Chelation Behaviors of 3,4,3-LI(1,2-HOPO) with Lanthanides and Actinides Implicated by Molecular Dynamics Simulations

The hydroxypyridinone ligand 3,4,3-LI(1,2-HOPO) (denoted as t-HOPO) is a potential chelator agent for decorporation of in vivo actinides (An), while its coordination modes with actinides and the dynamics of the complexes (An(t-HOPO)) in aqueous phase remain unclear. Here, we report molecular dynamics simulations of the complexes with key actinides (Am³⁺, Cm³⁺, Th⁴⁺, U⁴⁺, Np⁴⁺, Pu⁴⁺) to study their coordination and dynamic behaviors. For comparison, the complexation of the ligand with a ferric ion and key lanthanides (Sm³⁺, Eu³⁺, Gd³⁺) was also studied. The simulations show that the nature of metal ions determines the properties of the complexes. The t-HOPO in the Fe^III(t-HOPO)^1- complex ion formed a compact and rigid cage to encapsulate the ferric ion, which was hexa-coordinated. Ln³⁺/An³⁺ cations were ennea-coordinated with eight ligating oxygen atoms from t-HOPO and one from an aqua ligand, and An⁴⁺ cations were deca-coordinated with a second aqua ligand. The t-HOPO shows strong affinity for metal ions (stronger for An⁴⁺ than Ln³⁺/An³⁺) benefited from its high denticity and its flexible backbone. Meanwhile, the complexes displayed different dynamic flexibilities, with the An^IV(t-HOPO) complexes more significant than the Others, and in the An^IV(t-HOPO) complexes, the fluctuation of the t-HOPO ligand was highly correlated with that of the eight ligating O atoms. This is attributed to the more compact conformation of the ligand, which raises backbone tension, and the competition of the aqua ligand against the t-HOPO ligand in coordinating with the tetravalent actinides. This work enriches our understanding on the structures and conformational dynamics of the complexes of actinides with t-HOPO and is expected to benefit the design of HOPO analogues for actinide sequestering.