Curium(iii) citrate speciation in biological systems: a europium(iii) assisted spectroscopic and quantum chemical study

Abstract

Citrate complexes are the dominant binding form of trivalent actinides and lanthanides in human urine at pH < 6. Hence, an accurate prediction of the speciation of these elements in the presence of citrate is crucial for the understanding of their impact on the metabolism of the human organism and the corresponding health risks. We studied the complexation of Cm(III) and Eu(III), as representatives of trivalent actinides and lanthanides, respectively, in aqueous citrate solution over a wide pH range using time-resolved laser-induced fluorescence spectroscopy. Four distinct citrate complexes were identified and their stability constants were determined, which are MHCit(0), M(HCitH)HCit(2-), M(HCit)(2)(3-), and M(Cit)(2)(5-) (M = Cm, Eu). Additionally, there were also indications for the formation of MCit(-) complexes. Structural details on the EuHCit(0) and EuCit(-) complexes were obtained with FT-IR spectroscopy in combination with density functional theory calculations. IR spectroscopic evidence for the deprotonation of the hydroxyl group of the citrate ion in the EuCit(-) complex is presented, which also revealed that the complexation of the Eu(3+) ion takes place not only through the carboxylate groups, like in EuHCit(0), but additionally via the hydroxylate group. In both EuHCit(0) and EuCit(-) the carboxylate binding mode is mono-dentate. Under a very low metal : citrate ratio that is typical for human body fluids, the Cm(III) and Eu(III) speciation was found to be strongly pH-dependent. The Cm(III) and Eu(III) citrate complexes dominant in human urine at pH < 6 were identified to be Cm(HCitH)HCit(2-) and a mixture of Eu(HCitH)HCit(2-) and EuHCit(0). The results specify our previous in vitro study using natural human urine samples (Heller et al., Chem. Res. Toxicol., 2011, 24, 193-203).

Interaction of Eu(III) with mammalian cells: Cytotoxicity, uptake, and speciation as a function of Eu(III) concentration and nutrient composition

“…Table 2 summarizes the spectroscopic parameters that were determined for different samples. The Eu 3+ aqua ion exhibits two nearly symmetric luminescence peaks at 591.7 ± 0.2 nm and 616.4 ± 0.2 nm with a R E/M of 0.5 ± 0.2 and an emission lifetime of 110 ± 10 ls corresponding to 9.1 ± 0.5 water molecules in the first coordination shell (Bünzli and Choppin, 1989;Heller et al, 2012;Moulin et al, 1999). Compared to that, significant spectroscopic changes were observed for Eu(III) in DMEM and complete cell culture medium (cf.…”

“…The thermodynamic database used was the LLNL.dat, as delivered with GWB. This data base was modified, i.e., it was supplemented with current data for Eu(III) citrate species (Eu(HCit), Eu(HCitH)(HCit) 2À , Eu(HCit) 2 3À , EuCit 2 5À ) (Heller et al, 2012), EuPO 4 (s), EuOHCO 3 (c) (HYDRA database) (Puigdomenech, 2009) (Ansoborlo, 2013). Although various amino acids and other organic substances are present in the DMEM solution (cf.…”

“…(4) (Kimura and Choppin, 1994;Kimura et al, 1996). e Heller et al (2012), Bünzli and Choppin (1989) and Moulin et al (1999). f DMEM was prepared based on the product information given by Biochrom (2013), however, in the absence of any organic substances.…”

“…The experiments were performed as a function of the metal ion concentration and nutrient composition in order to correlate the behavior of the cells to the aqueous metal ion speciation. Besides the influence of fetal bovine serum (FBS) on the Eu(III) cytotoxicity and uptake, also that of citrate was studied because of its physiological relevance in all body fluids, especially in blood and urine (Boothby and Adams, 1934;Heller et al, 2011Heller et al, , 2012. The Eu(III) speciation in the nutrient media was investigated by thermodynamic modeling, solubility studies, ultrafiltration, ultracentrifugation, and time-resolved laser-induced fluorescence spectroscopy (TRLFS).…”

Curious curium

“…Because the energy and intensity of curium emission depend on the coordination of the metal ion, time-resolved laser-induced spectroscopy has been used extensively to characterize curium compounds. The high sensitivity of this technique is important for the detection and analysis of different species of curium in environmental and biological media 2 , especially relevant to current issues involving waste storage, remediation and potential transport in terrestrial and freshwater ecosystems. As hard Lewis acids, curium ions form strong hydrolysis complexes in neutral to basic solutions and very stable compounds with hard bases such as oxygen or fluoride donors.…”