Non-Heme Diiron Model Complexes Can Mediate Direct NO Reduction: Mechanistic Insight into Flavodiiron NO Reductases

Flavodiiron nitric oxide reductases (FNORs), a common enzyme family found in various types of pathogenic bacteria, are capable of reducing nitric oxide (NO) to nitrous oxide (N2O) as a protective detoxification mechanism. Utilization of FNORs in pathogenic bacteria helps them survive and proliferate in the human body, thus causing chronic infections. In this paper, we present a new diiron model complex, [Fe2((Py2PhO2)­MP)­(OPr)2]­(OTf), with bridging propionate ligands (OPr−) that is capable of directly reducing NO to N2O in quantitative yield without the need to (super)­reduce the complex. We first prepared the diferric precursor and characterized it by UV–vis, IR, NMR and Mössbauer spectroscopies, cyclic voltammetry, and mass spectrometry. This complex can then conveniently be reduced to the diferrous complex using CoCp2. Even though this diferrous complex is highly reactive, we have successfully isolated and characterized this species using X-ray crystallography and various spectroscopic techniques. Most importantly, upon reacting this diferrous complex with NO gas, we observe quantitative formation of N2O via IR gas headspace analysis, the first demonstration of direct NO reduction by a non-heme diiron model complex. This finding directly supports recent mechanistic proposals for FNORs.

黄素二铁一氧化氮还原酶（Flavodiiron nitric oxide reductases, FNORs）是一类广泛分布于多种病原菌中的常见酶家族，可通过将一氧化氮（nitric oxide, NO）还原为一氧化二氮（nitrous oxide, N2O）实现保护性解毒。病原菌中这类酶的存在可帮助菌体在宿主体内存活并增殖，进而引发慢性感染。本文报道了一种新型二铁模型配合物[Fe2((Py2PhO2)­MP)­(OPr)2]­(OTf)，其带有桥联丙酸配体（OPr−），可直接将一氧化氮转化为一氧化二氮且产率定量，无需对该配合物进行（超）还原处理。我们首先制备了该三价二铁前驱体，并通过紫外-可见光谱（UV–vis）、红外光谱（IR）、核磁共振波谱（NMR）、穆斯堡尔谱（Mössbauer）、循环伏安法以及质谱对其进行了表征。随后可通过二茂钴（CoCp2）方便地将该配合物还原为二价二铁配合物。尽管该二价二铁配合物具有极高的反应活性，我们仍成功分离得到该物种，并通过X射线晶体学与多种光谱技术对其进行了表征。最为重要的是，当该二价二铁配合物与一氧化氮气体反应后，我们通过红外气相顶空分析观测到一氧化二氮以定量产率生成，这是非血红素二铁模型配合物直接还原一氧化氮的首次验证。该发现直接佐证了当前关于黄素二铁一氧化氮还原酶（FNORs）的最新机理假说。