Phosphate and polyphosphate anion recognition by a dinuclear copper(ii) complex of an unsymmetrical squaramide

In the search for receptors suitable for the recognition of phosphate or polyphosphate anions, a new unsymmetrical squaramide-based ligand bearing dipicolylamine (dpa) and ethylpiperazine units (L) was designed and prepared. The acid-base reactions of L, its copper(ii) complexation behaviour and the binding of phosphate and polyphosphate anions by the copper(ii) complexes used as receptors were evaluated. ¹H and ¹³C NMR titrations of L performed in D₂O allowed the determination of its protonation sequence. The ligand L is able to coordinate two copper(ii) cations forming thermodynamically stable dinuclear complexes likely having two water molecules bound to each metal centre, as supported by DFT calculations. Coordinated water molecules can be replaced by the O-donors of the phosphate/polyphosphate anions. The potentiometric studies showed that at 2 : 1 Cu²⁺ : L ratio the dinuclear [Cu₂LH_-1]³⁺ species predominates from pH ∼ 5 to ∼7, and hydroxodinuclear species prevail at pH > 7. ¹H NMR experiments in both H₂O/D₂O 9 : 1 v/v and in DMSO proved that copper(ii) coordination provokes deprotonation of the squaramide NH bound to the ethylpiperazine moiety, resulting in [Cu₂LH_-1]³⁺ species. The dicopper(ii) complexes of L, [Cu₂LH_-i]^4-i, were used as the receptor for the uptake of some phosphate and polyphosphate anions. The receptor presents very high association constants with HPPi^3- and ATP^4- and the determined K_eff showed that at physiological pH ATP^4- is selectively taken from an aqueous solution containing phenylphosphate (PhPO₄^2-), aminoethylphosphate (Haep^-), AMP^2- and ADP^3-, but HPPi^3- strongly interferes. DFT calculations suggest that the strong interaction with HPPi^3- and ATP^4- is related to the simultaneous coordination of the polyphosphate unit to the two copper(ii) centres.