N-Arylsulfonamidocalix[4]arenes with narrow pH-responsive binding near neutral pH

Abstract

We report a series of N-arylsulfonamidocalix[4]arene hosts with tunable acidity and conformational flexibility designed to explore narrow pH-responsive binding. Using two cationic dyes as model guests, we performed a systematic analysis across pH 5.8–10.2 in a 1 : 1 (v/v) water : acetonitrile mixture (χ_H2O 0.74). Fluorescence experiments confirmed pH- and conformation-dependent affinity, with host Tf-SA4 (bearing the most acidic sulfonamide groups in the cone conformer) inducing a sharp fluorescence enhancement within a narrow range of pH_app 7.8 and 8.2 (ΔpH = 0.4). Detailed analysis revealed a 1 : 2 complex with coupled charge and geometry changes in the host that are pH-dependent and induce a steep increase in binding stability, consistent with a proposed “binding switch” over the narrow ΔpH = 0.4. This study introduces a proof-of-concept for a synthetic host with narrow pH responsiveness near neutral pH, offering a foundation for further research into N-arylsulfonamidocalixarenes for potential biomedical applications.