Retention mechanisms of dipeptides on superficially porous particle vancomycin- and teicoplanin-based chiral stationary phases

• Published in: Journal of Chromatography A Vol. 1730; p. 465135
• Main Authors: Reshetova, Elena N., Barashkova, Anna S., Garifullin, Bulat F.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 16-08-2024
• Subjects: Dipeptide; Molecular docking; Retention models; Teicoplanin; Vancomycin; Dipeptide; Vancomycin; Retention models; Teicoplanin; Molecular docking
• ISSN: 0021-9673
• DOI: 10.1016/j.chroma.2024.465135

•Enantioselectivity of adsorbents Chiral-T and Chiral-V to dipeptide stereoisomers evaluated.•High enantioseparation of dipeptides on Chiral-T demonstrated.•Structure-retention relationships qualitatively discussed.•Extended version of the Tsui model applied for description of dipeptide retention.•Interaction of dipeptide stereoisomers with chiral selectors modeled by molecular docking.
Chromatographic behavior of new chiral stationary phases (CSPs) Chiral-T and Chiral-V with teicoplanin and vancomycin antibiotics grafted onto superficially porous silica particles was studied in relation to dipeptide (DP) stereoisomers. The unbuffered water–methanol solutions were used as mobile phases (MPs). The effects of physical properties and molecular structure of analytes and selectors on retention and separation of DP stereoisomers are discussed herein. Chiral-T was evinced to exhibit high enantioselectivity, with highest α values attaining 16.5, 18.8 and 20.4 for Gly-Leu, dd/ll-Phe-Leu and ld/dl-Ala-Ala. At this point, Chiral-V did not exhibit enantioselectivity towards DP stereoisomers. The effect of MP composition on retention and enantioseparation of DPs was investigated. Lipophilicity of DPs was found to be an essential factor in the dependence of their retention vs. methanol concentration in МPs. Lipophobic DPs were eluted more quickly by water-rich solvents, with lipophilic DPs exhibiting an asymmetric U-shaped, or a descending dependence of retention factor vs. the methanol percentage on Chiral-T or Chiral-V, respectively. A theoretical model taking into account interaction of both solvents of a binary MP with both an analyte and adsorption sites was successfully applied so as to approximate and interpret the dependences of DP retention (monotonic and U-shaped) vs. a modifier content in MP. Water molecules were evinced to predominantly participate in competitive adsorption with DP molecules. The model predicted better solvation of lipophilic DPs by methanol and better solvation of lipophobic DPs by water. An attempt was made to verify the possibility of modeling by molecular docking the processes occurring during interaction between DP stereoisomers and CSPs, including consideration of the influence of competitive binding of eluent molecules in selector cavity.