Unravelling dispersion forces in liquid-phase enantioseparation. Part III: Interplay between dispersion, repulsion, and hydrophobic forces in the enantioseparation of planar chiral 3-substituted-1-iodoethynylferrocenes

Background: The detection of dispersion forces in enantioselective liquid chromatography (LC) is rather challenging because selectand, selector and mobile phase molecules may participate in multiple types of intra- and intermolecular noncovalent interactions of different strength. In this frame, the LC system can be used as a tool to evaluate the impact of changing the structures of selectand, chiral selector and separation medium, through fast analytical screenings. In the last few years, we studied the enantioseparations of chiral compounds containing the ethynylferrocene moiety as a test probe to identify dispersion forces in LC by using amylose carbamate-based chiral stationary phases (CSPs). Results: The results of the study have been reported in a series of three papers. In Part II, we confirmed that the high affinity observed for the second eluted (Rp)-enantiomer of the 1-(iodoethynyl)-3-phenylferrocene toward amylose phenylcarbamate-based selectors could be reasonably based on dispersion forces. In the present Part III of the series, we focus on the impact of changing the 3-aryl substituent of 1-(iodoethynyl)-3-arylferrocenes on the enantioseparation, considering the 1-(iodoethynyl)-3-phenylferrocene as reference for comparison. On this basis, the enantioseparations of seven planar chiral ferrocenes were performed and compared by using amylose-based CSPs. n-Hexane-based mixtures, polar organic solvents and aqueous organic mixtures were used with the aim of evaluating the impact of mobile phases of different polarity on the enantioseparations. The results of the chromatographic analyses confirmed the high and unique affinity of the second eluted (Rp)-enantiomer of the 1-(iodoethynyl)-3-(4-t-butyl)phenylferrocene toward the amylose-based CSPs. Significance: By using 1-(iodoethynyl)-3-arylferrocenes as test probes, this study confirmed that dispersion forces may turn steric repulsion into attraction with a strength depending on the structure of the 3-aryl group and on mobile phase polarizability. Furthermore, the possibility to deconvolute hydrophobic and dispersion forces in aqueous mobile phases was also demonstrated.