Biomimetic Charge‐Neutral Anion Receptors for Reversible Binding and Release of Highly Hydrated Phosphate in water

Control of phosphate capture and release is vital in environmental, biological, and pharmaceutical contexts. However, the binding of trivalent phosphate (PO43‐) in water is exceptionally difficult due to its high hydration energy. Based on the anion coordination chemistry of phosphate, in this study, four charge‐neutral tripodal hexaurea receptors (L1 ‐ L4), which were equipped with morpholine and PEG terminal groups to enhance their solubility in water, were synthesized to enable the pH‐triggered phosphate binding and release in aqueous solutions. Encouragingly, the receptors were found to bind PO43‐ anion in a 1:1 ratio via hydrogen bonds in 100% water solutions, with L1 exhibiting the highest binding constant (1.2´103 M‐1). These represent the first neutral anion ligands to bind phosphate in 100% water and demonstrate the potential for phosphate capture and release in water through pH‐triggered mechanisms, mimicking native phosphate binding proteins. Furthermore, L1 can also bind multiple bioavailable phosphate species, which may serve as model systems for probing and modulating phosphate homeostasis in biological and biomedical researches.