaction rate. In the later stage, the concentration of Mn(III) is very limited, so oxalic acid reacts directly with carbadox. Contrary to the promotion effect in the initial stage, the addition of organic compounds did not promote the reaction in the later stages. In addition, due to steric hindrance caused by its larger molecular structure, humic acid significantly inhibits the late reaction. Adding model organics will not affect the types of degradation products produced by Mn(III) and the oxalic acid degradation of CBX. The production of the reduction product m/z 247 further shows that the addition of model organics can affect the reaction by stabilizing Mn(III). Monitoring the fragment ion m/z 231 reflects the main core structure of carbadox, indicating that the main core structure will not change significantly during the reaction regardless of the presence of organic matter.

摘要 I
誌謝 VII
表目錄 X
圖目錄 X
第一章 前言 1
第二章 文獻回顧 4
2.1 卡巴得 4
2.1.1卡巴得之應用 6
2.1.2 卡巴得之毒性 7
2.1.3環境中之卡巴得 7
2.2 環境中的錳 9
2.2.1三價錳 9
2.2.2 氧化錳 11
2.3二氧化錳與草酸還原卡巴得 13
2.4天然有機物對環境中氧化還原反應的影響 17
2.5天然有機質對錳反應的影響 18
2.6模型有機質 19
第三章 材料與方法 21
3.1 藥品與溶劑 21
3.2 動力學實驗設置 21
3.3 二氧化錳之配置 22
3.4 分析與儀器 23
3.4.1以HPLC-FLD及HPLC-DAD分析卡巴得 23
3.4.2以HPLC-MS/MS分析卡巴得之降解產物 23
3.4.3總有機碳分析 24
第四章 結果與討論 25
4.1 卡巴得之穩定性 25
4.1.1 草酸存在下卡巴得之穩定性 27
4.1.2 模型有機質存在下卡巴得之穩定性 30
4.2 三價錳濃度對反應之影響 32
4.3模型有機質對降解反應的影響 35
4.4模型有機質對降解產物之影響 51
4.4.1模型有機質對降解產物種類之影響 52
4.4.2模型有機質對降解產物生成速率之影響 55
第五章 結論與建議 64
5.1結論 64
5.2建議 66
參考文獻 67

Adams, C., Wang, Y., Loftin, K., & Meyer, M. (2002). Removal of antibiotics from surface and distilled water in conventional water treatment processes. Journal of environmental engineering, 128(3), 253-260.
Azqueta, A., Arbillaga, L., Pachón, G., Cascante, M., Creppy, E. E., & de Cerain, A. L. (2007). A quinoxaline 1, 4-di-N-oxide derivative induces DNA oxidative damage not attenuated by vitamin C and E treatment. Chemico-biological interactions, 168(2), 95-105.
Baars, A., Jager, L., Spierenberg, T. J., De Graaf, G., & Seinhorst, J. (1991). Residues of carbadox metabolites in edible pork products. In Recent Developments in Toxicology: Trends, Methods and Problems (pp. 288-292): Springer.
Bearson, B. L., Allen, H. K., Brunelle, B. W., Lee, I. S., Casjens, S. R., & Stanton, T. B. (2014). The agricultural antibiotic carbadox induces phage-mediated gene transfer in Salmonella. Frontiers in microbiology, 5, 52.
Chamberlain, E., & Adams, C. (2006). Oxidation of sulfonamides, macrolides, and carbadox with free chlorine and monochloramine. Water Research, 40(13), 2517-2526.
Chen, K. L., & Elimelech, M. (2008). Interaction of fullerene (C60) nanoparticles with humic acid and alginate coated silica surfaces: measurements, mechanisms, and environmental implications. Environmental science & technology, 42(20), 7607-7614.
Chen, Q., Chen, Y., Qi, Y., Hao, L., Tang, S., & Xiao, X. (2008). Characterization of carbadox-induced mutagenesis using a shuttle vector pSP189 in mammalian cells. Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, 638(1-2), 11-16.
Chen, Q., Tang, S., Jin, X., Zou, J., Chen, K., Zhang, T., & Xiao, X. (2009). Investigation of the genotoxicity of quinocetone, carbadox and olaquindox in vitro using Vero cells. Food and chemical toxicology, 47(2), 328-334.
Chen, W. R., Liu, C., Boyd, S. A., Teppen, B. J., & Li, H. (2013). Reduction of carbadox mediated by reaction of Mn (III) with oxalic acid. Environmental science & technology, 47(3), 1357-1364.
