Unravelling dispersion forces in liquid-phase enantioseparation. Part II: Planar chiral 1-(iodoethynyl)-3-arylferrocenes

Background: In the first part of our study on possible contribution of dispersion forces in liquid-phase enantioseparations, the enantioseparation of the axially chiral 3,3'-dibromo-5,5'-bis-ferrocenylethynyl-4,4'-bipyridine with an amylose tris(3,5-dimethylphenylcarbamate)-based chiral column appeared reasonably consistent with a picture of the enantioselective recognition based on the interplay between hydrogen bond (HB), π-π stacking and dispersion interactions.

Results: In the second part of this study, we evaluated the impact of analyte and chiral stationary phase (CSP) structure, mobile phase and temperature on the enantioseparations of planar chiral 1-(iodoethynyl)-3-arylferrocenes (3-aryl = phenyl, 2-naphthyl, 4-methylphenyl, 4-t-butylphenyl) with polysaccharide-based chiral columns. The main aim of the present study was to understand the molecular bases of the high affinity observed for the second eluted (R_p)-enantiomer of some of these analytes toward amylose phenylcarbamate-based selectors when methanol-containing mixtures were used as mobile phases. Significantly, higher affinity of the second eluted (R_p)-enantiomer toward the selector could be also observed for the sterically hindered 1-(iodoethynyl)-3-(4-t-butylphenyl)ferrocene (k₂ = 6.21) compared to the smaller 1-(iodoethynyl)-3-(4-methylphenyl)ferrocenes (k₂ = 4.07) as 2.5% methanol was added to the n-hexane-based mobile phase.

Significance: This study reasonably showed that the contribution of dispersion forces may explain the unusually large retention of the second eluted enantiomers observed for the enantioseparation of some planar chiral 1-(iodoethynyl)-3-arylferrocenes with amylose-based selectors. Based on the obtained results, we can conclude that in liquid-phase enantioseparation steric repulsion can be turned into attraction depending on the features of analyte, selector, and mobile phase.