Unimolecular models to probe multiple-site concerted proton electron transfer

探测多位点协同质子电子转移的单分子模型

• 批准号: 8956321
• 负责人: Miriam A Bowring
• 金额: $ 4.93万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-28 至 2016-08-01
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8956321
• 关键词: Address; Affect; Age; Amyotrophic Lateral Sclerosis; Biochemical Reaction; Biological Models; Biological Process; Biology; Cell Respiration; Complex; Data; Data Collection; Development; Diffusion; Disease; Electron Transport; Electrons; Equation; Fluorescence; Foundations; Human body; Hydroquinones; Isotopes; Kinetics; Lasers; Measurement; Measures; Mitochondria; Mitochondrial Myopathies; Modeling; Molecular Structure; Movement; Nature; One-Step dentin bonding system; Oxidation-Reduction; Phenols; Photons; Photosynthesis; Physiologic pulse; Process; Property; Proteins; Protons; Reaction; Research; Respiratory Chain; Series; Site; Solvents; Structure; Surface; System; Temperature; Testing; Thermodynamics; Time; Tyrosine; Variant; Wolfram Syndrome; Work; base; biological systems; cofactor; complex biological systems; design; driving force; hydroquinone; improved; innovation; insight; interest; mathematical analysis; oxidation; photosystem II; physical property; public health relevance; theories

DESCRIPTION (provided by applicant): The movement of protons and electrons in proteins drives many essential processes in biology, including photosynthesis and cellular respiration. When one proton and one electron move simultaneously, the overall transfer is usually faster and more efficient than cases where protons and electrons move alone or one at a time. Surprisingly, this increased efficiency is observed even when the proton and electron move in opposite directions. For this reason, multiple-site concerted proton electron transfer (MS-CPET) is prevalent in biological systems, for instance in tyrosine oxidation in photosystem II and in hydroquinone oxidation as part of mitochondrial respiratory chains. Even though MS-CPET is biologically ubiquitous and crucial, its mechanism and properties are poorly understood. The aim of the proposed work is to develop a better understanding of how the rate and mechanism of MS-CPET are controlled. We propose to design and build a series of molecules that mimic MS-CPET from tyrosine. These synthetic substrates will contain a phenol to release the proton and electron, a photooxidant to receive the electron, and a base to receive the proton, all covalently tethered together. The synthetic systems will provide a unique opportunity to study MS-CPET at fast rates not limited by diffusion. The rates of MS- CPET will be measured by fluorescence quenching of the excited photooxidant moiety of the substrate. The rates for unimolecular MS-CPET will then be modeled using Marcus theory in order to understand how factors including thermodynamic driving force and molecular structure affect kinetic properties such as rate and whether the reaction involves more than one energy surface. Overall, the study of MS-CPET in unimolecular synthetic substrates will allow for the development of a fundamental and intuitive understanding of MS-CPET, which will provide insight into essential, complex biological systems.

描述（由申请人提供）：蛋白质中质子和电子的运动驱动生物学中的许多基本过程，包括光合作用和细胞呼吸。当一个质子和一个电子同时移动时，整体转移通常比质子和电子单独移动或一次移动一个的情况更快、更有效。令人惊讶的是，即使质子和电子沿相反方向移动，也能观察到效率的提高。因此，多位点协同质子电子转移 (MS-CPET) 在生物系统中很普遍，例如光系统 II 中的酪氨酸氧化和作为线粒体呼吸链一部分的对苯二酚氧化。尽管 MS-CPET 在生物学上无处不在且至关重要，但其机制和特性却知之甚少。拟议工作的目的是更好地了解 MS-CPET 的速率和机制是如何控制的。我们建议设计和构建一系列模仿酪氨酸 MS-CPET 的分子。这些合成底物将含有用于释放质子和电子的苯酚、用于接收电子的光氧化剂以及用于接收质子的碱，所有这些都共价连接在一起。该合成系统将为不受扩散限制的快速研究 MS-CPET 提供独特的机会。 MS-CPET 的速率将通过底物的激发光氧化剂部分的荧光猝灭来测量。然后，将使用马库斯理论对单分子 MS-CPET 的速率进行建模，以便了解热力学驱动力和分子结构等因素如何影响速率等动力学特性，以及反应是否涉及多个能量表面。总体而言，对单分子合成底物中 MS-CPET 的研究将有助于对 MS-CPET 产生基本且直观的理解，从而深入了解重要的复杂生物系统。