Defect‐Assisted Loading and Docking Conformations of Pharmaceuticals in Metal–Organic Frameworks
Yao Fu, Zhengzhong Kang, Weicheng Cao, Jinglin Yin, Yaoquan Tu, Jianhua Li, Hanxi Guan, Yiran Wang, Qi Wang, Xueqian Kong
Abstract
Abstract Understanding of drug–carrier interactions is essential for the design and application of metal–organic framework (MOF)‐based drug‐delivery systems, and such drug–carrier interactions can be fundamentally different for MOFs with or without defects. Herein, we reveal 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 MOFs without defects, the loading capacity is greatly reduced. We employed solid‐state NMR spectroscopy 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 were revealed.