Substitution of gadolinium ethylenediaminetetraacetate with phosphites: towards gadolinium deposit in nephrogenic systemic fibrosis

In neutral media, reactions of gadolinium ethylenediaminetetraacetates with phosphorous acid result in the formation of the mixed-ligand polymeric complex K3n[Gd(EDTA)(HPO3)]n·7nH2O (1) and dimeric complex Na6[Gd2(EDTA)2(HPO3)2]·2.5NaCl·21H2O (2) (H4EDTA = ethylenediaminetetraacetic acid) in warm solution. Further substitution with citric acid gives the monomeric gadolinium citrate with EDTA (NH4)2Na[Gd(EDTA)(H2cit)]·4H2O (3). The compounds were characterized by elemental analysis, single crystal X-ray diffraction, FT-IR, ESI-MS and thermogravimetric analysis. Structural analysis indicates that three coordinated water molecules in the gadolinium ethylenediaminetetraacetate trihydrates are replaced by phosphite ions (HPO32−) in the compounds 1 and 2. Gadolinium atoms are octa-coordinated by EDTA and the phosphite ion, the latter links adjacent Gd–EDTA units to generate an infinite one-dimensional chain in compound 1 and a dimeric octatomic ring in 2. In complex 3, coordinated water molecules were substituted by the α-hydroxy, α-carboxy and β-carboxy groups of citrate. Citrate is favourable for inhibiting the formation of Gd–EDTA phosphite. All the complexes are very easily soluble in water. The solution behavior of the isostructural lanthanum complexes was probed with 13C and 31P NMR spectra in D2O for comparison. ESI-MS analysis and recrystallization proved that complexes 1 and 2 dissociate to the monomeric unit of Gd–EDTA and free HPO32− in aqueous solution. Substitutions of gadolinium ethylenediaminetetraacetates to 1 and 2 are attributed to be the cause of nephrogenic systemic fibrosis in some way.