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: 7524986
• 负责人: JAMES M MAYER
• 金额: $ 30.23万
• 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/7524986
• 关键词: Affect; Amines; Antioxidants; Area; Attention; Award; Biochemical Process; Biochemical Reaction; Biochemistry; Bioenergetics; Biological; Biological Models; Biological Process; Biology; Catalysis; Chemicals; Chemistry; Class; 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; Numbers; Object Attachment; Oxidants; Oxidation-Reduction; Phenols; Process; Protein Dynamics; Protons; Public Health; Quinones; Range; Rate; Reaction; Reactive Oxygen Species; Research; Role; Ruthenium; Series; Sulfur; Superoxide Dismutase; System; Temperature; Theoretical model; Vanadium; Vitamin B 12; Vitamin E; Work; ascorbate; base; benzoquinone; chemical reaction; cofactor; computer studies; cytochrome c oxidase; design; driving force; insight; metalloenzyme; oxidation; photosystem II; 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有一个基本的和可预测的理解。这种质子耦合电子转移(PCET)过程在生物学的许多领域都是至关重要的，从生物能量学到许多金属酶的催化循环，再到捕捉活性氧物种。这里提出的研究集中于一个质子和一个电子在单个动力学步骤中转移的反应，称为协同质子和电子转移(CPET)。其中一组项目旨在建立氢原子转移(HAT)反应的统一图景。这些过程包括一个电子和一个质子从一个施主到一个受主的协同转移。正在开发模型系统来开发HAT的一般原理，并具体了解铁-组氨酸辅助因子的反应活性，包括线粒体Bc1复合体中Rieske铁-硫簇对苯二酚的氧化以及双(组氨酸)连接的血红素的化学。第二组项目研究了“分离的CPET”过程，在这个过程中，电子和质子转移到不同的受体。这类反应很少受到关注，但很可能涉及广泛的生物氧化还原反应。研究得最好的例子是光系统II中酪氨酰-Z自由基的形成；提出了这一过程的模型。在这些领域中的每一个领域，一些系统对特定的生化反应进行建模，而另一些系统则被设计成探索一般原理。例如，拟议的苯酚基化合物氧化研究将探索骨架运动如何影响氢转移，这是目前关于酶催化起源的一个很大的争论问题。这些研究将提供与当前CPET理论治疗的联系，基于我们的论证，即一系列氢原子转移反应遵循马库斯理论。综合起来，这些研究将发展质子-电子耦合转移的原理，并对广泛的生物过程产生新的见解。这些发生在生物学中的化学过程的基本原理是生物医学进步的基础的一部分。例如，电子转移反应的详细知识已被证明在生物学上非常重要。拟议的工作旨在为涉及电子和质子耦合转移的反应建立同样有价值的理解。与公共健康相关：这个项目正在开发对一类化学过程的预测性理解，这种化学过程在生物学中广泛存在，但几乎没有得到研究：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各个领域的核心。对这些化学过程的基本理解是生物医学进步的基础的一部分。