Mechanisms of the loading of ibuprofen into UiO-66s in various solvents: A combined experimental and MC simulation study

Metal-organic frameworks (MOFs), which exhibit high performances as drug carriers, attract increasing attention in drug delivery systems. The liquid-phase loading of drugs into MOFs is critical in determining their performances as drug carriers. Here, this study is the first to evaluate experimentally the influences of solvent polarity and the functional groups on drug-loading capacity and elucidate quantitatively mechanisms focusing on the MOF-drug-solvent interactions by grand canonical Monte Carlo (GCMC) and canonical MC (CMC) simulations. The drug-loading capacities of Universitetet i Oslo-66-X (X = NH₂, H, Br, NO₂) were investigated via experiments and molecular simulations. Experimentally, the drug-loading amount decreased with an increase in the solvent dipole moment and the shift of the functional groups from electron-donating to -withdrawing. These trends were attributed to variations in the MOF-drug and drug-solvent interactions. By combining the GCMC and CMC simulations, we investigated on the relationships between the energy components (|ΔE_{MOF–solvent}|, |E_2,MOF–drug|, and |E_{2,drug–solvent}|) and experimental drug-loading capacity. The balance of the intermolecular interactions between the MOF, drug, and solvent, particularly MOF-solvent interaction, was crucial in determining the drug-loading behavior. In ethanol, a higher MOF-drug interaction energy and lower drug-solvent interaction energy corresponded to a higher experimental drug loading. Overall, solvent dipole moment, electronic natures of the functional groups of the MOF, and the balance of MOF-drug-solvent interactions determined the drug-loading performance. These findings provide insights for use in the rational design of MOF-based drug carriers and contribute to a deeper understanding of adsorption behavior in the liquid phase.