Activeester

An active ester is an ester of a carboxylic acid in which the leaving group is highly activated, making the carbonyl more susceptible to nucleophilic attack than that of a standard ester. Activation of the carboxyl group creates an intermediate that undergoes rapid acyl transfer to nucleophiles such as amines or alcohols, forming amide or ester bonds under relatively mild conditions. This activated character is the basis for widespread use in synthetic and bioconjugation chemistry.

Common activating groups include N-hydroxysuccinimide (NHS), p-nitrophenol, and pentafluorophenol derivatives. NHS esters are among the most frequently used active esters in bioconjugation and peptide synthesis because they react readily with amines to form amide bonds, releasing NHS as a byproduct. Other activated phenol esters, such as pentafluorophenyl esters, offer similar reactivity profiles and can be chosen based on stability and reaction conditions. Active esters can be prepared by converting carboxylic acids with coupling reagents (for example, carbodiimides in the presence of NHS or HOBt) or by esterification with activated phenols.

Applications include peptide and protein synthesis, antibody–drug conjugation, small-molecule bioconjugation, and surface or polymer labelings. They are especially valued for enabling efficient coupling under mild, aqueous-compatible conditions, which helps preserve the integrity of sensitive biomolecules. Limitations include hydrolysis of the activated ester in water and moisture sensitivity, which necessitates careful handling and storage, typically in dry, low-temperature conditions.