Synthesis of Diiron Complexes of Relevence to Methane Monoxygenase

与甲烷单加氧酶相关的二铁配合物的合成

• 批准号: 7808749
• 负责人: Matthew A Cranswick
• 金额: $ 4.76万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-04-15 至 2012-04-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7808749
• 关键词: Active Sites; Aerobic; Amines; Anabolism; Bacteria; Biological; Carbon; Chemicals; Complex; Data; Electron Transport; Electronics; Enzymes; Hydrocarbons; Hydrogen Bonding; Iron; Kinetics; Lead; Ligands; Methane; Methane hydroxylase; Methanol; Methods; Mixed Function Oxygenases; Modeling; Natural Gas; Organism; Oxygen; Process; Property; Reaction; Research Project Grants; Ribonucleotide Reductase; Roentgen Rays; Route; Site; Source; Spectrum Analysis; Structure; Techniques; absorption; base; catalyst; data modeling; design; electronic structure; greenhouse gases; improved; insight; interest; novel; public health relevance; small molecule; social implication; success

DESCRIPTION (provided by applicant): Oxygen-activating diiron-enzymes are found in all aerobic organisms and utilize a diiron site to perform demanding chemical transformations. The major aim of this research project is to gain insight into the mechanism of oxygen-activation at diiron-enzyme active sites through the synthesis and characterization of high-valent, high-spin diiron-oxo complexes that mimic the structure and reactivity of key reaction intermediates. Specifically, novel diiron complexes will be utilized to model the reactive species of soluble methane monooxygenase (sMMO), an enzyme that utilizes methane as its sole source of carbon. The sequestration of methane by methanotropic bacteria is responsible for the elimination of nearly a billion tons of this potent greenhouse gas per year. In addition, there is considerable industrial interest in replicating the sMMO reaction to provide an environmentally-friendly process to generating methanol as a means of safely transporting natural gas reserves and as a chemical feedstock. The enzyme ribonucleotide reductase (RNR) also contains a similar diiron site that initiates long-range electron-transfer to the enzyme active site and is essential in DMA biosynthesis. Thus, understanding how the diiron site of sMMO and RNR activates oxygen to carry out their respective functions will have broad environmental and social implications. The crucial reactive intermediate in oxidizing methane to methanol is performed at a poorly understood diiron(IV)-oxo species known as intermediate Q, which is produced via the diiron(lll)-peroxo intermediate, P. Building upon the recent successes of generating high-valent diiron-complexes, this proposal describes the synthetic route to designing novel ligand motifs and small-molecule diiron model complexes that reproduce the geometric and electronic structures of P and Q. These diiron-complexes will be characterized by a variety of spectroscopic and structural methods, including electronic absorption, resonance Raman, Mossbauer and X-ray absorption spectroscopies, and their reactivity towards organic substrates will be evaluated. PUBLIC HEALTH RELEVANCE: This proposal outlines the synthesis of small-molecule diiron-complexes that replicate the structure and reactivities of important biological species and aims to further our understanding of how processes that require oxygen-activation are carried out at diiron centers by these enzymes. Additionally, this project may lead to better catalysts that will allow chemists to utilize oxygen to carry out environmentally friendly transformations of hydrocarbons, thereby reducing greenhouse emissions.

描述（由申请人提供）：氧活化二铁酶存在于所有需氧生物体中，并利用二铁位点来执行要求较高的化学转化。该研究项目的主要目的是通过模拟关键反应的结构和反应性的高价、高自旋二铁氧配合物的合成和表征，深入了解二铁酶活性位点的氧活化机制中间体。具体来说，新型二铁配合物将用于模拟可溶性甲烷单加氧酶（sMMO）的反应物种，sMMO是一种利用甲烷作为其唯一碳源的酶。甲烷氧化细菌对甲烷的封存每年消除近十亿吨这种强效温室气体。此外，工业界对复制 sMMO 反应有很大兴趣，以提供一种环保的工艺来生产甲醇，作为安全运输天然气储备的手段和作为化学原料。核糖核苷酸还原酶 (RNR) 也含有类似的二铁位点，可启动向酶活性位点的长程电子转移，并且在 DMA 生物合成中至关重要。因此，了解 sMMO 和 RNR 的二铁位点如何激活氧以发挥各自的功能将具有广泛的环境和社会影响。将甲烷氧化成甲醇的关键反应中间体是在一种知之甚少的二铁（IV）-氧代物质（称为中间体 Q）中进行的，它是通过二铁（III）-过氧中间体 P 产生的。 -价二铁配合物，该提案描述了设计新型配体基序和小分子二铁模型配合物的合成路线，这些配合物可再现 P 和 Q 的几何和电子结构。这些二铁配合物将通过各种光谱和结构方法进行表征，包括电子吸收、共振拉曼、穆斯堡尔和X射线吸收光谱，并将评估它们对有机底物的反应性。公共健康相关性：该提案概述了小分子二铁复合物的合成，该复合物复制了重要生物物种的结构和反应性，旨在进一步了解这些酶如何在二铁中心进行需要氧活化的过程。此外，该项目可能会产生更好的催化剂，使化学家能够利用氧气进行碳氢化合物的环保转化，从而减少温室气体排放。