GOALI: Cooperative Homogeneous-Heterogeneous Catalysis for Hydrogen Isotope Labeling of Pharmaceuticals

In this project, Professor Long Luo of the Department of Chemistry at the University of Utah is developing new ways to place special forms of hydrogen, known as deuterium and tritium isotopes, into pharmaceutical molecules. Compounds containing these isotopes are essential tools for tracking how medicines move through the body, measuring how drugs break down, and improving the safety and effectiveness of future therapies. Current methods for adding these isotopes are often slow, expensive, or limited to only certain types of molecules. This research will create faster and more versatile labeling strategies by combining two different catalytic approaches that work together to selectively modify complex drug molecules at late stages of synthesis. The broader impacts of the project include accelerating drug discovery and development, reducing the cost and time needed to produce labeled pharmaceuticals, and supporting advances in biomedical and chemical research using computational modeling tools including machine learning. The project will also provide interdisciplinary training for graduate students and postdoctoral researchers through collaborations between the University of Utah and Merck, while expanding public engagement with science through outreach and educational activities. This research aims to establish cooperative homogeneous–heterogeneous catalytic platforms for hydrogen isotope exchange (HIE) in pharmaceuticals by integrating photocatalysis, transition-metal catalysis, materials chemistry, and mechanistic analysis. The first objective focuses on enhancing surface-mediated hydrogen atom transfer pathways using cadmium sulfide quantum-dot gel photocatalysts with tailored crystal structures and metal-cation additives to improve deuterium and tritium incorporation efficiency. The second objective investigates the controlled in situ formation of palladium nanoparticles during homogeneous Pd catalysis to unlock complementary dual C–H activation pathways for multisite isotope labeling with tunable site selectivity. Through mechanistic studies, spectroscopy, surface analysis, computational modeling and machine learning, the project will generate fundamental insight into the interplay between homogeneous and heterogeneous catalysis in HIE chemistry while delivering practical isotope-labeling methods for pharmaceutical applications. 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.