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

Journal of Chromatography Open

Emmanuel Aubert¹  Sergio Cossu²  Paola Peluso³  Victor Mamane⁴  Bezhan Chankvetadze⁵  Roberto Dallocchio⁶  Barbara Sechi⁶  Alessandro Dessì⁶  Giuseppe Palmieri⁷  Ylenia Spissu⁷  Carla Rozzo⁸ 

[1] Institut de Chimie de Strasbourg, UMR CNRS 7177, Equipe LASYROC, 1 rue Blaise Pascal, 67008 Strasbourg Cedes, France.;Dipartimento di Scienze Molecolari e Nanosistemi DSMN, Università Ca' Foscari di Venezia, Via Torino 155, I-30172 Mestre Venezia, Italy;ISPA CNR, Sede secondaria di Sassari, Traversa La Crucca 3, Regione Baldinca, I-07100 Li Punti - Sassari, Italy;Institut de Chimie de Strasbourg, UMR CNRS 7177, Equipe LASYROC, 1 rue Blaise Pascal, 67008 Strasbourg Cedex, France;Institute of Physical and Analytical Chemistry, School of Exact and Natural Sciences, Tbilisi State University, Tbilisi, Georgia;Istituto di Chimica Biomolecolare ICB, CNR, Sede secondaria di Sassari, Traversa La Crucca 3, I-07100 Li Punti - Sassari, Italy;Unit of Cancer Genetics, Institute of Genetic and Biomedical Research IRGB, CNR, Traversa La Crucca 3, I-07100 Li Punti - Sassari, Italy;Université de Lorraine, CNRS, CRM2, F-54000 Nancy, France;

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

DOI  :  

来源: DOAJ

【 摘 要 】

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 π-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 (α) 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.

【 授权许可】

Unknown