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 (<b>THB-15O</b>) that completely encapsulates PQ²⁺ through the cooperative action of two receptor molecules to form a 2:1 inclusion complex, PQ²⁺⊂(<b>THB-15O</b>)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 <b>THB-15O</b> 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 <b>THB-15O</b> markedly attenuates paraquat cytotoxicity, while T<b>HB-15O</b> alone is well tolerated. These findings demonstrate complete supramolecular encapsulation as a practical detoxification strategy and provide a molecular blueprint for macrocyclic antidotes.