Chiral separation by a terminal chirality triggered P-helical quinoline oligoamide foldamer

• A quinoline oligoamide-grafted silica was synthesized as an HPLC stationary phase.
• The oligoamide adopted a helical chiral secondary structure on the silica surface.
• This new stationary phase showed enantioselectivity toward chiral aromatic compounds.
• Extremely high selectivity was observed toward same handedness of quinoline oligomers.

A P-helical quinoline oligoamide foldamer was grafted on silica and applied as an HPLC stationary phase for chiral separation. The P-handedness of the quinoline oligoamide foldamer was induced by a (1S)-camphanyl group, which was introduced at the N-terminus of a tetrameric quinoline oligoamide foldamer (Cmp-Q4). To immobilize the foldamer on porous silica particles, a trimethoxysilyl group was introduced at the opposing end of the foldamer. Elemental analysis indicated that the amount of foldamer on the silica surface was 0.57 μmol/m2. Circular dichroism and vibrational CD spectra of Cmp-Q4 and Cmp-Q4-immobilized silica (Sil-Q4-Cmp) suggested that the helical structure of Cmp-Q4 was altered on the silica surface whilst retaining a chiral structure. The chiral recognition ability of Sil-Q4-Cmp was evaluated with various aromatic enantiomers. Sil-Q4-Cmp showed enantio-selectivity for axially chiral molecules (e.g., αTrigger’s base = 1.26 and αBinaphthol = 1.07). Sil-Q4-Cmp showed remarkable recognition of helical octameric quinoline oligoamides with isobutoxy and triethylene glycol side chains (α = 10.35 and 14.98, respectively). In contrast, an (1S)-camphanyl group-immobilized porous silica showed no chiral recognition for any enantiomers tested in this study. To elucidate the chiral separation mechanism of Sil-Q4-Cmp, thermodynamic parameters were calculated using van’t Hoff plots. HPLC results and thermodynamic parameters suggested that the chiral recognition of Sil-Q4-Cmp is based on the helical structure of Cmp-Q4 and other thermally dependent interactions such as hydrophobic effects associated with aromatic stacking. This work represents the first known application of aromatic foldamers in chiral separation.