Computational Studies of Selective C-H Functionalization Reactions

在这个由化学结构、动力学和机理B计划和化学催化计划资助的项目中，匹兹堡大学化学系的刘鹏教授正在应用计算工具研究催化碳氢键功能化反应。本研究的目标是使用密度泛函理论(DFT)和其他计算方法进行计算，以模拟催化反应路径，并研究控制反应活性和选择性的因素。这些计算研究将提供对过渡金属络合物和生物工程酶催化的各种碳氢键功能化反应的机理理解。此外，还将探索新的计算方法来研究催化剂-底物相互作用及其对反应结果的影响，包括在反应活性和选择性预测的回归模型中合理设计特定问题描述符的数据驱动方法。该项目的教育和推广计划旨在最大限度地发挥现代计算机技术的力量，如虚拟现实，以促进有机化学概念的学习和促进合成有机化学的研究。计算工具，特别是密度泛函理论(DFT)计算，已成为研究催化碳氢键功能化反应的机理、反应性和选择性的有力力量。该项目旨在探索三种新的计算策略，以提供稳健和有意义的见解，以了解催化剂对反应活性和选择性的影响的根源。刘鹏教授和他的研究团队将(1)应用能量分解分析计算来分析催化剂和底物之间的非共价相互作用，并使用环应变能来分析过渡态扭曲；(2)利用力学的洞察力来选择和设计用于预测回归模型的特定问题的描述符；以及(3)执行混合量子力学/分子力学和从头算分子动力学模拟来研究生物工程酶催化的立体选择性反应。他们预计，这些新的计算策略可以通过提供具有化学意义的、实用的见解来指导实验反应和催化剂开发，从而提高基于DFT的机械复杂催化系统的计算研究的能力。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

In this project, funded by the Chemical Structure, Dynamics & Mechanisms B Program and the Chemical Catalysis program, Professor Peng Liu of the Department of Chemistry at the University of Pittsburgh is applying computational tools to study catalytic carbon hydrogen bond functionalization reactions. The goal of this research is to perform computations using density functional theory (DFT) and other computational methods to model catalytic reaction pathways and investigate factors that control reactivity and selectivity. These computational studies will provide mechanistic understanding of various carbon hydrogen bond functionalization reactions catalyzed by transition metal complexes and bioengineered enzymes. In addition, new computational approaches to investigate catalyst–substrate interactions and their impacts on reaction outcomes, including data-driven approaches to rationally design problem-specific descriptors in regression models for reactivity and selectivity predictions, will be explored. This project's educational and outreach plan aims to maximize the power of modern computer technology, such as virtual reality, to enhance learning of organic chemistry concepts and to facilitate synthetic organic chemistry research.Computational tools, in particular, density functional theory (DFT) calculations, have emerged as a potent force to investigate the mechanisms, reactivity, and selectivity of catalytic carbon hydrogen bond functionalization reactions. This project aims to explore three types of new computational strategies to provide robust and meaningful insights into the origin of catalyst effects on reactivity and selectivity. Professor Peng Liu and his research team will (1) apply energy decomposition analysis calculations to analyze non-covalent interactions between catalyst and substrate and use ring strain energies to analyze transition state distortion; (2) use mechanistic insights to select and design problem-specific descriptors for predictive regression models; and (3) perform hybrid quantum mechanics/molecular mechanics and ab initio molecular dynamics simulations to study stereoselective reactions catalyzed by bioengineered enzymes. They expect that these new computational strategies can increase the capability of DFT-based computational studies of mechanically complex catalytic systems by offering chemically meaningful, practical insights to guide experimental reaction and catalyst developments.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.