Sulfhydryl group

Since sulfur and oxygen belong to the same periodic table group, they share some similar chemical bonding properties. The chemistry of the sulfhydryl group is thus related to the chemistry of alcohols; thiols form thioethers, thioacetals and thioesters, in which the alcohol-derived oxygen atom is replaced by a sulfur atom in the oxygen-analogous compounds ethers, acetals, and esters.

The sulfur atom in the sulfhydryl group is quite nucleophilic, rather more so than the oxygen of an alcohol. The S-H group is fairly acidic (usual pK_a around 10-11), so in the presence of a base a thiolate anion is formed which is a very powerful nucleophile. The group (or its corresponding anion) is readily oxidized by reagents such as bromine, giving an organic disulfide R-S-S-R, or by more powerful reagents such as sodium hypochlorite, yielding sulfonic acids RSO₃H.

Because of the small electronegativity difference between sulfur and hydrogen, an S-H bond is practically nonpolar covalent. Thiols show little association by hydrogen bonding. They have lower boiling points and are less soluble in water and other polar solvents than alcohols of similar molecular weight.

As the functional group of the amino acid cysteine, the sulfhydryl group plays an important role in biological systems. When the sulfhydryl groups of two cysteine residues (as in monomers or constituent units) are brought near each other in the course of protein folding, an oxidation reaction can create a cystine unit with a disulfide bond (-S-S-). Disulfide bonds can contribute to a protein's tertiary structure if the cysteines are part of the same peptide chain, or contribute to the quaternary structure of multi-unit proteins by forming fairly strong noncovalent bonds between different peptide chains. Sulfhydryl groups in the active site of an enzyme can form noncovalent bonds with the enzyme's substrate as well, contributing to catalytic activity.

See also