Supramolecular umpolung: converting electron-rich resorcin[4]arenes into potent CH-bonding anion receptors and transporters

CH-hydrogen bonding anion receptors constitute an emerging class of anion sensors and transporters which, owing to their proteolytic and pH resistance, have great potential for biological applications. However, CH groups, being weak hydrogen bond donors, require additional enhancement of their binding properties. In this work, we demonstrate a new enhancement strategy that relies on the generation of large dipole moments by a combination of electron-donating and electron-withdrawing substituents. More specifically, the substitution of electron-rich resorcin[4]arenes with electron-withdrawing nitro groups in the upper rim induces a dipole moment of 15.8 D and concentrates electrostatic potential at the lower rim, leading to strong CH···anion binding at this remote site. As a result, tetranitroresorcin[4]arenes, available in just two synthetic steps, acquire high affinities towards halides (Ka(Cl-) = 1.36 × 105 M-1 in THF), remarkable tolerance to water, and selective chloride transport activity (EC50 = 0.012 mol%). A pivotal role of the seemingly innocent alkyl chains surrounding the binding site in making the receptors resistant to competitive aqueous/organic solvent mixtures and enabling anion transport is also demonstrated.