Enantiomeric Separation and Molecular Modelling of Bioactive 4-aryl-3,4-dihydropyrimidin-2(1H)-one Ester Derivatives on Teicoplanin-Based Chiral Stationary Phase

The enantiomeric separation of 15 racemic 4-aryl-3,4-dihydropyrimidin-2(1H)-one (DHP) alkoxycarbonyl esters, some of which proved to be highly active as A2B adenosine receptor antagonists, was carried out by HPLC on ChirobioticTM TAG, a chiral stationary phase (CSP) bearing teicoplanin aglycone (TAG) as the chiral selector. The racemic compounds were separated under polar organic (PO) conditions. Preliminarily, the same selectands were investigated on three different Pirkle-type CSPs in normal-phase (NP) conditions. A baseline separation was successfully obtained on TAG-based CSPs for the majority of compounds, some of which achieved high enantioselectivity ratios (α > 2) in contrast with the smaller α values (1–1.5) and the lack of baseline resolution observed with the Pirkle-type CSPs. In particular, the racemic tetrazole-fused DHP ester derivatives, namely compounds 8 and 9, were separated on TAG-based HPLC columns with noteworthy α values (8.8 and 6.0, respectively), demonstrating the potential of the method for preparative purposes. A competition experiment, carried out with a racemic analyte (6) by adding N-acetyl-d-alanine (NADA) to the mobile phase, suggested that H-bonding interactions involved in the recognition of the natural dipeptide ligand d-Ala-d-Ala into the TAG cleft should be critical for enantioselective recognition of 4-aryl DHPs by TAG. The X-ray crystal structure of TAG was elucidated at a 0.77 Å resolution, whereas the calculation of molecular descriptors of size, polar, and H-bond interactions, were complemented with molecular docking and molecular dynamics calculations, shedding light on repulsive (steric effects) and attractive (H-bond—polar and apolar) interactions between 4-aryl DHP selectands and TAG chiral selectors.

Comparative Chiral Separation of Thalidomide Class of Drugs Using Polysaccharide-Type Stationary Phases with Emphasis on Elution Order and Hysteresis in Polar Organic Mode

The enantioseparation of four phthalimide derivatives (thalidomide, pomalidomide, lenalidomide and apremilast) was investigated on five different polysaccharide-type stationary phases (Chiralpak AD, Chiralpak AS, Lux Amylose-2, Chiralcel OD and Chiralcel OJ-H) using neat methanol (MeOH), ethanol (EtOH), 1-propanol (PROP), 2-propanol (IPA) and acetonitrile (ACN) as polar organic mobile phases and also in combination. Along with the separation capacity of the applied systems, our study also focuses on the elution sequences, the effect of mobile phase mixtures and the hysteresis of retention and selectivity. Although on several cases extremely high resolutions (Rs > 10) were observed for certain compounds, among the tested conditions only Chiralcel OJ-H column with MeOH was successful for baseline-separation of all investigated drugs. Chiral selector- and mobile-phase-dependent reversals of elution order were observed. Reversal of elution order and hysteresis of retention and enantioselectivity were further investigated using different eluent mixtures on Chiralpak AD, Chiralcel OD and Lux Amylose-2 column. In an IPA/MeOH mixture, enantiomer elution-order reversal was observed depending on the eluent composition. Furthermore, in eluent mixtures, enantioselectivity depends on the direction from which the composition of the eluent is approached, regardless of the eluent pair used on amylose-based columns. Using a mixture of polar alcohols not only the selectivities but the enantiomer elution order can also be fine-tuned on Chiralpak AD column, which opens up the possibility of a new type of chiral screening strategy.

Evaluation of Poly(Glycidyl Methacrylate) Nanocoating for Chiral Separation with Glu-β-CD as Chiral Selector in Capillary Electrophoresis

In this paper, a capillary coated with poly(glycidyl methacrylate) nanoparticles (PGMA NPs) was prepared and applied to construct a capillary electrophoresis (CE) enantioseparation system with glucosyl-β-cyclodextrin (Glu-β-CD) as a chiral selector. The PGMA NP coating can be easily introduced through a simple ring-opening reaction. Two basic drugs were used as models to evaluate the separation performance of the PGMA coating. Under the optimal conditions selected, the separation of the two enantiomers was obtained.

Simultaneous Enantiomeric Separation of Carfentrazone-Ethyl Herbicide and Its Hydrolysis Metabolite Carfentrazone by Cyclodextrin Electrokinetic Chromatography. Analysis of Agrochemical Products and a Degradation Study

The different activity and toxicity that the enantiomers of agrochemicals may have requires the development of stereoselective analytical methodologies enabling the individual determination of each enantiomer. The aim of this work was to develop the first Electrokinetic Chromatography methodology enabling the simultaneous enantiomeric separation of carfentrazone-ethyl herbicide and its hydrolysis metabolite carfentrazone. The use of an anionic cyclodextrin as chiral selector (captisol at 2.5% (w/v)) in a 25 mM acetate buffer, at a temperature of 30 °C, and an applied voltage (reverse polarity) of −30 kV, allowed the simultaneous separation of the four enantiomers of the two compounds studied in 6.8 min with enantiomeric resolutions of 5.0 for carfentrazone-ethyl and 5.1 for carfentrazone. Analytical characteristics of the developed method were evaluated and found adequate to achieve the quantitation of carfentrazone-ethyl and carfentrazone. Analysis of a commercial herbicide formulation showed the potential of the method for the quality control of these agrochemical products. Degradation studies for carfentrazone-ethyl revealed that no significant degradation took place in cleaned sand samples while a significant but not stereoselective degradation took place in soils for the whole period of time considered (seven days).

Chiral Monolithic Silica-Based HPLC Columns for Enantiomeric Separation and Determination: Functionalization of Chiral Selector and Recognition of Selector-Selectand Interaction

This review draws attention to the use of chiral monolithic silica HPLC columns for the enantiomeric separation and determination of chiral compounds. Properties and advantages of monolithic silica HPLC columns are also highlighted in comparison to conventional particle-packed, fused-core, and sub-2-µm HPLC columns. Nano-LC capillary monolithic silica columns as well as polymeric-based and hybrid-based monolithic columns are also demonstrated to show good enantioresolution abilities. Methods for introducing the chiral selector into the monolithic silica column in the form of mobile phase additive, by encapsulation and surface coating, or by covalent functionalization are described. The application of molecular modeling methods to elucidate the selector–selectand interaction is discussed. An application for enantiomeric impurity determination is also considered.