Anthracene-isatoic anhydride hybrids for bioconjugation: chromophores with nucleophile dependent response

Abstract

The use of activated esters to label nucleophilic sites in biomolecules is a well established platform in bioconjugate chemistry. Here, we report the synthesis of a pair of anthracene–isatoic anhydride hybrid molecules that exhibit a characteristic spectroscopic response depending on the identity of the reacting nucleophile. A survey of substrates shows that primary amines, alcohols, and thiols can produce the corresponding acyl derivatives in good isolated yield. Spectroscopic studies show a strong donor–acceptor absorbance at >500 nm along with fluorescence into the near IR. Finally, we demonstrate the anthracene anhydride's potential as a bioconjugate reagent in the labeling of a lysine-containing 11-residue peptide. Owing to our novel platform's unique response against a range of nucleophiles, it is possible to determine the fate and target of the labeling reaction.