disulfide

Disulfide denotes a covalent bond between two sulfur atoms, S-S, typically formed by oxidation of two thiol groups (R–SH). The simplest form is the disulfide R–S–S–R. The S–S bond is about 2.05 Å long, with a bond dissociation energy around 60–65 kcal/mol, making it weaker than many carbon–carbon bonds and sensitive to redox changes.

Disulfide bonds can be intramolecular or intermolecular. They form when two thiols are oxidized, producing a disulfide and two protons or, in biological contexts, releasing electrons. They are cleaved back to thiols by reducing agents such as dithiothreitol (DTT) or beta-mercaptoethanol. Redox conditions and pH influence their stability.

In biology, disulfide bonds stabilize the three-dimensional structure of many extracellular proteins and can link polypeptide chains. Cystine is the oxidized dimer formed from two cysteine residues. Enzymes like protein disulfide isomerase (PDI) assist in forming and rearranging disulfides during protein folding. The cellular redox state is reported by the glutathione couple GSH/GSSG.

Disulfides also occur in organic chemistry and materials science as redox-active linkages and in disulfide-containing polymers and dyes. They participate in thiol–disulfide exchange reactions, enabling dynamic covalent chemistry and reversible cross-linking. Reduction of disulfides is a common laboratory step to reveal free thiols for further modification.