Charge-neutral urea cages as potent synthetic sulfate receptors in water

Strongly hydrated anions are challenging targets for molecular receptors. In nature, sulfate binding proteins use multiple neutral NH hydrogen bonds to surround the guest, resulting in sub-millimolar to sub-micromolar sulfate affinities. Synthetic receptors, however, have not yet achieved comparable efficiency and selectivity for sulfate solely by relying on hydrogen bonds or other ion-dipole interactions. Here we report charge-neutral macrotricyclic hexa-urea cages which exhibit strong sulfate affinities (6000 to 9000 M–1) in water with exceptional selectivity over hydrophobic anions. Unlike sulfate binding proteins where a low-polarity microenvironment enhances sulfate binding, the urea cages achieve high sulfate affinities with the urea binding sites exposed to water. The work demonstrates that synthetic receptors operating solely by neutral hydrogen bond donors can emulate the efficiency and selectivity of naturally occurring systems.