Comparative enantioseparation of chiral 4,4'-bipyridine derivatives on coated and immobilized amylose-based chiral stationary phases

Paola Peluso (1) , Barbara Sechi (1) , Giancarlo Lai (1) , Alessandro Dessì (2) , Roberto Dallocchio (1) , Sergio Cossu (3) , Emmanuel Aubert (4) , Robin Weiss (5) , Patrick Pale (5) , Victor Mamane (5) , Bezhan Chankvetadze (6)

1 UNISS - Università degli Studi di Sassari = University of Sassari [Sassari]
2 ICB - Istituto di chimica biomolecolare [Padova, Italy]
3 University of Ca’ Foscari [Venice, Italy]
4 CRM2 - Cristallographie, Résonance Magnétique et Modélisations
5 Institut de Chimie de Strasbourg
6 Tbilisi State University

The chromatographic performances of four coated and immobilized amylose phenylcarbamate-based chiral columns were evaluated and compared under normal phase (NP) elution conditions by using chiral 4,4'-bipyri-dine derivatives as analytes. n-Hexane/2-propanol 90:10 and n-hexane/2-propanol/methanol 90:5:5 mixtures were employed as mobile phases (MPs), and the effect of adding methanol in the MP on retention and selectivity was considered. The effect of temperature on retention and selectivity was also evaluated, and overall thermo-dynamic parameters associated with the analyte adsorption onto the CSP surface were derived from van't Hoff plots. Interesting cases of enantiomer elution order (EEO) reversal, which are dependent on the nature of polar modifier, analyte structure, column-type, and temperature, were observed. The impact of substitution pattern and electronic properties of analytes and selectors on the separation behaviour was investigated by correlating chro-matographic parameters and molecular properties determined by using density functional theory (DFT) calculations. Both coated and immobilized amylose tris(3,5-dimethylphenylcarbamate) columns allowed for the baseline enantioseparation (2.0 ≤ R S ≤ 4.9) of all 4,4'-bipyridines considered in this study. These results appear particularly useful because both enantiomers of these 4,4'-bipyridine derivatives are currently under investigation as new inhibitors of transthyretin fibrillogenesis, a biochemical phenomenon which is implicated to cause amyloid diseases.

Domaines: Chimie organique; Catalyse; Matériaux; Chimie analytique; Chimie de coordination

Paola Peluso, Barbara Sechi, Giancarlo Lai, Alessandro Dessì, Roberto Dallocchio, et al.. Comparative enantioseparation of chiral 4,4'-bipyridine derivatives on coated and immobilized amylose-based chiral stationary phases. Journal of Chromatography A, 2020, 1625, pp.461303. ⟨10.1016/j.chroma.2020.461303⟩. ⟨hal-02868910⟩