Peptidic Catalysts Conformationally Tuned for Fluoride Binding and Delivery

Knowledge on how fluoride interacts with peptides is currently limited to in silico studies. Here, we report an experimental investigation on the ability of peptidic scaffolds to bind fluoride using TBAF·3H₂O or CsF. For CsF, in-depth NMR and GOAT-DFT studies shed light on peptides acting as chelators to both fluoride and cesium ions. This finding led to the development of the first peptide-catalyzed fluorination reactions. These advances open a new avenue to investigate fluorination chemistry with peptide-based catalysts that are considered as the possible ancestors to enzymes.