Investigating the mechanism of proton translocation in solution: from small chemical systems to biomolecules

这项建议概述的主要研究主题是用计算方法研究水溶液中质子转移反应的机理。这些过程在许多化学和生化转化中起着重要作用，包括酸碱反应、酶催化、底物结合和能量转导。至少二十年来，人们一直在积极地研究散装水中、水与疏水介质之间的界面上以及与生物相关的体系中的质子转移反应。然而，随着最近超快、时间分辨振动光谱技术的出现，上述质子转移过程第一次可以用相关的空间和时间分辨率来直接探测。这为计算化学打开了新的机会，有助于促进我们对质子转移反应的基本理解。 本研究计划的一个关键目标是改进现有的计算方法，以补充上述光谱学技术。在这方面，我们将提出一种新的方法，使我们能够执行第一性原理分子动力学计算，这些计算可以与最近报道的一系列最先进的飞秒分辨UV泵/中红外探测器酸碱中和实验相关。这些理论研究的一个重要目标将是确定在水中包括酸碱中和的基本步骤，但由此获得的信息也将与表面和界面的过程相关。 对大块水的3d氢键网络中质子转移的研究将得到核量子效应的研究的补充。后一个项目将涉及调整和发展现有的计算方法，使人们能够计算和解释第一原理、热力学和动力学的同位素效应。

The major theme of research outlined in this proposal is the investigation of the mechanism of proton transfer reactions in aqueous solutions using computational approaches. These processes play a fundamental role in numerous chemical and biochemical transformations, including acid-base reactions, enzyme catalysis, substrate binding and energy transduction. Theoretical investigations of proton transfer reactions in bulk water, at the interface between aqueous and hydrophobic media, as well as in biologically-relevant systems have been actively pursued for at least two decades. However, with the recent advent of ultrafast, time-resolved vibration spectroscopy techniques, the aforementioned proton transfer processes can for the first time be directly probed with the relevant space and time resolution. This opens new opportunities for computational chemistry to contribute to the advancement of our fundamental understanding of proton transfer reactions. A key objective of the present research program is to improve the existing arsenal of computational methods that can complement the aforementioned spectroscopy techniques. In this vein a novel methodology will be presented, which allows us to perform first-principles molecular dynamics calculations that can be related to a recently reported series of state-of-the-art, femtosecond-resolved UV pump/mid-IR probe acid-base neutralization experiments. An important goal of these theoretical studies will be to establish the elementary steps comprising acid-base neutralization in water, but the information thus obtained will also be relevant to processes at surfaces and interfaces. The investigation of proton translocation in the 3D H-bond network of bulk water will be complemented by a study of nuclear quantum effects. The latter project will involve adapting and developing existing computational methodologies that allow one to compute and interpret first-principles thermodynamic and kinetic isotope effects.