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

Abstract

Understanding of drug-carrier interactions is essential for the design and application of metal-organic framework (MOF)-based drug-delivery systems,a nd such drug-carrier interactions can be fundamentally different for MOFs with or without defects.Herein, we reveal that the defects in MOFs play ak ey role in the loading of many pharmaceuticals with phosphate or phosphonate groups.T he host-guest interaction is dominated by the Coulombic attraction between phosphate/ phosphonate groups and defect sites,a nd it strongly enhances the loading capacity.F or similar molecules without ap hosphate/phosphonate group or for MOFs without defects,t he loading capacity is greatly reduced. We employed solid-state NMR spectroscopyand molecular simulations to elucidate the drug-carrier interaction mechanisms.T hrough as ynergistic combination of experimental and theoretical analyses,t he docking conformations of pharmaceuticals at the defects were revealed.

Molecular identification and quantification of defect sites in metal-organic frameworks with NMR probe molecules

“…Besides the chemical properties of defects, the accessibility of defects, based on their pore volume and connectivity, is also important. The accessibility of active sites can have a direct consequence on the catalytic activity, biological functionality, and adsorption properties 39 , 77 , 78 . The evaluation of accessibility can be achieved by varying the size of probe molecules.…”

“…The defects could fundamentally alter the chemical environment [23][24][25] as well as the spatial geometry and connectivity of the pore space [26][27][28][29] . It has been suggested by various studies that the defects could be one of the key contributors to the catalytic activities [30][31][32][33][34] , and could significantly affect adsorption and transport properties 29,[35][36][37][38][39] . The characterizations of defects are technically challenging as the structure of defect sites may be disordered and heterogeneous, and they could locate internally or at the particle surface 40,41 .…”

“…However, the direct characterizations of defects are limited by resolution and sensitivity, and lack of spatial and volumetric information. 25,39,60,61 In this work, we present an indirect strategy that utilizes phosphorus-containing probe molecules to characterize defects in MOFs, which can provide both molecular details and bulk quantifications. The indirect method is more sensitive and background-free (based on the receptive 31 P signal), and is highly chemical-specific and quantitative.…”

Defect self-assembly of metal-organic framework triggers ferroptosis to overcome resistance

“…The loading capacity of MOF was limited by the hydrophobic and hydrophilic properties of drugs, the drug molecular weight and drug leakage [ 24 ]. Recently, engineered defects in MOFs have been widely investigated for nanoscale drug delivery [ 25 ].…”

Molecular dynamics simulation study of drugs adsorption in UiO‐66

“…Among the nano-carriers of MOFs, UiO-66, composed of Zr 6 O 4 (OH) 4 clusters and terephthalic acid, is considered to be a promising nano-carriers for drug delivery due to high porosity and thermal and chemical stability. [15] Fu et al [16] revealed that the defects in UiO-66 play an important role in the loading of bioactive molecules, whereas the size of those bioactive molecules is the key factor to affect its loading capacity. Wang et al [17] loaded ibuprofen sodium (IBUNa) on UiO-66-PDC which exhibited ideal biocompatibility and excellent pH-response release, with a loading capacity of 27.60 wt%.…”