Unimolecular models to probe multiple-site concerted proton electron transfer

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，即使当质子和电子沿相反方向移动时，也观察到这种增加的效率。因此，多位点协同质子电子转移（MS-CPET）在生物系统中普遍存在，例如在光系统II中的酪氨酸氧化和作为线粒体呼吸链一部分的氢醌氧化中。尽管MS-CPET在生物学上普遍存在且至关重要，但其机制和性质仍知之甚少。所提出的工作的目的是开发一个更好地了解如何控制MS-CPET的速率和机制。我们建议设计和构建一系列分子，从酪氨酸模拟MS-CPET。这些合成底物将包含释放质子和电子的苯酚，接收电子的光氧化剂，以及接收质子的碱，所有这些都共价连接在一起。合成系统将提供一个独特的机会，研究MS-CPET在快速不受扩散的限制。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Marcus理论对单分子MS-CPET的速率进行建模，以了解包括热力学驱动力和分子结构在内的因素如何影响动力学性质，例如速率以及反应是否涉及一个以上的能量表面。总的来说，在单分子合成底物中的MS-CPET的研究将允许对MS-CPET的基本和直观的理解的发展，这将提供对基本的、复杂的生物系统的洞察。

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.