Exploring interaction modes between polysaccharide-based selectors and biologically active 4,4′-bipyridines by experimental and computational analysis

Roberto Dallocchio (1) , Alessandro Dessì (1) , Barbara Sechi (1) , Bezhan Chankvetadze (2) , Sergio Cossu (3) , Victor Mamane (4) , Emmanuel Aubert (5) , Carla Rozzo (6) , Giuseppe Palmieri (6) , Ylenia Spissu (7) , Paola Peluso (1)

1 ICB - Istituto di chimica biomolecolare [Padova, Italy]
2 Tbilisi State University
3 Université de Venise Ca’ Foscari | Università Ca’ Foscari di Venezia
4 Institut de Chimie de Strasbourg
5 CRM2 - Cristallographie, Résonance Magnétique et Modélisations
6 IRGB - Istituto di Ricerca Genetica e Biomedica
7 ISPA - Institute of Sciences of Food Production

In the last few years, chiral 4,4 ′-bipyridine derivatives have been developed for different applications in catalysis, enantioseparation science, supramolecular and theoretical chemistry by modulating the activity of the molecular system through the introduction of specific substituents in the heteroaromatic scaffold. More recently, the biological activity of 2 ′-substituted-3,3 ′ ,5,5 ′-tetrachloro-2-iodo-4,4 ′-bipyridines has been explored in the field of transthyretin (TTR) fibrillogenesis inhibition, and the anticancer cytotoxicity of some derivatives is currently under systematic investigation. In this frame, the high-performance liquid chromatography (HPLC) enantioseparation of four atropisomeric 2,2 ′-disubstituted-4,4 ′-bipyridines (R, R' = Ar, I), which contain multiple interaction sites, such as hydrogen bonding (HB) donors and acceptors, halogen bond (XB) donors, and-extended electronic clouds, was explored by using n-hexane (Hex)/2-propanol (2-PrOH) 90:10 v/v as a mobile phase (MP), and eight chiral columns with coated and immobilized amylose-and cellulose-based selectors. The impact of subtle structural variations of analytes and selectors on their mutual intermolecular interactivity was evaluated in terms of retention (k) and selectivity () factors. On this basis, chromatographic analysis based on systematic screening of analytes and selectors was integrated with electrostatic potential (V) analysis and molecular dynamics (MD) simulations as computational techniques. The effect of temperature on retention, selectivity, and enantiomer elution order (EEO) of the analytes with coated and immobilized amylose tris (3,5-dimethylphenylcarbamate) was also considered by comparing the variation of the thermodynamic profile associated with each enantioseparation. Chromatographic responses proved to be strictly dependent on specific regions within the analyte, and functions of different interactions sites of the analytes as the structure of the chiral selector changes were significantly disclosed.

Mots clés: Bipyridines; High-performance liquid chromatography; Molecular dynamics; Polysaccharide-based chiral stationary phases; Electrostatic potential; Enantioseparation

Domaines: Chimie analytique; Chimie théorique et/ou physique

Roberto Dallocchio, Alessandro Dessì, Barbara Sechi, Bezhan Chankvetadze, Sergio Cossu, et al.. Exploring interaction modes between polysaccharide-based selectors and biologically active 4,4′-bipyridines by experimental and computational analysis. Journal of Chromatography Open, 2022, 2, pp.100030. ⟨10.1016/j.jcoa.2022.100030⟩. ⟨hal-03534358⟩