Defect‐Assisted Loading and Docking Conformations of Pharmaceuticals in Metal–Organic Frameworks

The understanding of drug-carrier interactions is essential for the design and applications of metal-organic framework (MOF)-based drug delivery systems. While such drug-carrier interactions can be fundamentally different for MOFs with or without defects. In this work, we revealed that the defects in MOFs play a key role in the loading of many pharmaceuticals with phosphate or phosphonate groups. The host-guest interaction is dominated by the Coulombic attraction between phosphate/phosphonate groups and defect sites and it strongly enhances the loading capacity. For similar molecules without a phosphate/phosphonate group or for MOF without defects, the loading capacity is greatly reduced. We employed solid-state nuclear magnetic resonance (NMR) and molecular simulations to elucidate the drug-carrier interaction mechanisms. Through a synergistic combination of experimental and theoretical analyses, the docking conformations of pharmaceuticals at the defects have been revealed.