Mechanistic Insights into 5-Fluorouracil Adsorption on Clinoptilolite Surfaces: Optimizing DFT Parameters for Natural Zeolites, Part II

Even though clinoptilolite mineral is the most important natural zeolite for technical applications, the molecular-level insights and detailed knowledge of their true local structures and adsorption behavior are largely lacking. An experimental determination of their surface structures, in particular, could be very challenging due to the sensitivity of some facets to temperature and impurities. In this study, we present a robust multiscale modeling framework to investigate the adsorption of 5-fluorouracil, an anticancer drug, on dispersion-corrected density functional theory (DFT-D3)-optimized Na-clinoptilolite surfaces. Using a combination of interface force field and polymer consistent force field-based molecular dynamics with simulated annealing and parallel replica sampling, followed by DFT-D3 optimizations, we explore a wide configurational space of surface–molecule interactions. Our results show that Na-clinoptilolite surfaces support very strong adsorption, with adsorption energies ranging from −430.0 to −174.4 kJ/mol. Surface models with exposed Na cations consistently exhibit stronger binding, in contrast to their known steric hindrance effects in bulk environments. Furthermore, cation-free surfaces displayed relatively weaker interactions, yet configurations exposing the 8-membered rings (8 MR) demonstrated more favorable adsorption than those exposing 10 MR channels due to enhanced hydrogen bonding and spatial and entropic confinement effects. These findings reveal the importance of surface composition, local geometry, and configurational sampling in determining adsorption performance and lay the groundwork for future studies on cation-specific and multicationic clinoptilolite systems.