Efficient Removal of Short‐Chain Perfluoroalkyl Substances by Cavity‐Directed Aggregation in a Molecular Cage Host

ABSTRACT The removal of perfluoroalkyl substances (PFAS) from water is critical to protect human health and the environment. However, removing short‐chain PFAS remains a significant challenge, and a molecular‐level understanding of their binding is lacking. Here, we utilise a metal‐organic cage (MOC 1 ) as a model “pore” to elucidate the host‐guest chemistry of short‐ and long‐chain PFAS in water. X‐ray crystallography of six 1 ·(PFAS) n complexes reveals a broad range of PFAS are encapsulated as anionic aggregates, with the degree of guest‐guest aggregation decreasing as the fluoroalkyl chain length increases. 1 H and 19 F NMR spectroscopy, together with isothermal titration calorimetry reveal the cage host displays unusually large, entropy‐driven association constants in water (log K ≥ 5) which remain high for short‐chain PFAS. Doping mesoporous silica 60A with only ∼1 wt% of the cage results in a host‐in‐host adsorbent that removes >98% of short‐ and long‐chain PFAS at environmentally relevant concentrations under flow‐through conditions. The adsorbent exhibits rapid PFAS uptake with high selectivity over common water‐borne anions and full regenerability. These findings translate host‐guest chemistry into an effective materials platform for PFAS remediation, including short‐chain species that evade conventional removal methods.