Integrated experimental and theoretical approaches to investigate the molecular mechanisms of the enantioseparation of chiral anticonvulsant and antifungal compounds

• Published in: Journal of molecular structure 2022-12, Vol.1270, p.133905, Article 133905
• Main Authors: Gambacorta, Nicola, Özdemir, Zeynep, Doğan, İnci Selin, Ciriaco, Fulvio, Zenni, Yaren Nur, Karakurt, Arzu, Saraç, Selma, Nicolotti, Orazio
• Format: Article
• Language: English
• Subjects: Amylose tris(3,5-dimethyphenylcarbamate); Arylalkylazole; Chiralpak AD; Enantioseparation; Molecular modeling and dynamics
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2022.133905

•Four anticonvulsant compounds that we synthesized previously, have been separated by using HPLC.•The amylose tris(3,5-dimethylphenylcarbamate) was used as a chiral stationary phase for enantioseparation.•Mixtures of methanol:n-hexane in a different ratios were used as mobile phase and the effect of changes in hexane ratio on resolution have been investigated.•Molecular docking and dynamic studies have been performed. Previously, some racemic 1-(phenyl/4-chlorophenyl)-2-(1H-triazole-1-yl)ethanol ester derivatives having a stereogenic center in their structure were synthesized and investigated for their anticonvulsant and antifungal activities. In this work, the direct enantiomeric separations of four compounds (1–4) were developed on the commercially available chiral stationary phase amylose tris(3,5-dimethyphenylcarbamate) (Chiralpak AD) in the normal phase HPLC mode. The influences of the mobile phase composition were also investigated. By mobile phase modified with n-hexane, the retention times were shorter than with methanol. The best results were obtained for all compounds (1–4) using the mobile phase of methanol/n-hexane (80:20 v/v) at a flow rate of 0.5 mL/min and the resolutions of the enantiomers were 3.38, 2.84, 1.89, and 1.53, respectively. Thus, the proposed HPLC method can facilitate further chemical and pharmacological studies on compounds 1–4 and their enantiomers. In addition, the molecular mechanism behind the possible chiral recognition was discussed based on the experimental and theoretical results of the enantiomeric separation and molecular dynamics studies. [Display omitted]