Analytical Methods in Combinatorial Chemistry

by Yan, Bing

• ISBN13: 9781566768092
• ISBN10: 1566768098
• Edition: 1st
• Format: Hardcover
• Copyright: 2000-01-05
• Publisher: CRC Press

Summary

This volume summarizes most analytical technologies that are applied to solving various problems in broad areas of combinatorial chemistry: chemistry optimization, library synthesis, lead selection, and lead optimization. It also suggests many avenues for further research, especially the need for major breakthroughs to resolve the incompatibility between parallel synthesis and the serial analysis and purification. Filling the tremendous need for analytical methodologies in various phases of combinatorial chemistry, this book will be a necessary addition to the library of anyone using combinatorial chemistry. While there are several resources available on the subject, there are no other books that deal specifically with analytical issues in combinatorial chemistry. Not only an ideal companion to the comprehensive reference books used by chemists in combinatorial chemistry, it is a timely textbook for university and graduate students, introducing them to the updated applications of modern analyticaltechnologies in the rapidly growing field of combinatorial chemistry.

Table of Contents

Foreword	ix
Preface	xi
Acknowledgments	xv
Analytical Issues in Combinatorial Chemistry	1	(11)
Combinatorial Chemistry	1	(2)
Synthesis Methods	3	(3)
Analytical Challenges	6	(2)
References	8	(4)
An Examination of the Analytical Sample: Resin Support	12	(40)
Physical Properties of Resins	13	(6)
Resin Swelling and Solvation	19	(10)
Effects of the Solvated Resin on Solid-Phase Reactions	29	(17)
Summary	46	(6)
Solid-Phase Reaction Optimization Using FTIR Methods	52	(48)
Comparison of FTIR and Raman Techniques	53	(13)
The Monitoring of Reactions on Polystyrene-Based Resin	66	(20)
The Monitoring of Reactions on PS-Peg Resins: Comparing the Reaction Rate on PS and PS-Peg Resins	86	(7)
The Monitoring of Reactions on Surface-Functionalized Polymers	93	(3)
Summary	96	(1)
References	96	(4)
Reaction Optimization Using MS and NMR Methods	100	(26)
MS Methods	100	(1)
NMR Methods	101	(20)
Summary	121	(1)
References	122	(4)
Reaction Optimization Using Spectrophotometric and Other Methods	126	(32)
Qualitative Analysis of Amines	127	(3)
Quantitative Analysis of Amines	130	(7)
Quantitative Spectroscopic Methods for Organic Functional Groups	137	(9)
Combustion Elemental Analysis Methods	146	(5)
Electrochemical Methods	151	(2)
On-Resin X-ray, EPR, and Fluorescence Methods	153	(1)
Summary	154	(1)
References	154	(4)
Quality Control of Combinatorial Libraries	158	(29)
Analysis of Discrete Compound Libraries	158	(6)
Analysis of Pooled Libraries	164	(14)
HPLC for Analyzing Compounds from Discrete and Mixture Libraries	178	(4)
Summary	182	(1)
References	182	(5)
Selection of Active Compounds from Combinatorial Libraries	187	(50)
In-solution Screening of Combinatorial Libraries	187	(5)
Affinity Selection of Lead Compounds by Mass Spectrometry	192	(12)
Affinity Capillary Electrophoresis	204	(4)
Affinity NMR	208	(6)
Other Affinity Selection Methods	214	(3)
Encoding Methods	217	(13)
Summary	230	(2)
References	232	(5)
Optimization of Lead Compounds	237	(20)
Lead Compounds and Lead Optimization	237	(1)
Optimizing the In Vitro Activity: SAR by NMR	238	(10)
Optimizing Physiochemical Properties	248	(6)
Summary	254	(1)
Referencs	254	(3)
Final Thoughts and Future Perspectives	257	(8)
Reaction Optimization Efforts	258	(1)
Miniaturized Analysis	259	(1)
Parallel Analysis	260	(1)
HT NMR Data Interpretation	261	(1)
LC-NMR-MS	261	(1)
References	261	(4)
Index	265