Multiscale computational insights into 5-fluorouracil delivery via zeolite imidazole frameworks (ZIFs)

Zeolitic Imidazolate Frameworks (ZIFs) are considered as potential nanocarriers in biomedical applications such as storage and transportation of drugs, due to their low toxicity, high internal load and controlled release. In this work, the adsorption of the anticancer drug 5-Fluorouracil (5-FU) in selected ZIFs is studied by employing a multiscale computational scheme that includes semi-empirical computational techniques, Grand Canonical Monte Carlo (GCMC) and molecular dynamics simulations. Our investigation is based on ZIF-8 which is characterized by pH-sensitive controlled drug release. In order to improve the capacity and the drug interaction with the framework we expanded the parent ZIF-8, by replacing each imidazole linker with 3-(1H-pyrrol-3-yl)-pyridine. 5-FU shows enhanced binding affinity (34 kcal mol-1) in modified ZIF with respect to the parent ZIF-8 (12 kcal mol-1) (PM7). Moreover, GCMC simulations were employed to determine the loading of 5-FU in both ZIF compounds under different thermodynamic conditions and over a wide range of pressures, where it is revealed that the loading for the modified ZIF (2311 mg g-1) is four times higher than the loading for ZIF-8 (560 mg g-1). Moreover, molecular dynamics simulations offer a detailed comparison between the two ZIF materials in aqueous systems and provide deeper insight into their drug-material interactions.