POLYMER PARTICLES AS SEPARATION MEDIA FOR CHROMATOGRAPHY

Summary

Principal Investigator: JEAN FRECHET
Abstract: This continuation proposal is aimed at the design, preparation, and testing of advanced polymer beads for use as separation media in high- performance liquid chromatography (HPLC). These media will be designed to provide unmatched performance as a result of optimized physical properties and both bulk and surface chemistries. Our primary target is to develop very efficient polymeric stationary phases. Libraries of shape templates will be prepared, which use will enable the preparation of uniform 3 mu m beads with high porosity, well-defined regular surfaces, and tunable chemistry. Temperature gradients will be used during the staged templated suspension polymerization process to suppress the occurrence of micropores that appear to be the major problem of current polymer-based stationary phases. Synergistic effect of higher temperature and solvent that facilitates changes in conformation of polymer chains will be studied in detail and applied to the production of porous polymer beads with controlled topology of functionalities on the pore surface. Staying ahead of the current trend of rapid decrease in size of samples available for separations, our research will push even further the miniaturization of polymer-based separation technology using microcolumns and packed capillaries. Specific targets include functional beads and techniques for the separations of new generations of drugs as well as other biologically active compounds that will result from the discoveries of drug targets derived from the human genome. In particular, polymeric beads will be prepared with properties optimized for enantioselective chromatography. Advanced polymeric chiral stationary phases will be designed and optimized using the means of both computational and experimental combinatorial chemistry. First, methods of molecular docking will be used to explore virtual libraries of potential selectors and to facilitate the discovery of leads. Only more focused libraries will be then prepared in the laboratory. The chemistry of linkers will also be explored with the aim to reduce non-specific interactions and explore multiplicative as well as synergistic effects. The rational design of linkers, as well as newly prepared polymeric supports will enable the very efficient and/or selective separation of chiral drugs and their metabolites in addition to a number of other important enantiomers. This work will also contribute to the basic understanding of the effects of all of the critical elements of enantioselective separation media - the support, the linker, and the selector - on the recognition process.
Funding Period: 1990-07-01 - 2006-05-31
more information: NIH RePORT

Top Publications

  1. pmc In-column preparation of a brush-type chiral stationary phase using click chemistry and a silica monolith
    Michael D Slater
    Department of Chemistry, University of California, Berkeley, CA, USA
    J Sep Sci 32:21-8. 2009
  2. pmc Stability and repeatability of capillary columns based on porous monoliths of poly(butyl methacrylate-co-ethylene dimethacrylate)
    Laurent Geiser
    College of Chemistry, University of California, Berkeley, CA 94720 1460, USA
    J Chromatogr A 1140:140-6. 2007
  3. pmc Less common applications of monoliths. III. Gas chromatography
    Frantisek Svec
    Department of Chemistry, University of California, Berkeley, CA 94720, USA
    J Chromatogr A 1184:281-95. 2008
  4. pmc Optimization of the porous structure and polarity of polymethacrylate-based monolithic capillary columns for the LC-MS separation of enzymatic digests
    Sebastiaan Eeltink
    Department of Chemistry, University of California, Berkeley, CA 94720 1460, USA
    J Sep Sci 30:2814-20. 2007
  5. pmc In-line system containing porous polymer monoliths for protein digestion with immobilized pepsin, peptide preconcentration and nano-liquid chromatography separation coupled to electrospray ionization mass spectroscopy
    Laurent Geiser
    Department of Chemistry, University of California, Berkeley, CA 94720 1460, USA
    J Chromatogr A 1188:88-96. 2008
  6. pmc Stellan Hjertén's contribution to the development of monolithic stationary phases
    Frantisek Svec
    The Molecular Foundry, E O Lawrence Berkeley National Laboratory, Berkeley, CA 94720 8197, USA
    Electrophoresis 29:1593-603. 2008
  7. pmc CEC separation of peptides using a poly(hexyl acrylate-co-1,4-butanediol diacrylate-co-[2-(acryloyloxy)ethyl]trimethyl ammonium chloride) monolithic column
    Violaine Augustin
    College of Chemistry, University of California, Berkeley, CA 94720, USA
    Electrophoresis 29:3875-86. 2008

Scientific Experts

  • Frantisek Svec
  • Jean M J Frechet
  • Laurent Geiser
  • Sebastiaan Eeltink
  • Michael D Slater
  • Violaine Augustin
  • Timothy Stachowiak

Detail Information

Publications7

  1. pmc In-column preparation of a brush-type chiral stationary phase using click chemistry and a silica monolith
    Michael D Slater
    Department of Chemistry, University of California, Berkeley, CA, USA
    J Sep Sci 32:21-8. 2009
    ..The separation performance of these triazole linked stationary phases was demonstrated in enantioseparations of four model analytes, which afforded separation factors as high as 11.4...
  2. pmc Stability and repeatability of capillary columns based on porous monoliths of poly(butyl methacrylate-co-ethylene dimethacrylate)
    Laurent Geiser
    College of Chemistry, University of California, Berkeley, CA 94720 1460, USA
    J Chromatogr A 1140:140-6. 2007
    ..The stability of retention times was also monitored using a single monolithic column and no significant shifts in either retention times or back pressure was observed in a series of almost 2200 consecutive protein separations...
  3. pmc Less common applications of monoliths. III. Gas chromatography
    Frantisek Svec
    Department of Chemistry, University of California, Berkeley, CA 94720, USA
    J Chromatogr A 1184:281-95. 2008
    ..This review article focuses on monoliths in capillaries designed for separations in gas chromatography...
  4. pmc Optimization of the porous structure and polarity of polymethacrylate-based monolithic capillary columns for the LC-MS separation of enzymatic digests
    Sebastiaan Eeltink
    Department of Chemistry, University of California, Berkeley, CA 94720 1460, USA
    J Sep Sci 30:2814-20. 2007
    ..Our preparation technique affords monolithic columns with excellent column-to-column and run-to-run repeatability of retention times and pressure drops...
  5. pmc In-line system containing porous polymer monoliths for protein digestion with immobilized pepsin, peptide preconcentration and nano-liquid chromatography separation coupled to electrospray ionization mass spectroscopy
    Laurent Geiser
    Department of Chemistry, University of California, Berkeley, CA 94720 1460, USA
    J Chromatogr A 1188:88-96. 2008
    ..Successive protein injections confirmed both the repeatability of the results and the ability to reuse the bioreactor for at least 20 digestions...
  6. pmc Stellan Hjertén's contribution to the development of monolithic stationary phases
    Frantisek Svec
    The Molecular Foundry, E O Lawrence Berkeley National Laboratory, Berkeley, CA 94720 8197, USA
    Electrophoresis 29:1593-603. 2008
    ..The following text details his works in the field...
  7. pmc CEC separation of peptides using a poly(hexyl acrylate-co-1,4-butanediol diacrylate-co-[2-(acryloyloxy)ethyl]trimethyl ammonium chloride) monolithic column
    Violaine Augustin
    College of Chemistry, University of California, Berkeley, CA 94720, USA
    Electrophoresis 29:3875-86. 2008
    ..The fractions of eluent containing peptides of the digest separated in the monolithic column were collected and characterized using matrix-assisted laser desorption ionization mass spectrometry...