Discovering Modular Catalysts for Selective Synthesis with Computation

在化学系化学催化项目的支持下，科罗拉多州立大学(CSU)的罗伯特·佩顿教授正在研究新的计算模型和工具，这些模型和工具将指导发现合成方法，以访问药物中常见的化学基序。佩顿实验室的目标是开发新的理论和模拟方法，以加速发现新的催化剂和新的反应，用于高度选择性地构建类药物有机分子。将创建自动化工作流程，通过识别可以由较小的分子构建块组装的模块化结构来加速催化剂的发现。科罗拉多州立大学参与的科学家们将通过与实验者进行新的机械性合作，拓宽他们的视野，从而使这项基础科学成为可能。研究团队将包括本科生和研究生研究人员，他们将学习与现代STEM(科学、技术、工程和数学)工作场所很好地结合在一起的各种技能。这些团队将开展外联工作，制作介绍参与该项目的人员和研究的视频内容。该团队将通过科罗拉多州的外联活动，如CSU演讲，吸引更广泛的公众。在这一奖项下，科罗拉多州立大学的罗伯特·佩顿教授和他的研究团队将为发现和优化高选择性催化剂开发新的计算工作流程。这项工作致力于解决三类不同的催化剂和配体的模块化和可调性：基于尿素和肽基序的氢键供体，用于过渡金属催化的亚磷酸盐和亚磷酰胺配体，以及三烷氧基离子。在每个应用领域，Paton实验室将与合成专家合作，开发以物理-有机化学为基础的新的机械和统计模型。研究小组将建立高通量计算工作流程，以获得大型催化剂和配位体库的空间和电子描述符，以及结合化学信息学、半经验计算和基于量子化学的分析的多步协议。这些研究方法的预期结果包括在催化的三个重要领域中的新的机理理解，使用高通量和低通量技术的基于结构的催化剂设计的原理的更广泛的理解，以及已经通过计算确定的实验验证的结构。这个项目背后的一个中心原则是，来自机理研究和过渡态建模的概念见解有可能在广泛意义上影响反应设计的新量化描述符和新概念的发展。将详细的理论理解转化为实用的计算工具，有可能在日益复杂的环境中加速试剂/催化剂的设计。该奖项反映了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。

With the support of the Chemical Catalysis program in the Division of Chemistry, Professor Robert Paton of Colorado State University (CSU) is studying new computational models and tools that will guide the discovery of synthetic methods to access chemical motifs commonly found in medicines. The Paton laboratory aims to develop new methods of theory and simulation to accelerate the discovery of new catalysts and new reactions for the highly selective construction of drug-like organic molecules. Automated workflows will be created to accelerate catalyst discovery by identifying modular structures that can be assembled from smaller molecular building blocks. This fundamental science will be enabled by new mechanistic collaborations with experimentalists that broaden the horizons of the participating scientists at Colorado State University. The research team, which will include undergraduate and postgraduate researchers, will learn a diverse array of skills well-aligned with the modern STEM (science, technology, engineering and mathematics) workplace. The teams will conduct outreach efforts to create video content introducing the people and research involved in this project. The team will engage the broader public through outreach events in Colorado, such as CSU Speaks.Under this award, Professor Robert Paton and his research team at Colorado State University will develop new computational workflows for the discovery and optimization of highly selective catalysts. This work seeks to address the modularity and tunability of three distinct catalyst and ligand classes: hydrogen-bond donors based on urea and peptidic motifs, phosphite and phosphoramidite ligands used in transition metal catalysis, and trialkyloxonium ions. In each application area, the Paton laboratory will develop new mechanistic and statistical models grounded in physical-organic chemistry in collaboration with synthetic experts. The research team will establish high-throughput computational workflows to obtain steric and electronic descriptors for large catalyst and ligand libraries, and multistep protocols combining cheminformatics, semi-empirical calculations, and quantum chemical-based analyses. The projected outcomes of these research approaches include new mechanistic understanding in three important areas of catalysis, a broader understanding of the principles of structure-based catalyst design using high- and low-throughput techniques, and experimentally validated structures that have been identified computationally. A central principle underlying this program is that conceptual insights from mechanistic studies and transition state modeling have the potential to impact the development of new quantitative descriptors and novel concepts for reaction design in a broad sense. Translating a detailed theoretical understanding into practical computational tools has the potential to accelerate reagent/catalyst design in increasingly complex settings.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.