Covalent cucurbit[7]uril-dye conjugates for sensing in aqueous saline media and biofluids

摘要

Non-covalent chemosensing ensembles of cucurbit[n]urils (CBn) have been widely used in proof-ofconcept sensing applications, but they are prone to disintegrate in saline media, e.g. biological fluids. We show here that covalent cucurbit[7]uril-indicator dye conjugates are buffer- (10x PBS buffer) and salinestable (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 superset of 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 CBnIdye reporter pairs, the conjugate chemosensors can also operate through a S(N)2-type guest-dye exchange mechanism, which shortens assay times and opens new avenues for tailoring analyte-selectivity.