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.

项目摘要/摘要 拟议的研究将为质子耦合电子建立一个概念和定量的框架。 转移(PCET)过程，在此过程中，质子和电子在单个化学步骤中转移。这样的反应 是广泛的基本生化过程的关键，包括呼吸作用、光合作用和其他 生物能量学，氧化还原酶和其他金属酶的催化作用，以及反应的行为 氧气和抗氧化剂。这些化学反应与氢原子转移(HAT)不同，在HAT中 这两个粒子一起运动，进入质子和电子运动到(或来自)不同的过程。 地点(多位点协同质子-电子转移，MS-CPET)。建立在我们之前的研究和 上一阶段的具体进展。这个项目将考察这种反应的速度和选择性 受热化学以外的因素控制。 许多生化过程相互转化碳中心的自由基和C-H键，但它们的一些 在标准的有机化学中，反应几乎没有先例。例如，等能的和上坡的氢转移 碳原子之间的反应在溶液中非常缓慢，但这种反应被酶家族广泛使用 含有自由基-SAM和维生素B-12的辅因子，通常是可逆的。MS-CPET的解决方案例子很少 C-H键的反应，然而这些反应被预测用于生物学中的各种酶。使用以下工具进行实验 有机和过渡金属模型系统都将探索这些反应的基本性质。这些 将包括(I)缩短氢转移距离；(Ii)极性效应；和/或(Iii)具有 由于反应自由能表面的不对称性而产生的电子和质子。HAT和MS-CPET工艺 可能会以不同的方式涉及这些因素。 生物体系中O-H键的氧化通常是通过MS-CPET发生的，质子转移到 氢键碱基与长距离电子转移相耦合。例子包括酪氨酸-组氨酸 光系统II中的多个酪氨酸与核苷酸还原酶中的多个酪氨酸配对。我们最近对菲的研究- 苯酚-吡啶三元化合物提供了新的方法来解开影响这些反应的关键参数，他们的 本征势垒、振动耦合和氢键的性质。这些系统经历了非常迅速的 光诱导的PCET，包括第一个在Marcus倒区的PCET的例子，并且可以用 各种替换。这是一个研究氢气中MS-CPET关键参数的极好平台。 键合系统，这是常见的生化反应。 这个项目将构建对内在属性的更全面和更定量的理解 与一系列重要的生化过程相关的多氯联苯。关于这些基本的见解 C-H和O-H键的氧化还原反应将有助于揭示生物是如何进化来控制困难的转变的。