Hinokitiol, an Advanced Bidentate Ligand for Uranyl Decorporation

Abstract

Despite the critical role actinide decorporation agents play in the emergency treatment of people in nuclear accidents and other scenarios that may cause internal contamination of actinides, new ligands have seldom been reported in recent decades because the current inventory has been limited to only a handful of functional groups. Therefore, new functional groups are always being urgently sought for the introduction of advanced actinide decorporation agents. Herein, a tropolone derivative, 2-hydroxy-6-(propan-2-yl)cyclohepta-2,4,6-trien-1-one (Hinokitiol or Hino), is proposed to be a promising candidate for this purpose by virtue of its well-demonstrated high membrane permeability and high affinity for metal ions. The coordination stoichiometry of Hino with uranyl is demonstrated to be 3:1 both in an aqueous solution (pH 7.4) and in the solid state. The results of a liquid−liquid extraction experiment further show that Hino exhibits strong chelating ability and selectivity toward uranyl over biological essential metal ions (i.e., Mn 2+ , Zn 2+ , Co 2+ , and Ni 2+ ) with an extraction efficiency of >90.0%. The in vivo uranyl removal efficacies of Hino in kidneys and bone of mice are demonstrated to be 67.0% and 32.3%, respectively. On the basis of the observations described above, it is highly possible that further modification of Hino will lead to a large family of multidentate agents with enhanced uranyl decorporation ability.

In Vivo Uranium Decorporation by a Tailor-Made Hexadentate Ligand

“…An assay was first performed using ZnNa 3 -DTPA and TAM-2LI-MAM 2 as decorporation agents. Very significantly, in the TAM-2LI-MAM group, the U­(VI) removal efficiency increases to an ideal 95.4% in the kidneys and 81.2% in femurs (Figure b), which is the highest uranyl decorporation ratio reported so far based on a detailed comparison with several representative tetra- and bidentate ligands and ZnNa 3 -DTPA (Figure and Table S11). In sharp contrast, there is a minimal change in U­(VI) content in the ZnNa 3 -DTPA groups (Figure b).…”

Efficient removal of uranium from the kidneys by a picolinate-based pentadentate chelator

“…12 Consequently, bidentate chelating agents tend to bind uranyl with a high stoichiometry (2 : 1 or 3 : 1), a factor contributing to their limited removal efficiency due to the low local concentration of chelators under physiological conditions. 13,14 Subsequent studies on polydentate ligands forming 1 : 1 uranyl complexes suggest that ligands adhering to the planar coordination mode of uranyl are generally superior to those with mismatched geometries, potentially explaining the poor uranium removal rate of DTPA. Consequently, our recent work has focused on optimizing planar ligands from the perspectives of coordinating numbers and binding affinities.…”

Uranium extraction from seawater: material design, emerging technologies and marine engineering

“…However, benefiting from the latest advancement in uranium coordination chemistry, new effective ligands and promising design principles, such as the preorganization of collaborative ligands, have been developed recently. 104–107 More discussion in this regard will be presented in Section 3.2.3. With further studies on the mechanistic insights into the uranyl–ligand interactions, next-generation ligands with improved affinity and selectivity to uranyl ions in ocean environments could be envisioned.…”