Carole Bresson

A method to online quantify P and S along with elements representing radionuclides of interest in the nuclear sector, was developed by ICP-MS/MS operating in conditions mimicking miniaturized IMAC.

The objective of this work was to develop an actinide-specific monolithic support in capillary designed to immobilize precise Pu:Am ratios and its coupling to inductively coupled plasma mass spectrometry (ICP-MS) for immobilized metal affinity chromatography applications. This format offers many advantages, such as reducing the sample amount and waste production, which are of prime importance when dealing with highly active radioelements. Four organic phosphorylated-based monoliths were synthesized in situ through UV photo-polymerization in capillary and characterized. The capillary coupling to ICP-MS was set up in conventional laboratory using Th and Sm as chemical analogues of Pu and Am. A dedicated method was developed to quantify online Th and Sm amounts immobilized on the monolithic capillaries, allowing to select the best monolith candidate poly(BMEP-co-EDMA)_adp. By precisely adjusting the elemental composition in the loading solutions and applying the developed quantification method, the controlled immobilization of several Th:Sm molar ratios onto the monolith was successful. Finally, the capillary ICP-MS coupling was transposed in a glove box and by applying the strategy developed to design the monolithic support using Th and Sm, the immobilization of a 10.5 ± 0.2 (RSD = 2.3%, n = 3) Pu:Am molar ratio reflecting Pu ageing over 48 years was achieved in a controlled manner on poly(BMEP-co-EDMA)_adp. Hence, the new affinity capillary monolithic support was validated, with only hundred nanograms or less of engaged radioelements and can be further exploited to precisely determine differential interactions of Pu and Am with targeted biomolecules in order to better anticipate the effect of Am on Pu biodistribution. Graphical Abstract

A new method of HILIC coupled to ESIMS and ICPMS, combined with online specific isotopic dilution has been developed and downscaled to determine the affinity of hydrophilic molecules towards ^natSm and ^natNd.

A cyclic tetra-phosphorylated biomimetic peptide (pS1368) has been proposed as a promising starting structure to design a decorporating agent of uranyl (UO₂²⁺) due to its affinity being similar to that of osteopontin (OPN), a target UO₂²⁺ protein in vivo. The determination of this peptide’s selectivity towards UO₂²⁺ in the presence of competing endogenous elements is also crucial to validate this hypothesis. In this context, the selectivity of pS1368 towards UO₂²⁺ in the presence of Ca²⁺, Cu²⁺ and Zn²⁺ was determined by applying the simultaneous coupling of hydrophilic interaction chromatography (HILIC) to electrospray ionization (ESI–MS) and inductively coupled plasma (ICP-MS) mass spectrometry. Sr²⁺ was used as Ca²⁺ simulant, providing less challenging ICP-MS measurements. The separation of the complexes by HILIC was first set up. The selectivity of pS1368 towards UO₂²⁺ was determined in the presence of Sr²⁺, by adding several proportions of the latter to UO₂(pS1368). UO₂²⁺ was not displaced from UO₂(pS1368) even in the presence of a ten-fold excess of Sr²⁺. The same approach has been undertaken to demonstrate the selectivity of pS1368 towards UO₂²⁺ in the presence of Cu²⁺, Zn²⁺ and Sr²⁺ as competing endogenous cations. Hence, we showed that pS1368 was selective towards UO₂²⁺ in the presence of Sr²⁺, but also in the presence of Cu²⁺ and Zn²⁺. This study highlights the performance of HILIC-ESI-MS/ICP-MS simultaneous coupling to assess the potential of molecules as decorporating agents of UO₂²⁺. Graphical Abstract

