C. Hu, L. Grimm, A. Prabodh, A. Baksi, A. Siennicka, P. A. Levkin, M. M. Kappes and F. Biedermann, Chem. Sci., 2020, 11, 11142-11153.
Non-covalent chemosensing ensembles of cucurbit[n]urils (CBn) have been widely used in proof-of-concept sensing applications, but they are prone to disintegrate in saline media, e.g. biological fluids. We show here that covalent cucurbituril–indicator dye conjugates are buffer- (10× PBS buffer) and saline-stable (up to 1.4 M NaCl) and allow for selective sensing of Parkinson's drug amantadine in human urine and saliva, where the analogous non-covalent CB7?dye complex is dysfunctional. The in-depth analysis of the covalent host–dye conjugates in the gas-phase, and deionized versus saline aqueous media revealed interesting structural, thermodynamic and kinetic effects that are of general interest for the design of CBn-based supramolecular chemosensors and systems. This work also introduces a novel high-affinity indicator dye for CB7 through which fundamental limitations of indicator displacement assays (IDA) were exposed, namely an impractical slow equilibration time. Unlike non-covalent CBn?dye reporter pairs, the conjugate chemosensors can also operate through a SN2-type guest–dye exchange mechanism, which shortens assay times and opens new avenues for tailoring analyte-selectivity.