Quality of Combinatorial Libraries

A decade ago, combinatorial Hbraries were large and compounds from those libraries were characterized less rigorously. They were rarely purified nor analyzed for their yield and purity Recently, LC/MS/UV214 or LC/MS/ELSD has been used to characterize combinatorial Hbraries. These methods provide information regarding the identity and relative purity of compounds at a high throughput. 

Copyright 2003 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-30630-7 

Relative purity measurement and the relative purity-based reaction optimization have long been used in combinatorial synthesis. In order to make high-through-put purification a success, the yield-based optimization is essential. Chemiluminescent nitrogen detection (CLND) [4] with HPLC determines the quantitative yield after each reaction step during the library feasibility and rehearsal stages. The yield of each synthetic step provides guidance for the final library synthesis. 

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The use of computational tools to increase the quality of combinatorial libraries is becoming more and more popular. These methods can be applied to any library format, and their careful use may add significant value to the library. Their main apphcation is the selection of individuals/monomers for a library from the many virtual mono-mers/final compounds theoretically available by using all the easily accessible monomers. We will examine in detail the usefulness of computational tools for each library format through the presentation of the main reported approaches by leading groups in... 

As stated earlier, LC has emerged as the technique of choice for assessing the quality of combinatorial libraries. While this trend will certainly continue, LC, either alone, or in combination with other techniques, will continue to evolve. The trend towards shorter, smaller internal diameter columns will continue, however hardware limitations such as pressure limitations, system volume, injection overhead times and data storage must be overcome. A balance be-... 

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