A Hierarchical Molecular Encapsulation Strategy for Sustainable High-Performance Organic Solvent Nanofiltration Membranes

• Higher performance OSN membrane was prepared in a greener route by a hierarchical molecular encapsulation (HME) strategy. • By encapsulation-release of nanocapsules, in-situ cross-linked substrate was constructed with 10-fold lower CO 2 emissions and 90% higher dimethylformamide permeace. • Through cucurbit [6] uril-mediated host-guest chemistry, a highly permselective layer was formed exhibiting efficient separation for APIs solutions (>400 Da). • The scalability of HME-PA membrane was demonstrated in 1-meter Industrial-scale continuous production. Organic solvent nanofiltration (OSN) is pivotal for sustainable chemical separations, yet conventional membrane fabrication suffers from excess solvent consumption, environmental burdens, and performance trade-offs. Here, we present a hierarchical molecular encapsulation (HME) strategy that synergistically integrates protective-group chemistry and host-guest interactions to significantly advance OSN membrane production. By encapsulating cross-linkers within Boc-based nanocapsules for in situ release during phase inversion, this approach eliminates prolonged solvent immersion and intermittent replenishment while reducing cross-linking solution usage by 89%. The resulting solvent-resistant substrates feature rapid transport channels, enabling 90% higher dimethylformamide permeance than traditional methods. Concurrently, cucurbit [6] uril (CB [6] )-mediated host-guest chemistry is used to engineer the selective layer’s sub-nanometer pore structure, doubling the solvent permeability while maintaining >90% rejection of molecules larger than 400 Da. A demonstration of 1 m industrial-scale continuous production reveals an 89% reduction in module costs and 10-fold lower CO 2 emissions (validated via life-cycle assessment), with stable performance over 30 days. This work establishes a sustainable, scalable platform for industrial solvent recovery that resolves critical environmental and economic challenges.