Disulfide formation: practice and mechanism
A mild oxidant joins two SH groups into an S–S bridge (disulfide). Each SH group loses one H; nothing else changes.
Example
Mild oxidants join two thiol groups into an S–S bond, each SH group losing an H. Two cysteines give cystine. Disulfide bridges hold the folding of many proteins together and can be opened again by reduction.
Mechanism step by step
- 1
The weak base deprotonates the thiol to the thiolate (R–S⁻).
- 2
The thiolate attacks I₂: a sulfenyl iodide (R–S–I) and iodide form.
- 3
A second thiolate displaces the iodide: the disulfide R–S–S–R forms.
Practice tasks
Which product forms, which reagent is needed? After each answer you see the explanation.
Which main product forms?
Background
A redox reaction
Two thiol groups (R–SH) are oxidised to a disulfide bridge (R–S–S–R); each sulfur formally gives up one electron and one proton. In the lab mild oxidants such as iodine or air are enough. Reducing agents such as dithiothreitol (DTT) or mercaptoethanol split the bridge back into two thiols.
Disulfide bridges in proteins
Two cysteines form a cystine. Such bridges stabilise the tertiary structure of many proteins that work outside the cell, for example insulin (two chains joined by disulfide bridges) or antibodies. Inside the cell, which is reducing, they are rare.
An everyday example
Hair (keratin) contains many disulfide bridges. A perm opens them reductively, the hair is shaped, and the bridges are then re-formed by oxidation.
Typical mistakes
- Sulfonic acids only form with strong oxidants (e.g. excess H₂O₂, HNO₃). I₂ or air O₂ stop at the disulfide.
- A thioether (R–S–R) forms by alkylating a thiol, not by oxidation. Here two sulfur atoms join.
- SH is not exchanged for OH. On oxidation the sulfur stays on the carbon and bonds to a second S.
Frequently asked questions
How is a disulfide bridge opened again?
By reduction, e.g. with dithiothreitol (DTT) or β-mercaptoethanol. It is a redox equilibrium controlled by using an excess.
Why are thiols more easily oxidised than alcohols?
The S–H bond is weaker than O–H, and sulfur is larger and more polarisable. An S–S bond is stable, whereas an O–O bond (peroxide) is very weak.