Thioester

Structure and reactivity

The carbon–sulfur single bond adjacent to the carbonyl makes thioesters less stabilized by resonance than ordinary esters. This reduced delocalization renders the carbonyl more electrophilic, so thioesters are generally more reactive toward nucleophiles than corresponding esters or amides. Key structural points and comparisons appear in summaries such as comparative charts and mechanistic notes at reaction guides. Thioesters can form enolates and participate in classic condensations and acyl-transfer reactions.

Biological roles

Thioesters are central to metabolism. Acetyl‑CoA and other acyl‑CoA species are thioesters that serve as activated acyl donors in many biosynthetic and degradative pathways, including fatty acid synthesis and the citric acid cycle; useful introductions to these roles can be found at biochemical summaries and metabolic pathway resources. Enzyme-bound thioesters also appear on carrier proteins such as the acyl carrier protein (ACP) and drive otherwise unfavorable transformations by providing a relatively high-energy acyl linkage; further discussion is available at enzyme mechanisms and cellular energetics.

Synthesis and laboratory applications

Chemical preparation of thioesters commonly proceeds by coupling a carboxylic acid derivative with a thiol or by converting an acid to an activated intermediate (acid chloride, anhydride, or using carbodiimide coupling agents) before addition of a thiol; practical protocols are collected at experimental methods and synthetic notes. In organic synthesis thioesters are valued as acyl transfer reagents, intermediates in peptide ligation techniques, and partners in cross-coupling or Claisen-type condensations; selected applications are surveyed at synthetic applications and peptide chemistry.

Distinguishing features and notable facts

• Compared with esters and amides, thioesters are more reactive at the carbonyl and are thus useful as activated acyl donors in both enzymatic and synthetic contexts; see reactivity comparisons.
• They play a non-covalent and covalent role in metabolism: as small-molecule carriers (e.g., acetyl‑CoA) and as transient enzyme-bound intermediates; background information is at metabolism highlights.
• In laboratory work, handling of thiols and thioesters requires attention to odor and to potential side reactions such as disulfide formation; safety and handling notes are given at practical guidance.