Photogeneration of High-Valent Diiron Enzyme Mimics

高价二铁酶模拟物的光生作用

• 批准号: 6487181
• 负责人: Thomas G. Gray
• 金额: $ 3.66万
• 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/6487181
• 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淬火方法， 描述了高氧化态氧代桥连二铁酶模拟。 具体地，酶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）中间体在其催化过程中的关键接合点 自行车.这种不稳定的高氧化态是很难实现的模型 配合物简要回顾了相关的生物化学， 和光化学策略，旨在产生二铁中心， 氧化态一种广泛表征的氧键合二铁络合物， 在两端共价连接到研究充分的钌或钌上， 具有长寿命的三重激发态的发光团。电子激发 的光敏部分开始氧化还原级联，其中外部受体是 还原，并且一个或两个铁位点被氧化成铁（IV）。的命运 铁（IV）物种可以监测与时间分辨激光吸收 谱在另外的实验中，酶底物或底物 加入类似物，如果有的话，表征它们的氧化产物。 控制实验被描述以确认底物反应性确实 铁（IV）。该战略如果成功，将允许 FeIV、FeIV或FeIII、FeIV络合物对 可氧化底物，直接适用于生物化学研究， 氧化二铁酶其中的思想适用于铁酶，但扩展到 其他金属也是。