Disclosure of Key Stereoelectronic Factors for Efficient H2 Binding and Cleavage in the Active Site of [NiFe]-Hydrogenases
Disclosure of Key Stereoelectronic Factors for Efficient H2 Binding and Cleavage in the Active Site of [NiFe]-Hydrogenases
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DOI：
10.1021/ja408511y
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发表时间：
2014-02-05
影响因子：
15
通讯作者：
De Gioia, Luca
中科院分区：
文献类型：
--
作者：
Bruschi, Maurizio;Tiberti, Matteo;De Gioia, Luca
对[NiFe]-氢化酶的一系列DFT模型（从最小的NiFe簇到包括双金属辅因子的第一和第二配位圈的非常大的系统）进行了比较分析，目的是解开哪些立体电子性质的[NiFe]-氢化酶活性位点对于有效的H-2结合和切割至关重要。只有当H-2与Ni结合时，H-2与Ni-Sia氧化还原态的结合才在能量上有利（4.0 kcal mol（-1）），NiFe金属簇处于低自旋状态，并且Ni半胱氨酸配体具有特殊的跷跷板配位几何结构，其在酶中通过蛋白质环境稳定。Ni配位几何形状对H-2结合亲和力的影响，然后定量评估和合理化分析前线分子轨道和人口。还研究了导致H-2裂解的几种可能的反应途径。事实证明，一个两步的途径，其中H-2裂解发生在Ni-Sia氧化还原状态的酶，其特征在于非常低的反应势垒和有利的反应能量。更重要的是，跷跷板式的配位几何形状的Ni被发现是一个关键的功能，容易H-2裂解。Ni配位几何结构对[NiFe]-氢化酶活性位点中H-2结合和活化的关键影响的发现可用于新型仿生合成催化剂的设计。
A comparative analysis of a series of DFT models of [NiFe]-hydrogenases, ranging from minimal NiFe clusters to very large systems including both the first and second coordination sphere of the bimetallic cofactor, was carried out with the aim of unraveling which stereoelectronic properties of the active site of [NiFe]-hydrogenases are crucial for efficient H-2 binding and cleavage. H-2 binding to the Ni-SIa redox state is energetically favored (by 4.0 kcal mol(-1)) only when H-2 binds to Ni, the NiFe metal cluster is in a low spin state, and the Ni cysteine ligands have a peculiar seesaw coordination geometry, which in the enzyme is stabilized by the protein environment. The influence of the Ni coordination geometry on the H-2 binding affinity was then quantitatively evaluated and rationalized analyzing frontier molecular orbitals and populations. Several plausible reaction pathways leading to H-2 cleavage were also studied. It turned out that a two-step pathway, where H-2 cleavage takes place on the Ni-SIa redox state of the enzyme, is characterized by very low reaction barriers and favorable reaction energies. More importantly, the seesaw coordination geometry of Ni was found to be a key feature for facile H-2 cleavage. The discovery of the crucial influence of the Ni coordination geometry on H-2 binding and activation in the active site of [NiFe]-hydrogenases could be exploited in the design of novel biomimetic synthetic catalysts.