Analytical Methods in Combinatorial Chemistry, Second Edition

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 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 Background Examples Examples: Peptide secondary structure on resin support The monitoring of reactions on surface-functionalized polymers Techniques Examples Parallel reaction monitoring Reaction optimization using MS and NMR methods MS methods NMR methods Gel-phase NMR Magic angle spinning (MAS) NMROther 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 NMRAnalysis 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.