Tetraurea macrocycles: aggregation-driven binding of chloride in aqueous solutions

Artificial receptors that recognise anionic species via noncovalent interactions have a wide range of biomedical, industrial and environmental applications. A major challenge in this area of research is to achieve high affinity and selective anion binding in aqueous media. So far, only a few examples of receptors capable of strong (> 10 5 M -1 ) anion binding in solutions containing > 50% water are available and none show selectivity for chloride. We report here the discovery of a D 4h -symmetric fluorinated tetraurea macrocycle that fulfils this function owing to its unique self-assembly properties. The macrocycle has a strong tendency to self-associate into columnar aggregates via intermolecular hydrogen bonds and aromatic stacking. In aqueous solutions, macrocycle aggregation generates hydrophobic and size-selective binding pockets favourable for hydrogen bonding with chloride. As a result, micromolar affinity and highly selective chloride binding has been achieved with this simple small molecule (MW <700) in 60 vol% water/acetonitrile.