Peptidic Catalysts Conformationally Tuned for Fluoride Binding and Delivery

Knowledge on how fluoride interacts with peptides is currently limited to <i>in silico</i> 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.