Abstract Despite the widespread industrial and environmental relevance of clinoptilolite, a natural zeolite, its surface-level adsorption behavior remains largely underexplored , especially in the context of large pharmaceutical molecules and periodic density functional theory (DFT) slab models. Previous investigations have mainly focused on bulk properties, routinely reporting steric hindrance within micropores without taking the critical step of analyzing adsorption at the external surfaces. This gap persists due to experimental limitations in resolving surface terminations and the positions of extra-framework cations. In this work, we present a computationally elegant framework to explore molecular adsorption on cation-exchanged clinoptilolite surfaces. Using a hybrid multiscale approach that combines classical force-field-based molecular dynamics (MD) sampling with dispersion-corrected DFT (DFT-D3) refinement, we systematically evaluate the adsorption of 5-fluorouracil, an anticancer drug, across four representative systems: Na–, Ca–, Na–Ca–, and Na–Ca–K–clinoptilolite. Our results reveal a clear and reproducible trend in adsorption strength: Na–Ca–K > Na > Ca > Na–Ca, with the most favorable configuration reaching an adsorption energy of − 430.6 kJ/mol. The strongest binding occurs when the molecule coordinates with only one surface cation (typically Ca 2+ or closely spaced Na + ); the presence of additional, non-coordinating cations on the surface (e.g., K + ) nevertheless enhances adsorption by modulating the local electrostatic field. In contrast, direct mixed coordination to different cation types reduces adsorption strength. We also show that asymmetric Al distributions and accessible cation positions near the outer regions of the slab further amplify adsorption via favorable hydrogen bonding and spatial confinement. This study closes a crucial gap in the literature by providing quantitative insights and a mechanistic understanding of how surface cation composition and arrangement influence adsorption. Our findings offer valuable design principles for tailoring clinoptilolite surfaces and lay the groundwork for cation engineering in pharmaceutical loading, ion-exchange, and selective adsorption applications.
Saeed et al. (Sat,) studied this question.