Discovering Modular Catalysts for Selective Synthesis with Computation

在化学部化学催化计划的支持下，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合成方法的发现，以获得药物中常见的化学基序。Paton实验室旨在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，用于高选择性地构建药物样有机分子。将创建自动化工作流程，通过识别可以从较小分子构建块组装的模块化结构来加速催化剂发现。这一基础科学将通过与实验学家的新机械合作来实现，这些合作拓宽了科罗拉多州立大学参与科学家的视野。该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）工作场所保持一致的各种技能。这些小组将开展外联工作，制作视频内容，介绍参与该项目的人员和研究。该团队将通过在科罗拉多的外联活动，如CSU Speaks，吸引更广泛的公众参与。根据该奖项，科罗拉多州立大学的Robert Paton教授和他的研究团队将开发新的计算工作流程，用于发现和优化高选择性催化剂。这项工作旨在解决三个不同的催化剂和配体类的模块性和可调性：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酯和亚磷酰胺配体，和三烷基氧鎓离子。在每个应用领域，Paton实验室将与合成专家合作开发基于物理有机化学的新的机械和统计模型。研究团队将建立高通量计算工作流程，以获得大型催化剂和配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方案。这些研究方法的预计成果包括在催化的三个重要领域的新的机理理解，更广泛地理解基于结构的催化剂设计的原则，使用高通量和低通量技术，并通过实验验证的结构，已确定计算。该计划的核心原则是，从机理研究和过渡态建模的概念见解有可能影响新的定量描述符和新概念的发展，反应设计在广义上。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知识价值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.