Characterizing the Hydrophobic Contribution to Adsorption on Ligand-functionalized Surfaces
Year: 2026
Type: preprint
Abstract: The hydrophobicity of functionalized surfaces is critical, as these surfaces are widely used to modulate adsorption, self-assembly, fouling, and molecular recognition by controlling interfacial interactions with surrounding molecules. Despite their importance, characterizing the hydrophobicity of functionalized surfaces and quantifying its contribution to these phenomena remain challenging. Here, we use molecular dynamics simulations and enhanced sampling methods to quantify the hydrophobicity of surfaces functionalized with multimodal ligands, which can interact with solutes through multiple interaction modes. Specifically, we study a series of multimodal ligands grafted to these surfaces, including Nuvia cPrime, a commercially available glycine-based chromatography ligand, and its amino acid-derived analogs, which differ from it by additional chemical groups with systematically varied hydrophobicity. We quantify surface hydrophobicity from the free energy of removing interfacial water molecules and compare our results with ligand logP values, the solvent accessible surface areas (SASA) of ligand chemical groups, and protein-induced water displacement observed in molecular simulations. We then validate the relevance of the resulting hydrophobicity ordering using experimental protein binding trends. We find that water removal from small, localized regions centered on ligand clusters better captures adsorption-relevant surface hydrophobicity than removing water from the entire surface because these regions more closely represent proteinbinding sites. Additionally, we show that variations in ligand clustering across the same surface alter chemical group exposure, as indicated by SASA, resulting in spatial heterogeneity in surface hydrophobicity. Overall, this work provides a molecular-level approach for characterizing functionalized surface hydrophobicity and guiding the design of interfaces that control molecular adsorption.
Source: ChemRxiv
Institution: University of Virginia
Language: English
Subfield: Surfaces, Coatings and Films
Field: Materials Science
Domain: Physical Sciences
Open Access status: green
OpenAlex ID: W7223273488