Hydrogen sulfide (H2S) is an important biomolecule with high therapeutic potential. Here we leverage the inverse-electron demand Diels–Alder (IEDDA) click reaction between a thiocarbamate-functionalized trans-cyclooctene and a tetrazine to deliver carbonyl sulfide (COS), which is quickly converted to H2S by the uniquitous enzyme carbonic anhydrase (CA), thus providing a new strategy for bio-orthogonal COS/H2S donation.
