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.