2nd Edition

Analytical Methods in Combinatorial Chemistry

By Bing Yan, Bin Zhang Copyright 2011
    238 Pages 70 B/W Illustrations
    by CRC Press

    238 Pages 70 B/W Illustrations
    by CRC Press

    Since the publication of the benchmark first edition of this book, chemical library and combinatorial chemistry methods have developed into mature technologies. There have also been significant shifts in emphasis in combinatorial synthesis. Reflecting the growth in the field and the heightened focus on select areas, Analytical Methods in Combinatorial Chemistry, Second Edition updates a classic text and captures the current state of these technologies.

    Written by leaders in the field, this second edition includes several enhancements. A chapter on high-throughput analytical methods and informatics reflects the demand for quality control of library members. A new chapter focuses on high-throughput purification methods. All chapters have been updated with new data.

    Topics discussed in this second edition include:

    • Properties of solid-phase samples, analytical studies targeted to understand these properties, and resin swelling
    • Fourier Transform Infrared techniques
    • On-support mass spectrometry and nuclear magnetic resonance methods used in the reaction optimization stage
    • Combinatorial library analysis using spectrophotometric, fluorometric, and other methods
    • Quality control of combinatorial libraries
    • High-throughput purification methods
    • Future directions and analytical challenges

    The coming decade is sure to usher in a new wave of progress in this critical field. This volume provides not only an analysis of the recent developments in analytical methods, technologies and applications; it also provides a window on future possibilities.

    Analytical issues in combinatorial chemistry
    Combinatorial chemistry
    Synthesis methods
    Analytical challenges
    Properties of solid supports
    Reaction Optimization Stage
    Library synthesis stage
    Lead selection and optimization stage

    An examination of the analytical sample: resin support
    Physical properties of resins
    Resin type
    Resin bead size distribution
    Loading and the intraresin site distribution
    Thermal stability
    Chemical stability
    Resin swelling and solvation
    Effects of swelling on resin
    Effects of swelling on reagent and solvent molecules
    Swelling ability of solvents
    Dynamic resin solvation
    Effects of the solvated resin on solid-phase reactions
    The effects of support solvation on SPPS
    Resin support as another "solvent phase"
    Support effects on SPOS reaction kinetics
    Site separation and site interaction
    Solid support effects on product purity

    Solid-phase reaction optimization using FTIR
    Comparison of FTIR and Raman techniques
    Analysis of resin-bound compounds
    Comparison of techniques
    Monitoring of polymer-supported organic reactions
    The monitoring of reactions on polystyrene-based resin
    Yes-and-no information
    Reaction kinetics on resin support
    Quantitative estimation of chemical conversions (%) on resin
    The selection of optimal reaction conditions using single-bead IR
    The monitoring of reactions on PS-PEG resins: comparing the reaction rate on PS and PS-PEG resins
    Examples: Peptide secondary structure on resin support
    The monitoring of reactions on surface-functionalized polymers
    Parallel reaction monitoring

    Reaction optimization using MS and NMR methods
    MS methods
    NMR methods
    Gel-phase NMR
    Magic angle spinning (MAS) NMR
    Other NMR methods

    Reaction optimization using spectrophotometric and other methods
    Qualitative analysis of amines
    Quantitative analysis of amines
    Quantitative spectroscopic methods for organic functional groups
    Quantitation of aldehyde/ketone groups
    Quantitation of hydroxyl groups on resin
    Quantitation of carboxyl groups on resin
    Quantitation of polymer-supported sulfhydryl groups
    Combustion elemental analysis methods
    Analysis of resin-bound organic compounds
    Quantitatively monitoring SPOS reactions
    Electrochemical methods
    On-resin X-ray, EPR, SERS, and fluorescence methods

    Quality control of combinatorial libraries
    Analysis of discrete compound libraries
    MS analysis
    MS-guided purification
    High-throughput NMR
    Analysis of pooled libraries
    Theoretical calculation of mass distribution
    MS analysis
    High-resolution MS
    Tandem MS
    Liquid chromatography (LC)/MS and capillary electrophoresis (CE)/MS
    NMR methods for mixture analysis
    HPLC for analyzing compounds from discrete and mixture libraries
    HPLC with a chemiluminescence nitrogen detector (CLND)
    Evaporative light scattering detector (ELSD)

    High-throughput purification
    Nonchromatographic high-throughput purification methods
    Chromatographic high-throughput purification methods
    Supercritical fluid chromatographic purification methods
    Purification methods based on fluorous chemistry separation technique
    Fluorous liquid–liquid extraction (F-LLE)
    Fluorous solid-phase extraction (F-SPE)
    Fluorous HPLC (F-HPLC)
    Fluorous-flash chromatography (F-FC)

    Final Thoughts and Future Perspectives
    Stability of compound collections
    Nano-combinatorial library and associated analytical issues
    Green process and technologies


    Bing Yan received his Ph.D. from Columbia University with Koji Nakanishi in 1990. He is a faculty member at the Department of Chemical Biology and Therapeutics at St. Jude Children’s Research Hospital in Memphis, Tennessee, and an adjunct professor at Shandong University.

    Bin Zhang received his Ph.D. from the Institute of Inorganic and Analytical Chemistry and Radiochemistry at Saarland University (Germany) with Professor Doctor Horst P. Beck in 2003. He is an associate professor of analytical chemistry in the School of Chemistry and Chemical Engineering at Shandong University, China.