<p>Designing proper ligands for selective and effective separating Th/U is vital for achieving efficient utilization of nuclear fuel in the thorium molten salt reactors (TMSRs). Four novel diamide ligands L_H, L_α, L_β and L_γ were designed based on the pyrazole-substituted 4,5-diazafluorene framework, and the scalar relativistic density functional theory (DFT) calculations were performed to elucidate the complexation behavior and separation selectivity of Th⁴⁺/UO₂²⁺. The results revealed that the interactions between the metal centers and the donor atoms were coordination bonds and dominated by electrostatic and orbital interactions. Thermodynamic calculations indicated that the complexation strength and the coordination reactivity were both enhanced in solvents with higher polarity. Moreover, the β- and γ-substituted hydroxyl groups could improve the coordination ability of the ligands, and all studied ligands exhibited excellent selectivity for Th⁴⁺ over UO₂²⁺, with selectivity coefficient exceeding 99%. These findings may provide a theoretical strategy for the design of high-performance ligands applied to the nuclear fuel cycle of TMSRs.</p>