GOALI: Developing New Hydrogen Isotope Exchange Strategies for Isotope Labelling of Pharmaceuticals

About This Grant

With the support of the Chemical Catalysis and Chemical Synthesis programs in the Division of Chemistry, Dr. Long Luo of Wayne State University and Dr. Jingwei Li of Merck & Co are developing new methods for hydrogen isotope labeling of pharmaceuticals. With the use of heterogeneous photocatalysis and electrochemistry, the Luo team seeks to establish improved chemical methods for labeling pharmaceuticals and their precursors with either multiple hydrogen isotope atoms or selective labeling at specific sites. Hydrogen isotope incorporation at multiple sites will improve the diagnostic signals for detecting and quantifying drugs and drug metabolites in preclinical and clinical studies. In addition, the site-selective labeling will provide new tools for synthesizing drugs containing deuterium. This integrated university/industry research program will provide unique learning and training experience for graduate and undergraduate students, preparing this “next generation workforce” for a future in which multi- and inter-disciplinary research is the norm. Under this GOALI award, Dr. Long Luo of Wayne State University and Dr. Jingwei Li of Merck & Co will engage in synthetic methodology research toward new approaches to hydrogen isotope labeling of pharmaceuticals. The team will focus on: (1) developing heterogeneous photocatalysts to enable additional hydrogen isotope exchange sites relative to the conventional molecular photocatalysts utilizing their unique catalyst-substrate interface (For example, efforts to simultaneously activate benzylic and α-amine sites using metal chalcogenide quantum dot photocatalysts) and (2) developing electrochemical methods to achieve the hydrogen isotope exchange site selectivity among sites with similar chemical reactivity such as α-amino C-H bonds, utilizing the time-resolved redox environment provided by electrochemistry to control the reaction kinetics at different sites. The team will work to answer the following important scientific questions: (1) how can one achieve efficient hydrogen atom transfer via the heterogenous photocatalyst-substrate interface during a hydrogen isotope exchange reaction? (2) how can one control the reaction pathways of hydrogen isotope exchange reactions by tuning the electrochemical redox environment? The impact of this project will not be limited to the field of hydrogen isotope labeling of pharmaceuticals but will likely also provide new strategies for controlling reaction pathways in general for photocatalytic and electrochemical reactions. 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.