Molecular recognition of cyclophanes in water

Abstract

Molecular recognition in water, the biological solvent, always receives significant research focus in supramolecular chemistry. The mechanisms of molecular recognition in water is key to comprehending biological processes at the molecular level. Over the past five decades, supramolecular chemists have developed a vast array of synthetic receptors with highly diverse structures and recognition properties. Among them, cyclophanes represent an important family of macrocyclic receptors that have been extensively explored. The aromatic moieties in cyclophanes not only facilitate chemical modifications to impart water solubility but also enable forming hydrophobic cavities for guest inclusion in aqueous environments. Pioneered by Koga et al., who reported the first inclusion complex of cyclophanes in water and solid state, numerous water-soluble cyclophanes, including derivatives of blue box, calixarenes, resorcinarenes, pillararenes, octopusarenes, biphenarenes, coronarenes, and naphthotubes, etc., have been synthesized and subjected to investigation of the recognition capabilities in aqueous solutions. This review provides an overview of cyclophane receptors designed to bind organic guests in water. We categorize them into two classes based on the modifications made to their hydrophobic cavities: those with “exo-functionalized hydrophobic cavities” and those with “endo-functionalized hydrophobic cavities”. We introduce their distinctive features and discuss strategies to enhance recognition affinity and selectivity. This review aims to inspire the development of novel synthetic receptors with intriguing properties and foster practical applications of cyclophanes.