[2.2.2]Urea cryptand: an easily accessible neutral organic cage for anion binding in water

Binding hydrophilic anions such as sulfate in water is a significant academic challenge, in particular for neutral receptors. To achieve this, typically a large molecular receptor is designed that wraps around a bound anion in a hydrophobic microenvironment. Such receptors require multi-step synthesis and often display selectivity towards hydrophobic anions such as iodide. We here report the one-pot synthesis of a [2.2.2]urea cryptand (cage) and its ability to bind sulfate in water with sub-millimolar affinity achievable by incorporation into micelles. Unlike existing neutral receptors, the cage has >10-fold selectivity for sulfate against hydrophobic anions even in pure water. The cage displays rare slow-exchange NMR responses to divalent anions in DMSO-water allowing for simultaneous analysis of multiple divalent anions in water analogous to an ion chromatography instrument. Our results demonstrate the pre-organization of strong directional NH hydrogen bond donors in a cage scaffold as a synthetically less-demanding, yet effective approach to achieving selective binding of hydrophilic anions in water.