Hinokitiol, an Advanced Bidentate Ligand for Uranyl Decorporation

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., Mn²⁺, Zn²⁺, Co²⁺, and Ni²⁺) 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.