Development of Decorporation Agents for the Actinides

A Macrocyclic Chelator That Selectively Binds Ln4+ over Ln3+ by a Factor of 1029

“…Developing the chemistry of these ligands is needed to understand their possible applications. [117][118][119] While lanthanides and actinides can exhibit significantly different chemical behaviors, the use of lanthanides as actinide analogs has enabled the advancement of actinide chemistry and continues to be useful. [120][121][122][123][124][125][126][127] For example, Ce 4+ and Pu 4+ have nearly identical ionic radii (0.87 and 0.86 Å, respectively) 128 and similar shifts in the 4+/3+ reduction potentials in aqueous solutions.…”

The Influence of Linker Geometry in Bis(3‐hydroxy‐N‐methyl‐pyridin‐2‐one) Ligands on Solution Phase Uranyl Affinity

“…Significantly, the PEG-4Li-Me-3,2-HOPO ligand L 4 H 2 bound most strongly to the uranyl cation, which supports earlier observations from in vivo chelation studies and crystallographic studies. [32,36] The o-phenylene linker in L 7 H 2 imparted the second highest uranyl affinity, rivaling that of L 4 H 2 , and had a higher affinity than the similarly-sized L 2 H 2 . Because these results are generally independent of ligand acidity, it can be concluded that ligand geometry imparted by the linker structure (and perhaps ligand preorganization in the case of L 7 H 2 ) is responsible for the observed uranyl affinities.…”

“…Examples of biologically relevant investigations include that of Czerwinski and co-workers that addresses uranyl speciation with the naturally-occuring siderophore desferrioxamine (DFO) [29] as well as those by Durbin and co-workers that examine the in vivo decorporating ability of polybidentate catecholamides and their structural analogs towards the uranyl and transuranic cations. [30][31][32][33] These latter studies revealed that 4-or 5-carbon linear linkers provided optimal decorporating ability to poly-bidentate ligands, but the detailed thermodynamic rationale for this result is relatively unexplored.…”

Comparative Evaluation of Disodium Edetate and Diethylenetriaminepentaacetic Acid as Iron Chelators to Prevent Metal -Catalyzed Destabilization of a Therapeutic Monoclonal Antibody

“…The reported LD50 of DTPA (rat, IP) is 0.59 g/kg 38 . DTPA is hydrophilic and is unlikely to penetrate cells to any great extent 39 . Early pharmacokinetic studies in animals 40,41 and in humans 42 showed that DTPA is very poorly distributed into tissues and is rapidly eliminated from the body via urine excretion after either intravenous injection or inhalation.…”