Quinine carbamate chiral stationary phases: Systematic optimization of steric selector-selectand binding increments and enantioselectivity by quantitative structure-enantioselectivity relationship studies (original) (raw)
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Journal of Chromatography A, 2011
The natural alkaloid quinine (QN) was immobilized on porous silica particles, and part of the material was subsequently endcapped with n-hexyl hydrocarbon chains. Two synthetic strategies for silanization of the support were first compared. These columns were thoroughly evaluated in order to study the influence of endcapping in the enantiorecognition features. Enantioseparations of twenty N-derivatized 2,4-dinitrophenyl ␣-amino acids (DNP-amino acids) were studied by changing mobile phase pH, buffer concentration, type of organic solvent in the mobile phase, and column temperature. Maximum retention factors were observed at pH ≈6, at this intermediate pH the tertiary amine of the quinine is protonated to a high degree and therefore available for strong electrostatic interactions with unprotonated anionic DNP-amino acids. The enantioselectivity factors, however, increased as the pH did in the range between 5 and 7. The increase in ionic strength had influence on retention, but not on enantioselectivity, allowing the use of this variable for optimization of retention factors. Finally, the thermodynamic transfer parameters of the enantiomers from the mobile to both CSPs (with and without endcapping, QN-CSP(EC) and QN-CSP, respectively) were estimated from van't Hoff plots within the range of 10-40 • C. Thus, the differences in the transfer enthalpy, ( H • ), and transfer entropy, ( S • ), enabled an investigation of the origin of the differences in interaction energies.
Journal of Chromatography A, 2005
The enantioseparation of 2,2,2-trifluoro-1-(9-anthryl)ethanol on silica-bonded quinidine carbamate was examined under linear chromatographic conditions. The significant impact of nonselective adsorption on the retention was demonstrated. The influences of a polar additive in the mobile phase on the retention, the selectivity and the thermodynamic quantities of the retention were measured. A small effect of the pressure on the selectivity and on the accuracy of the thermodynamic measurements was observed.
Chirality, 2005
The enantiodiscriminating potential of the weak anion exchange-type quinine-based chiral stationary phases (CSPs) for direct enantiomer separation of racemic 2-methoxy-2-(1-naphthyl)propionic acid (selectand, SA) was studied. The influence of structure variations of the selector (SO) in the carbamate functional group and/or in the C 6V position of quinoline moiety on retention and enantioselectivity was investigated. Systematic chromatographic studies were made to gain more insight into the overall chiral recognition mechanism for a given mobile phase. In this context, the tert-butylcarbamoyl quinine and the corresponding diisopropylphenyl-derived selector provided the highest resolution and enantioselectivity under polar-organic conditions with the elution order of (R) before the (S) enantiomer. When the bulkiness of the substituents in the C 6V position of the SO was increased, the selectivity was decreased in all cases. Alkylation of the nitrogen atom in the carbamate functionality of the SO resulted in the complete loss of enantiomer separation, confirming the crucial importance of the hydrogen-bond formation involved in the stereodiscriminating events. In addition, ten different mono-, bi-, or trivalent acids, necessary as competitor molecules (counter-ions) of the mobile phase, were screened to judge their influence on retention and overall enantioselectivity. Among them, acetic acid, formic acid, N-acetylglycine, and glycolic acid proved to be the most promising counter-ions with R s values of 6.35, 6.81, 8.19, and 7.34, respectively. On the basis of chromatographic data, a tentative molecular recognition model was proposed. Simultaneous ion-pairing and hydrogen bonding, in concert with pÀp stacking and steric interactions, were expected to be responsible for chiral recognition mechanism. This was partially corroborated by structural and/or conformational analysis of the tert-butylcarbamoyl quinine-2-methoxy-2-(1-naphthyl)propionic acid (SO-SA) complex. Chirality 17:S134-S142, 2005.
Journal of Chromatography A, 2005
The retention and the separation of the enantiomers of 1-phenylpropanol (1PP), 2-phenylpropanol (2PP), and 3-chloro-1-phenylpropanol (3CPP) on silica-bonded quinidine carbamate under normal phase HPLC conditions were investigated. A relatively high selectivity of the stationary phase for 3CPP and 1PP (α ≈ 1.07 − 1.09) was achieved with eluents containing ethyl acetate as the polar modifier. These mobile phases were examined in detail. Based on the set of chromatographic and thermodynamic data collected, conclusions regarding the mechanism of enantioselectivity and the structure of the selector chiral center are made.
Talanta, 2007
A tert-butyl carbamoylated quinine-based chiral stationary phase (CSP) for direct enantiomer separation of various natural and unnatural amino acid derivatives was studied. The influence of functional groups in the amino acid side chains upon the enantioseparation is discussed with the aim of realizing contributions to their overall chiral recognition. The effects of various amines as co-modifiers upon retention and overall enantioselectivity of amino acid derivatives in polar organic solvents was systematically investigated. In general, retention times decreased with increasing amine concentrations without a distinct alteration of enantioselectivity. All analytes were rapidly resolved on the CSP with the methanol-based mobile phase containing 87 mM acetic acid and 7 mM triethylamine.
