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

<p>Artificial receptors that recognise anionic species <i>via</i>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<sup>5</sup>M<sup>-1</sup>) anion binding in solutions containing > 50% water are available and none show selectivity for chloride. We report here the discovery of a <i>D</i><sub>4h</sub>-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 <i>via</i>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 <a>60 vol% water/</a>acetonitrile.</p>