No abstract

The chromatographic performances of four coated and immobilized amylose phenylcarbamate-based chiral columns were evaluated and compared under normal phase (NP) elution conditions by using chiral 4,4'-bipyridine derivatives as analytes. n-Hexane/2-propanol 90:10 and n-hexane/2-propanol/methanol 90:5:5 mixtures were employed as mobile phases (MPs), and the effect of adding methanol in the MP on retention and selectivity was considered. The effect of temperature on retention and selectivity was also evaluated, and overall thermodynamic parameters associated with the analyte adsorption onto the CSP surface were derived from van't Hoff plots. Interesting cases of enantiomer elution order (EEO) reversal, which are dependent on the nature of polar modifier, analyte structure, column-type, and temperature, were observed. The impact of substitution pattern and electronic properties of analytes and selectors on the separation behaviour was investigated by correlating chromatographic parameters and molecular properties determined by using density functional theory (DFT) calculations. Both coated and immobilized amylose tris(3,5-dimethylphenylcarbamate) columns allowed for the baseline enantioseparation (2.0 ≤ R S ≤ 4.9) of all 4,4'-bipyridines considered in this study. These results appear particularly useful because both enantiomers of these 4,4'-bipyridine derivatives are currently under investigation as new inhibitors of transthyretin fibrillogenesis, a biochemical phenomenon which is implicated to cause amyloid diseases.

The chalcogen bond (ChB) is a noncovalent interaction based on electrophilic features of regions of electron charge density depletion (σ-holes) located on bound atoms of group VI. The σ-holes of sulfur and heavy chalcogen atoms (Se, Te) (donors) can interact through their positive electrostatic potential (V) with nucleophilic partners such as lone pairs, π-clouds, and anions (acceptors). In the last few years, promising applications of ChBs in catalysis, crystal engineering, molecular biology, and supramolecular chemistry have been reported. Recently, we explored the high-performance liquid chromatography (HPLC) enantioseparation of fluorinated 3-arylthio-4,4′-bipyridines containing sulfur atoms as ChB donors. Following this study, herein we describe the comparative enantioseparation of three 5,5′-dibromo-2,2′-dichloro-3-selanyl-4,4′-bipyridines on polysaccharide-based chiral stationary phases (CSPs) aiming to understand function and potentialities of selenium σ-holes in the enantiodiscrimination process. The impact of the chalcogen substituent on enantioseparation was explored by using sulfur and non-chalcogen derivatives as reference substances for comparison. Our investigation also focused on the function of the perfluorinated aromatic ring as a π-hole donor recognition site. Thermodynamic quantities associated with the enantioseparation were derived from van’t Hoff plots and local electron charge density of specific molecular regions of the interacting partners were inspected in terms of calculated V. On this basis, by correlating theoretical data and experimental results, the participation of ChBs and π-hole bonds in the enantiodiscrimination process was reasonably confirmed.

Planar chiral ferrocenes are well‐known compounds that have attracted interest for application in synthesis, catalysis, material science, and medicinal chemistry for several decades. In spite of the fact that asymmetric synthesis procedures for obtaining enantiomerically enriched ferrocenes are available, sometimes, the accessible enantiomeric excess of the chiral products is unsatisfactory. In such cases and for resolution of racemic planar chiral ferrocenes, enantioselective high‐performance liquid chromatography (HPLC) on polysaccharide‐based chiral stationary phases (CSPs) has been used in quite a few literature articles. However, although moderate/high enantioselectivities have been obtained for planar chiral ferrocenes bearing polar substituents, the enantioseparation of derivatives containing halogens, or exclusively alkyl groups, remains rather challenging. In this study, the enantioseparation of ten planar chiral 1,2‐ and 1,3‐disubstituted ferrocenes was explored by using five polysaccharide‐based CSPs under multimodal elution conditions. Baseline enantioseparations were achieved for nine analytes with separation factors (α) ranging from 1.20 to 2.92. The presence of π‐extended systems in the analyte structure was shown to impact affinity of the most retained enantiomer toward amylose‐based selectors, observing retention times higher than 80 min with methanol‐containing mobile phases (MPs). Electrostatic potential (V) analysis and molecular dynamics (MD) simulations were used in order to study interaction modes at the molecular level.

Despite the increasing number of applications based on halogen bond (XB), asymmetric catalysis purely based on such supramolecular interactions still remains a huge challenge. The first step toward its development is the design of appropriate XB chiral donor molecules with good catalytic properties. In this context, we report the synthesis of a series of iodinated compounds based on the triazole or triazolium ring and possessing the planar chirality of ferrocene. Their XB donor property was attested by X‐ray diffraction analysis, showing short I⋅⋅⋅N and I⋅⋅⋅F interactions in the triazole‐based derivatives and in the tetrafluoroborate salt of a idodotriazolium, respectively. The potential of these compounds to act as XB‐based catalysts was demonstrated in the aza‐Diels‐Alder reaction involving an imine and a diene. Whereas triazole‐based derivatives were inactive in this reaction, the triflate salts of iodotriazoliums delivered the expected cycloadduct with high yield.