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.