Sulfhydryls

Sulfhydryls, also called thiol groups, are chemical functional groups consisting of a sulfur atom bonded to a hydrogen atom, written as –SH. They are common in organic molecules and are especially prominent in the amino acid cysteine, where the side chain ends in a sulfhydryl group. Sulfhydryls are versatile in chemistry and biology due to the nucleophilic character of the sulfur atom.

In nomenclature, the substituent is called sulfanyl in systematic naming, but the term thiol is widely used in practice. Aliphatic thiols have pKa values around 8–9, so at physiological pH a significant fraction can exist as the thiolate anion (RS−), which is a stronger nucleophile. Sulfhydryl groups are relatively reactive and are readily oxidized to form disulfide bonds (RS–SR), a central feature in many structural and catalytic processes.

Biologically, sulfhydryl groups are abundant in proteins through cysteine residues. Free sulfhydryls can participate in catalysis, metal binding, and redox reactions, while disulfide bonds contribute to the stabilization of protein structure. Glutathione, a small molecule with a cysteine-derived thiol, serves as a major cellular redox buffer. Thiol groups also undergo a variety of post-translational modifications, such as S-nitrosylation, S-glutathionylation, and sulfenylation, which play roles in redox signaling and regulation.

Chemically, sulfhydryls react with alkylating agents to form thioethers and with acyl groups to form thioesters. They are frequently involved in redox chemistry, including cycles of oxidation and reduction that regulate enzyme activity, protein folding, and metabolic pathways. Some sulfhydryl-containing compounds have characteristic odors and can react with electrophiles, influencing their handling and stability.