Sulfate Recognition in Water via Charge-Assisted Hydrogen Bonding

Achieving selective molecular recognition of hydrophilic anions in water remains a formidable challenge due to the competitive nature of water and the high hydration energies of target anions such as sulfate. Here, we report the design, synthesis, and characterization of a simple dicationic tetralactam macrocycle (BPTL²⁺·2Cl⁻) capable of binding highly hydrated anions in water via charge-assisted hydrogen bonding. Structural, spectroscopic, thermodynamic, and computational studies reveal that BPTL²⁺ exhibits a strong binding affinity for sulfate (K_a = 2892 M⁻¹), driven primarily by entropic gain from water release and reinforced by electrostatic and hydrogen bonding interactions. Single-crystal X-ray diffraction and DFT-optimized structures confirm the formation of directional [N─H•••O] and [C─H•••O] hydrogen bonds. Comparative studies with a control macrocycle (6Na⁺•HCTL^6-) that has a charge-neutral binding cavity underscore the essential role of cationic charge in overcoming desolvation enthalpic penalties. The receptor displays anti-Hofmeister selectivity, preferentially binding more hydrophilic anions. This work provides fundamental insights into the mechanisms of anion recognition in water. It establishes charge-assisted hydrogen bonding as a powerful strategy for developing next-generation receptors for sensing, separation, sequestration, transport, and catalysis in aqueous environments.