Davies, S. H., & Morgan, J. J. (1989). Manganese (II) oxidation kinetics on metal oxide surfaces. Journal of Colloid and Interface Science, 129(1), 63-77.
Davis, J. A. (1984). Complexation of trace metals by adsorbed natural organic matter. Geochimica et Cosmochimica Acta, 48(4), 679-691.
De Graaf, G., Jager, L., Baars, A., & Spierenburg, T. J. (1988). Some pharmacokinetic observations of carbadox medication in pigs. Veterinary Quarterly, 10(1), 34-41.
Dellwig, O., Schnetger, B., Brumsack, H.-J., Grossart, H.-P., & Umlauf, L. (2012). Dissolved reactive manganese at pelagic redoxclines (part II): Hydrodynamic conditions for accumulation. Journal of marine systems, 90(1), 31-41.
Ding, Y., Teppen, B. J., Boyd, S. A., & Li, H. (2013). Measurement of associations of pharmaceuticals with dissolved humic substances using solid phase extraction. Chemosphere, 91(3), 314-319.
Evanko, C. R., & Dzombak, D. A. (1998). Influence of structural features on sorption of NOM-analogue organic acids to goethite. Environmental science & technology, 32(19), 2846-2855.
Fourest, E., & Volesky, B. (1995). Contribution of sulfonate groups and alginate to heavy metal biosorption by the dry biomass of Sargassum fluitans. Environmental science & technology, 30(1), 277-282.
Giguère, S., Prescott, J. F., & Dowling, P. M. (2013). Antimicrobial therapy in veterinary medicine: John Wiley & Sons.
Gombotz, W. R., & Wee, S. (1998). Protein release from alginate matrices. Advanced drug delivery reviews, 31(3), 267-285.
Gu, B., Schmitt, J., Chen, Z., Liang, L., & McCarthy, J. F. (1994). Adsorption and desorption of natural organic matter on iron oxide: mechanisms and models. Environmental science & technology, 28(1), 38-46.
Harrington, J. M., Parker, D. L., Bargar, J. R., Jarzecki, A. A., Tebo, B. M., Sposito, G., & Duckworth, O. W. (2012). Structural dependence of Mn complexation by siderophores: donor group dependence on complex stability and reactivity. Geochimica et Cosmochimica Acta, 88, 106-119.
Hodgkinson, A. (1977). Oxalic acid in biology and medicine. London—New York.
Johnson, K. L., McCann, C. M., Wilkinson, J.-L., Jones, M., Tebo, B. M., West, M., Elgy, C., Clarke, C. E., Gowdy, C., & Hudson-Edwards, K. A. (2018). Dissolved Mn (III) in water treatment works: Prevalence and significance. Water Research, 140, 181-190.
Johnson, S. B., Yoon, T. H., & Brown, G. E. (2005). Adsorption of organic matter at mineral/water interfaces: 5. Effects of adsorbed natural organic matter analogues on mineral dissolution. Langmuir, 21(7), 2811-2821.
Johnston, A. (1992). Evaluation of certain veterinary drug residues in food: World Health Organization Technical Report Series No. 815, WHO, Geneva, 1992, SFr 9.00, ISBN 924-120-8155, 66 pp. In: Elsevier.
Kim, Y., Lee, K.-B., & Choi, K. (2016). Effect of runoff discharge on the environmental levels of 13 veterinary antibiotics: A case study of Han River and Kyungahn Stream, South Korea. Marine pollution bulletin, 107(1), 347-354.
Klausen, J., Haderlein, S. B., & Schwarzenbach, R. P. (1997). Oxidation of substituted anilines by aqueous MnO2: Effect of co-solutes on initial and quasi-steady-state kinetics. Environmental science & technology, 31(9), 2642-2649.
Laha, S., & Luthy, R. G. (1990). Oxidation of aniline and other primary aromatic amines by manganese dioxide. Environmental science & technology, 24(3), 363-373.
Lauridsen, M. G., Lund, C., & Jacobsen, M. (1988). Determination and Depletion of Residues in Carbadox, Tylosin, and Virginiamycin in Kidney, Liver, and Muscle of Pigs in Feeding Experiments. Journal of the Association of Official Analytical Chemists, 71(5), 921-925.
Le, T., Zhu, L., Shu, L., & Zhang, L. (2016a). Simultaneous determination of five quinoxaline-1, 4-dioxides in animal feeds using an immunochromatographic strip. Food Additives & Contaminants: Part A, 33(2), 244-251.
Le, T., Zhu, L., & Yu, H. (2016b). Dual-label quantum dot-based immunoassay for simultaneous determination of Carbadox and Olaquindox metabolites in animal tissues. Food chemistry, 199, 70-74.
