Tunable Anion Recognition at the Lower Rim of Resorcin[4]arenes: Strength, Selectivity, and Transport

Selective anion binding and transport are crucial in many chemical and biological settings. CH-bonding receptors-which rely on nonclassical CH···anion hydrogen bonds, offer a pH-independent alternative to conventional hosts; however, their design is challenged by the inherently weak nature of CH···anion interactions. In this study, we present modified resorcin[4]-arenes as versatile scaffolds to address this challenge. By introducing electron-withdrawing groups (EWGs) at the upper rim, we convert π-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 the highest value in the series for the CN-substituted receptor: <i>K</i> _a(Cl^-, THF) = 7 × 10⁵ M^-1. The log<i>K</i> _a values correlate with the electrostatic potential (ESP) at the binding site, calculated by DFT methods. In addition, the incorporation of 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. 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 analogue, emphasizing that the most strongly binding receptors are not necessarily the most efficient transporters. Detailed analysis of molecular lipophilicity potential (MLP) maps shows that subtle differences in upper- and lower-rim polarity, as well as excessive hydrophilicity at the lower rim, can diminish transport efficiency by hindering membrane reorientation or promoting interfacial anchoring. These mechanistic and structure-activity insights provide clear design principles for developing next-generation CH-bonding transporters with improved performance. Collectively, these results highlight the potential of resorcin[4]-arenes as tunable platforms for tailoring anion binding strength, selectivity, and anionophoric properties through simple peripheral modifications.