Coupled Transfers of Electrons and Protons

电子和质子的耦合转移

• 批准号: 10330703
• 负责人: JAMES M MAYER
• 金额: $ 41.88万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10330703
• 关键词: Affect; Anthracenes; Antioxidants; Behavior; Biochemical Process; Biochemical Reaction; Bioenergetics; Biological Models; Biology; Carbon; Catalysis; Chemicals; Coupled; Electron Transport; Electrons; Enzymes; Family; Free Energy; Histidine; Hydrogen; Hydrogen Bonding; Location; Nature; Organic Chemistry; Oxidation-Reduction; Oxidoreductase; Phenols; Photosynthesis; Process; Property; Protons; Reaction; Reactive Oxygen Species; Research; Respiration; Ribonucleotide Reductase; Site; Surface; System; Transition Elements; Triad Acrylic Resin; Tyrosine; Vitamin B 12; base; biological systems; chemical reaction; cofactor; experimental study; insight; metalloenzyme; novel strategies; oxidation; particle; photosystem II; pyridine

PROJECT SUMMARY/ABSTRACT The proposed research will develop a conceptual and quantitative framework for proton-coupled electron transfer (PCET) processes, in which the proton and electron transfer in a single chemical step. Such reactions are key to a wide range of essential biochemical processes, including respiration, photosynthesis and other aspects of bioenergetics, catalysis in oxidoreductases and other metalloenzymes, and the behavior of reactive oxygen species and antioxidants. These chemical reactions vary from hydrogen atom transfer (HAT), in which the two particles move ‘together,’ to processes where the proton and electron move to (or come from) different locations (multiple-site concerted proton-electron transfers, MS-CPET). Building on our prior studies and the specific advances in the last period. this project will examine how the rates and selectivities of such reactions are controlled by factors beyond the thermochemistry. Many biochemical processes interconvert carbon-centered radicals and C–H bonds, yet some of their reactions have little if any precedent in standard organic chemistry. For example, isoergic and uphill H-transfer between carbon atoms are extremely slow in solution, yet such reactions are widely used by the enzyme families with radical-SAM and vitamin B-12 cofactors, often reversibly. There are few solution examples of MS-CPET reactions of C–H bonds, yet these are predicted to be used in various enzymes in biology. Experiments using both organic and transition metal model systems will probe the essential properties of these reactions. These will include (i) shortening the H-transfer distance; (ii) polar effects; and/or (iii) having asynchronous transfer of the electron and proton due to asymmetry of the reaction free energy surface. HAT and MS-CPET processes may involve these factors in different ways. The oxidations of O–H bonds in biological systems often occur by MS-CPET, with proton transfer to a hydrogen-bonded base coupled to long-distance electron transfer. Examples range from the tyrosine-histidine pair in photosystem II to the multiple tyrosines in ribonucleotide reductases. Our recent studies of anthracene- phenol-pyridine triads provide new approaches to disentangle the key parameters affecting these reactions, their intrinsic barriers, vibronic couplings, and the nature of the hydrogen bonds. These systems undergo very rapid photo-induced PCET, including the first example of PCET in the Marcus Inverted Region, and can be tuned with various substitutions. This is an excellent platform to investigate the key parameters of MS-CPET in hydrogen- bonded systems, which are common biochemical reactions. This project will construct a more comprehensive and quantitative understanding of the intrinsic properties of PCET that are relevant to a range of important biochemical processes. These fundamental insights about redox reactions of C–H and O–H bonds will help unravel how biology evolved to control difficult transformations.

项目概要/摘要 拟议的研究将为质子耦合电子开发一个概念和定量框架 转移（PCET）过程，其中质子和电子在单个化学步骤中转移。 是一系列重要生化过程的关键，包括呼吸、光合作用和其他 生物能学、氧化还原酶和其他金属酶的催化作用以及反应性的行为等方面 这些化学反应不同于氢原子转移（HAT），其中 两个粒子“一起”移动，质子和电子移动到（或来自）不同的过程 位置（多位点协同质子电子转移，MS-CPET）。 该项目将研究此类反应的速率和选择性。 受热化学以外的因素控制。 许多生化过程会以碳为中心的自由基和 C-H 键相互转化，但其中的一些过程 标准有机化学中几乎没有先例，例如等能氢转移和上坡氢转移。 碳原子之间的反应在溶液中极其缓慢，但此类反应被酶家族广泛使用 与自由基-SAM 和维生素 B-12 辅助因子一起，通常是可逆的 MS-CPET 的解决方案示例很少。 C-H 键的反应，但预计这些反应将用于生物学中的各种酶实验。 有机和过渡金属模型系统都将探讨这些反应的基本性质。 将包括 (i) 缩短 H 传输距离；(ii) 极性效应；和/或 (iii) 具有异步传输 HAT 和 MS-CPET 过程中由于反应自由能表面的不对称而产生的电子和质子。 可能以不同的方式涉及这些因素。 生物系统中 O-H 键的氧化通常通过 MS-CPET 发生，质子转移到 与长距离电子转移偶联的氢键碱基的例子包括酪氨酸-组氨酸。 光系统 II 与核糖核苷酸还原酶中的多个酪氨酸配对。 苯酚-吡啶三联体提供了新的方法来解开影响这些反应的关键参数，它们的 这些系统的内在振动耦合和氢键的性质发生得非常快。 光诱导的 PCET，包括马库斯倒置区域中 PCET 的第一个例子，并且可以通过 这是研究 MS-CPET 在氢中的关键参数的绝佳平台。 键合系统，这是常见的生化反应。 该项目将构建对其内在属性的更全面和定量的理解 PCET 与一系列重要的生化过程相关。 C-H 和 O-H 键的氧化还原反应将有助于揭示生物学如何进化以控制困难的转变。