Leenheer, J. A., & Croué, J.-P. (2003). Peer reviewed: characterizing aquatic dissolved organic matter. In: ACS Publications.
Lewis, B., & Landing, W. (1991). The biogeochemistry of manganese and iron in the Black Sea. Deep Sea Research Part A. Oceanographic Research Papers, 38, S773-S803.
Lin, K., Liu, W., & Gan, J. (2009). Oxidative Removal of Bisphenol A by Manganese Dioxide: Efficacy, Products, and Pathways. Environmental science & technology, 43(10), 3860-3864.
Liou, S. Y., & Chen, W. R. (2018). Oxidative transformation kinetics and pathways of albendazole from reactions with manganese dioxide. Journal of Hazardous Materials, 347, 299-306.
Macalady, D. L., & Walton-Day, K. (2011). Redox chemistry and natural organic matter (NOM): Geochemists’ dream, analytical chemists’ nightmare. In Aquatic Redox Chemistry (pp. 85-111): ACS Publications.
Macintosh, A. I., Lauriault, G., & Neville, G. A. (1985). Liquid chromatographic monitoring of the depletion of carbadox and its metabolite desoxycarbadox in swine tissues. Journal of the Association of Official Analytical Chemists, 68(4), 665-671.
Mandernack, K. W., Post, J., & Tebo, B. M. (1995). Manganese mineral formation by bacterial spores of the marine Bacillus, strain SG-1: evidence for the direct oxidation of Mn (II) to Mn (IV). Geochimica et Cosmochimica Acta, 59(21), 4393-4408.
McArdell, C. S., Stone, A. T., & Tian, J. (1998). Reaction of EDTA and related aminocarboxylate chelating agents with CoIIIOOH (heterogenite) and MnIIIOOH (manganite). Environmental science & technology, 32(19), 2923-2930.
Morgan, J. J. (2000). Manganese in natural waters and earth’s crust: Its availability to organisms. Metal ions in biological systems, 37, 1-34.
Murray, J. W., Dillard, J. G., Giovanoli, R., Moers, H., & Stumm, W. (1985). Oxidation of Mn (II): Initial mineralogy, oxidation state and ageing. Geochimica et Cosmochimica Acta, 49(2), 463-470.
Nabuurs, M., Van Der Molen, E., De Graaf, G., & Jager, L. (1990). Clinical signs and performance of pigs treated with different doses of carbadox, cyadox and olaquindox. Journal of Veterinary Medicine Series A, 37(1‐10), 68-76.
Oldham, V. E., Miller, M. T., Jensen, L. T., & Luther III, G. W. (2017a). Revisiting Mn and Fe removal in humic rich estuaries. Geochimica et Cosmochimica Acta, 209, 267-283.
Oldham, V. E., Mucci, A., Tebo, B. M., & Luther III, G. W. (2017b). Soluble Mn (III)–L complexes are abundant in oxygenated waters and stabilized by humic ligands. Geochimica et Cosmochimica Acta, 199, 238-246.
Perez, J., & Jeffries, T. W. (1992). Roles of manganese and organic acid chelators in regulating lignin degradation and biosynthesis of peroxidases by Phanerochaete chrysosporium. Applied and Environmental Microbiology, 58(8), 2402-2409.
Post, J. E. (1999). Manganese oxide minerals: Crystal structures and economic and environmental significance. Proceedings of the National Academy of Sciences, 96(7), 3447-3454.
Qin, W., Tan, P. Y., Song, Y., Wang, Z. H., Nie, J. X., & Ma, J. (2021). Enhanced transformation of phenolic compounds by manganese(IV) oxide, manganese(II) and permanganate in the presence of ligands: The determination and role of Mn(III). Separation and Purification Technology, 261.
Song, Y., Jiang, J., Ma, J., Zhou, Y., & von Gunten, U. (2019). Enhanced transformation of sulfonamide antibiotics by manganese(IV) oxide in the presence of model humic constituents. Water Research, 153, 200-207.
Stone, A. T. (1987a). Microbial metabolites and the reductive dissolution of manganese oxides: oxalate and pyruvate. Geochimica et Cosmochimica Acta, 51(4), 919-925.
Stone, A. T. (1987b). Reductive dissolution of manganese (III/IV) oxides by substituted phenols. Environmental science & technology, 21(10), 979-988.
Stone, A. T., & Morgan, J. J. (1984). Reduction and dissolution of manganese (III) and manganese (IV) oxides by organics: 2. Survey of the reactivity of organics. Environmental science & technology, 18(8), 617-624.
