thioesters

Thioesters are esters in which a sulfur atom replaces the alkoxy oxygen of a typical carboxylate ester. The general structure is R-CO-S-R', with the acyl group attached to sulfur rather than oxygen. Thioesters are common in biology and organic synthesis as activated acyl donors.

They form by condensation of carboxylic acids with thiols, or by enzymatic or chemical activation of carboxyl groups. A key biological pathway involves acyl-CoA synthetases that couple fatty acids to coenzyme A in the presence of ATP, producing acyl-CoA thioesters (and AMP and PPi). In nonbiological settings, thioesters can be prepared by reacting carboxylic acids with thiols under activating conditions or via conversion of acid chlorides to thioesters.

Thioesters are typically more reactive toward hydrolysis and acyl-transfer reactions than their oxygen esters. The carbonyl is less stabilized by resonance with the sulfur substituent, making the acyl group more electrophilic and the thioester a more efficient acyl donor. This reactivity is exploited in metabolism and in synthetic chemistry to move acyl groups between carriers and enzymes.

Biological importance includes acetyl-CoA and other acyl-CoAs, which channel carbon units into pathways such as the citric acid cycle, fatty acid synthesis, and degradation. Thioester-linked intermediates also appear in protein S-acylation (palmitoylation), where fatty acyl groups attach reversibly to cysteine residues and influence protein localization and function.

Thioesters hydrolyze to a carboxylic acid and a thiol: R-CO-S-R' + H2O → R-COOH + R'-SH. Enzymes called thioesterases catalyze this hydrolysis or enable acyl transfer, regulating metabolic remodeling and biosynthetic processes.