Design, preparation and application of a Pirkle-type chiral stationary phase for enantioseparation of some racemic organic acids and molecular dynamics studies

Reşit Çakmak, Selami Ercan, Murat Sünkür, Hayrullah Yılmaz and Giray Topal

Department of Chemistry, Faculty of science and Art, Batman University, 72100, Batman, Türkiye,

Department of Nursing, School of Health Science, Batman University, 72060, Batman, Türkiye

Department of Chemistry, Faculty of Education, Dicle University, 21280, Diyarbakır, Türkiye

Abstract: This study consists of two parts. In the first part of the study; a Pirkle-type chiral stationary phase was prepared by synthesizing an aromatic amine derivative of (R)-2-amino-1-butanol as a chiral selectorand binding to L- tyrosine -modified cyanogen bromide (CNBr)-activated Sepharose 4B and then, packed into the separation column. T he chromatographic performance of the separation column was evaluated w ith racemic mandelic acid and 2-phenylpropionic acid by using phosphate buffers at three different pHs as mobile phase. In the resolution processes, t he prepared solutions were loaded onto the separation column at two different concentrations and at three different pHs for each racemic organic acid, separately. Enantiomeric excess (ee % ) of the eluates was determined on CHIRALPAK AD-H chiral analytical column by HPLC. The maximum ee% for mandelic acid and 2-phenylpropionic acid was determined to be 60.84 and 27.4, respectively. Separation factors (k 1 ’, k 2 ’, α, and Rs) were calculated for each acid. The structures of the obtained compounds were characterized using the spectroscopic methods (NMR, and elemental analysis). In the second part of the study; enantioselective interactions between the prepared CSP and the analytes have been widely studied by docking, molecular dynamics simulation and quantum mechanical computation methods. The reason of column eluation of rac-2-phenylpropionic acid with lower enantiomeric yield was explained by these techniques.

Keywords: Pirkle-type chiral stationary phase; enantioseparation; molecular dynamics; docking .©2017 ACG Publications. All rights reserved.