Molecular Simulation of Stationary Phase Materials in Liquid Chromatography

Molecular simulation models of monomeric and polymeric stationary phases used for liquid chromatography have been employed to investigate the molecular-level structural features that control shape-selective separations. These simulations are consistent with experimental data that characterize molecular level order and disorder, and they provide a representation of the physical alkyl-modified surfaces that aids the interpretation of chromatographic processes. These results illustrate the potential for computational techniques to predict the molecular recognition capabilities of stationary phases and are currently being applied to the simulation of perfluoroalkanes and towards the design of novel chromatographic materials.

The experimental characterization of particular functional sites within chromatographic materials remains a challenge with current analytical instrumentation. However, computational techniques that elucidate the structural features of stationary phases provide an estimation of the potential molecular sites that may be involved in chromatographic retentive processes. The application of simulation techniques may also prove useful in the prediction of molecular recognition properties. Computational simulations provide insights that may lead to the design of new chromatographic materials to address emerging measurement challenges.

Molecular dynamic (MD) simulations of C₈-, C₁₈-, and C₃₀-modified silicas have been carried out to study changes in stationary phase architecture that may result from variations in chain length, bonding density, synthetic approach, and temperature. Surface densities ranged from 1.6 μmol/m² to 5.9 μmol/m² for C₈, C₁₈, and C₃₀ ligands, and some models were constructed of three oligomer units to approximate bonding in polymeric phases. Simulations were carried out with the COMPASS potential model, over time periods long enough so that the structural features were constant (> 800 ps). Analytical shape computation techniques were applied for the detection of cavities and the calculation of molecular surface properties of isolated cavity features and other ordered formations within these resultant alkyl stationary phase simulation models. MD simulations of solvated fluoroalkanes with two types of model potentials (with or without explicit atomic charges) have been carried out to describe the interaction of perfluorinated species in various solvent environments. Complementary ab initio models are being constructed to directly compare with these force field-based simulations and reconcile any influence of explicit charge on the MD simulations results. Perfluoroalkyl-based stationary phase models will be constructed in a similar fashion to the alkylsilane models (various surface coverages, temperatures, etc.) and simulated with the appropriate model potentials. 

Major Accomplishments:

• Simulations have been completed that are consistent with spectroscopic and chromatographic studies of molecular order within alkyl-modified surfaces
• Results provide a compelling molecular-level vision of alkyl-modified surfaces that will guide future development of materials for chromatographic and biotechnological applications  
• Publications of results for both alkylsilane and perfluoroalkane MD simulations in high-impact peer-reviewed publications (Analytical Chemistry and Journal of Physical Chemistry B)