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

本提案中概述的主要研究主题是利用计算方法研究水溶液中质子转移反应的机制。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。质子转移反应在散装水中的理论研究，在水和疏水介质之间的界面，以及在生物相关系统中已经积极地进行了至少二十年。然而，随着超快、时间分辨振动光谱技术的出现，上述质子转移过程首次可以用相关的空间和时间分辨率直接探测。这为计算化学提供了新的机会，有助于提高我们对质子转移反应的基本理解。

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.