J Chromatogr a, 2005
The enantioseparation of 2,2,2-trifluoro-1-(9-anthryl)ethanol on silica-bonded quinidine carbamate was examined under linear chromatographic conditions. The significant impact of nonselective adsorption on the retention was demonstrated. The influences of a polar additive in the mobile phase on the retention, the selectivity and the thermodynamic quantities of the retention were measured. A small effect of the pressure on the selectivity and on the accuracy of the thermodynamic measurements was observed.
Chirality, 1997
A series of enantiomeric amides have been chromatographed on three amylose-based chiral stationary phases (CSPs): amylose tris(3,5-dimethylphenylcarbamate) (AD-CSP), amylose tris(S-phenylethylcarbamate) (AS-CSP), and amylose tris(Rphenylethyl-carbamate) (AR-CSP). The relative retentions and enantioselectives of the solutes on the three CSPs were compared and basic structure-retention relationships developed to describe the chromatographic results. The data indicate that for these solutes the observed elution order was a function of the chirality of the amylose backbone, while the magnitude of the enantioselective separations was affected by the chirality of the carbamate side chain.
Tetrahedron: Asymmetry, 2008
A chiral stationary phase (CSP) based on O-9-(2,6-diisopropylphenylcarbamoyl)quinine (DIPPCQN) as a chiral selector (SO) exhibits remarkable stereoselectivity for the four stereoisomers of permethrinic acid, 3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylic acid (DCCA), a precursor and prime metabolite of the pyrethroid-type insecticide permethrin. The four individual isomers of DCCA were crystallized as salts of DIPPCQN for crystal structure analysis to further our understanding of chiral recognition. Xray diffraction structures revealed that the diastereomeric complexes displayed only minor differences in their geometries with regard to specific binding interactions. The common feature is an ionic hydrogen bond, which holds the SO-selectand (SO-SA) complexes together and fixes the individual ligands in the same single point in the binding pocket of the SO. Stereoselectivity seems to arise from distinct orientations of the cyclopropane ring and/or its substituents, which means that it is most likely the result of a plethora of weak non-covalent interactions (dispersion forces) or different steric environments for the substituents of the distinct guest stereoisomers. Herein, other interactive and discriminative forces are also discussed on the basis of the additivity of SO-SA binding contributions in accordance to a linear-free energy model for chiral distinction. The chiral recognition mechanism as deduced from the diffraction data has been complemented by DFT computations, liquid chromatographic thermodynamic analysis, and 1 H NMR spectroscopy measurements. DFT computations (geometry optimization at the Hartree-Fock level and single point energy calculations at the B3LYP level) could correctly reproduce the relative binding strengths for the two enantiomers of cis-and trans-DCCA (DDH À4.2 and À0.52 kJ mol À1 , respectively) and thus the chromatographic elution order of the enantiomers. Liquid chromatographic thermodynamic investigations are in reasonable agreement with the relative trends regarding enantiomer affinity and the difference in enthalpy changes upon complexation. 1 H NMR experiments in acetonitrile-D 3 confirmed that the anti-open conformation of the quinine carbamate SO is, like in the solid-state, the preferential binding conformation in solution phase as well. Other interactions than the ionic hydrogen bond could not be derived from 1 H NMR measurements and thus, in sharp contrast to X-ray diffraction, the 1 H NMR experiments undertaken did not allow to infer stereoselectivity contributions.
Journal of Chromatography B: Biomedical Sciences and Applications, 1997
A method is proposed for the sensitive chiral analysis of amino acid enantiomers by high-performance liquid chromatography (HPLC). Thus the enantiomers of a mixture of seven racemic amino acids were resolved as their DNP derivatives from each other and from the peak of the hydrolyzed reagent, employing a quinine carbamate-based chiral anion exchange-type chiral stationary phase (CSP) and aqueous buffered mobile phases. However, the initial isocratic chromatogram yielded many peak overlaps although the corresponding enantiomers were well resolved. Therefore, the separation of the complex mixture had to be optimized; we utilized the commercial computer method development software ORYLAB. First, the influence of the manifold mobile phase parameters and chromatographic conditions (pH, type and content of organic modifier, buffer concentration, temperature, type of co-ion, etc.) on retention and resolution was studied by isocratic elution. Furthermore, with such optimized conditions linear and multi-segmented organic modifier and buffer salt gradients, respectively, were simulated with the computer program and experimentally verified. Average errors of prediction of retention times lay between 2 and 8%. Finally, a highly improved HPLC gradient method resulted in almost all components being baseline separated and equally spaced and accelerated by a factor of more than 3 compared to the initial run.