On-Demand Inhibition of Ciprofloxacin's Activity by Cucurbit[7]uril Supramolecular Chemistry.

On-demand inhibition of antibiotic activity presents a promising strategy to mitigate the growing risk of antimicrobial resistance, a major challenge in modern therapeutics. Herein, we demonstrate a supramolecular strategy for the on-demand inhibition of ciprofloxacin via complexation with cucurbit[7]uril (CB[7]). This approach involves conjugating a CB[7] guest molecule to a nonpharmacophore moiety of the antibiotic. The resulting host-guest complexation significantly increases the drug's molecular size, sterically hindering its passage through bacterial porins and preventing it from reaching its intracellular target. This mechanism enables the selective deactivation of antibacterial activity and facilitates subsequent adsorption and recovery of the antibiotic. As a proof-of-concept, this work establishes a simple supramolecular method to control antibiotic efficacy, offering a potential strategy to reduce the environmental accumulation of active antibiotics.