Electrospray ionization mass spectrometry (ESIMS) is traditionally used to analyse organic molecules, but can also be used to carry out elemental speciation studies. The challenge is here to determine the isotopic composition of elements contained in chemical species by this technique, in addition to their quantification and structural characterisation. In the present work, we determined by ESIMS the isotope ratios of samarium (Sm) and neodymium (Nd) involved in complexes containing polyaminocarboxylic acids, namely EDTA and DTPA. To this end, we developed a user-friendly deconvolution method to remove the ligand isotopic contributions from the abundance ratios measured in the ESI mass spectra of the complexes, and thus obtaining the isotopic composition of the free lanthanides. By applying the deconvolution method to EDTA complexes containing natural and enriched samarium, we obtained the ^natSm and the ^147–149Sm isotopic composition directly from the mass spectra of the chemical species recorded by commercial ESI mass spectrometers, equipped with a triple quadrupole analyser (QqQ) or a linear ion trap (LIT). The isotopic composition of ^natSm and ^147–149Sm were determined with a trueness better than 3.5% and 2% by ESI-QqQ-MS and better than 1% and 2% by ESI-LIT-MS, with a repeatability globally better than 3% at k = 2, for isotopes of relative abundances greater than 1% in samples. This method was successfully applied to determine ^natNd and ^natSm isotopic compositions from ^natNd–EDTA, ^natSm–DTPA and ^natNd–DTPA mass spectra.

This article reviews the elemental and isotopic analysis of radionuclides using collision–reaction cell technology in ICP-MS applications.

The impact of the contamination of living organisms by actinide elements has been a constant subject of attention since the 1950s. But to date still little is understood. Ferritin is the major storage and regulation protein of iron in many organisms, it consists of a protein ring and a ferrihydric core at the center. This work sheds light on the interactions of early actinides (Th, Pu) at oxidation state +IV with ferritin and its ability to store those elements at physiological pH compared to Fe. The ferritin–thorium load curve suggests that Th^IV saturates the protein (2840 Th atoms per ferritin) in a similar way that Fe does on the protein ring. Complementary spectroscopic techniques (spectrophotometry, infrared spectroscopy, and X‐ray absorption spectroscopy) were combined with molecular dynamics to provide a structural model of the interaction of Th^IV and Pu^IV with ferritin. Comparison of spectroscopic data together with MD calculations suggests that Th^IV and Pu^IV are complexed mainly on the protein ring and not on the ferrihydric core. Indeed from XAS data, there is no evidence of Fe neighbors in the Th and Pu environments. On the other hand, carboxylates from amino acids of the protein ring and a possible additional carbonate anion are shaping the cation coordination spheres. This thorough description from a molecular view point of Th^IV and Pu^IV interaction with ferritin, an essential iron storage protein, is a cornerstone in comprehensive nuclear toxicology.

The study of isotopic variations of endogenous and toxic metals in fluids and tissues is a recent research topic with an outstanding potential in biomedical and toxicological investigations. Most of the analyses have been performed so far in bulk samples, which can make the interpretation of results entangled, since different sources of stress or the alteration of different metabolic processes can lead to similar variations in the isotopic compositions of the elements in bulk samples. The downscaling of the isotopic analysis of elements at the sub-cellular level, is considered as a more promising alternative. Here we present for the first time the accurate determination of Cu isotopic ratios in four main protein fractions from lysates of neuron-like human cells exposed in vitro to 10 μM of natural uranium for seven days. These protein fractions were isolated by Size Exclusion Chromatography and analysed by Multi-Collector Inductively Coupled Plasma Mass Spectrometry to determine the Cu isotopic variations in each protein fraction with regard to the original cell lysate. Values obtained, expressed as δ⁶⁵Cu, were −0.03 ± 0.14 ‰ (U_c, k = 2), −0.55 ± 0.20 ‰ (U_c, k = 2), −0.32 ± 0.21 ‰ (U_c, k = 2) and +0.84 ± 0.21 ‰ (U_c, k = 2) for the four fractions, satisfying the mass balance. The results obtained in this preliminary study pave the way for dedicated analytical developments to identify new specific disease biomarkers, to gain insight into stress-induced altered metabolic processes, as well as to decipher metabolic pathways of toxic elements.