水體環境中碳酸氫根離子強化五氟尿嘧啶之光解機制

Abstract

五氟尿嘧啶是過去四十年來最廣泛使用的抗腫瘤藥物之一，主要用以治療大腸癌和胰臟癌。然而，釋放到環境水體中之五氟尿嘧啶易引起了具不確定性的生態衝擊及環境風險。光解為環境中污染物自然降解的諸多重要途徑之一，其對各類新興污染物尤其重要。在環境光解系統中，溶解性有機物 (DOMs)、硝酸根離子和碳酸氫根-硝酸根離子系統皆為不容忽視的光敏性物質。在現有認知中，碳酸氫根離子需與氫氧自由基反應產生碳酸根自由基才具有反應性；然而，本研究首次出現即使在僅含碳酸氫根離子的水溶液中，五氟尿嘧啶的光解速度仍顯著提升，此加速降解之現象被稱為碳酸氫根強化光解 (bicarbonate enhanced photolysis)。研究結果顯示，直接光解及碳酸氫根強化光解下的五氟尿嘧啶半生期分別為24.5 ± 4.6 小時和 11.5 ± 1.3 小時 (在pH 7 時)；五氟尿嘧啶的光解速度在pH 8及pH 9時最快，pH 7次之。 五氟尿嘧啶的主要光解途徑為光水解反應，其主要產物為5-fluoro-6-hydroxyhydrouracil (5FUHy)，此產物不易直接與間接光解，即便在景美溪水中，經過40小時光照後濃度僅減少不到20%。在pH值分別為6、7、8和9之情況下，5FUHy的產率分別為64%、 63%、 53%及12%；而在碳酸氫根強化光解下，5FUHy的產率分別為59%、40%、14%及1.3%。根據本研究提出的反應機構模型，碳酸氫根離子會與激發態之五氟尿嘧啶反應，並產生水解產物以外的副產物；然而碳酸氫根離子不具強化光水解反應之作用，此表示存在環境中的碳酸氫根離子作用於強化並加速光水解以外的反應途徑，且因此改變了污染物的產物組成及宿命。此模式成功地預測了五氟尿嘧啶在景美溪水中的水解產率，結果顯示碳酸氫根離子對其水解產率之影響顯著高於硝酸根離子及溶解性有機物。 此外，碳酸氫根強化光解對於氨甲蝶呤 (methotrexate) 亦有顯著之作用；然而其光解強化機制不同於五氟尿嘧啶，此顯示了碳酸氫根強化光解取決於反應物本身的性質。

5-fluorouracil is an antineoplastic drug that has been widely used in colorectal and pancreatic cancer treatment over the past 40 years, and its presence in aqueous environments is a potential risk to ecological systems and humans. Sunlight photodegradation is one of the most significant natural attenuation processes for various emerging contaminants. Dissolved organic matter, nitrates and bicarbonate enhanced nitrate systems are known photosensitizers. In this study, the action of bicarbonate alone was found to increase the direct photolysis rate of 5-fluorouracil for the first time, and the reaction mechanism was investigated. The half-lives of direct and bicarbonate enhanced photolysis were 24.5 ± 4.6 h and 11.5 ± 1.3 h (at pH 7), respectively. The reaction was fastest at pHs 9 and 8, followed by pHs 7 and 6. The primary pathway for the direct photolysis of 5-fluorouracil was photohydration, which resulted in a hydration product, 5-fluoro-6-hydroxyhydrouracil (5FUHy). 5FUHy is resistant to direct and indirect photolysis and was degraded by less than 20% in Jingmei River (JMR) water. The yields of 5FUHy by direct photolysis at pHs 6, 7, 8 and 9 were 64%, 63%, 53% and 12%, respectively. In bicarbonate enhanced photolysis, the 5FUHy yields decreased to 59%, 40%, 14% and 1.3% at pHs 6, 7, 8 and 9, respectively. A model of 5-fluorouracil photolysis was developed and used to predict that the bicarbonate directly reacted with the excited state of 5-fluorouracil but did not enhance the photohydration process. Other photodegradation byproducts and pathways were also proposed. The presence of bicarbonate was found to increase the 5-fluorouracil photolysis rates through pathways other than photohydration by changing the proportions of the photodegradation byproducts and the fate of pollutants. The model predicted the yield of 5FUHy in JMR water accurately, demonstrating that the actions of nitrate and dissolved organic matter in the photohydration process were not as significant as those of bicarbonate and pH. The phenomenon of bicarbonate enhanced photolysis was also shown with methotrexate. However, its degradation mechanism was different from that of 5-fluorouracil, indicating that the enhancement was compound dependent.