thiolating

Thiolating is the chemical process of introducing thiol groups (-SH) into a molecule or converting existing functionalities into thiol derivatives. The term combines the root thio- for sulfur and -lation, indicating the formation of a sulfhydryl-bearing species. Thiolation is used across organic synthesis, bioconjugation, and materials science to enable subsequent reactions that rely on sulfhydryl reactivity or disulfide formation.

In organic synthesis, common thiolation strategies include substitution of leaving groups by thiolate nucleophiles to form thioethers (R-S-R). Thiol-ene and thiol-yne reactions add thiols across carbon–carbon multiple bonds to give flexible thioether linkages. Carbonyl compounds can be thiolated to give thioacetals or thioketals, which serve as protective groups for carbonyls. Additionally, thiolating reagents and strategies are used to attach sulfhydryl groups to surfaces or to biomolecules, enabling later ligations or metal coordination.

Applications span several fields. In bioconjugation, thiolation allows attachment of dyes, drugs, or probes to proteins and nucleic acids, often via selective chemistry with maleimides or other electrophiles. In materials science and surface chemistry, thiolated molecules form self-assembled monolayers on metals such as gold, or function as linkers in polymers and nanoparticles. In synthetic chemistry, installing thiol groups can activate substrates for disulfide exchange and catalytic cycles.

Practical considerations include the tendency of thiols to oxidize to disulfides, odor and handling concerns, and the need to control pH and atmosphere to preserve free thiols. Selectivity is important when multiple reactive sites are present, and protection or masking strategies may be employed when difference in reactivity is required.