Characterizing the Hydrophobic Contribution to Adsorption on Ligand-functionalized Surfaces
4 affiliations
- 1Department of Chemical Engineering
- 2University of Virginia
- 3Bio-Rad Laboratories,
- 4Process Chromatography Division
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.
Related
- Guest-guest interactions and their impact on molecular mobility: a simulation study of 5-fluorouracil adsorption and diffusion in hydrophobic zeolites
- Achieving Accurate Prediction of Water Adsorption in Mildly Hydrophobic MOFs
- Super-Hydrophobic Macroporous TPU Gels for Oil-Water Separation and Organic Pollutant Adsorption.
- Adsorption of Levofloxacin onto Chitosan- and Layered Double Hydroxide-Functionalized Montmorillonite
- 3D Printing of Hydrophobic Porous Materials and Their Application for the Adsorption of Organic Pollutants
BibTeX
@misc{nematipour2026characterizing,
title = {{Characterizing the Hydrophobic Contribution to Adsorption on Ligand-functionalized Surfaces}},
author = {Adel Nematipour and Janani Ram and Md Jakir Hossen and Raghav Kasi and Sushmita Koley and Christopher Belisle and Nicholas Vecchiarello and Camille Bilodeau},
howpublished = {ChemRxiv},
year = {2026},
month = oct,
doi = {10.26434/chemrxiv.15010950/v1},
url = {https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010950/v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Characterizing the Hydrophobic Contribution to Adsorption on Ligand-functionalized Surfaces
AU - Adel Nematipour
AU - Janani Ram
AU - Md Jakir Hossen
AU - Raghav Kasi
AU - Sushmita Koley
AU - Christopher Belisle
AU - Nicholas Vecchiarello
AU - Camille Bilodeau
PY - 2026
DA - 2026/10/23
PB - ChemRxiv
DO - 10.26434/chemrxiv.15010950/v1
UR - https://chemrxiv.org/doi/full/10.26434/chemrxiv.15010950/v1
AB - 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.
ER -