Quinine carbamate chiral stationary phases: systematic optimization of steric selector-selectand binding increments and enantioselectivity by quantitative structure-enantioselectivity relationship studies.
A series of quinine carbamate-based chiral stationary phases (CSPs) differing solely in the carbamate residue have been devised and a congeneric set of N-3,5-dinitrobenzoyl (DNB) amino acids (AAs) was separated into enantiomers on these CSPs by HPLC using a buffered hydro-organic mobile phase. Some details on retention and chiral recognition mechanisms have been investigated by application of quantitative structure-property relationship (QSPR) studies using the linear free energy relationship methodology, i.e., the extrathermodynamic approach. Retention factors of the high affinity enantiomer (log k2) and enantioselectivities (log alpha) were correlated with Taft's steric parameter as structural descriptor for the variability in the carbamate and AA residues, and statistically significant QSPR models could be obtained. They confirmed that the variance in the dependent variable (log k2, log alpha) is mainly associated with the steric bulkiness of the selectors' carbamate and of the AA residues. The retention factor of the second eluted enantiomers and the enantioselectivity first increased with steric bulkiness of the carbamate and AA residues, which may be explained by stronger dispersive interactions. After reaching an optimum, the dependent variable, however, declined with further increase of the steric bulkiness of the substituents, probably because of steric hindrance. The variability of the retention factors of the first eluted enantiomer could not be explained by steric descriptors. Instead, it has become obvious that the retention arises mainly from interactions of the DNB-AA and the quinine carbamate backbone, as it turned out to be more or less constant and solely to a minute amount modulated by the carbamate residue and the AA side chain. The QSPR models were fully in agreement with an earlier postulated chromatographically and spectroscopically derived hypothetical selector-selectand binding model.
Lämmerhofer
Michael
M
Christian Doppler Laboratory for Molecular Recognition Materials, Department of Analytical Chemistry, University of Vienna, Vienna, Austria. Michael.Laemmerhofer@univie.ac.at
Franco
Pilar
P
Lindner
Wolfgang
W
D000596:Amino Acids / Q000737:chemistry; D002219:Carbamates / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015394:Molecular Structure; D011803:Quinine / Q000737:chemistry*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000596:Amino Acids; D002219:Carbamates; D011803:Quinine