Identification of chemically selective displacers using parallel batch screening experiments and quantitative structure efficacy relationship models.
Parallel batch screening experiments were carried out to examine how displacer chemistry and salt counterions affect the selectivity of batch protein displacements in anion exchange chromatographic systems. The results indicate that both salt type and displacer chemistry can have a significant impact on the amount of protein displaced. Importantly, the results indicate that, by changing the displacer, salt counterion, or both, one can induce significant selectivity changes in the relative displacement of two model proteins. This indicates that highly selective separations can be developed in ion exchange systems by the appropriate selection of displacer chemistry and salt counterion. The experimental batch screening data were also used in conjunction with various molecular descriptors to generate quantitative structure efficacy relationship (QSER) models based on a support vector machine feature selection and regression tool. The models resulted in good correlations and successful predictions for an external test set of displacers. A star plot approach was shown to be a powerful tool to aid in the interpretation of the QSER models. These results indicate that this modeling approach can be employed for the a priori prediction of displacer efficacy as well as for providing insight into displacer design and the selection of proper mobile-phase conditions for highly selective separations.
Department of Chemical and Biological Engineering and Department of Chemistry, Rensselaer Polytechnic Institute, Troy, New York 12180, USA.
Nihal
N
Tugcu
Asif
A
Ladiwala
Curt M
CM
Breneman
Steven M
SM
Cramer
D000465:Algorithms; D000837:Anion Exchange Resins / Q000737:chemistry*; D001052:Apoferritins / Q000737:chemistry; D001667:Binding, Competitive; D002851:Chromatography, High Pressure Liquid; D002852:Chromatography, Ion Exchange / Q000379:methods; D003198:Computer Simulation; D005087:Glucan 1,4-alpha-Glucosidase / Q000737:chemistry; D006841:Hydrocarbons, Aromatic / Q000737:chemistry; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D008970:Molecular Weight; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D012044:Regression Analysis; D012965:Sodium Chloride / Q000737:chemistry; D055672:Static Electricity; D013431:Sulfates / Q000737:chemistry; D013499:Surface Properties
D000837:Anion Exchange Resins; D006841:Hydrocarbons, Aromatic; D008024:Ligands; D013431:Sulfates; C012036:sodium sulfate; D012965:Sodium Chloride; D001052:Apoferritins; D005087:Glucan 1,4-alpha-Glucosidase