Molecular mechanisms of cisplatin–MOF interactions: structure–property relationships for nanoscale drug delivery

Effective cisplatin delivery requires a balance between drug loading and retention within the carrier. Here, density functional theory, grand canonical Monte Carlo, and molecular dynamics simulations were combined to investigate how framework chemistry and pore geometry govern cisplatin adsorption in ZIF-8, UiO-66, and Mg-MOF-74. The comparison reveals that retention depends on the spatial organization of adsorption contacts and pore constraints as well as framework–guest attraction. Cooperative interfacial polarization and multipoint anchoring favor local stabilization in ZIF-8, while cage confinement restricts molecular migration. Although ZIF-8 and UiO-66 provide comparable average stabilization of the loaded drug population, the greater mobility in UiO-66 demonstrates the additional role of pore geometry in controlling retention. In Mg-MOF-74, continuous channels support efficient pore filling at high fugacity despite weaker average binding. These findings connect electronic interactions, adsorption-site occupation, and molecular transport within a common structure–property framework. ZIF-8 emerges as a favorable candidate when drug retention is the primary objective, while the contrasting behavior of the three frameworks provides a basis for balancing loading capacity and mobility in MOF-based cisplatin carriers.