Abstract
The importance of chirality in drug development is unquestionable, with chiral liquid chromatography (LC) being the most adequate technique for its analysis. Among the various types of chiral stationary phases (CSPs) for LC, brush-type CSPs provide the base for interaction analysis of CSPs and enantiomers, which provide valuable results that can be applied to interaction studies of other CSP types. In order to analyze the influence of aromatic interactions in chiral recognition, we designed a set of ten new brush-type CSPs based on (S)-N-(1-aryl-propyl)-3,5-dinitrobenzamides which differ in the aromatic unit directly linked to the chiral center. Thirty diverse racemates, including several nonsteroidal anti-inflammatory drugs and 3-hydroxybenzodiazepine drugs, were used to evaluate the prepared CSPs. Chromatographic analysis showed that the three new CSPs separate enantiomers of a wide range of compounds and their chromatographic behavior is comparable to the most versatile brush-type CSP—Whelk-O1. The critical role of the nonbonding interactions in positioning of the analyte (naproxen) in the cleft of CSP-6, as well as the analysis of interactions that make enantioseparation possible, were elucidated using computational methods. Furthermore, the influence of acetic acid as a mobile phase additive, on this enantiorecognition process was corroborated by calculations.
Highlights
Chirality is an essential property in the development of pharmaceutical drugs, as well as in agrochemistry, food science, etc
We evaluated the prepared chiral stationary phases (CSPs) using thirty diverse racemates, including several nonsteroidal anti-inflammatory and 3-hydroxybenzodiazepine drugs
The prepared CSPs differ in the aromatic unit directly linked to the chiral center, which enabled us to elucidate the influence of the size and substitution of aromatic moiety on the enantiorecognition process
Summary
Chirality is an essential property in the development of pharmaceutical drugs, as well as in agrochemistry, food science, etc. It was put into the foreground in 1992 when the FDA issued its policy statement concerning the development of stereoisomeric drugs [1]. The need for fast, simple and reliable methods for separation of enantiomers, determination of enantiomeric excess (ee) and absolute configuration (AC) has increased. Chiral liquid chromatography (chiral LC) has a great influence on the determination of absolute configuration [3], its main role is being the most powerful method for the separation of enantiomers [4] and for measuring the enantiopurity of organic compounds.
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