Octaproline, a conformationally flexible chiral selector in liquid chromatographic enantioseparation

•Enantiorecognition in oligoproline CSPs depends on chiral selector conformation.•Mobile phase composition determines reversible conformational changes on oligoproline.•Hydrogen bonding is fundamental in enantiorecognition by oligoproline-derived CSPs.•Protic solvents promote enantioselective rigid ordered oligoproline structure.

A proline octapeptide-derived chiral selector (CS) end-capped using a pivaloyl group was covalently linked to a silica gel chromatographic matrix by the C-terminal group. The chromatographic behaviour of the resulting chiral stationary phase (CSP) using different conditions was compared to those containing 3,5-dimethylphenylcarbamate residues on the proline units. An enantioseparation ability highly dependent on the mobile phase used is observed for these CSPs. When mixtures of alkane/alcohol or alkane/ether are used as mobile phase a similar enantioselectivity is obtained. Nevertheless, in the presence of chlorinated solvents, and without a hydrogen bonding donor in the mobile phase, enantioselectivity is extremely reduced. The reversibility of this phenomenon, attributed to a conformational change in the CS, is examined.