Understanding Coupled Transfers of Electrons and Protons Relevant to Biological C

描述（由申请人提供）：拟议研究的目标是发展对电子转移和质子转移耦合过程的基本和预测性理解。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，从生物能学到许多金属酶的催化循环，再到活性氧的捕获。本文提出的研究集中在一个质子和一个电子在一个动力学步骤中转移的反应，称为协调质子和电子转移（CPET）。其中一组项目旨在建立氢原子转移（HAT）反应的统一图像。这是一个电子和质子从单一供体向单一受体协调转移的过程。目前正在开发模型系统，以发展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复合体中Rieske铁-硫簇的醌氧化和组氨酸连接血红素的化学反应。第二组项目研究“分离CPET”过程，其中电子和质子转移到不同的受体。这些反应很少受到关注，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tyroyl - z自由基的形成；提出了这一过程的模型。在这些领域中，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，提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，这是目前关于酶催化起源的争论的一个问题。这些研究将在我们证明一系列氢原子转移反应遵循马库斯理论的基础上，为当前CPET的理论处理提供联系。汇集在一起，这些研究将发展耦合质子-电子转移的原理，并对广泛的生物过程产生新的见解。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中是非常重要的。这项工作旨在为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。公共卫生相关性：该项目正在发展对一类化学过程的预测性理解，这类化学过程在生物学中广泛发生，但很少得到研究：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多种领域的核心。对这些化学过程的基本理解是生物医学进步的基础之一。

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.