thioester

A thioester is an organic compound in which a carbonyl group is bonded to sulfur in place of the alkoxy oxygen of a typical ester. Its general structure is R-CO-S-R'. The carbonyl carbon is attached to a sulfur atom and to an R' group, while the other substituent is an acyl or alkyl group.

Thioesters are typically more reactive toward nucleophiles than oxygen esters. This increased reactivity arises from reduced resonance stabilization of the carbonyl in thioesters and the larger, more polarizable sulfur atom, which weakens the C=O bond and facilitates acyl transfer. As a result, thioesters serve as effective acyl donors in both chemical and enzymatic reactions. They are also generally more readily hydrolyzed than corresponding oxygen esters.

Formation methods include direct condensation of a carboxylic acid with a thiol in the presence of activating reagents, or conversion of acyl chlorides or anhydrides to thioesters using thiolate salts. In biology, thioesters are produced by acyl-CoA synthetases that couple carboxylates with coenzyme A (CoA) in an ATP-dependent process, releasing AMP and pyrophosphate.

Biological significance is widespread. Acyl-CoA thioesters, such as acetyl-CoA and fatty acyl-CoAs, act as key carriers of acyl groups in metabolism, enabling energy production, fatty acid oxidation, and biosynthetic pathways. The high-energy character of some thioester hydrolysis contributes to driving metabolic reactions. In chemical biology, thioesters are also used as intermediates in methods such as native chemical ligation for protein synthesis.