Functional modeling of tyrosinase. Mechanism of phenol ortho-hydroxylation by dinuclear copper complexes
Functional modeling of tyrosinase. Mechanism of phenol ortho-hydroxylation by dinuclear copper complexes
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DOI：
10.1021/ic9601100
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发表时间：
1996-12-18
影响因子：
4.6
通讯作者：
Ugo, R
中科院分区：
文献类型：
--
作者：
Casella, L;Monzani, E;Ugo, R
采用一系列带多苯并咪唑配体的双核铜(I)配合物研究了4-羟基苯甲酸甲酯(1)在乙腈中的氧合反应。该反应模拟了铜酶酪氨酸酶的活性，因为反应的初始产物是邻儿茶酚，甲基3,4 -二羟基苯甲酸酯(2)。所研究的配体体系包括α， α '-bis{bis[2-（1-甲基-2-苯并咪唑基）-乙基]氨基}-m-二甲苯(L-66) α, α '-bis{bis[2-（1-甲基-2-苯并咪唑基）甲基]氨基}-m-二甲苯（L-55）， α, α '-bis{[（1-甲基-2-苯并咪唑基）甲基][2-（1-甲基-2-苯并咪唑基）乙基]氨基}-m-二甲苯（L-56）和α， α '-bis{[（2-吡啶基）甲基][2-（1-甲基-2-苯并咪唑基）乙基]氨基}-m-二甲苯（L-5p6）。其中最有效的铜(I)配合物是由L-66衍生的，而其单核铜(I)类似物与配体N， N-双[2-（1-甲基-2-苯并咪唑）乙基]胺在单加氧酶反应中无活性。当反应在低温（-40℃）下进行时，邻苯二酚2是苯酚羟基化的唯一产物。随着温度的升高，甲基2-[4-（碳甲氧基）苯氧基]- 3,4 -二羟基苯甲酸甲酯(4)成为反应的主要产物。甲基2-[4-（碳甲氧基）苯氧基]- 3,4 -二羟基苯甲酸甲酯(4)，形式上是由Michael将起始苯酚加入到4-碳甲氧基- 1,2 -苯醌(3)中产生的，可能是由游离酚酸酯和一些中间的儿茶酚铜物质之间的反应产生的。为了深入了解反应的机理，研究了L-66、L-55和L-6配合物的二铜(I)-酚酸加合物和二铜(II)-儿茶酚酸加合物，在少数情况下，对含有儿茶酚酸单阴离子或儿茶酚酸双阴离子的加合物进行了分离和光谱表征。结果表明，单加氧酶反应的最终产物为二铜(II)-儿茶酚酸离子配合物。提出了一种仿生苯酚邻羟基化的机制，并讨论了其与酪氨酸酶的可能相关性。
The copper-mediated oxygenation of methyl 4-hydroxybenzoate (1) in acetonitrile has been investigated by employing a series of dinuclear copper(I) complexes with polybenzimidazole ligands. The reaction mimics the activity of the copper enzyme tyrosinase, since the initial product of the reaction is the o-catechol, methyl 3, 4-dihydroxybenzoate (2). The ligand systems investigated include alpha, alpha'-bis{bis[2-(1-methyl-2-benzimidazolyl)-ethyl]amino}-m-xylene (L-66) alpha, alpha'-bis{bis[2-(1-methyl-2-benzimidazolyl)methyl]amino}-m-xylene (L-55), alpha, alpha'-bis{[(1-methyl-2-benzimidazolyl)methyl][2-(1-methyl-2-benzimidazolyl)ethyl]amino}-m-xylene (L-56), and alpha, alpha'-bis{[(2-pyridyl)methyl][2-(1-methyl-2-benzimidazolyl)ethyl]amino}-m-xylene (L-5p6). The most effective among the dicopper(I) complexes is that derived from L-66, while its mononuclear Cu(I) analogue, with the ligand N, N-bis[2-(1-methyl-2-benzimidazolyl)ethyl]amine is inactive in the monooxygenase reaction. The catechol 2 is the only product of phenol hydroxylation when the reaction is carried out at low temperature (-40 degrees C). As the temperature is increased, methyl 2-[4-(carbomethoxy)phenoxy]-3, 4-dihydroxybenzoate (4), formally resulting from Michael addition of the starting phenol to 4-carbomethoxy-1, 2-benzoquinone (3) and probably resulting from the reaction between free phenolate and some intermediate copper-catecholate species, becomes a major product of the reaction. In order to gain insight into the mechanism of the reaction, the dicopper(I)-phenolate adducts and dicopper(II)-catecholate adducts of the L-66, L-55, and L-6 complexes have been studied, In a few cases the adducts containing catecholate monoanion or catecholate dianion have been isolated and spectrally characterized. It has been shown that the final product of the monooxygenase reaction corresponds to the dicopper(II)-catecholate dianion complex. A mechanism for the biomimetic phenol ortho-hydroxylation has been proposed and its possible relevance for tyrosinase discussed.