Modular click chemistry

M.G. Finn
Professor Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, Georgia, USA
Valery V. Fokin
Associate Professor of Chemistry, The Scripps Research Institute, La Jolla, California, USA
K. Barry Sharpless
W.M. Keck Professor of Chemistry, The Scripps Research Institute, La Jolla, California, USA

Finn, Fokin, and Sharpless are suggested as possible Nobel Prize winners for “the development of modular click chemistry”

Nature produces millions of organic chemicals, and makes them in ways that are efficient in the use of materials and energy, in high yields but without wasteful by-products, in water as the solvent, and with exactly the right structure. This means that if there is a left-handed or right-handed form of the molecule, then only the desired one is constructed. So-called “click chemistry” aims to do the same. The collaborative efforts of Finn, Fokin, and Sharpless have opened up new routes for chemical synthesis by the click method.

The most successful click example is the Huisgen cyclo-addition reaction which results in the formation of a five-membered ring with three adjacent nitrogen atoms. This and several other click-like reactions are in Sharpless and Finn’s initial paper of 2001 in which they introduced the concept (Angewandte Chemie International Edition, 40: 2004-21) and which has been cited more than 4,200 times. In this they paper they note that nature prefers to make small molecular units in which carbon is bonded to atoms other than carbon, and then to “stitch” these together to make proteins and carbohydrates. This they define as click chemistry.

Click chemistry is finding application in two main areas: the life sciences and the material sciences. An example of the former is the addition of a labeling group to a biomolecule, a configuration that has potential for diagnostic applications. In materials, click chemistry is permitting the formation of things like polymers and surface coatings with unusual properties.

The trio of researchers has copied nature by using water as a solvent in place of the organic solvents that chemists generally use. Their 2005 paper (Angewandte Chemie International Edition, 44: 3275-9) has been cited more than 600 times. It showed that organic compounds could be made in aqueous solution despite the starting materials not being water-soluble and that reactions went quicker, at ambient temperatures and gave high yields, a technique they describe as “on water.”

Finn has also adopted the click approach to using acetylcholinesterase enzyme to assemble molecules (see Angewandte Chemie International Edition, 41: 1053-7; cited 428 times), as well as in polymer formation and modification along with other kinds of reactions, such as ones that are also reversible.

Folkin has concentrated on reactions catalyzed by metals. His 2002 paper with Sharpless (Angewandte Chemie International Edition, 41: 2596-9), on the stepwise Huisgen process which uses a copper(I) catalyst, has been cited more than 4,000 times. The use of the click method to assemble complex dendrimers with relative ease (Angewandte Chemie International Edition, 43: 3928-32) has collected 668 citations.

Should the trio be selected by the Nobel committee, this would be the second Nobel Prize in chemistry for Sharpless. He gained his previous prize in 2001 “for his work on chirally catalyzed oxidation reactions.” The prize was shared with William S. Knowles and Ryoji Noyori “for their work on chirally catalyzed hydrogenation reactions.”

Commentary on the Chemistry Laureates by John Emsley, Chemistry correspondent, ScienceWatch. Dr. Emsley is based at the Department of Chemistry, University of Cambridge, UK.