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猝灭方法 描述了高氧化态氧桥二铁酶模拟。 具体来说，可溶性甲烷单加氧酶 (MMO) 和 I 类酶 核糖核苷酸还原酶 (RR) 通过二铁 (IV) (MMO) 进行或 铁(III)-铁(IV) (RR)中间体在其催化的关键时刻 循环。如此不稳定的高氧化态很难在模型中实现 复合物。对相关生物化学进行了简要回顾，然后是合成 和设计光化学策略以在必要的条件下产生二铁中心 氧化态。一种广泛表征的氧键二铁络合物是 两端共价连接到经过充分研究的钌或铼 具有长寿命三重激发态的荧光团。电子励磁 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 可以通过时间分辨激光吸收来监测铁 (IV) 物质 光谱学。在另外的实验中，酶底物或底物 添加类似物，并表征它们的氧化产物（如果有）。 描述了对照实验以确认底物反应性确实 源自铁(IV)。该战略如果成功，将允许 FeIV FeIV 或 FeIII FeIV 络合物反应性的定量描述 可氧化底物，可直接应用于生物化学研究 氧化二铁酶。其中的想法适用于铁酶，但扩展到 其他金属也是如此。