Collaborative Research: Leveraging Spatial Constraints to Tailor the Free Energy Landscapes of Heterogenized Molecular Catalysts

Johns Hopkins University, Baltimore MD

Investigators

Abstract

With the support of the Chemical Catalysis program in the Division of Chemistry, Professor Jason Bates of the University of Virginia and Professor Brandon Bukowski of Johns Hopkins University are studying new approaches to improve the productivity and durability of molecular catalysts through supporting them on nanostructured solids. These fundamental approaches will enable more efficient, flexible, and sustainable pharmaceutical manufacturing processes by developing catalysts that are not only more active, but also longer lasting and safer to use in continuous flow systems. These advances will help facilitate a transition to a distributed manufacturing model that can respond quickly to shifting or localized demand. Combined experimental and computational studies in this project will focus on asymmetric hydrogenation, which is an important catalytic reaction in pharmaceutical production, and computational methods and models will be made broadly accessible to the community. Educational and outreach efforts will train undergraduate and graduate students in cutting-edge experimental and machine learning techniques and engage high school students through hands-on science programs. The team will build strong inter-institutional collaborations through regular student exchanges, helping to prepare the next generation of scientists and engineers. With the support of the Chemical Catalysis program in the Division of Chemistry, Professor Jason Bates of the University of Virginia and Professor Brandon Bukowski of Johns Hopkins University are studying the impact of solid support structure on heterogenized asymmetric hydrogenation catalysts. By integrating experimental and theoretical approaches, the project will establish a materials-driven approach to molecular catalyst design, leveraging the structural features of zeolites as tunable, non-coordinating solid supports for cationic complexes. Hierarchical and nanosheet zeolite structures will be targeted to exploit partial confinement at zeolite nanopore mouths while maintaining substrate accessibility. The team will combine synthesis, spectroscopic characterization, kinetic analysis, and ab initio microkinetic modeling to systematically explore how support structure influences catalytic behavior. These insights will inform the development of predictive computational tools to guide the design of zeolite–ligand pairs across a broad chemical space, to reshape reaction energy landscapes and suppress off-cycle deactivation pathways. Integrating advances from zeolite synthesis, molecular catalysis, and computational catalysis, this project offers a blueprint for discovering supported catalysts that outperform their homogeneous analogues. The experimental and computational approaches will be extensible beyond asymmetric hydrogenations, offering the potential to improve the reactivity of other key reactions facilitated by molecular catalysts, such as cross-couplings and selective oxidations. 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.