A fluorescent squaratide platform for anion-responsive optical switching

Squaratides are peptide-squaramide hybrid scaffolds that combine the modularity of peptide synthesis with the strong H-bond donor properties of squaramides, making them attractive platforms for anion recognition. Here, we report the synthesis and spectroscopic evaluation of Sq-2-Lys-Naph, a novel fluorescent squaratide receptor, prepared by incorporation of a naphthalimide-based fluorescent amino acid into a macrocyclic squaratide framework using solid-phase peptide synthesis. Sq-2-Lys-Naph displays green emission in solution and exhibits a pronounced fluorescence "turn-off" response to F^-, with less pronounced responses observed for a range of other halides and oxoanions under the same conditions. UV/Vis, ¹H and ¹⁹F NMR spectroscopic studies are consistent with an initial interaction of F^- with the squaramide NH groups at low loading, followed by proton transfer and deprotonation at higher F^- concentrations. Competitive fluorescence and NMR experiments also show that the F^--induced quenched state can be perturbed by AcO^-, leading to partial recovery of emission and reappearance of squaramide NH signals in the NMR. These results demonstrate the potential of squaratides as modular fluorescent platforms for anion recognition, in which sequence-defined molecular design can be used to tune both anion binding and optical response.