sulfhydryl

Sulfhydryl, also called a thiol, is a functional group consisting of a sulfur atom bonded to a hydrogen atom and to the rest of the molecule via the sulfur atom, represented as –SH. It is the sulfur analogue of alcohols and is uniquely reactive due to the polarizable sulfur and the relatively acidic hydrogen.

Sulfhydryl groups occur in many organic compounds. The best-known example is the amino acid cysteine, which contains a terminal thiol. In proteins, cysteine residues can form disulfide bonds (R-S-S-R) that stabilize tertiary and quaternary structure and participate in redox signaling. Glutathione, a tripeptide with a thiol, acts as a major cellular antioxidant and participates in detoxification processes.

Chemistry: The thiol functional group has a pKa around 8–9 in water, so at physiological pH a significant fraction exists as the thiolate RS−. Thiolates are strong nucleophiles and participate in substitution and addition reactions. Oxidation of two thiols yields a disulfide; further oxidation can give sulfinic and sulfonic acids. Thiols can be reduced back to thiols by agents such as dithiothreitol (DTT), beta-mercaptoethanol, or TCEP.

Applications and properties: In analytical chemistry, thiols react with Ellman's reagent (DTNB) to give a colored product, enabling quantification of free thiol groups. They are also used to label cysteine residues with various reagents and to study protein folding and redox states. Some low-molecular-weight sulfhydryl compounds have strong odors and can be hazardous in concentrated form.