Microscopic simulation of solute transfer in reversed phase liquid chromatography

Solute retention in reversed phase liquid chromatography is driven by the free energy gradient on passing from the polar mobile phase into the nonpolar stationary phase. Only a partial understanding of retention exists currently. We present large scale molecular dynamics simulations of the transfer of a simple nonpolar solute from a water/methanol solvent mixture into a C₁₈ stationary phase at room temperature. In addition to a detailed examination of the local environment of the solute, we compute the excess chemical potential profile. The overall free energy change is consistent in magnitude with that expected for hydrophobic transfer from water rich to oil phases, but specific interfacial effects draw into question bulk partitioning models.