Retention Mechanisms in Chromatography

The main goals of our research on retention mechanisms in chromatography are to provide microscopic-level insight into chromatographic separation processes and to predict retention times using novel simulation techniques and transferable force fields.

Simulating the Chromatographic Column

chromatography columnThis figure shows a snapshot of one of our recent reversed-phase liquid chromatography simulations with a dimethyl octadecylsilane (C18) stationary phase and aqueous mobile phase. This chromatographic system was studied to determine the microscopic-level structure of the bonded phase in contact with the aqueous mobile phase with different type amd amount of organic modifier (methanol or acetonitrile). This study will provide insight into the experimentally observed phenomenon of retention loss when using mobile phases with high water content.

Gas-liquid and reversed-phase liquid chromatography are the principal methods for the analysis and separation of organic and biological molecules, as evidenced by their extensive use throughout the scientific community. In industry alone, more than half the cost of manufacturing arises from separation processes, with chromatography playing a central role, in particular, for high-value-added products like pharmaceuticals. However, despite such wide-spread use, many fundamental questions on the retention process remain unanswered, largely due to the complexity of chromatographic systems and the lack of microscopic-level information. Unanswered questions regarding the theory of retention include:

  • What is the relative importance of partition and adsorption equilibria?
  • To what extent does the mobile phase alter the structure and properties of the stationary-phase?
  • Do dangling hydroxyl groups at the surface of the silica substrate influence retention?

Without these answers, there is great difficulty, first, in predicting the retention properties of any solute and, then, in designing novel stationary phases with improved retention characteristics. In a recent article in the journal, Analytical Chemistry, trying to do so was compared to climbing Mt. Everest:

Retention by theory

"It is considered the 'Mt. Everest' of separation science: Given just a structure and experimental conditions, accurately predict the retention characteristics of a solute molecule. J. Ilja Siepmann and colleagues at the University of Minnesota and Rohm and Haas take on the challenge and, using powerful molecular simulations and transferable force fields, obtain microscopic pictures of the partitioning of 10 alkanes between a helium vapor phase and a squalene liquid phase in gas-liquid chromatography. The analysis is made even more difficult because the alkanes include two sets of topological isomers, such as 2,5-dimethylhexane and 3,4-dimethylhexane, which are constructed from the same set of methyl, methylene, and methine 'building blocks'."

Anal. Chem. A-pages 185A (2000)


Recent Chromatography Publications

J.L. Rafferty, J.I. Siepmann, and M.R. Schure, "A molecular simulation study of the effects of stationary phase and solute chain length in reversed-phase liquid chromatography," J. Chromatogr. A 1223, 24-34 (2012).

J.L. Rafferty, J.I. Siepmann, and M.R. Schure, "Retention mechanism for polycyclic aromatic hydrocarbons in reversed-phase liquid chromatography with monomeric stationary phases," J. Chromatogr. A 1218, 9183-9193 (2011).

J.L. Rafferty, J.I. Siepmann, and M.R. Schure, "Mobile phase effects in reversed-phase liquid chromatography: A comparison of acetonitrile/water and methanol/water solvents as studied by molecular simulation," J. Chromatogr. A 1218, 2203-2213 (2011).

J.L. Rafferty, J.I. Siepmann, and M.R. Schure, "Investigation of the driving forces for retention in reversed-phase liquid chromatography: Monte Carlo simulations of solute partitioning between n-hexadecane and various aqueous-organic mixtures," Fluid Phase Equil. 290, 25-35 (2010).

J.L. Rafferty, J.I. Siepmann, and M.R. Schure, "The effects of chain length, embedded polar groups, pressure, and pore shape on structure and retention in reversed-phase liquid chromatography: Molecular-level insights from Monte Carlo simulations," J. Chromatogr. A 1216, 2320-2331 (2009).