Exploring second coordination sphere effects in flavodiiron nitric oxide reductase model complexes
Exploring second coordination sphere effects in flavodiiron nitric oxide reductase model complexes
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DOI：
10.1039/d3dt02828c
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发表时间：
2023-10-31
影响因子：
4
通讯作者：
Lehnert，Nicolai
中科院分区：
文献类型：
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作者：
Bracken，Abigail J.;Dong，Hai T.;Lehnert，Nicolai
黄二铁一氧化氮还原酶（FNORs）使病原体对哺乳动物重要的免疫防御剂一氧化氮（NO）具有抵抗力，使这些病原体在人体内增殖，可能引起慢性感染。了解FNORs如何介导NO减少的机制有助于开发针对耐药菌株的新治疗方法。最近的密度泛函理论计算表明，第二配位球（SCS）酪氨酸残基提供了一个氢键，这对于FNORs活性位点将NO还原为N2O至关重要[J]。吕波，毕斌，赖伟，陈红华，黄二铁NO还原酶一氧化氮还原活性的来源及其在第二配位球中的关键作用。化学。, Int。编辑，2019,58,3795-3799]。具体来说，这个氢键稳定了亚硝酸盐中间体，减少了N-N耦合步骤的能垒。同时，Fe⋯Fe距离的作用及其对N-N耦合步骤的影响尚未得到充分研究。在本研究中，我们将H[BPMP]（= 2,6-二[[二（2-吡啶基甲基）氨基]甲基]-4-甲基苯酚）配体配以SCS酰胺基团，并研究了相应的与0-2桥接乙酸配体的双铁配合物。这些酰胺基团可以与桥接的醋酸配体形成氢键，并可能与这些模型配合物中的配位NO基团形成氢键。同时，通过改变桥接乙酸配体的数量，我们可以系统地改变Fe⋯Fe距离。然后研究了这些配合物与NO的反应性，并观察了稳定的铁(II) -NO配合物的形成。通过单电子还原，这些NO配合物形成二硝基铁配合物（dnic），并利用IR和EPR光谱对其进行了进一步的表征。
Flavodiiron nitric oxide reductases (FNORs) equip pathogens with resistance to nitric oxide (NO), an important immune defense agent in mammals, allowing these pathogens to proliferate in the human body, potentially causing chronic infections. Understanding the mechanism of how FNORs mediate the reduction of NO contributes to the greater goal of developing new therapeutic approaches against drug-resistant strains. Recent density functional theory calculations suggest that a second coordination sphere (SCS) tyrosine residue provides a hydrogen bond that is critical for the reduction of NO to N2O at the active site of FNORs [J. Lu, B. Bi, W. Lai and H. Chen, Origin of Nitric Oxide Reduction Activity in Flavo-Diiron NO Reductase: Key Roles of the Second Coordination Sphere, Angew. Chem., Int. Ed., 2019, 58, 3795–3799]. Specifically, this H-bond stabilizes the hyponitrite intermediate and reduces the energetic barrier for the N–N coupling step. At the same time, the role of the Fe⋯Fe distance and its effect on the N–N coupling step has not been fully investigated. In this study, we equipped the H[BPMP] (= 2,6-bis[[bis(2-pyridylmethyl)amino]methyl]-4-methylphenol) ligand with SCS amide groups and investigated the corresponding diiron complexes with 0–2 bridging acetate ligands. These amide groups can form hydrogen bonds with the bridging acetate ligand(s) and potentially the coordinated NO groups in these model complexes. At the same time, by changing the number of bridging acetate ligands, we can systematically vary the Fe⋯Fe distance. The reactivity of these complexes with NO was then investigated, and the formation of stable iron(II)–NO complexes was observed. Upon one-electron reduction, these NO complexes form Dinitrosyl Iron Complexes (DNICs), which were further characterized using IR and EPR spectroscopy.