Synthesis and Spectroscopy of Ferric Superoxo Models for Non-Heme Enzyme Intermediates

非血红素酶中间体三价铁超氧模型的合成和光谱分析

• 批准号: 9398610
• 负责人: Caleb James Allpress
• 金额: $ 0.02万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-16 至 2017-02-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9398610
• 关键词: Acidity; Acids; Active Sites; Anabolism; Antibiotics; Binding; Biochemical Reaction; Biological; Ceruloplasmin; Characteristics; Chemistry; DNA; Deoxyribonucleotides; Electron Spin Resonance Spectroscopy; Enzymes; Ferritin; Frequencies; Generations; Goals; Hydrogen Bonding; Investigation; Iron; Ligands; Methodology; Methods; Modeling; Modification; Mono-S; Mononuclear; Mossbauer Spectroscopy; Nuclear; Outcomes Research; Oxides; Oxygen; Oxygenases; Pathway interactions; Penicillins; Process; Property; Raman Spectrum Analysis; Reaction; Reactive Oxygen Species; Reporting; Research; Role; Series; Site; Spectrum Analysis; Stretching; Structure; Superoxides; System; Techniques; Temperature; Viscosity; X-Ray Crystallography; alkalinity; clorobiocin; cold temperature; design; flexibility; oxidation; prevent; public health relevance

 DESCRIPTION (provided by applicant): Non-heme, iron-containing oxygenases are involved in various biomedically important processes, including the biosynthesis of antibiotics (including chlorobiocin and penicillin), the generation of deoxyribonucleotides (key building blocks of DNA), and the storage of iron to prevent damaging Fenton-type chemistry (via the ferroxidase site of ferritin). Understanding how oxygenases use activated iron-oxygen species to carry out these transformations is of paramount importance. Despite the wealth of studies on the role of iron-oxo and iron-peroxo species, there is a paucity of spectroscopically accessible iron-superoxo compounds known. This is surprising given that iron-superoxo species are proposed as early intermediates in the catalytic cycles of almost every non-heme iron-containing oxygenase enzyme. The goal of this proposal is to generate spectroscopically tractable Fe(III)-superoxo species of relevance to non-heme iron-containing oxygenases. This will be accomplished by developing a synthetic methodology for mononuclear non-heme Fe(III)-superoxo species. We hypothesize that by appropriate combination of reaction conditions and ligand design features (including ligand basicity, steric bulk and hydrogen bond donor ability) we will be able to generate the first synthetic mononuclear non-heme Fe(III)-superoxo species. We will also apply similar design principles to the generation of Fe(III)-superoxo compounds from dinuclear precursors containing a Fe(II) center. The synthetic Fe(III)-superoxo compounds will be comprehensively characterized by a variety of spectroscopic methods including UV-vis, XAS, resonance Raman, EPR, and Mössbauer spectroscopy. This will allow the establishment of an understanding of the relationship between primary- and secondary- coordination sphere features of the compounds to the structural and electronic features of iron-superoxo species. To date no non-heme iron-superoxo compound has been fully characterized by a combination of Raman, EPR and Mössbauer spectroscopy, and this is a significant gap in understanding for the field. In fact, only a single such superoxo compound has been characterized by resonance Raman, and the O-O stretching frequency of 1310 cm-1 is anomalously high compared to other known superoxide compounds (1043-1207 cm-1). The reactivity of the synthesized Fe(III)-superoxo compounds will also be explored in order to establish a reactivity relationship to electronic and structural parameters. Overall, this research has the potential to be transformative to understanding the role of superoxide intermediates in the field of non-heme iron-containing oxygenases.

 描述（适用提供）：非血清，含铁的氧酶参与了各种重要的重要过程，包括抗生素的生物合成（包括毒素和青霉素），脱氧核糖核苷酸的产生，脱氧核糖核苷酸的产生（DNA的关键构件），以及防止FERNON-FERTOR CEMNITIT（防止FERNON）（通过FERTRAINTIN）（通过FERNON）（通过FERRAINT）（通过）（通过FERRAINTIN）（通过FERRAINTIN）（通过FERRANIN）（通过FERRAIN）（通过）。了解氧酶如何使用活化的铁氧进行这些转化至关重要。尽管对铁氧和铁 - 过敏物种的作用进行了丰富的研究，但已知的光谱可访问的铁 - 苏耐氧化合物却很少。这是令人惊讶的，因为在几乎所有非血红素含氧酶的催化循环中提出了铁蛋白氧化物种。该提案的目的是产生与非血红素含铁氧酶相关的光谱易探针（III） - 舒张物种。这将通过为单核非血红素（III） - 舒张物种开发合成方法来实现。我们假设通过反应条件和配体设计特征的适当组合（包括配体碱度，空间体积和氢键供体能力），我们将能够生成第一个合成的单核非血清（III） - 舒张物种。我们还将将类似的设计原理应用于含有Fe（II）中心的双核前体的Fe（iii） - 舒张化合物的产生。合成的Fe（III） - 舒张化合物将以各种光谱法的特征进行全面特征，包括UV-VIS，XAS，Resonance Raman，EPR和Mössbauer光谱。这将允许建立对化合物的原代和次级协调球之间与铁 - 舒福氧种类的结构和电子特征之间的关系的理解。迄今为止，还没有完全表征非血红素铁氧化化合物，它以拉曼，EPR和Mössbauer光谱的结合，这是对田间理解的显着差距。实际上，与其他已知的超氧化物化合物（1043-1207 cm-1）相比，只有一种这种超氧化合物的特征是共振拉曼，而1310 cm-1的o-o拉伸频率异常高。还将探索合成的Fe（III） - 舒张化合物的反应性，以建立与电子和结构参数的反应性关系。总体而言，这项研究有可能变革地了解超氧化物中间体在非血红素含氧酶领域的作用。