Tritiation reaction takes a new tack

To study how drugs and drug candidates behave in biological systems, scientists often replace a hydrogen atom in a compound of interest with an atom of the isotope tritium, which acts a radioactive beacon. Chemists led by Tobias Ritter at the Max Plank Institute for Coal Research report a new tritium-installation method that sidesteps challenges associated with other methods for tritiation (Nature 2021, DOI: 10.1038/s41586-021-04007-y).

The reaction capitalizes on the reactivity of thianthrenium salts, which Ritter’s team reported in 2019. Chemists can selectively place thianthrenium salts in the para position of aromatic groups. The thianthrenium group can then be replaced with tritium via hydrogenolysis using a homogeneous palladium catalyst and tritium gas. Although chemists have previously used hydrogenolysis to place tritium in molecules, they typically relied on heterogeneous catalysts, such as palladium on a carbon support, to do so. Heterogeneous catalysts tend to be less selective than homogeneous catalysts in hydrogenolysis reactions, and can react with other groups such as halides or nitriles on complex molecules.

Ritter’s team used the reaction to tack tritium onto several complex molecules, including the antiparasitic compound LHVS (shown). The new tritiation reaction doesn’t require an inert atmosphere or dry conditions, which makes it easy to execute, the chemists say.