Strock, T. J., Sassman, S. A., & Lee, L. S. (2005). Sorption and related properties of the swine antibiotic carbadox and associated N-oxide reduced metabolites. Environmental science & technology, 39(9), 3134-3142.
Taube, H. (1947). Catalysis of the reaction of chlorine and oxalic acid. Complexes of trivalent manganese in solutions containing oxalic acid. Journal of the American Chemical Society, 69(6), 1418-1428.
Taube, H. (1948). Catalysis by manganic ion of the reaction of bromine and oxalic acid. Stability of manganic ion complexes. Journal of the American Chemical Society, 70(11), 3928-3935.
Tebo, B. M., Bargar, J. R., Clement, B. G., Dick, G. J., Murray, K. J., Parker, D., Verity, R., & Webb, S. M. (2004). Biogenic manganese oxides: properties and mechanisms of formation. Annu. Rev. Earth Planet. Sci., 32, 287-328.
Tebo, B. M., & Emerson, S. (1986). Microbial manganese (II) oxidation in the marine environment: a quantitative study. Biogeochemistry, 2(2), 149-161.
Ukrainczyk, L., & McBride, M. B. (1993). Oxidation and dechlorination of chlorophenols in dilute aqueous suspensions of manganese oxides: Reaction products. Environmental Toxicology and Chemistry: An International Journal, 12(11), 2015-2022.
Van Aken, B., & Agathos, S. (2002). Implication of manganese (III), oxalate, and oxygen in the degradation of nitroaromatic compounds by manganese peroxidase (MnP). Applied microbiology and biotechnology, 58(3), 345-351.
Van der Molen, E., Baars, A., De Graaf, G., & Jager, L. (1989a). Comparative study of the effect of carbadox, olaquindox and cyadox on aldosterone, sodium and potassium plasma levels in weaned pigs. Research in veterinary science, 47(1), 11-16.
Van der Molen, E., De Graaf, G., & Baars, A. (1989b). Persistence of carbadox-induced adrenal lesions in pigs following drug withdrawal and recovery of aldosterone plasma concentrations. Journal of Comparative Pathology, 100(3), 295-304.
Wang, D., Shin, J. Y., Cheney, M. A., Sposito, G., & Spiro, T. G. (1999). Manganese dioxide as a catalyst for oxygen-independent atrazine dealkylation. Environmental science & technology, 33(18), 3160-3165.
Wang, H., Liu, Y., Hu, G., Ye, Y., Pan, L., Zhu, P., & Yao, S. (2020). Ultrasensitive electrochemical sensor for determination of trace carbadox with ordered mesoporous carbon/GCE. Journal of Electroanalytical Chemistry, 857, 113736.
Wang, H., Yao, H., Sun, P., Li, D., & Huang, C.-H. (2016). Transformation of tetracycline antibiotics and Fe (II) and Fe (III) species induced by their complexation. Environmental science & technology, 50(1), 145-153.
Wang, Y., & Stone, A. T. (2008). Phosphonate-and carboxylate-based chelating agents that solubilize (hydr) oxide-bound MnIII. Environmental science & technology, 42(12), 4397-4403.
Wu, Y., Wang, Y., Huang, L., Tao, Y., Yuan, Z., & Chen, D. (2006). Simultaneous determination of five quinoxaline-1, 4-dioxides in animal feeds using ultrasonic solvent extraction and high-performance liquid chromatography. Analytica chimica acta, 569(1-2), 97-102.
Xu, L., Xu, C., Zhao, M. R., Qiu, Y. P., & Sheng, G. D. (2008). Oxidative removal of aqueous steroid estrogens by manganese oxides. Water Research, 42(20), 5038-5044.
Yakushev, E., Pollehne, F., Jost, G., Kuznetsov, I., Schneider, B., & Umlauf, L. (2007). Analysis of the water column oxic/anoxic interface in the Black and Baltic seas with a numerical model. Marine Chemistry, 107(3), 388-410.
Yao, W. S., & Millero, F. J. (1996). Adsorption of phosphate on manganese dioxide in seawater. Environmental science & technology, 30(2), 536-541.
Zhang, H., & Huang, C.-H. (2005). Reactivity and transformation of antibacterial N-oxides in the presence of manganese oxide. Environmental science & technology, 39(2), 593-601.
周庭宇. (2018). 溶解性有機質對Mn(II)與Cu(II)降解四環素之影響. (碩士), 國立成功大學, 台南市.