Liquid Chromatography Enantioseparations of Halogenated Compounds on Polysaccharide‐Based Chiral Stationary Phases: Role of Halogen Substituents in Molecular Recognition

Abstract

Halogenated chiral molecules have become important in several fields of science, industry, and society as drugs, natural compounds, agrochemicals, environmental pollutants, synthetic products, and chiral supports. Meanwhile, the perception of the halogen moiety in organic compounds and its role in recognition processes changed. Indeed, the recognition of the halogen bond as an intermolecular interaction occurring when the halogen acts as a Lewis acid had a strong impact, particularly in crystal engineering and medicinal chemistry. Due to this renewed interest in the potentialities of chiral organohalogens, here we focus on selected recent applications dealing with enantioseparations of halogenated compounds on polysaccharide-based chiral stationary phases (CSPs), widely used in liquid chromatography (LC). In particular, recently the first case of halogen bonding-driven high-performance LC (HPLC) enantioseparation was reported on a cellulose-based CSP. Along with enantioseparations performed under conventional HPLC, representative applications using supercritical fluid chromatography (SFC) are reported.

Preparation and evaluation of regioselectively substituted amylose derivatives for chiral separations

“…For their distinguished chiral recognition abilities, polysaccharide derivatives, especially the benzoates and phenylcarbamates of cellulose and amylose, are recognized as the most powerful chiral stationary phases (CSPs) in high-performance liquid chromatography (HPLC). [1][2][3][4][5][6][7][8][9][10] Generally, these derivatives are homogeneously substituted, which means that they bear the same substituent at 2-, 3-, and 6-positions of a glucose ring. The heterosubstituted polysaccharide derivatives having different substituents at 2, 3positions and 6-position has also been obtained.…”

Enantioselective separation of twelve pairs of enantiomers on polysaccharide‐based chiral stationary phases and thermodynamic analysis of separation mechanism

“…For the chloro‐substituted CSPs (Chiralpak IC and Chiralpak ID), the presence of chlorine atoms on the phenyl ring may be the reason for their higher enantioselectivity abilities. The chlorine atom was reported to have a double role : (a) the stereoelectronic properties of the chlorine (electron‐withdrawing inductive effect) can influence close sites. In detail, the chloro‐substituted phenyl ring was π‐acidic, and could promote π‐π interaction with π‐basic phenyl ring of the enantiomer, further leading to a better chiral recognition.…”

State-of-the-art and recent developments of immobilized polysaccharide-based chiral stationary phases for enantioseparations by high-performance liquid chromatography (2013–2017)

“…have also been determined, especially in commercial products or biological samples (pharmaceutical formulations, human urine, human or animal blood, human plasma, animal serum, etc.). Another heterogeneous group of analytes, including connectors for building metal-organic frameworks [116,117,124], intermediates for the synthesis of pharmaceuticals [111], natural and synthetic compounds [39,113,121,120], biological compounds [82,112,58,71,78,86,[61][62][63]77,75], natural alkaloids [121], biomolecules [115,54], organometallic compounds [119] and chiral metabolites [103,108,100,97,102,59,63,52] has been enantioseparated with these immobilized polysaccharides CSPs (see Table 2-4). Fig.…”

“…Peluso and coworkers pointed out a contribution of halogen bonding interaction for analyte stereorecognition by cellulose tris-(3,5-dimethylphenylcarbamate) [116,117]. Studies on the elucidation of the chiral recognition mechanism of polysaccharide chiral selectors have been performed by various techniques including chromatography, NMR spectroscopy, vibrational circular dichroism spectroscopy or molecular modeling as summarized earlier in [1,[125][126][127][128], while applications to chiral separations as well as studies on the separation ability of the selectors can be found in [12][13][14]16,124,129,130].…”

“…The influence of the 2,2'-alkyl chains of atropisomeric 1,1'-bibenzimidazole derivatives on an amylose tris- (3,5-dimethylphenylcarbamate) stationary phase was studied and it was noted that the chain length affected binding strength (accounted for analysis time) as well as enantiomer elution order [122]. The effect of halogen substitution in a large variety of structurally diverse analytes has also been summarized recently [124]. Ramisetti et al [95] studied the mechanism of separation between a Chiralpak IE column and R-Besinfloxacin.…”