Cyclic Thiosulfinates: Synthesis and Applications in Chemical Biology and Materials Science

Cyclic thiosulfinates (CTs) constitute a distinct class of organosulfur compounds characterized by a polarized ─S(═O)─S─ motif and inherent ring strain, which together dictate their unique reactivity toward thiols. Recent advances in synthetic methodologies, particularly the controlled oxidation of cyclic disulfides, have enabled access to stable CTs with tunable ring sizes and substitution patterns. Mechanistic studies reveal that ring-induced hyperconjugation and conformational constraints enhance nucleophilic substitution, allowing for selective cross-linking of proximal thiols while minimizing the modification of isolated thiols. These properties have positioned CTs as valuable tools in chemical biology for selective thiol targeting and protein cross-linking in complex biological environments. Concurrently, CTs are gaining prominence as dynamic covalent cross-linkers in materials science. This review highlights recent progress in the synthesis, reactivity, and applications of CTs across chemical biology and materials science.