Unimolecular models to probe multiple-site concerted proton electron transfer

描述(申请人提供)：蛋白质中的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作用。当一个质子和一个电子同时运动时，整个转移通常比质子和电子单独运动或一次一个运动的情况更快和更有效。令人惊讶的是，即使当质子和电子朝相反的方向移动时，也能观察到这种效率的增加。因此，多位协同质子电子转移(MS-CPET)在生物系统中广泛存在，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在生物学上是普遍存在的，也是至关重要的，但其机制和特性却鲜为人知。拟议工作的目的是更好地了解MS-CPET的速度和机制是如何控制的。我们计划从酪氨酸出发设计和构建一系列模拟MS-CPET的分子。这些合成底物将含有释放质子和电子的苯酚、接收电子的光氧化剂和接收质子的碱，所有这些都是共价连接在一起的。这些合成系统将为快速研究MS-CPET提供一个独特的机会，而不受扩散的限制。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，单分子MS-CPET的速率将使用Marcus理论进行建模，以了解热力学推动力和分子结构等因素如何影响速率等动力学性质，以及反应是否涉及一个以上的能面。总体而言，单分子合成底物中的MS-CPET的研究将有助于对MS-CPET的基本和直观的理解，这将有助于深入了解基本的、复杂的生物系统。

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.