The docking of chiral epoxides on the Whelk-O1 stationary phase: a molecular dynamics study

The docking of analytes on the Whelk-O1 chiral stationary phase is explored for two chiral epoxides in a hexane solvent. Density functional theory calculations are employed to develop flexible models for R/S-styrene oxide (phenyl oxirane) and (R,R/S,S)-stilbene oxide (2,3-diphenyl oxirane). Molecular dynamics simulations of the racemates in the presence of the Whelk-O1 chiral stationary phase reveal the distribution of the enantiomers at the interface. The importance of hydrogen bonding and ring-ring interactions is explored along with an examination of the major docking arrangements. The interactions between the Whelk-O1 molecules and the chiral epoxide enantiomers are quite distinct and consistent with the experimental elution orders [S.E. Schaus, B.D. Brandes, J.F. Larrow, M. Tokunage, K.B. Hansen, A.E. Gould, M.E. Furrow, E.N. Jacobsen, J. Am. Chem. Soc. 124 (2001) 1307] and separation factors [W.H. Pirkle, C.J. Welch, Tetrahedron: Asymm. 5 (1994) 777]. The impact of a polar solvent modifier is examined for R/S-styrene oxide where selectivity in 80:20 n-hexane:2-propanol is assessed.