Functionalized Cucurbit[7]urils for Molecular Recognition: Electrochemiluminescence- and Fluorescent-based Sensing Strategies

Over recent years, supramolecular chemistry has gained tremendous popularity and has significantly contributed to advances across various scientific disciplines, ranging from drug delivery to molecular machinery. Supramolecular chemists rely on dynamic, non-covalent intermolecular interactions – such as π-π stacking, hydrophobic effects, electrostatic interactions, hydrogen bonding, and solvent effects – to design molecular assemblies with unique physicochemical properties. While early research centered around naturally occurring cyclodextrins, the synthetic macrocyclic family of cucurbit[n]urils (CBn) has since taken center stage. Among them, cucurbit[7]uril (CB7) has gained particular prominence due to its good water solubility, rigid hydrophobic cavity, and high binding affinities for a wide range of biorelevant analytes. With a cavity size that is especially well-matched to small drug-like molecules and biological metabolites, CB7 has become a preferred platform for designing host-guest systems in aqueous and physiological environments. CB7 has been widely applied in fluorescence-based chemosensing,
particularly through indicator displacement assays (IDAs) using non-covalent bound dyes. ... mehrWhile
effective, these systems often suffer from limited stability in high-salt conditions, which can lead to
dissociation of the host-dye complex. To address this issue, covalent conjugation of the dye directly to the CB7 framework offers a robust alternative, enhancing both stability and sensing performance.
Furthermore, covalent modifications enable additional functionalization for improved selectivity,
opening the door to more targeted analyte recognition.
In this thesis, unimolecular CB7-dye conjugates were successfully synthesized and evaluated for their potential in biomedical sensing. The first project focused on a CB7-ruthenium(II) tris(bipyridine) conjugate, which was investigated for both photoluminescent and electrochemiluminescent (ECL) applications. In both detection modes, supramolecular proximity effects near the CB7 portals played a central role in modulating the signal. Notably, the system enabled the sensitive ECL-based detection of spermidine, a cancer-associated biogenic amine, with a limit of detection (LOD) of 76 nM, providing an alternative to standard ELISA methods.
In a second project, a library of seven CB7-coumarin conjugates was synthesized to explore analytes
discrimination in complex conditions. The sensing behavior was strongly influenced by pH, salt type, and ionic strength, which were used as orthogonal parameters to tune selectivity. By combining multiple sensor conditions, the system was capable of distinguishing between structurally similar analytes, including closely related steroid hormones. Together, these findings underscore the power of CB7 as a versatile host in aqueous chemosensing, especially when integrated into covalently linked, unimolecular sensor designs.