Confinement Effects on Distribution and Transport of Neutral Solutes in a Small Hydrophobic Nanopore

Molecular dynamics simulations are used to study confinement effects in small cylindrical silica pores with extended hydrophobic surface functionalization as realized, for example, in reversed-phase liquid chromatography (RPLC) columns. In particular, we use a 6 nm cylindrical and a 10 nm slit pore bearing the same C18 stationary phase to compare the conditions inside the smaller-than-average pores within an RPLC column to column averaged properties. Two small, neutral, apolar to moderately polar solutes are used to assess the consequences of spatial confinement for typical RPLC analytes with water (W)-acetonitrile (ACN) mobile phases at W/ACN ratios between 70/30 and 10/90 (v/v). The simulated data show that true bulk liquid behavior, as observed over an extended center region in the 10 nm slit pore, is not recovered within the 6 nm cylindrical pore. Instead, the ACN-enriched solvent layer around the C18 chain ends (the ACN ditch), a general feature of hydrophobic interfaces equilibrated with aqueous-organic liquids, extends over the entire pore lumen of the small cylindrical pore. This renders the entire pore a highly hydrophobic environment, where, contrary to column-averaged behavior, neither the local nor the pore-averaged sorption and diffusion of analytes scales directly with the W/ACN ratio of the mobile phase. Additionally, the solute polarity-related discrimination between analytes is enhanced. The consequences of local ACN ditch overlap in RPLC columns are reminiscent of ion transport in porous media with charged surfaces, where electrical double-layer overlap occurring locally in smaller pores leads to discrimination between co-and counterionic species.