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標題: | 氨甲蝶呤於自然水體中自身催化光解機制與生物吸附之探討 The Self-Sensitization Photodegradation and Biosorption of Methotrexate in Natural Water System |
作者: | Chia-Jung Tsai 蔡佳蓉 |
指導教授: | 林郁真(Yu-Chen Lin) |
關鍵字: | 氨甲蝶呤,自身催化光降解,三重激發態,單重激發態氧,生物吸附,金屬螯合, Methotrexate,self-sensitized photodegradation,pteridine,singlet oxygen,biosorption,chelation., |
出版年 : | 2016 |
學位: | 碩士 |
摘要: | 氨甲蝶呤 (Methotrexate,MTX) 普遍用於抗癌藥物已達五十年之久,其抗葉酸與抗代謝之功能用以治療白血病、淋巴瘤、類風濕性關節炎等癌症及自身免疫疾病。然而,病患於療程中攝入Methotrexate 後,常會引發骨髓抑制、結腸炎、慢性肝病毒等副作用;若Methotrexate經由廢水處理等途徑釋放至環境水體時,勢必增加水中生態環境不確定之風險及衝擊。自然光降解不僅為Methotrexate 重要的降解途徑之一,Methotrexate 更可經由自身參與反應進行催化光解。本研究旨在研究比較Methotrexate 於去離子水與環境水中自身催化之光解機制,並探討水中各種反應性物質對Methotrexate 光解之影響。此外,本研究亦針對Methotrexate 於自然水體中的生物吸附機制進行探討。Methotrexate 之自身催化光解主要是由單重激發態氧(1O2)、三重激發態之Methotrexate(3MTX*)與其蝶呤結構光降解副產物之三重激發態(3PT*)共同誘發作用。當Methotrexate 受到光照之後,可吸收光能而被激發產生3MTX*,3MTX*可進一步自然光解產生蝶呤結構之光解副產物(PT),PT 亦可經由光照激發為3PT*而參與Methotrexate 之光降解。此外,3MTX*與3PT*皆可經由能量轉移產生1O2。1O2、3MTX*與3PT*可與基態之Methotrexate 反應而增加蝶呤副產物PT之生成,進而促成Methotrexate 之自身催化光解。研究顯示3MTX*為自身催化中關鍵之反應物質。添加三重激發態抑制劑後,3MTX*所誘導之自身催化光解程序便無法作用,光解之效能亦同時大幅降低。而由子結構測試可知,蝶呤副產物PT 如2,4-diamino-6-(hydroxymethyl)pteridine (DHP)可於光照後產生3PT* 而促進Methotrexate 自身催化光解。
在環境水體中,Methotrexate 之偵測濃度小至ppb 等級、大至ppm 等級,而不同的Methotrexate 初始濃度會引起不同的光解機制;當環境水體中Methotrexate 的濃度較低時(<20ppb),1O2 於其自身催化光解中扮演極關鍵之角色。而在重水中,1O2 具有較長的壽命,促使Methotrexate 之光解速度顯著上升。此外,當水體中含飽和氧氣時其光解速度亦顯著加速。然而環境水體中Methotrexate 濃度較高時(>2,000 ppb),因溶氧與3MTX*與3PT*結合致使水中Methotrexate 光解之速率降低。 研究中以景美溪為例,Methotrexate 除了自身催化光解外,其分布與宿命亦受間接光解與其他自然消解途徑之影響。當模擬之水樣含有與景美溪等量的硝酸、碳酸、溶解性有機物質,並將pH 值調整至與景美溪相同,其光解結果與景美溪十分相似。此結果亦顯示硝酸、碳酸、溶解性有機物質、pH 值皆為環境水體中影響Methotrexate 間接光解之關鍵因子;同時Methotrexate 於自然水體中可被生物吸附。於景美溪水中添加1000 ppb 之Methotrexate 時,約有118 至136 ppb 濃度的Methotrexate 可在無光照之環境中被生物吸附,這些被吸附的Methotrexate 在陽光下會被脫附並進行光解。研究中亦發現,鐵離子的存在會影響Methotrexate於水中之分佈;當於去離子水中添加5 ppm 鐵離子時,約有15.2 ppb 的Methotrexate 能與鐵離子螯合。綜上所述,環境中Methotrexate 的偵測濃度可能被低估,且在無陽光照射之水體中,Methotrexate 可能因被生物吸附與螯合而難以進行降解。 Methotrexate is used as an antifolate drug in the treatment of a number of cancers and autoimmune diseases for over 50 years. Since methotrexate can cause many side effects in human bodies, the presence of methotrexate in surface water may pose a high risk to environmental ecological systems and raise a significant concern. This work showed sunlight photodegradation is an important natural attenuation process for methotrexate, and it undergoes significant self-sensitized photodegradation; the photodegradation rate is enhanced with the increasing initial methotrexate concentrations. The main objectives of this work were to study the mechanism of self-sensitized photodegradation in both deionized and surface waters (i.e. Jing-Mei River water, JMR) to investigate the effect of reactive species on the photolysis rates, and to study the biosorption behavior of methotrexate in the real water systems. The results indicated that self-sensitized photodegradation of methotrexate is induced by singlet oxygen (1O2), triplet excited state of methotrexate (3MTX*), and triplet excited state of pteridine structure (3PT*) from methotrexate’s phototransformation byproducts. After sunlight irradiation, methotrexate absorbs photons and form its triplet excited state 3MTX*, and consequently undergo direct photolysis to produce phototransformation byproducts containing pteridine structure (PT). PT can also absorb photons to form its triplet excited state 3PT*. Both 3MTX* and 3PT* react with oxygen to form 1O2. 