Evaluation of Aqueous and Nonaqueous Binary Solvent Mixtures as Mobile Phase Alternatives to Water–Acetonitrile Mixtures for Hydrophilic Interaction Liquid Chromatography by Molecular Dynamics Simulations

The retentive principle of hydrophilic interaction liquid chromatography (HILIC) with a water (W)–acetonitrile (ACN) mobile phase (MP) and a hydrophilic stationary phase is the formation of a W-rich layer with a rigid and diffuse part in the immediate and extended surface region, respectively. Through molecular dynamics simulations of the adsorption of W–acetone (Ace), W–methanol (MeOH), and MeOH–ACN mixtures to a hydrophilic silica surface, we evaluate their MP potential for aqueous and nonaqueous HILIC. We analyze solvent and hydrogen-bond density profiles, solvent–surface coordination, as well as local solvent orientation, mobility, and composition. Our data show that W–Ace mixtures closely mimic the behavior of W–ACN mixtures, whereas W–MeOH mixtures fail as HILIC MP because the similar affinity of the silica surface for W and MeOH prevents preferential adsorption of W. MeOH–ACN mixtures form a rigid MeOH layer that reverses the surface polarity and prohibits formation of a diffuse MeOH layer in the e...