Effects of preorganization in the chelation of UO22+by hydroxamate ligands: cyclic PIPO−vs.linear NMA−

Sornosa-Ten, Alejandra; Jewuła, Paweł; Fodor, Tamás; Brandès, Stéphane; Sladkov, Vladimir; Rousselin, Yoann; Stern, Christine; Chambron, Jean‐Claude; Meyer, Michel

doi:10.1039/c8nj00166a

Cited by 13 publications

(28 citation statements)

References 74 publications

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“…The main difference between DFO* and DFOcyclo* is the cyclic structure of the additional hydroxamic acid group derived from 1,2-PIPOH. While open-chain hydroxamic acids, including DFO, are known to exist as a mixture of two E ( trans ) and Z ( cis ) isomers [28–30], the Z configuration of the hydroxamate group is imparted by the cyclic structure of PIPO - , and is obviously more favourable for Zr 4+ coordination and could therefore result in a more stable complex [31]. The crystal structure of a Zr 4+ complex in which the metal is coordinated by four 1,2-PIPO - chelates has been reported previously [32].…”

Section: Resultsmentioning

confidence: 99%

Direct comparison of the in vitro and in vivo stability of DFO, DFO* and DFOcyclo* for 89Zr-immunoPET

Raavé

Sandker

Adumeau

et al. 2019

Eur J Nucl Med Mol Imaging

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Purpose Currently, the most commonly used chelator for labelling antibodies with 89 Zr for immunoPET is desferrioxamine B (DFO). However, preclinical studies have shown that the limited in vivo stability of the 89 Zr-DFO complex results in release of 89 Zr, which accumulates in mineral bone. Here we report a novel chelator DFOcyclo*, a preorganized extended DFO derivative that enables octacoordination of the 89 Zr radiometal. The aim was to compare the in vitro and in vivo stability of [ 89 Zr]Zr-DFOcyclo*, [ 89 Zr]Zr-DFO* and [ 89 Zr]Zr-DFO. Methods The stability of 89 Zr-labelled chelators alone and after conjugation to trastuzumab was evaluated in human plasma and PBS, and in the presence of excess EDTA or DFO. The immunoreactive fraction, IC 50 , and internalization rate of the conjugates were evaluated using HER2-expressing SKOV-3 cells. The in vivo distribution was investigated in mice with subcutaneous HER2 + SKOV-3 or HER2 − MDA-MB-231 xenografts by PET/CT imaging and quantitative ex vivo tissue analyses 7 days after injection. Results 89 Zr-labelled DFO, DFO* and DFOcyclo* were stable in human plasma for up to 7 days. In competition with EDTA, DFO* and DFOcyclo* showed higher stability than DFO. In competition with excess DFO, DFOcyclo*-trastuzumab was significantly more stable than the corresponding DFO and DFO* conjugates ( p < 0.001). Cell binding and internalization were similar for the three conjugates. In in vivo studies, HER2 + SKOV-3 tumour-bearing mice showed significantly lower bone uptake ( p < 0.001) 168 h after injection with [ 89 Zr]Zr-DFOcyclo*-trastuzumab (femur 1.5 ± 0.3%ID/g, knee 2.1 ± 0.4%ID/g) or [ 89 Zr]Zr-DFO*-trastuzumab (femur 2.0 ± 0.3%ID/g, knee 2.68 ± 0.4%ID/g) than after injection with [ 89 Zr]Zr-DFO-trastuzumab (femur 4.5 ± 0.6%ID/g, knee 7.8 ± 0.6%ID/g). Blood levels, tumour uptake and uptake in other organs were not significantly different at 168 h after injection. HER2 − MDA-MB-231 tumour-bearing mice showed significantly lower tumour uptake ( p < 0.001) after injection with [ 89 Zr]Zr-DFOcyclo*-trastuzumab (16.2 ± 10.1%ID/g) and [ 89 Zr]Zr-DFO-trastuzumab (19.6 ± 3.2%ID/g) than HER2 + SKOV-3 tumour-bearing mice (72.1 ± 14.6%ID/g and 93.1 ± 20.9%ID/g, respectively), while bone uptake was similar. Conclusion 89 Zr-labelled DFOcyclo* and DFOcyclo*-trastuzumab...

