Reactivity of Manganese and Iron Metalloenzyme Models

描述(由申请人提供)：拟议研究的目标是调查锰和铁的络合物作为利用氧气的血红素金属酶的模型的反应性。细胞色素P450、过氧化物酶、过氧化氢酶、血红素加氧酶、一氧化氮合酶和细胞色素C氧化酶等血红素酶都依赖于锰或铁的活性中心来执行一系列涉及O2或其衍生物的关键生物学功能。尽管这些酶的功能高度多样化，但有一些机制上的共同点，涉及将这些系统结合在一起的关键中间体。这些关键中间体涉及高价金属氧基(M=O)和金属(氢)过氧基(M-OO(H))物种。了解这些物种的反应性和光谱特征至关重要，但关于这些物种的许多问题仍然存在，部分原因是与研究哪些是不稳定且往往短暂的中间体有关的挑战。我们将通过合成类比方法解决有关高价M=O物种及其前体M-OO(H)的基本问题。我们将利用被称为腐拉津(CZS)和腐蚀剂(CORS)的配体来进行这项研究。这些配体旨在稳定高氧化态(如MVO)。它们还支持低价络合物，如MIII和MIV，将用于研究O-O切割事件。本方案的目的是1)合成新型高价(Cz)M(O)和(Cor)M(O)配合物，确定它们的结构和光谱性质，并考察它们在生物相关转化中的反应活性；2)确定(Cz)M和(Cor)M对O-O裂解/O2活化的反应性。合成方法，包括配体设计和配位化学，将被用来构建新的感兴趣的模型配合物。我们将把(Cz)M和(Cor)M(M=Mn，Fe)配合物的结构和电子性质与直接生物相关的反应(如氢原子转移(HAT)、氧原子转移(OAT)和电子转移(ET)过程)的反应活性联系起来。将通过对含有C-H键和O-H键的一系列HAT底物、O原子受体底物和ET试剂的产物分析和动力学测量来研究反应活性和机理。对我们的锰和铁的化学进行比较，应该会得出关于为什么大自然选择铁或锰来执行特定功能的见解。将获得关于仿生HAT、OAT、ET和相关反应机理的基本信息。

DESCRIPTION (provided by applicant): The goal of the proposed research is to investigate the reactivity of manganese and iron complexes as models of heme metalloenzymes that utilize dioxygen. Heme enzymes such as cytochrome P450, peroxidases, catalases, heme oxygenase, nitric oxide synthase and cytochrome C oxidase all rely upon Mn or Fe active sites to perform an impressive range of critical biological functions involving O2 or its derivatives. Although the functions of these enzymes are highly diverse, there are some mechanistic commonalities involving key intermediates that bring these systems together. These key intermediates involve high-valent metal-oxo (M=O) and metal-(hydro)peroxo (M-OO(H)) species. Understanding the reactivity and spectroscopic features of these species is critically important, yet many questions remain about these species in part because of challenges associated with studying what are unstable and often short-lived intermediates. We will address fundamental questions regarding high-valent M=O species and their precursors, M-OO(H), through a synthetic analog approach. We will utilize ligands known as corrolazines (Czs) and corroles (Cors) to carry out this research. These ligands are designed to stabilize high oxidation states (e.g. MVO). They also support lower-valent complexes such as MIII and MIV, which will be used to study O-O cleavage events. Aims of this proposal are 1) to synthesize novel high-valent (Cz)M(O) and (Cor)M(O) complexes, determine their structural and spectroscopic properties, and examine their reactivity in biologically relevant transformations and 2) to determine the reactivity of (Cz)M and (Cor)M toward O-O cleavage/O2 activation. Synthetic methods, including ligand design and coordination chemistry, will be used to construct new model complexes of interest. We will correlate the structural and electronic properties of the (Cz)M and (Cor)M (M = Mn, Fe) complexes with reactivity in reactions of direct biological relevance (e.g. hydrogen-atom-transfer (HAT), oxygen-atom-transfer (OAT), and electron-transfer (ET) processes). Reactivity and mechanism will be studied through analysis of products and kinetic measurements with a range of HAT substrates containing C-H and O-H bonds, O-atom acceptor substrates, and ET agents. Comparison of our Mn and Fe chemistry should yield insights regarding why Nature chooses Fe or Mn to perform specific functions. Fundamental information regarding the mechanisms of biomimetic HAT, OAT, ET and related reactions will be obtained.