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Heterogeneous Adsorption in Chiral LC
Uppsala University, Medicinska vetenskapsområdet, Faculty of Pharmacy, Department of Medicinal Chemistry.
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The adsorption of chiral drugs on proteins immobilized on silica shows an heterogeneous adsorption behavior on multiple sites. The theory of nonlinear chromatography was used for a systematic study on this behavior - linear chromatography can only measure the "global" retention.

Frontal analysis in the staircase mode was used for studies on the adsorption of model compounds on two different protein columns; β-blockers to cellobiohydrolase I and analytes of different protolytic classes to α1-acid glycoprotein. It was found that the compounds were retained at different kinds of sites, nonselective and enantioselective, and the adsorption was best fitted by the bi-Langmuir model.

With increasing the eluent pH the interaction of both enantiomers of the amines to both types of sites was increased on α1-acid glycoprotein. In the case of cellobiohydrolase I (Cel7A) only the interaction of the second eluted enantiomer increased, resulting in a dramatic increase of the enantioselectivity with increasing pH. When increasing the eluent pH the linear retention of the second eluted enantiomer switches from exothermic to endothermic behavior on Cel7A, this point depends on the relative retention on endothermic enantioselective sites. The hydrophobicity of the compound was found to be an important property regarding retention behavior for both enantiomers and on both types of sites on Cel7A. A very interesting feature was observed: 2-phenylbutyric acid has a maximum of retention at an intermediate eluent pH on α1-acid glycoprotein and from nonlinear studies it was shown that this originates from maximum interaction strength at the enantioselective sites. For both columns, there is a 1:1 stochiometry at the enantioselective site.

Protein columns sometimes shows slow and heterogeneous kinetics, and simulation studies were performed to illustrate the consequences of such a behavior. The relations between (i) the coefficient of kinetics (ii) the column length and (iii) the linear flow rate were investigated. A conclusion for the homogeneous case, is that the solution of all skewed peaks is perfectly Gaussian, if the column hold-up time is high enough.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2002. , 48 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Pharmacy, ISSN 0282-7484 ; 267
Keyword [en]
Pharmaceutical chemistry
Keyword [sv]
Farmaceutisk kemi
National Category
Medicinal Chemistry
Research subject
Analytical Pharmaceutical Chemistry
Identifiers
URN: urn:nbn:se:uu:diva-1770ISBN: 91-554-5244-2 (print)OAI: oai:DiVA.org:uu-1770DiVA: diva2:161345
Public defence
2002-03-22, lecture hall B41, Uppsala Biomedical Centre, Uppsala, 13:15
Opponent
Available from: 2002-02-25 Created: 2002-02-25Bibliographically approved
List of papers
1. Apparent and True Enantioselectivity in Enantioseparations
Open this publication in new window or tab >>Apparent and True Enantioselectivity in Enantioseparations
2000 In: Chirality, Vol. 12, no 7, 558-564 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-89665 (URN)
Available from: 2002-02-25 Created: 2002-02-25Bibliographically approved
2. Dependence on the Mobile-Phase pH of the Adsorption Behavior of Propranolol Enantiomers on a Cellulase Protein Used as the Chiral Selector
Open this publication in new window or tab >>Dependence on the Mobile-Phase pH of the Adsorption Behavior of Propranolol Enantiomers on a Cellulase Protein Used as the Chiral Selector
1999 In: J. Am. Chem. Soc., Vol. 121, no 6, 1164-1174 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-89666 (URN)
Available from: 2002-02-25 Created: 2002-02-25Bibliographically approved
3. Retention Mechanism of β-blockers on an Immobilized Cellulase. Relative Importance of the Hydrophobic and Ionic Contributions to Their Enantioselective and Nonselective Interactions
Open this publication in new window or tab >>Retention Mechanism of β-blockers on an Immobilized Cellulase. Relative Importance of the Hydrophobic and Ionic Contributions to Their Enantioselective and Nonselective Interactions
2000 In: Anal. Chem, Vol. 72, no 16, 3908-3915 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-89667 (URN)
Available from: 2002-02-25 Created: 2002-02-25Bibliographically approved
4. Influence of the Solute Hydrophobicity on the Enantioselective Adsorption of β-blockers on a Cellulase Protein Used as the Chiral Selector
Open this publication in new window or tab >>Influence of the Solute Hydrophobicity on the Enantioselective Adsorption of β-blockers on a Cellulase Protein Used as the Chiral Selector
2001 In: J. Chromatogr. A, Vol. 905, no 1-2, 3-17 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-89668 (URN)
Available from: 2002-02-25 Created: 2002-02-25Bibliographically approved
5. Investigation of the Heterogeneous Adsorption Behavior of Selected Enantiomers on Immobilized α1 - Acid Glycoprotein (CHIRAL-AGP®)
Open this publication in new window or tab >>Investigation of the Heterogeneous Adsorption Behavior of Selected Enantiomers on Immobilized α1 - Acid Glycoprotein (CHIRAL-AGP®)
In: Anal. Chem.Article in journal (Refereed) Submitted
Identifiers
urn:nbn:se:uu:diva-89669 (URN)
Available from: 2002-02-25 Created: 2002-02-25Bibliographically approved
6. Peak Tailing and Mass Transfer Kinetics in Linear Chromatography - Dependence on the Column Length and the Linear Velocity of the Mobile Phase
Open this publication in new window or tab >>Peak Tailing and Mass Transfer Kinetics in Linear Chromatography - Dependence on the Column Length and the Linear Velocity of the Mobile Phase
1999 In: J. Chromatogr. A, Vol. 831, no 1, 17-35 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:uu:diva-89670 (URN)
Available from: 2002-02-25 Created: 2002-02-25Bibliographically approved

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