Functionalization\nStrategy in 2D Flexible Zn(BTTB)-MOF\nfor Improving Storage and Release of Anticancer Drugs: A Comprehensive\nComputational Investigation

A multiscale\ncomputational approach was used to investigate\nthe\ninteraction, adsorption, and diffusion of three anticancer drugs,\n5-fluorouracil (5-FU), busulfan (BU), and cisplatin (CIS), within\nthe pores of a 2D flexible Zn-based MOF (Zn(BTTB)-MOF) functionalized\nwith –NH<sub>2</sub>, –NO<sub>2</sub>, −OH, and\n-SH groups. The DFT analysis results indicated that adding functional\ngroups to the H<sub>3</sub>BTTB organic linker created additional\nbinding sites, resulting in stronger interactions between the drugs\nand the modified structures by 17.5% for NO<sub>2</sub>–Zn(BTTB)-MOF···5-FU\nto 115% for OH-Zn(BTTB)-MOF···BU in binding energies.\nOur grand canonical Monte Carlo (GCMC) studies revealed that both\nfunctionalized and pristine structures exhibited a high drug-loading\ncapacity, increasing to ∼13, 15, and 24% for CIS, 5-FU, and\nBU, respectively. Molecular dynamics (MD) simulations indicated a\ndecrease in the dynamics of the modified structures as a function\nof simulation time, with calculated diffusion coefficients ranging\nfrom (0.78–15.4) × 10<sup>–12</sup> m<sup>2</sup>·s<sup>–1</sup>, consistent with previous findings in\ndrug release. The study highlights the significance of adding functional\ngroups to the Zn(BTTB)-MOF organic linker, as it significantly enhances\nthe binding energy of anticancer drugs. Functionalized Zn(BTTB)-MOF\nenhances drug interactions due to additional binding sites, increasing\ndrug-loading capacity and resulting in slower drug diffusion, making\nit more effective for anticancer drug delivery.