Reactivity of Manganese and Iron Metalloenzyme Models

描述（由申请人提供）：拟议研究的目标是研究锰和铁络合物作为利用分子氧的血红素金属酶模型的反应性。血红素酶如细胞色素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氧化酶都依赖于Mn或Fe活性位点来执行涉及O2或其衍生物的令人印象深刻的重要生物功能。虽然这些酶的功能是高度多样化的，有一些机制的共性涉及关键中间体，使这些系统在一起。这些关键中间体涉及高价金属氧代（M=O）和金属（氢）过氧（M-OO（H））物种。了解这些物种的反应性和光谱特征至关重要，但仍存在许多关于这些物种的问题，部分原因是与研究不稳定且通常寿命短的中间体相关的挑战。我们将通过合成类似物的方法解决关于高价M=O物种及其前体M-OO（H）的基本问题。我们将利用被称为corrolazines（Czs）和corrolles（Cors）的配体进行这项研究。这些配体被设计用于稳定高氧化态（例如MVO）。它们还支持低价复合物，如MIII和MIV，它们将用于研究O-O裂解事件。该方案的目的是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，并检测它们在生物相关转化中的反应性; 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，将用于构建新的模型感兴趣的配合物。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（例如氢原子转移（HAT）、氧原子转移（OAT）和电子转移（ET）过程）中的反应性相关联。反应性和机制将通过分析产品和动力学测量与一系列的HAT基板含有C-H和O-H键，O-原子受体基板，和ET剂进行研究。我们的Mn和Fe化学的比较应该产生关于为什么大自然选择Fe或Mn执行特定功能的见解。将获得关于仿生HAT、OAT、ET及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.