Poly-proline-based chiral stationary phases: A molecular dynamics study of triproline, tetraproline, pentaproline and hexaproline interfaces

Poly-proline chains and derivatives have been recently examined as the basis for new chiral stationary phases in high performance liquid chromatography [1], [2], [3], [4] and [5]. The selectivity of poly-proline has been measured for peptides with up to ten proline units [1]. In this article, we employ molecular dynamics simulations to examine the interfacial structure and solvation of surface-bound poly-proline chiral selectors. Specifically, we study the interfacial structure of trimethylacetyl-terminated poly-proline chains with three-to-six prolines. The surface includes silanol groups and end-caps, to better capture the characteristics of the stationary phase, and the solvent is either a polar water/methanol or a relatively apolar n-hexane/2-propanol mixture. We begin with a comprehensive ab initio study of the conformers, their energies, and an assessment of conformer flexibility. Force fields have been developed for each poly-proline selector. Molecular dynamics simulations are employed to study the preferred backbone conformations and solvent hydrogen bonding for different poly-proline/solvent interfaces. For triproline, the effect of two different terminal groups, trimethylacetyl and t-butyl carbamate are compared.

► Poly-proline chiral stationary phases are examined using MD simulations.
► Interfacial structure in n-hexane/2-propanol and water/methanol is studied.
► For the trimer, the interface is compared for two terminal groups, TMA and BOC.
► The number of conformers observed at interface is largest for tetramer.
► The selectors are bent and more compact in water/methanol.