Chiral Separation Through Hydrogen Bonding

Affinity liquid chromatography and chiral separations (enantiomer separations) require similar analyte properties. The solutes may have interactions through hydrogen-bonding, ligand formation, or Coulombic forces with the surface of stationary phase materials or the sites of additives however, the selectivity is controlled by the steric effects of the structures of the analyte molecules and the recognition molecules (chiral selectors). 

Chiral Separation Through Combination of Charge Transfer and Hydrogen Bonding and Electrostatic Interactions. The separations described above involve solely charge transfer complexes between a chiral Tc-acceptor... 

Chiral Separation Where the Leading Interaction Is Established Through Hydrogen-Bonding... 

CHIRAL SEPARATION WHERE THE LEADING INTERACTION IS ESTABLISHED THROUGH HYDROGEN BONDING... 

Separation of enantiomers by physical or chemical methods requires the use of a chiral material, reagent, or catalyst. Both natural materials, such as polysaccharides and proteins, and solids that have been synthetically modified to incorporate chiral structures have been developed for use in separation of enantiomers by HPLC. The use of a chiral stationary phase makes the interactions between the two enantiomers with the adsorbent nonidentical and thus establishes a different rate of elution through the column. The interactions typically include hydrogen bonding, dipolar interactions, and n-n interactions. These attractive interactions may be disturbed by steric repulsions, and frequently the basis of enantioselectivity is a better steric fit for one of the two enantiomers. ... 

Analytical Properties Substrate has 20 chiral centers and 7 aromatic rings surrounding 4 cavities (A, B, C, D) substrate has a relative molecular mass of 1885 separation occurs through chiral hydrogen bonding sites, 7i-7i interactions, and inclusion complexation in polar organic, normal, and reverse mobile phases useful for the resolution of a, (3, and y or cyclic amino acids, small peptides, and N-derivatized amino acids Reference 49, 50... 

Interactions even weaker than ionic bonds can be used to separate enantiomers. Chromatographic separation relies on a difference in affinity between a stationary phase (often silica) and a mobile phase (the solvent travelling through the stationary phase, known as the eluent) mediated by, for example, hydrogen bonds or van der Waals interactions. If the stationary phase is made chiral by bonding it with an enantiomerically pure compound (often a derivative of an amino acid), chromatography can be used to separate enantiomers. 

Compared to CMP, the mechanism of separation on a chiral stationary phase is easier to predict, due to a much simpler system. Because the ligand is immobilized to a matrix and is not constantly pumped through the system, the detection limits for the enantiomers are much lower. Depending on the ligand immobilized to the matrix, one can have different types of interactions between the selectand and selector metal complexes, hydrogen-bonding, inclusion, tt-tt interactions, and dipole interactions, as well as a combination thereof. 

For characterization and exploitation of the diamide-phase system, a chiral diamide, e,g., (Ill) was examined as a modifier in the mobile phase (solvent) in conjunction with a non-bonded (bare) silica. Such a chiral carrier separated enantiomeric N-acyl-d-amino acid esters and amides with separation factors comparable to those for bonded stationary phase systems. The resolution can be as cribed to diastereomeric complexation through amide-amide hydrogen bonding between the amide additive and enantiomeric solute molecules in the carrier solvent, followed by separation of the diastereomeric complexes by the (achiral) silica phase. This process should be applicable as widely as that involving chiral diamide-bonded stationary phase systems. 

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