Photogeneration of High-Valent Diiron Enzyme Mimics

高价二铁酶模拟物的光生作用

• 批准号: 6626180
• 负责人: Thomas G. Gray
• 金额: $ 4.16万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-03-11 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6626180
• 关键词: X ray crystallography; atomic absorption spectrometry; biomimetics; biotechnology; catalyst; chemical synthesis; cofactor; electrochemistry; electron transport; emission spectrometry; enzyme substrate; iron metabolism; iron sulfur protein; mass spectrometry; methane monooxygenase; nuclear magnetic resonance spectroscopy; oxidation; photochemistry; postdoctoral investigator; ribonucleotide reductase; synthetic enzyme

DESCRIPTION: (provided by applicant) A novel, laser flash-quench approach to high oxidation state oxo-bridged diiron enzyme mimicry is described. Specifically, the enzymes soluble methane monooxygenase (MMO) and class I ribonucleotide reductase (RR) proceed through diiron(IV) (MMO) or iron(III)-iron(IV) (RR) intermediates at critical junctures in their catalytic cycles. Such unstably high oxidation states are difficult to achieve in model complexes. A brief review of relevant biochemistry is followed by the synthetic and photochemical strategy devised to generate diiron centers in the requisite oxidation states. An extensively characterized oxo-bondged diferric complex is tethered covalently, at both ends, to well-studied ruthenium or rhenium lumophores possessing long-lived triplet excited states. Electronic excitation of the photoactive part begins a redox cascade, where an external acceptor is reduced and one or both ferric sites are oxidized to iron(IV). The fate of the iron(IV) species can be monitored with time-resolved laser absorption spectroscopy. In additional experiments, enzyme substrates or substrate analogues are added, and their oxidation products, if any, are characterized. Control experiments are described to confirm that substrate reactivity indeed originates from iron(IV). The strategy, if successful, would allow a quantitative description of FeIV FeIV or FeIII FeIV -complex reactivity towards oxidizable substrates, with direct applicability to biochemical research in oxodiiron enzymes. The ideas within are applied to iron enzymes, but extend to other metals as well.

描述：(由申请人提供)一种新颖的激光闪光猝灭方法 描述了高氧化态氧桥联双铁酶的模拟。 具体地说，可溶性甲烷单加氧酶(MMO)和I类 核糖核苷酸还原酶(RR)通过二铁(IV)(MMO)或 铁(III)-铁(IV)(RR)催化关键节点中间体 循环。这种不稳定的高氧化态很难在模型中实现 复合体。简要回顾了相关的生物化学，然后是合成的 以及设计的光化学策略，以在必要的条件下产生双铁中心 氧化态。一种广泛表征的氧键二铁络合物是 在两端共价连接到经过充分研究的Ru或Re上 具有长寿命三重态激发态的发光体。电子励磁 光活性部分开始氧化还原级联，其中外部受体 还原，一个或两个铁中心被氧化成铁(IV)。美国人的命运 铁(IV)物种可用时间分辨激光吸收进行监测 光谱学。在额外的实验中，酶底物或底物 加入类似物，并对其氧化产物(如果有的话)进行表征。 描述了对照实验，以证实底物的反应性确实 来源于铁(IV)。这一战略如果成功，将允许 FeIV FeIV或FeIII FeIV的定量描述-FeIV的络合物反应性 可氧化底物，直接适用于生物化学研究 氧化二铁酶。里面的想法适用于铁酶，但扩展到 其他金属也是如此。