A Template‐Free Pd2L4 Cage with up to Nanomolar Affinity for Chloride in Aqueous Solutions**.

Selective binding of chloride over the other most abundant anions in living organisms is pivotal due to its essential role in physiological functions. Herein, we report a template‐free Pd2L4 cage exhibiting high selectivity for medium‐sized halides (i. e. Cl−, Br−) in water owing to the size‐discriminatory nature of the cage cavity. In pure water, this cage displays high selectivity and micromolar affinity for chloride. The cage shows no binding towards other biologically more abundant essential anions such as phosphates, carboxylates, or bicarbonate. This cage shows an unprecedented nanomolar affinity with 1 : 1 binding stoichiometry for chloride in aqueous‐DMSO media. This high affinity was achieved with the best use of traditional hydrogen bonding and electrostatic interactions, as confirmed by single‐crystal X‐ray diffraction analysis. This well‐defined cage sequestrates F− by cleaving a B−F bond in BF4− in a facile manner in a nonpolar solvent or in the presence of excess ligand. This cage also demonstrates capture of the sub‐ppm chloride level that is present in commercial D2O samples. [ABSTRACT FROM AUTHOR]