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

Europium(LII) F-7(0) --> D-5(0) excitation spectroscopy is used to determin e 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 t hose metal complexes that contain negatively charged ligands and more than one water molecule in the first coordination sphere of EU3+ have their wate r molecules displaced by saturating concentrations of carbonate or phosphat e. Conditional dissociation constants, K-d's, for Eu3+-ligand complexes wit h phosphate or carbonate are determined from titrations wherein the EU3+ ex cited state lifetimes are monitored. For phosphate, K-d's lie in the range 1.2-90 mM, whereas for carbonate, the range is 35-200 mM. The titrations al so indicate that only a single anion binds to a metal chelate complex and t hat the single anion may, under saturating anion concentrations, displace o n average more than one, but not all, first coordination sphere water molec ules. Eu3+7F0 --> D-5(0) excitation spectra indicate that, in some cases, m any different Eu3+-containing species are in fast exchange in the presence of added anion, presumably involving different numbers of first coordinatio n sphere water molecules. Our results show that, under physiological condit ions, phosphate and carbonate will, on average, displace less than half of a water molecule from the first coordination sphere of a typical contrast a gent and suggest that the effect on proton spin relaxation is likely to be minimal.