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Section: Resultsmentioning

confidence: 99%

Direct comparison of the in vitro and in vivo stability of DFO, DFO* and DFOcyclo* for 89Zr-immunoPET

Raavé

Sandker

Adumeau

et al. 2019

Eur J Nucl Med Mol Imaging

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“…All thermodynamic complex formation studies were performed in 0. The detailed procedure and equipment used to perform potentiometric and direct spectrophotometric titrations has been described in detail elsewhere (Sornosa-Ten et al, 2018).…”

Section: Thermodynamic Complexation Studiesmentioning

confidence: 99%

Efficiency of dihydroxamic and trihydroxamic siderochelates to extract uranium and plutonium from contaminated soils

Février

Coppin

Pierrisnard

et al. 2021

Journal of Environmental Radioactivity

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Actinide-based mineral phases occurring in contaminated soils can be solubilized by organic chelators excreted by plants, such as citrate. Herein, the efficiency of citrate towards U and Pu extraction is compared to that of siderophores, whose primary function is the acquisition of iron(III) as an essential nutrient and growth factor for many soil microorganisms. To that end, we selected desferrioxamine B (DFB) as an emblematic bacterial trishydroxamic siderophore and a synthetic analog, abbreviated (L Cy,Pr )H2, of the tetradentate rhodotorulic acid (RA) produced by yeasts. Firstly, the uranyl speciation with both ligands was assessed in the pH range 2-11 by potentiometry and visible absorption spectrophotometry. Equilibrium constants and absorption spectra for three [UO2(DFB)Hh] (h-1)+ (h = 1-3) and five [UO2(L Cy,Pr )lHh] (2+h-2l)+ (-1  h  1 for l = 1 and h = 0-1 for l = 2) solution complexes were determined at 25.0 °C and I = 0.1 M KNO3. Similar studies for the Fe 3+ /(L Cy,Pr ) 2system revealed the formation of five species having [

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“…have also shown that thorium binding gives rise to a typical band centered at 230 nm ( ε = 17 600 M −1 cm −1 ), with a significant absorption around 200 nm [29]. Accordingly, an experimental ACE setup equipped with an UV detector could be used to monitor the migration in the capillary, despite the fact that thorium(IV) is spectroscopically silent, unlike uranium(VI) [6,44]. Hence, all injected samples contained a fixed amount of ligand (10 –4 M), while runs were made in triplicates using HClO 4 /NaClO 4 solutions as BGE ( I = 0.1 M) containing increasing amounts of thorium(IV) (0–5 × 10 –3 M).…”

Section: Resultsmentioning

confidence: 99%

“…In that respect, attempts to use ESI‐MS have been reported [3‐5]. In spite of the mild ionization processes and rapid solvent evaporation in the source, both the abundance and nature of the gas‐phase species do not necessarily mirror the solution speciation at a given concentration level [6,7], as equilibria for labile species are displaced while droplets are concentrating.…”

Section: Introductionmentioning

confidence: 99%

Assignment of complex species by affinity capillary electrophoresis: The case of Th(IV)‐desferrioxamine B

2020

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The electrophoretic mobility change of desferrioxamine B (DFO) was monitored by UV absorption spectrophotometry upon increasing the thorium(IV) concentration in the background electrolyte at two acidities ([HClO4]Tot = 0.0316 and 0.0100 M). These data enabled to assess the speciation model and to determine the equilibrium constant of [Th(DFO)H2]3+ at fixed ionic strength (I = 0.1 M (H,Na)ClO4). Affinity capillary electrophoresis (ACE) turned out to be most helpful in identifying the complexed species by ascertaining its charge and protonation state. The assignment of the correct stoichiometry relied on the reliable estimation of the electrophoretic mobility by assuming similar hydrodynamic radii for (DFO)H4+ and the chelate. The value of the apparent equilibrium constant (log β112 = 38.7 ± 0.4) obtained by ACE compares favorably well with those reported in the literature for thorium and a range of other metal ions, according to a linear free‐energy relationship. This method is useful for studying metal‐ligand binding equilibria and provides valuable information for further modelling the behavior of tetravalent actinides under environmental conditions. Structural information about the prevalent solution species in acidic conditions was gained by DFT calculations, confirming the bishydroxamato coordination mode of Th4+ by the diprotonated ligand.

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Effects of preorganization in the chelation of UO₂²⁺by hydroxamate ligands: cyclic PIPO⁻vs.linear NMA⁻

Abstract: Thanks to preorganization, 1,2-PIPOH, the six-membered ring cyclic hydroxamic acid, binds uranyl six times more strongly than its linear, methyl-substituted homolog (NMAH).

Cited by 13 publications

References 74 publications

Direct comparison of the in vitro and in vivo stability of DFO, DFO* and DFOcyclo* for 89Zr-immunoPET

Direct comparison of the in vitro and in vivo stability of DFO, DFO* and DFOcyclo* for 89Zr-immunoPET

Efficiency of dihydroxamic and trihydroxamic siderochelates to extract uranium and plutonium from contaminated soils

Assignment of complex species by affinity capillary electrophoresis: The case of Th(IV)‐desferrioxamine B

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