Tuneable anion recognition at the lower rim of resorcin[4]arenes: strength, selectivity, and transport

Selective anion binding and transport are critical in many chemical and biological settings. CH-bonding receptors, which rely on nonclassical CH⋅⋅⋅anion hydrogen bonds, offer a pH-independent alternative to traditional hydrogen-bonding hosts; however, their design is challenged by the inherently weak nature of CH⋅⋅⋅anion interactions. This study presents modified resorcin[4]arenes as versatile scaffolds to address this challenge. By the introduction of electron-withdrawing groups (EWGs) at the upper rim, we effectively convert electron-rich resorcin[4]arenes into potent anion receptors. A series of resorcin[4]arenes bearing -Br, -CHO, -NO2, and -CN substituents exhibit a systematic enhancement in anion binding affinity, reaching a record value for the CN-substituted receptor: Ka (Cl⁻, THF) = 7×10⁵ M−1. The logKa values of this series of receptors correlate strongly with the electrostatic potential (ESP) at the anion binding site, calculated by DFT methods. In addition, incorporating hydroxyl-terminated alkyl chains at the lower rim promotes the formation of higher-order complexes and further boosts anion binding, even in competitive aqueous–organic media. Notably, these hydroxyalkyl-footed receptors display exceptional selectivity for HSO4−, with a selectivity factor of 17 over similar tetrahedral oxyanions. Transmembrane anion transport studies in large unilamellar vesicles reveal that the nitro-substituted resorcin[4]arene is by far the most effective chloride transporter in this series, followed by the CN-substituted one, emphasizing that the most strongly binding receptors are not necessarily the most efficient transporters. Collectively, these results highlight the potential of resorcin[4]arenes as tuneable platforms for tailoring anion binding strength, selectivity, and anionophoric properties through simple peripheral modifications.