Optimizing Enantiomeric Resolution of Chiral Triazoles in Supercritical Fluid Chromatography.

Chirality plays a crucial role in the pharmacological activity of triazoles, a key scaffold in antifungal agents and various therapeutic applications. This study focuses on optimizing the enantiomeric resolution of chiral triazoles using supercritical fluid chromatography (SFC) and 10 different columns, either immobilized or coated, chlorinated or nonchlorinated, cellulose or amylose-based chiral stationary phases (CSPs). Four novel triazoles and two marketed ones (tebuconazole and hexaconazole) were separated to determine optimal resolution conditions.

Insights into the separation, enantioseparation and recognition mechanisms of methamphetamine isotopologues on achiral and polysaccharide-based chiral columns in high-performance liquid chromatography.

Background: Isotopologues resulting from the labelling of molecules with deuterium have attracted interest due to the isotope effect observed in chemistry and biosciences. Isotope effect may also play out in noncovalent interactions and mechanisms leading to intermolecular recognition. In chromatography, differences in retention time between isotopologues, as well as between isotopomers have been observed resulting in two different elution sequences (isotope effects): the normal isotope effect when heavier isotopologues retain longer than lighter analogues, and the inverse isotope effect featuring the opposite elution order.

First separation of commendamide enantiomers.

N-(3-hydroxyacyl)glycines are compounds of remarkable interest due to their biogenic origin and bioactivity and as precursors of the corresponding 3-acyloxy derivatives which represent an important class of bioactive products of bacterial origin. Commendamide [N-(3-hydroxypalmitoyl)glycine] (1) is a gut microbiota-derived bioactive metabolite that is structurally like endogenous long-chain N-acyl-amino acids belonging to the endocannabinoidome, a complex lipid signaling system involved in several aspects of mammalian physiology and pathology. Thanks to this structural similarity, this compound and its analogues, like the N-(3-hydroxymyristoyl)glycine 2, exert a remarkable bioactivity in mammals, for instance, through activation of G-protein-coupled receptors (GPCRs).

Unravelling dispersion forces in liquid-phase enantioseparation. Part II: Planar chiral 1-(iodoethynyl)-3-arylferrocenes.

Background: In the first part of our study on possible contribution of dispersion forces in liquid-phase enantioseparations, the enantioseparation of the axially chiral 3,3'-dibromo-5,5'-bis-ferrocenylethynyl-4,4'-bipyridine with an amylose tris(3,5-dimethylphenylcarbamate)-based chiral column appeared reasonably consistent with a picture of the enantioselective recognition based on the interplay between hydrogen bond (HB), π-π stacking and dispersion interactions.

Results: In the second part of this study, we evaluated the impact of analyte and chiral stationary phase (CSP) structure, mobile phase and temperature on the enantioseparations of planar chiral 1-(iodoethynyl)-3-arylferrocenes (3-aryl = phenyl, 2-naphthyl, 4-methylphenyl, 4-t-butylphenyl) with polysaccharide-based chiral columns. The main aim of the present study was to understand the molecular bases of the high affinity observed for the second eluted (R)-enantiomer of some of these analytes toward amylose phenylcarbamate-based selectors when methanol-containing mixtures were used as mobile phases.

Molecular modeling study to unravel complexation of daclatasvir and its enantiomer by β-cyclodextrins. Computational analysis using quantum mechanics and molecular dynamics.

A computational study was performed to unravel mechanisms underlying capillary electrophoresis enantioseparations of daclatasvir and its (R,R,R,R)-enantiomer with native and methylated β-cyclodextrins (β-CDs) as chiral selectors. Considering the enantioseparation results as benchmark, the structures of β-CD and seven methylated β-CDs were optimized by quantum mechanics, and their topography and computed molecular properties were compared. Furthermore, the electron charge density distribution of the macrocycles was also evaluated by calculating the molecular electrostatic potential of pivotal regions of native and methylated β-CDs.