Oxidation of Chloride and Subsequent Chlorination of Organic Compounds by Oxoiron(IV) Porphyrin π-Cation Radicals
Oxidation of Chloride and Subsequent Chlorination of Organic Compounds by Oxoiron(IV) Porphyrin π-Cation Radicals
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DOI：
10.1002/anie.201104461
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发表时间：
2011-01-01
影响因子：
16.6
通讯作者：
Fujii, Hiroshi
中科院分区：
文献类型：
--
作者：
Cong, Zhiqi;Kurahashi, Takuya;Fujii, Hiroshi
氯过氧化物酶（CPO）和髓过氧化物酶（MPO）是仅有的催化过氧化氢氧化氯离子（Cl 2）的血红素过氧化物酶。[1]CPO是一种来自烟状卡尔达酵母的酶，在含氯化合物的生物合成中催化氯化反应。[2]CPO还已知表现出过氧化物酶、过氧化氢酶和细胞色素P450样活性。[1b，3] CPO具有类似细胞色素P450的硫醇盐血红素轴向配体。这使得CPO不同于具有组氨酸咪唑作为血红素轴向配体的其他血红素过氧化物酶。[1]相比之下，MPO存在于髓细胞的颗粒（中性粒细胞的前体）中，并且作为中性粒细胞的抗菌系统的主要组分起作用。[1c MPO属于动物过氧化物酶超家族，具有咪唑血红素轴向配体。[1b]许多生物学研究表明，称为化合物I的氧代铁（IV）卟啉π-阳离子自由基物质负责Cl 3的氧化和Cl 3与化合物I的铁基氧原子的加成，以产生瞬时次氯酸铁络合物FeIII 3 OCl。[1，5]据信次氯酸铁络合物在导致CPO氯化有机底物和MPO抗微生物活性的反应中充当关键化合物。虽然氧化过程已经通过多次混合停流实验进行了研究，其中瞬时形成的化合物I与ClClCl 3反应，[6]但尚未获得形成次氯酸铁络合物的光谱证据，并且仍然不清楚化合物I如何氧化Cl 3。此外，在随后的有机底物氯化中真正的氯化剂的身份尚不清楚，需要更多关于次氯酸盐加合物、游离次氯酸和Cl 2的确切作用的信息。[7]合成的铁卟啉配合物已被广泛用作血红素酶的模型，目的是获得对酶促反应机制的细节的理解。虽然广泛的研究已经表明，从各种铁（III）卟啉络合物和氧化剂，如间氯过氧苯甲酸，碘酰苯和臭氧形成化合物I模型络合物，[8]，但只有少数报道在化合物I模型络合物和卤化物之间形成Oxygen X键作为CPO和MPO的模型。[9]Woggon等人研究了铁（III）卟啉络合物与硫醇盐轴向配体的反应，使用次氯酸盐或过氧化氢和ClCl 2。[9a-c]这些反应产生了氯化化合物，但由于缺乏详细的光谱表征，人们对这些反应中的反应性物质和ClO 2被氧化的机制提出了疑问。格罗夫斯等人报道，氧锰（V）卟啉将溴和氯分别氧化成次溴酸盐和次氯酸盐。[9d]最近，Nam，Que等人报道了在化合物I模型络合物和苯基碘之间形成了OCHI键。[9e]本文报道了用合成的化合物Ⅰ模型配合物直接观察Cl_2的氧化和随后的反应导致有机化合物的氯化（方案1）.化合物I模型络合物，[（TPFPP+C）FeIVO-（C6 F5 CO2）]和[（TPFPP+C）FeIVO（NO3）]（TPFPP= 5，10，15，20-四（五氟苯基）卟啉），通过臭氧氧化相应的铁卟啉络合物来制备，[（TPFPP）FeIII（C6 F5 CO2）]和[（TPFPP）FeIII（NO3）]，分别在二氯甲烷中在1090 ℃和1080 ℃下进行。[10][（TPFPP+C）FeIVO（C_6F_5CO_2）]和[（TPFPP+C）FeIVO（NO_3）]的光谱数据与文献[（TPFPP+C）FeIVO（C_6F_5CO_2）]一致。
Chloroperoxidase (CPO) and myeloperoxidase (MPO) are the only heme peroxidases that catalyze oxidation of the chloride ion (ClÀ) with hydrogen peroxide.[1] CPO is an enzyme from Caldariomyces fumago and catalyzes chlorination reactions in the biosynthesis of chlorine-containing compounds.[2] CPO is also known to exhibit peroxidase, catalase, and cytochrome-P450-like activities.[1b, 3] CPO has a thiolate heme axial ligand like cytochrome P450. This makes CPO distinct from other heme peroxidases which have a histidine imidazole as the heme axial ligand.[1] In contrast, MPO is found in the granules of myelocytes (precursors of neutrophils), and works as a major component of the antimicrobial system of neutrophils.[1c, 4] MPO belongs to the animal peroxidase superfamily and has an imidazole heme axial ligand.