3MTX*, 3PT*, 1O2 are all found reactive toward ground state of methotrexate, the degradation of methotrexate can produce more pteridine phototransformation byproducts, which can be excited and back to attack its parent compound, methotrexate. Results from the elimination of 3MTX* using sorbic acid indicated that 3MTX* is the most important reactant, which initiates the self-sensitized photoreactions. The substructure test showed that the PT substructure (i.e. 2,4-diamino-6-(hydroxymethyl) pteridine (DHP)) later forms 3PT* after irradiation and enhanced the methotrexate photodegradation rates. The different initial concentration of methotrexate resulted in different photochemical behaviors. In the case of low methotrexate concentrations (< 20 ppb), 1O2 plays an important role in methotrexate self-sensitized photodegradation. The D2O and saturated oxygen experiments both showed an enhanced degradation rate of methotrexate. In the case of the high methotrexate concentrations (> 2,000 ppb), the presence of oxygen decreased the overall methotrexate degradation rate by quenching 3MTX* and 3PT*. Environmental concentrations of methotrexate ranged from ppb level in rivers to ppm level in hospital effluent waters. As a result, the hotodegradation behaviors may not be similar in different environmental water systems. The self-sensitized photodegradation was also observed in JMR river waters and the indirect photolysis reactions as well as other attenuation processes were also bserved and significantly affect the occurrence and distribution of methotrexate in the aquatic environment. Nitrate, DOM, bicarbonate and pH value were found to be the major parameters affecting the indirect photolysis. Simulated JMR water spiking with these parameters (NO3=1.1mg N/L, TOC = 2.4 mg- C/L, bicarbonate = 1.45mM, pH=7.45 in DI) showed identical degradation behavior with filtered JMR water. Biosorption of methotrexate is observed in the natural water environment. An amount of 118-136 ppb of methotrexate was found to be biosorbed when 1000 ppb methotrexate was spiked into JMR water in the dark, and was found to be desorbed and undergo photodegradation under sunlight irradiation. The autoclaved experiments demonstrated the adsorption is attributed to the microorganisms. The presence of ferrous ion can also chelate methotrexate. About 15.2 and 18.9 ppb of methotrexate were found being chelated in the presence of 5, and 50 ppm of ferrous ion in DI water, respectively. These observations strongly suggest that reported methotrexate concentrations in water could be an underestimation of how much was released and really existed in the natural environments. |
URI: | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78061 |
DOI: | 10.6342/NTU201602864 |
全文授權: | 有償授權 |
顯示於系所單位: | 環境工程學研究所 |
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