Angewandte Chemie International Edition
© WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
For full article and contact information, see Angew. Chem. Int. Ed. 1999, 38 (1/2), 102 - 105
Catalyst Buckshot Hits the Mark
Chemists search for a reaction accelerator among hundreds of molecules /
Chance lends a hand
In Cologne, chemists Albrecht Berkessel and David A. Hérault used some lessons from Nature in their search for a catalyst to shift a chemical reaction into top gear. Using amino acids and metal ions from Nature’s construction kit, they built a series of artificial proteins of which several did indeed accelerate their reaction, much as enzymes do in nature.
Enzymes are proteins that are essential to make viable most of the vital chemical reactions in our cells. Although their functions are diverse, many enzymes have a similar structure; they often contain – tucked into tailored "pockets" made of amino acids – a metal ion which directs the actual reaction. The ion "fishes" the necessary molecules out of the cellular fluid and binds them together into new compounds. The design of the pocket thus takes on an important role: its shape determines, for example, the form of the reaction product. Chemists have long been trying to recreate enzymes in their reaction flasks, with infrequent success, because of the complexity of the prototypes.
This is where a sort of "shotgun blast" approach, which Berkessel and Hérault aimed at their problem, could be helpful. They did not try the conventional design of synthesizing a specific molecule that should, according to computer simulations for example, accelerate the desired reaction. Instead, with the help of a "molecular construction kit", they quickly synthesized 625 mini-enzyme candidates containing metal ions in a procedure known as combinatorial synthesis. Each of these molecules differs from the others in only one specific place, and thus has a slightly different shape from the 624 other compounds. The hope was that among so many candidates, there should be at least one with a suitable "pocket".
When they mixed the starting materials for a test reaction into this molecular soup, Berkessel and Hérault had only to determine which of the many constructed molecules undertook the desired job. The chemical shotgun blast was successful; after the reaction, the researchers were indeed able to fish three catalysts out of their reaction flask. These, incidentally, gave themselves away by their turquoise color – the test used by the chemists was the synthesis of a dye closely related to "jeans blue" indigo.