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Unlocking the potential of hydrogen deuterium exchange via an iterative continuous-flow deuteration process

Year: 2025

Type: article

Abstract: Labelled compounds bearing hydrogen isotopes are keystones in diverse areas constituting a multi-billion dollar global market including drugs, diagnostics, biology, toxicology and smart materials. While hydrogen deuterium exchange (HDE) methods hold promise as relevant tools for the late-stage and one-step preparation of deuterium-labelled compounds, they often fall short in achieving sufficient isotopic purity combined either with a site-selectivity or with a full deuteration process, highlighting the need for further development and optimisation. This report pinpoints an approach to unlock the potential of HDE using the concept of iterative runs in continuous-flow technology (recirculation process). This closed-loop process grants access now to deuterated compounds with high isotopic purities, labelled at a precise site or perdeuterated on demand, in a fast, productive, and environmentally friendly way. Hydrogen deuterium exchange (HDE) methods hold promise as relevant tools for the late-stage and one-step preparation of deuterium-labelled compounds, but they often fall short in achieving sufficient isotopic purity combined either with a site-selectivity or with a full deuteration process. Here, the authors report an approach to unlock the potential of HDE using the concept of iterative runs in continuous-flow technology.

Source: Nature Communications

DOI: 10.1038/s41467-025-56600-8

Authors: Kevin Tatoueix, Marco Lepron, Cédric Barboux, Marie-Christine Scherrmann, Grégory Pieters, Sophie Feuillastre