LFER and CoMFA studies on optical resolution of ?-alkyl ?-aryloxy acetic acid methyl esters on DACH-DNB chiral stationary phase

Abstract

The HPLC resolution of a series of racemic alpha-substituted alpha-aryloxy acetic acid methyl esters I on a pi-acid N,N'-(3,5-dinitrobenzoyl)-trans-1,2-diaminocyclohexane as chiral selector was modelled by linear free energy-related (LFER) equations and comparative molecular field analysis (CoMFA). Our results indicate that the retention process mainly depends on solute lipophilicity and steric properties, whereas enantioselectivity is primarily influenced by electrostatic and steric interactions. CoMFA provided additional information with respect to the LFER study, allowed the mixing of different subsets of I and led to a quantitative 3D model of steric and electrostatic factors responsible for chiral recognition.

Mining Chromatographic Enantioseparation Data Using Matched Molecular Pair Analysis

“…Data used in that earlier study and this one required that there be a clearly defined structure for the molecule being separated, that there be a single stereogenic center, and that the reported value of α be within a reasonable range (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12).…”

“…It would be useful to predict in advance which CSP to choose for a particular molecule. There are longstanding rules of thumb to aid in the prediction of enantioseparability for specific CSPs [1][2][3][4][5][6][7], and several attempts have been made over the years to create more broadly applicable statistical models of enantioseparation based on literature data [8][9][10][11]. Recently, we attempted to generate descriptor-based QSAR (quantitative structure-activity relationship) enantioselectivity models [12] for a subset of 19 CSPs based on literature data compiled in ChirBase, a database containing more than 200,000 entries of literature-reported chromatographic enantioseparations [13].…”

Teicoplanin-Based Enantiomeric Separations in CZE Using a Partial Filling Technique

“…According to a strategy successfully applied by us to the study of the enantioresolution in HPLC [42,43], electrophoretic and modeling experiments have been planned to derive quantitative structure-enantioselectivity and structure-electrophoretic mobility relationships for properly designed sets of chiral compounds. …”

Linear free energy relationship as a tool for characterization of three teicoplanin‐based chiral stationary phases under various mobile phase compositions

“…Although LFER is frequently used to characterize chromatographic RP systems, just a few papers that utilized the LFER model to describe chiral separation systems can be found in the literature [32,33]. In our previous paper [34], we have compared three teicoplanin-based CSPs on the basis of the calculated regression coefficients of the LFER equation.…”