Supramolecular Umpolung via Esterification: Converting Electron-Rich Phenolic Macrocycles into CH-Bonding Anion Receptors and Transporters

CH-bonding anion receptors are supramolecular hosts that combine high chemical robustness, reduced propensity for deprotonation, and distinctive selectivity patterns, which make them attractive for transmembrane transport and medicinal applications. Their broader use is, however, limited by the scarcity of scaffolds capable of forming strong CH···anion interactions. Here, we present a general and operationally simple “supramolecular umpolung” strategy that converts π-electron-rich oligophenolic macrocycles into CH-bonding anion receptors and transporters via esterification of their OH groups. Resorcinarenes and pyrogallolarenes were transformed into acetyl (−OAc), triflate (−OTf), and pentafluorobenzenesulfonate (−OPFB) esters. The −OTf and −OPFB derivatives show high anion binding affinities across diverse media, while −OTf derivatives also act as excellent anion transporters in lipid bilayers, outperforming benchmark tetranitroresorcinarene. Per-triflated pyrogallolarene combines high chloride affinity (Ka ≈ 1010 M–1 in THF), outstanding Cl–/NO3– antiport transport activity (EC50,270s = 0.0017 mol %), and very low protonophoric activity. Electrostatic surface potential (ESP) and molecular lipophilicity potential (MLP) analyses show that a highly positive ESP at the CH-binding site and a uniformly lipophilic external surface are crucial for effectiveness. Overall, esterification of oligophenolic macrocycles provides a general route to CH-bonding anion receptors and transporters that approach the performance of the best NH-based systems and exhibit very low protonophoric activity, thus overcoming a key limitation of conventional hydrogen-bonding anionophores.