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

Abstract

In neutral media, reactions of gadolinium ethylenediaminetetraacetates with phosphorous acid result in the formation of the mixed-ligand polymeric complex K_3n[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.