In-crystal reaction cycle of a toluene-bound diiron hydroxylase
In-crystal reaction cycle of a toluene-bound diiron hydroxylase
复制标题
DOI：
10.1038/nature21681
复制
发表时间：
2017-04-13
期刊：
影响因子：
64.8
通讯作者：
Fox, Brian G.
中科院分区：
文献类型：
--
作者：
Acheson, Justin F.;Bailey, Lucas J.;Fox, Brian G.
芳香亲电取代反应是一类重要的有机化学反应。酶通过使用O-2、电子和金属或其他辅助因子来产生这些高能反应所需的强亲电体。虽然进行亲电芳香取代反应的氧化剂的性质已经从许多方法中推导出来，但很难确定它们的结构。在这里，我们显示了在与甲苯反应过程中形成的二铁羟化酶中间体的结构。通过密度泛函理论对活性中心模型进行几何优化，结果表明该中间体是一种具有离域芳基特征的芳基过氧Fe ~（2+）/Fe ~（3+）物种.该结构表明，二铁中心的羧酸根配体可以通过从金属结合水转移质子来触发O-O键的均裂裂解。我们的工作提供了空间和电子的限制，需要提出一个全面的机制，占许多先前的实验结果的二铁酶芳烃羟基化。
Electrophilic aromatic substitution is one of the most important and recognizable classes of organic chemical transformation. Enzymes create the strong electrophiles that are needed for these highly energetic reactions by using O-2, electrons, and metals or other cofactors. Although the nature of the oxidants that carry out electrophilic aromatic substitution has been deduced from many approaches, it has been difficult to determine their structures. Here we show the structure of a diiron hydroxylase intermediate formed during a reaction with toluene. Density functional theory geometry optimizations of an active site model reveal that the intermediate is an arylperoxo Fe2+/Fe3+ species with delocalized aryl radical character. The structure suggests that a carboxylate ligand of the diiron centre may trigger homolytic cleavage of the O-O bond by transferring a proton from a metal-bound water. Our work provides the spatial and electronic constraints needed to propose a comprehensive mechanism for diiron enzyme arene hydroxylation that accounts for many prior experimental results.