Combinatorial chemistry, representation

Mixtures containing up to several thousand distinct chemical entities are often synthesized and tested in mix-and-split combinatorial chemistry. The descriptor representation of a mixture may be approximated as the descriptor average of its individual component molecules, e.g., using atom-pair and topological torsion descriptors. 

Figure 8.15 Schematic representation of resin-bound dynamic combinatorial chemistry and structures of the family of intercalating DNA binding agents M, [54],...

Figure 7.2 Schematic representation of target-tempiated in situ dynamic combinatorial chemistry.

Other approaches for presenting information to facilitate the visualization of meaningful patterns for rapid decision involve combinatorial chemistry-related applications. For example, methods for the analysis of combinatorial chemistry-derived samples provide visual representations of the 96-well plate (Figure 5.5) (Yates et al., 2001). Following the LC/MS analysis, an automated analysis is performed, according to preestablished thresholds to search for the protonated molecule ion of the analyte. If the ion is found, then the visual representation of the corresponding well is marked with a distinguishing color scheme. In this way, the scientist quickly inspects the visual representation to make decisions. 

Figure 5.5 Visual representation of the results obtained from LC/MS analysis of a combinatorial chemistry library from a 96-well plate. Visualization of the information allows for rapid inspection of data. (Reprinted with permission from Yates et al., 2001. Copyright 2001 American Chemical Society.)...

Additional information on the representation of combinatorial chemistry is given in Appendix 12-2. 

The structural representation of combinatorial chemistry consists of a generic structure plus a list of substituents that may be present in that structure. 

Figure 16 Schematic representation of a three-dimensional microchannel circuit for combinatorial chemistry.

Dynamic combinatorial chemistry (DCC) is founded on the study and the construction of mixtures of discrete constituents which are produced by reversible molecular or supramolecular associations [1, 2], The composition of a dynamic combinatorial library (DCL) is thermodynamically driven and, as such, is able to adapt itself to any parameter that - permanently or transiently - modifies its constitution/energy potential surface [3,4], Thus, in the presence of various internal or external parameters, the involved equilibria can be displaced toward the amplification of given products through an adaptation process that will occur through an in situ screening of these species. A schematic representation using Emil Fisher lock-and-key metaphora can be used to illustrate these concepts (Fig. 1). 

Fig. 1 Representation of (a) target oriented synthesis (TOS), (b) combinatorial chemistry and (c) diversity oriented synthesis (DOS) in chemical space [2]...

Products/technologies The company tailors its combinatorial chemistry methodologies to meet specific client needs. It offers three main levels of products and services, which include a fully integrated lead discovery, expansion, and optimization service design and synthesis of high-purity, diverse or focused representational arrays and supply of custom-designed combinatorial synthesis sets. 

Often the search spaces of combinatorial chemistry are described by generic structural formulas [11], and this is true in particular for patent libraries in chemistry [329]. There are only very few structure generators that allow the use of generic structural formulas to their full potential. Moreover, there is not yet a standardized and comprehensive format for the representation of generic structural formulas. 

Microfluidic Systems for Combinatorial Chemistry, Figure 6 Schematic representation of the microfluidic circuit using an array of the valves from Fig. 3, to control the sample flows and the junction circuits. Basically similar to the layout from Fig. 5, this circuit has a more complicated way of leading the fluids into the vent. Arrows indicate the protective flows... 

The chemically apparent representation allows the use of non-standard genetic operators that can efficiently exploit the rich combinatorial chemistry of the search space. Also, some of these operators include in them details of design acceptability such as maximum length to ensure that the offspring they produce do not violate these constraints. 

Recently, Markush structures have also been used to represent combinatorial libraries. The representations and search systems useful for Markush structures in patents are also potentially useful for combinatorial libraries (see Combinatorial Chemistry and Combinatorial Libraries Structure-Activity Analysis). 

Chemical Abstracts Service Information System Combinatorial Chemistry Combinatorial Libraries Structure-Activity Analysis Structural Similarity Measures for Database Searching Structure and Substructure Searching Structure Databases fracture Representation. 

Chemometrics Multivariate View on Chemical Problems Combinatorial Chemistry Factual Information Databases Fuzzy Methods in Chemistry Infrared Data Correlations with Chemical Structure Infrared Spectra Interpretation by the Characteristic Frequency Approach Inorganic Chemistry Databases Inorganic Compound Representation NMR Chemical Shift Computation Ab Initio NMR Chemical Shift Computation Structural Applications NMR Data Correlation with Chemical Structure Online Databases in Chemistry Spectroscopy Computational Methods Standard Exchange Formats for Spectral Data Structure and Substructure Searching Structure Determination by Computer-based Spectrum Interpretation Structure Generators Synthesis Design. 

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