Molecular structure combinatorial chemistry

The chemical world is often divided into measurers and makers of molecules. This division has deep historic roots, but it artificially impedes taking advantage of both aspects of the chemical sciences. Of key importance to all forms of chemistry are instruments and techniques that allow examination, in space and in time, of the composition and characterization of a chemical system under study. To achieve this end in a practical manner, these instruments will need to multiplex several analytical methods. They will need to meet one or more of the requirements for characterization of the products of combinatorial chemical synthesis, correlation of molecular structure with dynamic processes, high-resolution definition of three-dimensional structures and the dynamics of then-formation, and remote detection and telemetry. 

On the other hand, there is considerable interest to quantify the similarities between different molecules, in particular, in pharmacology [7], For instance, the search for a new drug may include a comparative analysis of an active molecule with a large molecular library by using combinatorial chemistry. A computational comparison based on the similarity of empirical data (structural parameters, molecular surfaces, thermodynamical data, etc.) is often used as a prescreening. Because the DFT reactivity descriptors measure intrinsic properties of a molecular moiety, they are in fact chemical fingerprints of molecules. These descriptors establish a useful scale of similarity between the members of a large molecular family (see in particular Chapter 15) [18-21],... 

Despite the remarkable progress in the field of molecular recognition, it is still extremely difficult to predict a priori the structure of a selective, high-affinity ligand for a metal ion such as Hg ". The approach we intend to pursue is to take advantage of combinatorial chemistry methods—a collection of technical advances that allow one to seriously consider undertaking the synthesis of hundreds or even thousands of compounds simultaneously —to carry out the parallel synthesis of a set of fOO potentially selective high-affinity fluorescent chemosensors for mercury. 

Bohm, H.-J. and Stahl, M. (2000) Structure-based library design molecular modeling merges with combinatorial chemistry. Curr. Opin. Chem. Biol. 4, 283-286. 

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