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 Wacetone (Ace), Wmethanol (MeOH), and MeOHACN mixtures to a hydrophilic silica surface, we evaluate their MP potential for aqueous and nonaqueous HILIC. We analyze solvent and hydrogen-bond density profiles, solventsurface coordination, as well as local solvent orientation, mobility, and composition. Our data show that WAce mixtures closely mimic the behavior of WACN mixtures, whereas WMeOH mixtures fail as HILIC MP because the similar affinity of the silica surface for W and MeOH prevents preferential adsorption of W. MeOHACN mixtures form a rigid MeOH layer that reverses the surface polarity and prohibits formation of a diffuse MeOH layer in the extended surface region. Generally, a rigid layer at a hydrophilic surface is formed by binary mixtures whose solvents have sufficiently different hydrogen-bonding abilities, and a diffuse layer is formed when the rigid layer maintains hydrophilic properties.