Distinct Interfacial Behaviors of Nucleosides on a Polyacrylamide-Grafted Surface: A Molecular Dynamics Study on Adsorption and Transport

Elucidating the microscopic adsorption mechanisms of polar nucleosides is essential for understanding their separation behavior in hydrophilic interaction liquid chromatography (HILIC). This study employs all-atom molecular dynamics simulations combined with umbrella sampling to systematically characterize the adsorption thermodynamics and transport dynamics of uracil, cytidine, and uridine at the interface between acetonitrile solution and a polyacrylamide (PAM)-grafted surface. Simulation results demonstrate that binding affinity is strongly dependent on the solute structure, following the order: uridine > cytidine > uracil. This thermodynamic preference is associated with distinct molecular orientations, with uridine adopting a horizontal configuration that facilitates favorable interactions with the polymer matrix, whereas uracil and cytidine maintain predominantly vertical alignments. Solvation structure analysis further reveals that such stability arises from a collective balance between desolvation penalties and polymer interactions: uridine is stabilized within the dense polymer region through minimized solvent contact, while other solutes reside in more solvent-accessible environments. In addition, diffusion analysis highlights anisotropic transport constraints dictated by the polymer layer, where parallel diffusion is suppressed near the substrate due to steric hindrance, while perpendicular diffusion retains significant mobility. These findings provide fundamental insights into the synergistic roles of polymer conformation and analyte-specific orientation, offering a theoretical basis for optimizing HILIC separation performance.