Computational insights into PFOS and PFOA encapsulation within a covalent "cage-of-cages" architecture

The widespread contamination of water by per- and polyfluoroalkyl substances (PFAS) demands the development of efficient and selective removal strategies. In this study, we use computational methods to investigate the potential of a covalently bonded "cage-of-cages" molecular architecture for PFAS sequestration, employing density functional theory (DFT), molecular dynamics (MD), nudged elastic band (NEB) calculations, and noncovalent interaction (NCI) analyses. DFT calculations show stronger binding of perfluorooctanesulfonic acid (PFOS) (–33.07 kcal/mol) relative to perfluorooctanoic acid (PFOA) (−24.63 kcal/mol), primarily driven by van der Waals and electrostatic interactions within the confined cage interior. MD simulations confirm the stable confinement of both PFAS molecules in water, while NEB calculations reveal a higher relative desorption energy barrier for PFOS (109.18 kcal/mol) compared with PFOA (99.84 kcal/mol), implying stronger retention of PFOS within the cage cavity. Collectively, these findings demonstrate that hierarchical molecular cages served as promising supramolecular platforms for PFAS sequestration, offering a mechanistic computational basis for future experimental validation and rational adsorbent design.