Adsorption of 5-fluorouracil, an anticancer drug, in faujasite-type zeolites: Understanding storage and release with density functional theory calculations

Zeolites have been proposed as carrier materials for the encapsulation and controlled release of the anticancer drug 5-fluorouracil (5-FU). Besides, they could also find use in the adsorption-based removal of 5-FU from water, for example in the treatment of hospital effluents. In the present work, dispersion-corrected density functional theory (DFT) calculations and DFT-based ab initio molecular dynamics (AIMD) simulations are employed to study the interaction of 5-FU with faujasite-type zeolites having different Si/Al ratios. Comparing distinct local arrangements of Al atoms and charge-balancing protons, it is evaluated to what extent “multi-site” interactions, i.e., interactions of 5-FU with more than one proton, affect the adsorption energy. While the most pronounced increase in interaction strength occurs when moving from an all-silica zeolite to a protonic zeolite having a single proton in one twelve-membered ring, a significant additional stabilisation arises if a second framework proton is present in the same ring. Typically, several hydrogen bonds are formed between 5-FU and protonic zeolite frameworks, with 5-FU simultaneously acting as donor and acceptor. AIMD simulations confirm the stability of these hydrogen bonds at room temperature in the absence of water. Additionally, infrared spectra are predicted for selected low-energy configurations in order to facilitate an experimental identification of different bonding environments. AIMD simulations probing the competitive adsorption of 5-FU and water show that the high affinity of water to the framework protons causes a breaking of hydrogen bonds, framework deprotonation, and a displacement of 5-FU from its initial position. Exposure of dehydrated 5-FU@FAU composites to water might thus be a useful approach to trigger 5-FU release in drug delivery applications.