Thiolysis

Thiolysis is a chemical reaction in which a thiol (R-SH) acts as a nucleophile to cleave a bond in another molecule, often by exchanging a sulfur-containing group for a leaving group. The term is used in several contexts, including thiolysis of thioesters, thiol-disulfide exchange, and degradation or modification of sulfur-containing polymers and biomolecules.

In thioester thiolysis, a thiol attacks the thioester carbonyl, producing an acyl transfer and exchange of thioester partners: R-C(=O)-S-R' + R''-SH → R-C(=O)-S-R'' + R'-SH. This transthioesterification is central to methods such as native chemical ligation in peptide synthesis and other acyl-transfer strategies.

In disulfide thiolysis, a thiol or thiolate exchanges with a disulfide, cleaving the original bond and forming a new disulfide or thiol. This thiol-disulfide exchange operates under mild conditions and is a common mechanism in redox biology and dynamic covalent chemistry. Reaction rates depend on pH, thiol pKa, and the substituents on the sulfur-containing groups.

Applications: thiolysis is used to activate or cleave thioester or disulfide linkages in biochemical and materials contexts. In biochemistry, it underpins peptide ligation strategies and redox regulation; in polymer science, it enables controlled degradation or remodeling of disulfide- or thioester-containing networks.

See also: thiol-disulfide exchange, transthioesterification, native chemical ligation.