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

ABSTRACT 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 ( K a = 1.5 × 10 7 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.