Tunable Anion Recognition at the Lower Rim of Resorcin[4]arenes: Strength, Selectivity, and Transport
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Tunable Anion Recognition at the Lower Rim of Resorcin[4]arenes Strength, Selectivity, and Transport.pdf (4.81 MB)
0000-0002-1344-751X Date
2025
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American Chemical Society
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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: Ka(Cl–, THF) = 7 × 105 M–1. The logKa 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.
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JACS Au 2025, 5, 10, 5137–5146 // https://doi.org/10.1021/jacsau.5c01041