Complete Supramolecular Encapsulation of Paraquat for Detoxification

Partial complexation of paraquat (PQ2+), a bipyridinium herbicide with high acute toxicity and no specific antidote, has been well established, whereas its complete encapsulation for detoxification remains largely unexplored. Here, we report a trimacrocyclic hexasubstituted benzene receptor (THB-15O) that completely encapsulates PQ2+ through the cooperative action of two receptor molecules to form a 2:1 inclusion complex, PQ2+⊂(THB-15O)2. The complexation is established by 1H NMR titrations in solution, unambiguously confirmed by single-crystal X-ray diffraction in the solid state, and supported by DFT, independent gradient model (IGM) analyses, and molecular dynamics (MD) simulations. The two THB-15O units assemble into a near-enclosed supramolecular "shell" that physically isolates the guest and could suppress PQ2+-induced oxidative stress. In 3T3 fibroblasts, co-incubation with THB-15O markedly attenuates paraquat cytotoxicity, while THB-15O alone is well tolerated. These findings demonstrate complete supramolecular encapsulation as a practical detoxification strategy and provide a molecular blueprint for macrocyclic antidotes.