Kinetically Inert Macrocyclic Europium(III) Receptors for Phosphate

The significant role that phosphate plays in environmental water pollution and biomedical conditions such as hyperphosphatemia highlights the need to develop robust receptors that can sequester the anion effectively and selectively from complex aqueous media. Toward that goal, four macrocyclic tris-bidentate 1,2-hydroxypyridonate (HOPO) europium(III) complexes containing either a cyclen, cyclam, TACN, or TACD ligand cap were synthesized and evaluated as phosphate receptors. The solubility of Eu^III-TACD-HOPO in water was insufficient for luminescent studies. Whereas Eu^III-cyclen-HOPO is eight coordinate with two inner-sphere water molecules, both Eu^III-cyclam-HOPO and Eu^III-TACN-HOPO are nine coordinate with three inner-sphere water molecules, suggesting that the two coordination states are very close in energy. As observed previously with linear analogues of tripodal HOPO complexes, there is no relationship between the number of inner-sphere water molecules and the affinity of the complex for phosphate. Whereas all three complexes do bind phosphate, Eu^III-cyclen-HOPO has the highest affinity for phosphate with the anion displacing both of its inner-sphere water molecules. On the other hand, only one or two of the three inner-sphere water molecules of Eu^III-TACN-HOPO and Eu^III-cyclam-HOPO are displaced by phosphate, respectively. All three complexes are highly selective for phosphate over other anions, including arsenate. All three complexes are highly stable. Eu^III-cyclen-HOPO and, to a lesser extent, Eu^III-TACN-HOPO are more kinetically inert than the linear Eu^III-Ser-HOPO. Eu^III-cyclam-HOPO, on the other hand, is not. This study highlights the significant effect that minor changes in the ligand cap can have on both the ligand exchange rate and affinity for phosphate of tripodal 1,2-dihydroxypyridinonate complexes.