Abstract
Analyte retention in reversed-phase liquid chromatography decreases with increasing solute polarity of a compound, whereby the parameters of the water-organic solvent (W-OS) mobile phase can influence the retention order of the compounds (selectivity). Through molecular dynamics simulations in a slit-pore model of a silica-based, endcapped, C(18) stationary phase equilibrated with W-methanol and W-acetonitrile mobile phases, we investigate how the system discriminates between small, neutral compounds with low to moderate solute polarity at the molecular level. The experimental retention behavior of the analyte ensemble was recovered by the stationary phase-averaged number of bonded-phase contacts per analyte molecule, which depends on the number of hydrophobic structural elements in a compound and its average penetration depth into the bonded-phase chains. Evasion of W contacts by the hydrophobic structural elements pushes an analyte molecule deeper into the bonded-phase chains, but only as far as allowed by its hydrogen-bond requirements, which limit the analyte density in the solvated stationary phase to locations with sufficient W density. Selectivity effects arise when mobile phase-induced changes in stationary-phase solvation alter the density limitations of a compound relative to another. Differential analyte retention results therefore from the solute-specific response to the mobile phase-controlled W density distribution in the system.