利用核磁共振儀研究水楊酸氧化還原變化建立觀測氫氧自由基清除之模式

NMR Studies on Redox Changes of Salicylates as a Hydroxyl Radical Scavenger

陳育欣(Yu-Shin Chen)

指導教授 ： 陳建志 博士

臺北醫學大學/醫學院/醫學科學研究所/碩士(2001年)

摘要

活性氧與發炎性及退化性疾病相關已普遍被接受，使用來清除活性氧的天然抗氧化物大部分集中在酚類化合物。阿斯匹靈是酚類化合物，被廣泛使用於治療止痛消炎與類風濕性關節炎上。它的代謝物水楊酸，參與了很多氧化還原反應。大多數研究證實，水楊酸可以抑制氧化壓力，是經由直接跟氫氧自由基的中和作用。在一些測定氫氧自由基方法中，ESR雖可以直接測到自由基，但不能測定反應前後構造的改變。在我們的實驗中，NMR僅需要些許製備，就可擁有直接觀察產物構造變化的能力。水楊酸與經由芬頓反應產生的氫氧自由基作用，會產生一些氫氧基化衍生物，而在芬頓反應之後，水楊酸的NMR氫譜顯示，在化學位移6.9、7.38、7.76 ppm的三個位置上的氫光譜會逐漸減少，就以氫譜積分值的變化，觀察水楊酸的氫氧化速率。水楊酸在這個方式中，顯示有清除氫氧自由基的能力，我們就使用不同的抗氧化物或氫氧自由基清除劑，在水楊酸存在下，來測量其清除氫氧自由基的能力。Vitamin C、Tiron和DMSO 對於水楊酸氫氧化有高抑制的效果，而Mannitol和NAC在防止水楊酸氫氧化的效果較差。而以這核磁共振光譜學研究水楊酸氫氧化變化，來評估一些抗氧化物的氧化還原作用是一個新的模式。

關鍵字

核磁共振儀 ； 水楊酸 ； 氫氧自由基

並列摘要

It is widely accepted that reactive oxygen species (ROS) are involved in the pathogenesis of inflammatory and degenerative diseases. Natural antioxidants used for scavenging ROS have been focused on phenolic compounds. Aspirin, a phenolic compound, is commonly used as analgesic and in the treatment of rheumatic arthritis. The metabolites of aspirin, salicylates, involved in many redox reactions. Most studies demonstrated that salicylates decrease the oxidative stress via reacting with free radicals. Electron spin resonance spectroscopic is a well known technique to detect radicals directly, but it lacks the ability to determine the structural changes between reactants and products. In our experiments, NMR offers an ability to observe the real-time changes of products with some preparation. Salicylate reacted with hydroxyl radical via Fenton reaction and produced several hydroxylated derivatives. The proton spectra of salicylate reveals the diminish of proton δ6.9 (C3, 5-2H), δ7.4 (C4-H) and δ7.7 (C6-H) after Fenton reaction. Hydroxylation rate of salicylate was therefore detected by measuring the proton integral changes. Salicylate exhibited a hydroxyl radical scavenging ability in a time dependent manner. Different antioxidants or scavengers were measured for the ability to clear hydroxyl radical in the presence of salicylate. Vitamin C, tiron and DMSO highly inhibited the hydroxylation of salicylate. In contrast, mannitol and NAC have low preventing ability on the hydroxylation of salicylate. The use to NMR spectrometry to follow the hydroxylation of salicylate could be a new approachl to evaluate the redox potential of many antioxidants.

並列關鍵字

NMR ； salicylic acid ； hydroxyl radical

參考文獻

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