Fate of free radicals generated during one-electron reductions of 4-alkyl-1,4-peroxyquinols by cytochrome P-450.
Fate of free radicals generated during one-electron reductions of 4-alkyl-1,4-peroxyquinols by cytochrome P-450.
复制标题
细胞色素 P-450 对 4-烷基-1,4-过氧化醌进行单电子还原时产生的自由基的命运。
DOI：
10.1021/tx00006a010
复制
发表时间：
1988
影响因子：
4.1
通讯作者：
Thompson,JA
中科院分区：
文献类型：
--
作者：
Yumibe,NP;Thompson,JA
由血红素蛋白的氧-氧键的单电子还原和随后的均裂产生的自由基可能是有机氢过氧化物毒性的某些方面的原因。本文研究了2，6-二叔丁基-4-烷基-4-氢过氧细胞六-2，5-二烯酮（1，4-过氧喹啉）的4-烷基取代基对大鼠肝微粒体细胞色素P-450自由基产生的影响。从过氧喹啉的均裂的醌氧基自由基进行8-切断，产生醌和烷基自由基，这个过程发生的频率越来越高的稳定性的烷基自由基的增加。本文还研究了适当取代的过氧喹啉类化合物产生的苄基和2-苯乙基自由基的命运。前者转化为苯甲醇、苯甲醛和甲苯，后者转化为2-苯基乙醇、苯乙醛、乙苯、苯乙烯和苯甲醛。氧-18标记研究表明，80-85%的苯甲醇从氢过氧化物中掺入氧，其余的来自分子氧。这表明，主要的反应途径涉及重组之间的苄基自由基和铁结合的羟基自由基的P-450的中间复合物。相比之下，来自2-苯乙基的约50%的2-苯基乙醇结合了来自水的氧和来自O2的余量。提出了两种可能的机理来解释从水中生成含氧的2-苯基乙醇和同时生成苯乙烯的过程：（a）P-450中间体与水进行氧交换，然后与P-450络合物发生夺氢和自由基重组反应;或（B）自由基氧化成2-苯乙基阳离子，然后质子消除和水合。
Free radicals resulting from the one-electron reduction and subsequent homolytic cleavage of oxygen-oxygen bonds by heme proteins are likely to be responsible for some aspects of the toxicity of organic hydroperoxides. In the present work, effects of the 4-alkyl substituent of 2, 6-di-tert-butyl-4-alkyl-4-hydroperoxycytohexa-2, 5-dienones (1, 4-peroxyquinols) on radical production were investigated with microsomal cytochrome P-450 from rat liver. Quinoxy radicals from homolysis of the peroxyquinols underwent 8-scission to produce a quinone and an alkyl radical, and this process occurred with increasing frequency as the stability of the alkyl radical increased. The fateof benzyl and 2-phenylethyl radicals generated from the appropriately substituted peroxyquinols was investigated also. The former was converted to benzyl alcohol, benzaldehyde, and toluene and the latter to 2-phenylethanol, phenylacetaldehyde, ethylbenzene, styrene, and benzaldehyde. Oxygen-18 labeling studies demonstrated that 80-85% of the benzyl alcohol incorporated oxygen from the hydroperoxide and the balance from molecular oxygen. This indicates that the predominant reaction pathway involved recombination between the benzyl radical and the iron-bound hydroxyl radical of theP-450 intermediate complex. By contrast, about 50% of 2-phenylethanol from the 2-phenylethyl radical incorporated oxygen from water and the balance from 02. Two alternative mechanisms are proposed to explain theformation of 2-phenylethanol that contained oxygen from water and the concurrent formationof styrene:(a) oxygen exchange of the P-450 intermediate with water, followed by hydrogen abstraction and radical recombination reactions with the P-450 complex, or (b) oxidation of the radical to the 2-phenylethyl cation followed by proton elimination and hydration.