sulfitolysis

Sulfitolysis is a chemical reaction in which sulfite (SO3^2−) or bisulfite (HSO3^−) ions react with a substrate to cleave bonds and introduce sulfonate-containing fragments. In biomolecules, the term is most commonly applied to the cleavage of disulfide bonds (R–S–S–R') in proteins and peptides. Under aqueous conditions, sulfite can attack the disulfide bond, generating intermediates that eventually lead to bond cleavage and the introduction of sulfonate-related functionalities on sulfur. The overall result is the disruption of the covalent S–S linkage and formation of sulfur-containing fragments bearing sulfonate or related groups. The reaction generally proceeds under mild, near-neutral to slightly basic pH and can be influenced by temperature and additives.

Applications of sulfitolysis include protein chemistry and structural analysis, where it is used to map disulfide linkages and to convert disulfide bonds into sulfonated derivatives that are easier to analyze or manipulate in subsequent steps. By transforming cystine or other sulfur–sulfur linkages into sulfonated sulfur species, researchers can facilitate peptide sequencing, fragmentation studies, or preparation of restricted or modified forms of proteins for analytical workflows. In synthetic organic chemistry, sulfitolysis can serve as a mild method for cleaving certain sulfur-containing linkages, though its use is more specialized compared with standard reductive or alkylative strategies.

Limitations include incomplete cleavage for hindered disulfides, competing side reactions with other nucleophiles, and sensitivity to reaction conditions such as pH and sulfite concentration. Safety considerations center on the potential for sulfite reagents to provoke allergies or respiratory reactions in sensitive individuals, requiring appropriate handling and disposal.