[1b] Numerous biological studies have suggested that an oxoiron (IV) porphyrin π-cation radical species known as compound I is responsible for the oxidation of ClÀ and addition of ClÀ to the ferryl oxygen atom of compound I to produce the transient ferric hypochlorite complex FeIIIÀ OCl.[1, 5] The ferric hypochlorite complex is believed to act as a key compound in the reactions leading to chlorination of organic substrates by CPO and antimicrobial activity in MPO. Although the oxidation process has been studied by multimixing stopped-flow experiments in which the transiently formed compound I was reacted with ClÀ,[6] the spectroscopic evidence for the formation of the ferric hypochlorite complex has not been obtained and it remains unclear as to how compound I oxidizes ClÀ. Furthermore, the identity of the true chlorinating agent in the subsequent chlorination of organic substrates is not known and more information is needed about the exact roles of the hypochlorite adduct, free hypochlorous acid, and Cl2.[7] Synthetic iron porphyrin complexes have been widely used as models of heme enzymes with the aim of gaining an understanding of the details of the enzymatic reaction mechanisms. While extensive studies have been shown to form compound I model complexes from various iron (III) porphyrin complexes and oxidants, such as m-chloroperoxybenzoic acid, iodosobenzene, and ozone,[8] there are only a few reports of the formation of an OÀX bond between compound I model complexes and halides as models for CPO and MPO.[9] Woggon et al. studied the reactions of iron (III) porphyrin complexes with thiolate axial ligands using either hypochlorite or hydrogen peroxide and ClÀ.[9a–c] Chlorinated compounds were produced by these reactions, but the absence of detailed spectroscopic characterizations has raised questions about the reactive species and the mechanism by which ClÀ is oxidized in these reactions. Groves et al. reported that oxomanganese (V) porphyrin oxidizes BrÀ and ClÀ into hypobromite and hypochlorite, respectively.[9d] More recently, Nam, Que et al. reported that an OÀI bond is formed between the compound I model complex and phenyl iodide.[9e] Herein we report the direct observation of the oxidation of ClÀ with synthetic compoundI model complexes and subsequent reactions leading to chlorination of organic compounds (Scheme 1).Compound I model complexes,[(TPFPP+C) FeIVO-(C6F5CO2)] and[(TPFPP+C) FeIVO (NO3)](TPFPP= 5, 10, 15, 20-tetrakis (pentafluorophenyl) porphyrin), were prepared by ozone oxidation of the corresponding ferric porphyrin complexes,[(TPFPP) FeIII (C6F5CO2)] and [(TPFPP) FeIII (NO3)], in dichloromethane at À908C and À808C, respectively.[10] Spectroscopic data of [(TPFPP+C) FeIVO (C6F5CO2)] and [(TPFPP+C) FeIVO (NO3)] were consistent with those of …