Control of phosphate capture and release is vital in environmental, biological, and pharmaceutical contexts. However, the binding of trivalent phosphate (PO ) 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 (L-L), which were equipped with morpholine and polyethylene glycol 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 PO anion in a 1 : 1 ratio via hydrogen bonds in 100 % water solutions, with L exhibiting the highest binding constant (1.2×10 M). 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, L can also bind multiple bioavailable phosphate species, which may serve as model systems for probing and modulating phosphate homeostasis in biological and biomedical researches.
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