Cooperative Metal Ion Binding to a Cucurbit[7]uril-Thioflavin T Complex: Demonstration of a Stimulus-Responsive Fluorescent Supramolecular Capsule

We report an intriguing noncovalent interaction of thioflavin T (ThT), a fibril diagnostic dye, with the versatile macrocyclic host molecule cucurbit[7]uril (CB7) in the presence of metal cations. ThT forms both 1:1 (CB7 center dot ThT) and 2:1 [(CB7)(2 center dot)ThT] complexes with C137 host, leading to specific structural arrangements. Addition of competitive guests like metal cations to the 1:1 stoichiometric complex displays expected competitive binding interactions with C137, leading to decreased fluorescence intensity from ThT. However, addition of metal ions to the 2:1 complex leads to unusual enhancement in the fluorescence emission (similar to 270-fold in the presence of Ca2+ and similar to 160-fold in the presence of Na+). These contrasting observations on the fluorescence enhancement with change in the stoichiometric equilibrium have been investigated explicitly for a feasible binding model. Detailed photophysical characterization with supporting data from NMR and anisotropy measurements has led to the revelation of a novel stimulus-responsive cooperative metal ion binding to the stoichiometrically selected (CB7)(2)center dot ThT complex, demonstrating a highly fluorescent supramolecular nanocapsule. The first example of a noncovalently packed fluorescent complex became feasible due to the structural arrangement of the host-guest complex in the 2:1 stoichiometry with two CB7 portals providing strong negative charge density for the metal ions to group and seal the complex, thus protecting the incorporated dye. To further strengthen the usefulness of the supramolecular capsule established here, rupture of the capsular complex has been demonstrated with a strong competitive guest, 1-amantadine hydrochloride, which helped in disrupting the capsule to release the dye. It is proposed here that by judicious design of the chromophore (guest) structure, such capsular assemblies can be explored for the binding and release of drug molecules, for fluorescence on-off systems, and as building blocks for molecular architectures displaying unique properties.