Binding of Bioactive Ammonium Ions in Water with a Cavity-Based Selectivity: Water Solubilization versus Micellar Incorporation

Many bioactive molecules contain primary ammonium groups, generating significant interest in developing selective receptors for ammonium ions. A promising strategy involves the use of polyaromatic cavitands to achieve size and shape selectivity through their cavity. However, designing effective receptors for ammonium ions in aqueous media is challenging due to the competitive nature of water. Calix[5]arenes are known to selectively bind primary ammonium ions over secondary, tertiary, and quaternary ammonium ions in organic solvents. Here, we report on the binding properties of a calix[5]arene, which bears carboxyl groups on its small rim, in organic solvents and aqueous media. This receptor was transferred in water either through deprotonation of its carboxyl groups or by incorporation into dodecylphosphocholine micelles. ¹H Nuclear Magnetic Resonance data confirmed the <i>endo</i> complexation of various primary ammonium ions in not only organic solvents but also both aqueous media. Cavity-based selectivity was also observed, validating the cavitand strategy for the selective binding of ammonium ions in water. Unique binding properties, driven by the calix[5]arene's intrinsic recognition ability and the hydrophobic effect, were observed in water. Notably, binding affinities for dopamine and lysine derivatives with log <i>K</i>_a values of >3.9 were determined. The direct solubilization of the receptor outperformed micellar incorporation due to the hydrophilic nature of the primary ammonium ions, which hinders their uptake into micelles. These results offer promising perspectives for the development of efficient chemosensors for the characterization of bioactive ammonium ions in water.