Synthetic heme/copper assemblies: toward an understanding of cytochrome c oxidase interactions with dioxygen and nitrogen oxides.
Synthetic heme/copper assemblies: toward an understanding of cytochrome c oxidase interactions with dioxygen and nitrogen oxides.
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DOI：
10.1021/acs.accounts.5b00265
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发表时间：
2015-08-18
影响因子：
18.3
通讯作者：
Karlin KD
中科院分区：
文献类型：
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作者：
Hematian S;Garcia-Bosch I;Karlin KD
我们在合成生物无机化学领域的长期定位一直是设计配体并生成铜和/或铁离子的配位配合物，这些配合物与二氧（O2）和/或氮氧化物(例如，一氧化氮（NO（g)）和亚硝酸盐（NO2 -））反应。作为这项工作的灵感，我们转向线粒体细胞色素c氧化酶，它负责双氧消耗，也是线粒体内NO(g)和亚硝酸盐的主要目标。在这篇文章中，我们从两个方面强调了合成血红素/铜配合物的最新研究进展。首先，设计、合成和表征新的o2加合物，这些加合物的进一步研究将为o2还原裂解化学提供新的见解。其次，我们描述了相关的血红素/Cu结构如何将亚硝酸盐离子还原为NO(g)或相反，将NO(g)氧化为亚硝酸盐。氮氧化物的反应是CcO功能的一部分，这与细胞的o2平衡密切相关。我们首次发现还原血红素/Cu化合物与O2反应生成μ-氧血红素- feii -o - cuii (L)产物；讨论了它们的性质。o原子来源于双氧，对这些体系的研究导致了三种不同类型的血红素-过氧配合物的构建和表征，两种高自旋和一种低自旋。最近的研究包括一种合成低自旋血红素-过氧化物-铜配合物的新方法，采用“裸”合成子，其中铜配体的密度和几何类型可以改变。结果是这样的复合体的集合；描述了光谱和结构特征（通过DFT计算）。其中一些化合物对还原剂/质子具有反应性，影响随后的O-O裂解。这指出了配体环境的细微改善如何导致所需的局部结构和最终优化的反应性，正如已知的那样发生在酶活性位点。另一个研究领域集中在血红素/Cu组装体介导亚硝酸盐和NO(g)之间的氧化还原相互作用。在亚硝酸盐还原酶化学中，铜中心充当路易斯酸，而血红素是提供电子的氧化还原活性中心。亚硝酸盐在接近亚铁血红素中心时的取向和n原子的结合是重要的。此外，对NO(g)氧化酶化学进行了详细的光谱和动力学研究，与理论计算非常吻合，揭示了中间体和关键的机制步骤。因此，我们认为化学和生化血红素/Cu介导的亚硝酸盐还原酶和NO(g)氧化酶化学都需要n原子与铁血红素结合以及铜离子o原子配位，通过三元O-Fe-N螯合环过渡态进行。本文首次讨论了血红素/Cu体系相互转化NO(g)和亚硝酸盐的重要机理特征。
Our long-time niche in synthetic biological inorganic chemistry has been to design ligands and generate coordination complexes of copper and/or iron ions, those reacting with dioxygen (O2) and/or nitrogen oxides (e.g., nitric oxide (NO(g)) and nitrite (NO2−)). As inspiration for this work, we turn to mitochondrial cytochrome c oxidase which is responsible for dioxygen consumption and is also the predominant target for NO(g) and nitrite within mitochondria. In this Account, we highlight recent advances in studying synthetic heme/Cu complexes in two respects. First, there is the design, synthesis and characterization of new O2-adducts whose further study will add insights into O2-reductive cleavage chemistry. Second, we describe how related heme/Cu constructs reduce nitrite ion to NO(g) or the reverse, oxidize NO(g) to nitrite. The reactions of nitrogen oxides occur as part of CcO’s function, which is intimately tied to cellular O2-balance. We had first discovered that reduced heme/Cu compounds react with O2 giving μ-oxo heme-FeIII-O-CuII(L) products; their properties are discussed. The O-atom is derived from dioxygen and interrogations of these systems led to the construction and characterization of three distinctive classes of heme-peroxo-complexes, two high-spin and one low-spin species. Recent investigations include a new approach to the synthesis of low-spin heme-peroxo-Cu complexes, employing a “naked” synthon, where the copper ligand denticity and geometric types can be varied. The result is a collection of such complexes; spectroscopic and structural features (by DFT calculations) are described. Some of these compounds are reactive toward reductants/protons effecting subsequent O-O cleavage. This points to how subtle improvements in ligand environment lead to a desired local structure and resulting optimized reactivity, as known to occur at enzyme active-sites. The other sector of research is focused on heme/Cu assemblies mediating the redox interplay between nitrite and NO(g). In the nitrite reductase chemistry, the cupric center serves as a Lewis acid while the heme is the redox active center providing the electron. The orientation of nitrite in approaching the ferrous heme center and N-atom binding are important. Also, detailed spectroscopic and kinetic studies of the NO(g) oxidase chemistry, in excellent agreement with theoretical calculations, reveal the intermediates and key mechanistic steps. Thus, we suggest that both chemical and biochemical heme/Cu mediated nitrite reductase and NO(g) oxidase chemistry require N-atom binding to a ferrous heme along with cupric ion O-atom coordination, proceeding via a three-membered O-Fe-N chelate ring transition state. These important mechanistic features of heme/Cu systems interconverting NO(g) and nitrite are discussed for the first time.