Stability Assessment\nin Aqueous and Organic Solvents\nof Metal–Organic Framework PCN 333 Nanoparticles through a\nCombination of Physicochemical Characterization and Computational\nSimulations

Mesoporous metal–organic frameworks (MOFs) have\nbeen recognized\nas powerful platforms for drug delivery, especially for biomolecules.\nUnfortunately, the application of MOFs is restricted due to their\nrelatively poor stability in aqueous media, which is crucial for drug\ndelivery applications. An exception is the porous coordination network\n(PCN)-series (e.g., PCN-333 and PCN-332), a series of MOFs with outstanding\nstability in aqueous media at the pH range from 3 to 9. In this study,\nwe fabricate PCN-333 nanoparticles (nPCN) and investigate their stability\nin different solvents, including water, ethanol, and methanol. Surprisingly,\nthe experimental characterizations in terms of X-ray diffraction,\nBrunauer–Emmett–Teller (BET), and scanning electron\nmicroscopy demonstrated that nPCN is not as stable in water as previously\nreported. Specifically, the crystalline structure of nPCN lost its\ntypical octahedral shape and even decomposed into an irregular amorphous\nform when exposed to water for only 2 h, but not when ethanol and\nmethanol were used. Meanwhile, the porosity of nPCN substantially\ndiminished while being exposed to water, as demonstrated by the BET\nmeasurement. With the assistance of computational simulations, the\nmechanism behind the collapse of PCN-333 is illuminated. By molecular\ndynamics simulation and umbrella sampling, we elucidate that the degradation\nof PCN-333 occurs by hydrolysis, wherein polar solvent molecules initiate\nthe attack and subsequent breakage of the metal–ligand reversible\ncoordination bonds.