Hydrogen Isotope Labeling of Pharmaceuticals via Dual Hydrogen Isotope Exchange Pathways

Isotopic labeling is a powerful technique extensively used in the pharmaceutical industry. By tracking isotope-labeled molecules, researchers gain unique and invaluable insights 20 into the pharmacokinetics and pharmacodynamics of new drug candidates. Hydrogen isotope labeling is particularly important as hydrogen is ubiquitous in organic molecules in biological systems, and it can be introduced effectively through late-stage hydrogen isotope exchange (HIE). However, most of the current methods require directing groups, which leaves a gap for simultaneously labeling multiple sites with varying types of C-H bonds in the molecules. Herein, we demonstrate a heterogeneous photocatalytic system that proceeds via a unique dual HIE pathway mechanism—one occurs in the reaction solution and the other on the catalytic surface—to address it. This protocol has been successfully applied to the high incorporation of deuterium and tritium in 26 commercially available drugs.