Stacking Tetraurea Macrocycles as Self-Assembled Chloride Receptors 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 rare examples of receptors capable of strong (>105 M-1) anion binding in solutions containing > 50% water are available and none show selectivity for the highly biologically relevant anion chloride. We report here the discovery of a D4-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 interactions. In aqueous solutions, macrocycle aggregation generates size-selective and hydrophobic binding

pockets favourable for interactions with chloride via urea hydrogen bond donors. As a result, micromolar affinity and highly selective chloride binding has been achieved with this simple small molecule (MV < 700) in 60 vol% water/acetonitrile.