Molecular dynamics insights into limited impact of nanoscale defects on lithocholic acid adsorption on graphene

Lithocholic acid (LCA), a bile acid metabolite with demonstrated lifespan-extension capabilities, holds considerable biomedical promise. The development of nano-enabled platforms, such as those based on two-dimensional (2D) materials, is crucial to empower its future applications in drug delivery and sensing. For fundamental mechanistic studies, graphene serves as an ideal model system owing to its structural simplicity and computational tractability, which allow for precise control and reliable simulation of its surface properties, such as through defect engineering. However, the adsorption behavior of LCA on graphene surfaces, particularly the mechanistic role of surface defects that are central to tailoring material properties, remains inadequately characterized. To elucidate the underlying physical principles governing this interaction, we employed molecular dynamics simulations to systematically compare LCA binding on ideal graphene (I-Gra) and a series of defective graphene (D-Gra) models with varying defect sizes and edge chemistries. Our results reveal that the binding free energy of LCA converges to a similar value across all surfaces, indicating a limited impact of nanoscale defects. Structural analysis shows that while hydrophilic defect edges form strong, localized hydrogen bonds with water, the overall architecture of the interfacial hydration layer remains largely preserved. This confinement of defect influence leads to minimal variation in the non-polar solvation free energy, the key thermodynamic term governing hydrophobic adsorption. Consequently, the adsorption strength exhibits remarkable robustness against the investigated defects. These findings elucidate a defect-insensitive adsorption mechanism, highlighting that the continuous hydrophobic graphene plane, not localized defect features, dominates the interaction. This insight provides a crucial theoretical foundation for predicting the performance of realistic, non-ideal graphene interfaces in LCA-related biomedical applications.