Molecular Dynamics Study of the Relation between Analyte Retention and Surface Diffusion in Reversed-Phase Liquid Chromatography

In reversed-phase liquid chromatography (RPLC), analyte molecules retained on the hydrophobic stationary phase can undergo fast surface diffusion within an acetonitrile (ACN)-rich border layer between the stationary phase and the water (W)–ACN mobile phase. We perform molecular dynamics simulations in an RPLC mesopore model employing an endcapped C 18 phase to determine retention and diffusive mobility data for four analytes at solvent ratios between 80/20 and 10/90 (v/v) W/ACN. Simulated retention data are validated by experimental retention factors acquired over the full range of studied W/ACN ratios. Our data show that for a given analyte, the lateral mobility gain from surface diffusion increases with the retention factor because both decrease with the elution strength (ACN content) of the mobile phase. A general correlation between analyte retention and surface diffusion is, however, ruled out, as analyte properties influence retention and surface diffusion differently. Complementary simulations of bulk diffusion in W–ACN mixtures show that the lateral mobility of analyte molecules in the ACN ditch can be higher than expected from the local solvent ratio. This occurs only for W-rich mobile phases, when analyte molecules have numerous contacts with bonded-phase groups, and suggests a bonded-phase contribution to surface diffusion through lubrication of retained analytes.