US-France Cooperative Research: Molecular Dynamics Simulation of Proton Transfer Reactions in Solution

该奖项将支持科罗拉多大学James Hynes博士和法国巴黎皮埃尔和玛丽居里大学液体物理理论实验室Daniel Borgis博士之间的合作研究。该项目的目标是发展一种改进的理论来处理溶液中的简单质子转移反应。蛋白质在溶液中的转移反应在化学中起着核心作用，特别是在酸碱化学和酶催化中。然而，目前还没有对这些反应及其速率进行全面的分子水平描述。在某种程度上，这是由于它们的特殊特性，其中包括量子质子穿过势垒而不是经典的热激活，以及周围极性溶剂分子与质子强耦合的基本参与。借助理论和计算机模拟技术的最新进展，研究人员提出在极性溶剂中进行模型质子转移反应的分子动力学计算机模拟。将计算反应速率，并确定溶剂极性和动力学的作用，以及某些分子振动。最初将采用简单而真实的模型来阐明基本的反应特征并建立模拟技术。然后，研究的系统将发展到更现实的系统，直接适用于实验研究。重点将放在可以指导实验解释的计算量（例如溶剂依赖性、同位素效应）上。该项目有望对质子转移反应进行详细的微观描述。提出的研究应该为理解这一重要的反应类别提供理论见解，也应该为探索溶剂极性和动力学对这些速率的影响的新实验提供动力。该项目将受益于这两位研究人员在这一快速发展的物理化学领域的互补专业知识。

This award will support collaborative research between Dr. James Hynes, University of Colorado, and Dr. Daniel Borgis, Laboratoire de Physique Theoretique des Liquides, University of Pierre and Marie Curie, Paris, France. The objective of the project is to develop an improved theory for treating simple proton transfer reactions in solution. Protein transfer reactions in solution play a central role in chemistry, in particular in acid-base chemistry and enzyme catalysis. However, no comprehensive molecular level description of such reactions and their rates yet exist. In part, this is due to their special character, which includes quantum proton tunnelling through a barrier rather than classical thermal activation over it, and an essential involvement of the surrounding polar solvent molecules strongly coupled to the proton. Aided by recent advances in theoretical and computer simulation techniques, the investigators propose to perform molecular dynamics computer simulation of model proton transfer reactions in polar solvents. Reaction rates will be calculated and the role of solvent polarity and dynamics, and of certain molecular vibrations, will be determined. Simple yet realistic models will be initially employed to clarify the essential reaction features and to establish the simulation techniques. The systems studied will then progress to even more realistic systems directly susceptible to experimental investigation. Emphasis will be placed on calculating quantities (e.g. solvent dependence, isotope effects) which can guide the interpretation of experiments. A detailed microscopic description of proton transfer reactions is expected to result from the project. The proposed study should provide theoretical insight into understanding this important reaction class and also should provide an impetus for new experiments to probe the influence on these rates of solvent polarity and dynamics. The project will benefit for the complementary expertise of the two investigators in this rapidly developing area of physical chemistry.