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 (C-18 vs C-8) and ligand (C-8) 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 C-8 chains are better solvated and more often in an upright and stretched conformation than C-18 chains, which leads to a higher maximum ACN excess in the ditch. High ligand density reinforces this effect. The ACN-excess advantage of C-8 phases translates not necessarily into faster surface diffusion, because the shorter chains have lower bonded-phase mobility. Surface diffusion on a C-8 phase is generally slower than that on a C-18 phase, but surface diffusion on a high-density C-8 phase can be faster than on a C-18 phase when the ACN content of the mobile phase is low.