Stationary-Phase Contributions to Surface Diffusion in Reversed-Phase Liquid Chromatography: Chain Length versus Ligand Density

Fast surface diffusion in reversed-phase liquid chromatography (RPLC) describes a complex phenomenon that exists in a narrow ditch region where the silica-tethered alkyl chains of the stationary phase meet the water–acetonitrile (ACN) mobile phase. The lateral mobility of analyte molecules in the ACN-rich ditch can exceed their bulk diffusivity in the mobile phase. Through molecular dynamics simulations using an established RPLC mesopore model and analyte set we study how chain length (C₁₈ vs C₈) and ligand (C₈) density of the stationary phase contribute to the lateral mobility gain from surface diffusion at low and high ACN content of the mobile phase. The simulations show that C₈ chains are better solvated and more often in an upright and stretched conformation than C₁₈ chains, which leads to a higher maximum ACN excess in the ditch. High ligand density reinforces this effect. The ACN-excess advantage of C₈ phases translates not necessarily into faster surface diffusion, because the shorter chains have lower bonded-phase mobility. Surface diffusion on a C₈ phase is generally slower than that on a C₁₈ phase, but surface diffusion on a high-density C₈ phase can be faster than on a C₁₈ phase when the ACN content of the mobile phase is low.