Molecular Cages as Probes in Indicator Displacement Assays: The Case of Scopolamine Detection

A study of the Pd-based molecular cage C1 host-guest properties against fluorescein and the drug scopolamine is reported. C1 forms an interpenetrated structure C1₂ in the presence of ≥40% water in H₂O/DMSO solvent mixtures. The presence of fluorescein (FL) induces the disassembly of the C1₂ structure to form the [FL₂⊂C1] complex. Moreover, the addition of scopolamine (SCOP, a drug typically involved in drug-facilitated sexual assaults) to [FL₂⊂C1] results in fluorescein release and the formation of [SCOP⊂C1₂], obtaining a fluorescence signal proportional to the concentration of scopolamine with a limit of detection as low as 59.4 µg mL^-1. A good selectivity for scopolamine against other drugs such as MDMA, cocaine, GBL, and ketamine is observed. This is the first scopolamine detection method described to date using a molecular cage and one of the very few examples of the use of cages in indicator displacement assays. Similar concepts could be applied to the design of other molecular cage-based sensors for the detection of target analytes.