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: 7937540
• 负责人: JAMES M MAYER
• 金额: $ 18.73万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7937540
• 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）：拟议的研究的目的是对电子传输和质子传递的过程进行基本和预测的理解。这种质子耦合电子转移（PCET）过程在许多生物学领域至关重要，从生物能学到众多金属酶的催化循环，再到活性氧的诱捕。此处提出的研究集中于一个反应，其中一个质子和一个电子转移在单个动力学步骤中，称为协同的质子和电子转移（CPET）。一组项目旨在建立氢原子转移（HAT）反应的统一图片。这些过程涉及电子和质子从单个供体转移到单个受体的过程。正在开发模型系统来开发HAT的一般原理，并特别了解铁 - 抗苷辅助因子的反应性，包括线粒体BC1复合物中Rieske Iron-Sulfur簇的喹酮氧化和BIS（组氨酸）粘性血液的化学。第二组项目检查了“分开的CPET”过程，其中电子和质子转移到不同受体。这种反应很少受到关注，但很可能参与了广泛的生物氧化还原反应。最有研究的例子是在光系统II中的酪体-Z自由基的形成。提出了此过程的模型。在这些领域的每个领域中，某些系统都会对特定的生化反应进行建模，而另一些系统旨在探测一般原则。例如，提出的对苯酚基化合物氧化的研究将探测框架运动如何影响氢转移，这是关于酶促催化起源的许多当前争论的问题。这些研究将与CPET的当前理论治疗相关，这是基于我们证明的一系列氢原子转移反应遵循Marcus理论的联系。这些研究汇集在一起​​，将开发耦合的质子电子转移的原理，并为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的基础的一部分。例如，事实证明，可用于电子传输反应的详细知识在生物学中非常重要。拟议的工作旨在为涉及电子和质子传输的反应建立类似的宝贵理解。公共卫生相关性：该项目正在对一类化学过程进行预测理解，这些化学过程在生物学中广泛但很少进行研究：电子和质子的耦合转移。这些化学反应对像生物能学和抗氧化剂的作用一样多样化。对这些化学过程的基本了解是建立生物医学进步的基础的一部分。