Functionalization Strategy in 2D Flexible Zn(BTTB)-MOF for Improving Storage and Release of Anticancer Drugs: A Comprehensive Computational Investigation

A multiscale computational approach was used to investigate the interaction, adsorption, and diffusion of three anticancer drugs, 5-fluorouracil (5-FU), busulfan (BU), and cisplatin (CIS), within the pores of a 2D flexible Zn-based MOF (Zn(BTTB)-MOF) functionalized with –NH2, –NO2, −OH, and -SH groups. The DFT analysis results indicated that adding functional groups to the H3BTTB organic linker created additional binding sites, resulting in stronger interactions between the drugs and the modified structures by 17.5% for NO2–Zn(BTTB)-MOF···5-FU to 115% for OH-Zn(BTTB)-MOF···BU in binding energies. Our grand canonical Monte Carlo (GCMC) studies revealed that both functionalized and pristine structures exhibited a high drug-loading capacity, increasing to ∼13, 15, and 24% for CIS, 5-FU, and BU, respectively. Molecular dynamics (MD) simulations indicated a decrease in the dynamics of the modified structures as a function of simulation time, with calculated diffusion coefficients ranging from (0.78–15.4) × 10–12 m2·s–1, consistent with previous findings in drug release. The study highlights the significance of adding functional groups to the Zn(BTTB)-MOF organic linker, as it significantly enhances the binding energy of anticancer drugs. Functionalized Zn(BTTB)-MOF enhances drug interactions due to additional binding sites, increasing drug-loading capacity and resulting in slower drug diffusion, making it more effective for anticancer drug delivery.