Approaches to the analysis of single beads for Combinatorial chemistry
Approaches to the analysis of single beads for Combinatorial chemistry
In many solid-phase combinatorial syntheses a single bead is taken as representative of a batch of beads. The variability within a batch of beads therefore crucially influences the success of an analytical or synthetic procedure. The determination of the active group loading of individual beads was achieved for thiol derivatised and amine derivatised beads with a detection limit of 0.1 μmol/g resin (NH2) and the protocol subsequently applied to the individual analysis of a sample of beads to achieve a distribution graph of loadings. A low-volume flow-injection colorimetric apparatus was constructed for the analysis of the small sample volumes produced. The data compiled illustrates that the relative standard deviation within a batch of beads an be high, up to 31% from the batches analysed, highlighting the risk associated with using a single bead as a representative of the whole batch. The novel determination of the mass of single beads provided an alternative to gravimetric analysis by mass estimation by chemical means. By successfully combining this approach with a method for the determination of amine sites the loading of single beads was accurately determined. The handling and manipulation of single, and small numbers of resin beads was achieved using a unique low-volume manipulation apparatus specifically designed for this application. A number of the analytical protocols developed were carried out by employing this apparatus greatly improving the ease of handling, and also the throughput time.
Apparatus was also developed for the removal of unbound compound from a single bead by electrophoresis. Groups of compounds were driven from the resin beads onto a thin-layer silica chromatography plate within a few seconds, where they could be separated by TLC. Laser confocal microscopy was used to identify the physical structures and characteristics of single resin beads by detection of the emitted fluorescence from a derivatised bead. The images viewed provided information on the consequences of solvent swelling of polymer resins.
University of Southampton
Freeman, Catherine E
26d8b6a5-8d36-43cc-9d83-0d63b8980f04
2001
Freeman, Catherine E
26d8b6a5-8d36-43cc-9d83-0d63b8980f04
Freeman, Catherine E
(2001)
Approaches to the analysis of single beads for Combinatorial chemistry.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
In many solid-phase combinatorial syntheses a single bead is taken as representative of a batch of beads. The variability within a batch of beads therefore crucially influences the success of an analytical or synthetic procedure. The determination of the active group loading of individual beads was achieved for thiol derivatised and amine derivatised beads with a detection limit of 0.1 μmol/g resin (NH2) and the protocol subsequently applied to the individual analysis of a sample of beads to achieve a distribution graph of loadings. A low-volume flow-injection colorimetric apparatus was constructed for the analysis of the small sample volumes produced. The data compiled illustrates that the relative standard deviation within a batch of beads an be high, up to 31% from the batches analysed, highlighting the risk associated with using a single bead as a representative of the whole batch. The novel determination of the mass of single beads provided an alternative to gravimetric analysis by mass estimation by chemical means. By successfully combining this approach with a method for the determination of amine sites the loading of single beads was accurately determined. The handling and manipulation of single, and small numbers of resin beads was achieved using a unique low-volume manipulation apparatus specifically designed for this application. A number of the analytical protocols developed were carried out by employing this apparatus greatly improving the ease of handling, and also the throughput time.
Apparatus was also developed for the removal of unbound compound from a single bead by electrophoresis. Groups of compounds were driven from the resin beads onto a thin-layer silica chromatography plate within a few seconds, where they could be separated by TLC. Laser confocal microscopy was used to identify the physical structures and characteristics of single resin beads by detection of the emitted fluorescence from a derivatised bead. The images viewed provided information on the consequences of solvent swelling of polymer resins.
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Published date: 2001
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Local EPrints ID: 464477
URI: http://eprints.soton.ac.uk/id/eprint/464477
PURE UUID: d9c97ff7-f6e1-43cc-8a5b-de0fa4c25ad6
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Date deposited: 04 Jul 2022 23:40
Last modified: 16 Mar 2024 19:32
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Catherine E Freeman
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