Folding Dynamics of 3,4,3-LI(1,2-HOPO) in Its Free and Bound State with U(4+) Implicated by MD Simulations

The octadentate hydroxypyridonate ligand 3,4,3-LI(1,2-HOPO) (t-HOPO) shows strong binding affinity with actinide cations and is considered as a promising decorporation agent used to eliminate in vivo actinides, while its dynamics in its unbound and bound states in the condensed phase remain unclear. In this work, by means of MD simulations, the folding dynamics of intact t-HOP(O) in its neutral (t-HOPO0) and in its deprotonated state (t-HOPO(4)(−)) were studied. The results indicated that the deprotonation of t-HOPO in the aqueous phase significantly narrowed the accessible conformational space under the simulated conditions, and it was prepared in a conformation that could conveniently clamp the cations. The simulation of U(IV)-t-HOPO showed that the tetravalent uranium ion was deca-coordinated with eight ligating O atoms from the t-HOPO(4)(−) ligand, and two from aqua ligands. The strong electrostatic interaction between the U(4+) ion and t-HOPO(4)(−) further diminished the flexibility of t-HOPO(4)(−) and confined it in a limited conformational space. The strong interaction between the U4+ ion and t-HOPO(4)(−) was also implicated in the shortened residence time of water molecules.