Binding of Bioactive\nAmmonium Ions in Water with a\nCavity-Based Selectivity: Water Solubilization versus Micellar Incorporation

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