Combinatorial chemistry involves the synthesis of, the computer simulation of, or both, a large number of different molecules and the selective testing of these to find ones with desired characteristics.
Although combinatorial chemistry has only really been taken up by industry since the 1990s, its roots can be seen as far back as the 1960s when a researcher at Rockefeller University, Bruce Merrifield, started investigating the solid-state synthesis of peptides. In the 1980s researcher H. Mario Geysen developed this technique further, creating arrays of different peptides on separate supports.
In its modern form, combinatorial chemistry has probably had its biggest impact in the drug industry. Researchers attempting to improve the activity of a drug or decrease side effects create a 'library' of many different compounds. Creation of the library of real chemicals is now often preceded by the creation of virtual compounds, using a computer program to combine one or more promising core structures with all possible combinations of various promising R groups.
Structural, chemical, physical, and synthetic descriptions of these compounds (core structures, R groups, and complete compounds) are stored in databases, and sophisticated computer algorithms help identify which ones have potential for further development.
In the past decade there has been a lot of research and development in combinatorial chemistry applied to the discovery of new compounds and materials. This work was pioneered by P.G. Schultz et al. in the mid nineties (Science, 1995, 268: 1738-1740) in the context of luminescent materials obtained by co-deposition of elements on a silicon substrate. Since then the work has been pioneered by several academic groups as well as industries with large R&D programs (Symyx Technologies, GE, etc).
