Tritiation tricks with thianthrenium salts

Abstract

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 as a radioactive beacon. Chemists led by Tobias Ritter at the Max Planck Institute for Kohlenforschung 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