A Portal-Preorganized Cucurbit[7]uril-Ruthenium Conjugate Enables Motif-Selective Protein Sensing

We report a portal-preorganized cucurbit[7]uril (CB7)-ruthenium conjugate that reprograms CB7 recognition without modifying the host cavity itself. Covalent integration of a tris(2,2′-bipyridine)ruthenium(II) chromophore at the CB7 portal yields the unimolecular receptor CB7-Rubpy, in which guest binding is directly coupled to emission. The proximal Ru chromophore attenuates binding of classical polycationic CB7 guests while enhancing recognition of aromatic peptide and protein motifs, producing a selectivity shift of nearly two orders of magnitude relative to native CB7. CB7-Rubpy thereby converts CB7 from a charge-selective host into a motif-selective receptor for aromatic protein epitopes, displaying high affinity for insulin (Ka = 1.5 × 107 M−1) and submicromolar detection capability. The same motif-selective recognition enables monitoring of aromatic motif accessibility during protein refolding. These findings establish portal-preorganized chromophore integration as a design strategy for coupling selectivity tuning and signal transduction in CB-based receptors.