Understanding Coupled Transfers of Electrons and Protons Relevant to Biological C

了解与生物 C 相关的电子和质子的耦合转移

• 批准号: 7677910
• 负责人: JAMES M MAYER
• 金额: $ 31.53万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-02-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7677910
• 关键词: Affect; Amines; Antioxidants; Area; Attention; Award; Biochemical Process; Biochemical Reaction; Biochemistry; Bioenergetics; Biological; Biological Models; Biological Process; Biology; Catalysis; Chemicals; Chemistry; Cleaved cell; Cobalt; Collaborations; Complex; Coupled; Coupling; Cytochromes; Dependence; Electron Transport; Electronics; Electrons; Enzymes; Foundations; Goals; Heme; Histidine; Hydrogen; Hydrogen Bonding; Iron; Isotopes; Kinetics; Knowledge; Measures; Metalloproteins; Metals; Mitochondria; Modeling; Motion; Oxidants; Oxidation-Reduction; Phenols; Process; Protein Dynamics; Protons; Quinones; Reaction; Reactive Oxygen Species; Research; Role; Ruthenium; Series; Sulfur; Superoxide Dismutase; System; Temperature; Theoretical model; Vanadium; Vitamin B 12; Vitamin E; Work; ascorbate; base; biological systems; chemical reaction; cofactor; computer studies; cytochrome c oxidase; design; driving force; insight; metalloenzyme; oxidation; photosystem II; public health relevance; reaction rate; research study; theories

DESCRIPTION (provided by applicant): The goal of the proposed research is to develop a fundamental and predictive understanding of processes in which electron transfer and proton transfer are coupled. Such proton-coupled electron transfer (PCET) processes are critical in many areas of biology, from bioenergetics to the catalytic cycles of numerous metalloenzymes, to the trapping of reactive oxygen species. The studies proposed here focus on reactions in which one proton and one electron transfer in a single kinetic step, termed concerted proton and electron transfer (CPET). One set of projects are designed to build a unified picture of hydrogen atom transfer (HAT) reactions. These are processes which involve the concerted transfer of an electron and a proton from a single donor to a single acceptor. Model systems are being developed to develop the general principles of HAT and to understand specifically the reactivity of iron-histidine cofactors, including quinone oxidation by the Rieske iron-sulfur cluster in the mitochondrial bc1 complex and the chemistry of bis(histidine)-ligated hemes. A second set of projects examine `separated CPET' processes, in which the electron and proton transfer to different acceptors. Such reactions have received little attention but are likely to be involved in a wide range of biological redox reactions. The best-studied example is the formation of the tyrosyl-Z radical in photosystem II; models for this process are proposed. In each of these areas, some systems model specific biochemical reactions while others are designed to probe general principles. For example, the proposed studies of oxidation of phenol-base compounds will probe how framework motions affect hydrogen transfers, an issue of much current debate regarding the origins of enzymatic catalysis. These studies will provide connections to current theoretical treatments of CPET, building on our demonstration that a range of hydrogen atom transfer reactions follow Marcus theory. Brought together, these studies will develop the principles of coupled proton-electron transfers and produce new insights into a wide range of biological processes. Such fundamental principles of chemical processes that occur in biology are part of the foundation for biomedical advances. For instance, the detailed knowledge available for electron transfer reactions has proven to be of great importance in biology. The work proposed aims to build a similarly valuable understanding for reactions that involve coupled transfers of electrons and protons. PUBLIC HEALTH RELEVANCE: This project is developing a predictive understanding of a class of chemical processes that occur widely in biology but have received little study: coupled transfers of electrons and protons. These chemical reactions are central to fields as diverse as bioenergetics and the action of antioxidants. A fundamental understanding of these chemical processes is a part of the foundation on which biomedical advances will be built.

描述（由申请人提供）：拟议研究的目标是对电子转移和质子转移耦合的过程形成基本和预测性的理解。这种质子耦合电子转移（PCET）过程在生物学的许多领域都至关重要，从生物能学到众多金属酶的催化循环，再到活性氧的捕获。这里提出的研究重点是在一个动力学步骤中一个质子和一个电子转移的反应，称为协同质子和电子转移（CPET）。一组项目旨在构建氢原子转移（HAT）反应的统一图景。这些过程涉及电子和质子从单个供体到单个受体的协同转移。正在开发模型系统，以开发 HAT 的一般原理，并具体了解铁-组氨酸辅助因子的反应性，包括线粒体 bc1 复合物中 Rieske 铁-硫簇对醌的氧化以及双（组氨酸）连接的血红素的化学。第二组项目研究“分离的 CPET”过程，其中电子和质子转移到不同的受体。此类反应很少受到关注，但可能涉及广泛的生物氧化还原反应。研究最好的例子是光系统 II 中酪氨酰-Z 自由基的形成；提出了该过程的模型。在每个领域，一些系统模拟特定的生化反应，而另一些系统则旨在探索一般原理。例如，拟议的酚基化合物氧化研究将探讨框架运动如何影响氢转移，这是当前关于酶催化起源的争论的一个问题。这些研究将提供与当前 CPET 理论治疗的联系，以我们证明一系列氢原子转移反应遵循马库斯理论为基础。这些研究汇集在一起​​，将开发耦合质子电子转移的原理，并对广泛的生物过程产生新的见解。生物学中发生的化学过程的基本原理是生物医学进步基础的一部分。例如，电子转移反应的详细知识已被证明在生物学中非常重要。拟议的工作旨在对涉及电子和质子耦合转移的反应建立类似的有价值的理解。公共健康相关性：该项目正在开发对生物学中广泛发生但很少研究的一类化学过程的预测性理解：电子和质子的耦合转移。这些化学反应是生物能量学和抗氧化剂作用等多种领域的核心。对这些化学过程的基本了解是生物医学进步的基础的一部分。