NSF Award
2400056
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.<br/><br/>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.<br/><br/>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.
