Density Functional Theory Study of Encapsulation of an Anticancer Drug Molecule Fluorouracil (5‐FU) on M‐MOF‐74 (M = Cu and Zn) for Targeted Drug Delivery

Metal–organic frameworks (MOFs) are promising candidates for drug delivery due to their high loading capacity, large surface area, stability, biodegradability, and biocompatibility. The anticancer drug fluorouracil (5‐FU) is effective but faces challenges in encapsulation and delivery. Density functional theory has been used to study the M‐MOF‐74 (M = Cu and Zn) as nanocarriers for 5‐FU. Cluster calculations (Gaussian09, WB97XD/3‐21 G*) and structure optimization (Quantum ESPRESSO, generalized gradient approximation, Perdew–Burke–Ernzerhof‐D2) reveal strong binding energies of 5‐FU on Cu and Zn‐MOFs to be 41.35 and 42.51 kcal mol −1 , respectively. Changes in the highest occupied molecular orbital–lowest unoccupied molecular orbital gaps, electrostatic potential surfaces, and charge transfer from natural bond orbital analysis indicate that both the MOFs can encapsulate 5‐FU as nanodrug carriers, suggesting potential candidates for targeted cancer therapy. Cu‐MOF‐74 has tremendous efficacy to release the drug at the targeted cancerous tissue site readily due to its strong desorption energy.