一种新型羟基自由基产生分子机理的研究

羟基自由基(·OH)被公认是生物系统中最具活性的活性氧物种,能导致生物体内DNA,蛋白质和脂质氧化损伤.目前,关于·OH的产生机理,最被广泛接受的是过渡金属离子催化的Fenton反应.五氯酚(PCP)是一种重要的工农业生物杀灭剂,主要用作木材保护.采用水杨酸羟基化法和电子自旋共振自旋捕获等作为分析手段,发现H2O2和五氯酚的代谢产物之一四氯-1,4-苯醌(TCBQ)能通过不依赖于金属离子的途径产生·OH;进一步的研究发现,TCBQ而非其相应的半醌自由基对·OH的产生极其重要.TCBQ和H2O2反应的主要产物被鉴定为三氯羟基-1,4-苯醌(TrCBQ-OH),其中的氧原子被证明来源于H2O2.基于这些数据和分析,提出以下假设:TCBQ和H2O2反应产生·OH不是通过依赖于半醌自由基的有机Fenton反应进行,而是H2O2对TCBQ进行亲核攻击,形成不稳定的三氯氢过氧基-1,4-苯醌(TrCBQ-OOH)中间产物,其可均裂产生·OH和三氯羟基-1,4-苯醌自由基(TrCBQ-O·).上述反应途径展示了一类新型的·OH产生机理,即·OH的形成不需要具有氧化还原活性的过渡金属离子参与.该机理可部分解释五氯酚等其他多卤...

A novel mechanism for metal-independent production of hydroxyl radicals

The hydroxyl radical (•OH) has been considered to be one of the most reactive oxygen species produced in biological systems. It has been shown that •OH can cause DNA, protein, and lipid oxidation. One of the most widely accepted mechanisms for •OH production is the transition metal- catalyzed Fenton reaction. Pentachlorophenol (PCP) has been widely used as a wood preservative. Using the salicylate hydroxylation assay and electron spin resonance (ESR) spin-trapping methods, we found that •OH can be produced by H₂O₂ and tetrachloro-1, 4-benzoquinone (TCBQ) (one of the major carcinogenic metabolites of PCP) independent of transition metal ions. Further studies showed that TCBQ, but not its corresponding semiquinone radical, the tetrachlorosemiquinone radical (TCSQ•), is essential for •OH production. The major reaction product between TCBQ and H₂O₂ was identified to be the ionic form of trichloro-hydroxy-1, 4-benzoquinone (TrCBQ-OH), and H₂O₂ was found to be the source and origin of the oxygen atom inserted into the reaction product TrCBQ-OH. Based on these data, we propose that •OH production by H₂O₂ and TCBQ is not through a semiquinone-dependent organic Fenton reaction, but rather through the following novel mechanism: a nucleophilic attack of H₂O₂ on TCBQ, forming a trichloro- hydroperoxyl-1, 4-benzoquinone (TrCBQ-OOH) intermediate, which decomposes homolytically to produce •OH. These findings represent a novel mechanism of •OH formation not requiring the involvement of redox-active transition metal ions, and may partly explain the potential carcinogenicity of widely used biocides such as PCP and other polyhalogenated aromatic environmental pollutants.