Displacement of Inner-Sphere Water Molecules from Eu3+ Analogues of Gd3+ MRI Contrast Agents by Carbonate and Phosphate Anions: Dissociation Constants from Luminescence Data in the Rapid-Exchange Limit

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Abstract
Europium(III) 7F0 → 5D0 excitation spectroscopy is used to determine if the anions carbonate and phosphate present in physiological fluids are able to displace water molecules from the first coordination sphere of Eu3+ analogues of Gd3+ MRI contrast agents. A lengthening of the Eu3+ excited state lifetime in the presence of millimolar concentrations of carbonate or phosphate indicates that water molecules are displaced by an anion. Only those metal complexes that contain negatively charged ligands and more than one water molecule in the first coordination sphere of Eu3+ have their water molecules displaced by saturating concentrations of carbonate or phosphate. Conditional dissociation constants, Kd's, for Eu3+−ligand complexes with phosphate or carbonate are determined from titrations wherein the Eu3+ excited state lifetimes are monitored. For phosphate, Kd's lie in the range 1.2−90 mM, whereas for carbonate, the range is 35−200 mM. The titrations also indicate that only a single anion binds to a metal chelate complex and that the single anion may, under saturating anion concentrations, displace on average more than one, but not all, first coordination sphere water molecules. Eu3+ 7F0 → 5D0 excitation spectra indicate that, in some cases, many different Eu3+-containing species are in fast exchange in the presence of added anion, presumably involving different numbers of first coordination sphere water molecules. Our results show that, under physiological conditions, phosphate and carbonate will, on average, displace less than half of a water molecule from the first coordination sphere of a typical contrast agent and suggest that the effect on proton spin relaxation is likely to be minimal.