Click Chemistry Meets Materials Science

By Jason Socrates Bardi

"If I have seen further it is by standing upon ye shoulders of giants."

—Isaac Newton, from a Letter to Robert Hooke, February 5, 1676.

Most people probably look at materials purely in terms of the uses to which they are applied: copper wires and aluminum siding, for example. It's no secret that these applications are determined by the properties of the materials—copper conducts electricity well and is the material of choice used in millions of miles of electrical wire; aluminum is cheap and resistant to oxidation, which makes it a favorite to enrobe houses.

For a classically trained chemist like Research Associate David Díaz at The Scripps Research Institute, the fascination for materials science comes from understanding the chemical processes that determine the properties of materials. Copper conducts electricity well because it has an unpaired electron in its ground state that can move freely from one copper atom to another in a wire (electrical current being simply the movement of electrons). Aluminum materials resist corrosion because they form oxidation-resistant aluminum oxide on their surfaces.

Díaz has been working with a different type of material in the last few years—gels—with his advisor Associate Professor M.G. Finn and their collaborators Assistant Professor Valery Fokin and Nobel laureate Professor K. Barry Sharpless.

I caught up with Díaz as he was preparing to head to the 230th national meeting of the American Chemical Society (ACS) in Washington, D.C., last month, and he described with enthusiasm some of the results that he and his colleagues have obtained while working with gels in the last few years.

In Between Solid and Liquid

Gels are a strange group of materials in that they are somewhere in between solids and liquids. They are mostly composed of material like water, which should be a liquid at room temperature but because of cohesive forces between molecules other than water that are mixed in, gels are solids at temperatures well above the melting point. "Solid" is, of course, a relative term because gels are often wobbly—think Jell-O™.

This unusual property of being solid at a temperature when 99 percent retained mass should be liquid makes gels useful in far-flung applications. Gelatin, a collagen-based substance obtained from bones, has been used in culinary dishes for centuries. In one new application, some gels are helping to make artificial bones. Also, water-based gels, known as hydrogels, are so effective at absorbing liquid that dehydrated hydrogel crystals are being used in products from cat litters to slow-releasing medicines.

Generally, the cohesive forces between molecules in a gel are non-covalent, in other words non-permanent ionic attractions, such as hydrogen bonds. While these cohesions are enough to render a liquid solid, they are not so stable under heat, and gels can melt when heated up—a fact to which anyone who has ever placed a bowl of Jell-O™ in the microwave can attest (don't try this at home).

This is especially the case with a class of gels called organogels, which are similar to hydrogels except that they are mostly organic solvents, as opposed to mostly water. Unlike hydrogels, some organogels are liquid at room temperature. It's no surprise, then, that some scientists would like to find ways to stabilize such gels so that they are still solid at higher heats.

"However," says Díaz, "to modify the properties of those materials is not so easy."

The thermal solidity of a material like a gel has been stabilized in the past principally by adding copious amounts of metals or other compounds to the gel that make networked connections of covalent bonds. The disadvantage is that they may interfere with the uses for which the gels are intended, for example, by making them toxic or changing necessary properties such as the temperature at which they melt.

But that is not likely to be the case with click chemistry.

Click chemistry, a modular protocol for organic synthesis developed by Scripps Research Professor K. Barry Sharpless and his colleagues, relies on using energetic yet stable building blocks like azides and alkynes that react with each other in a highly efficient and irreversible spring-loaded reaction. Click chemistry is an excellent tool for changing the property of a gel, says Díaz, because it can be used to connect molecules together in the gel without adding in a lot of metal ions—it requires only a minimal, "catalytic" amount of copper to be added. And the things that it connects—azides and alkynes—are themselves small and so do not disturb the properties of the gel before they are "clicked" together.

"When you have something that you have to connect, click chemistry is a good thing," says Díaz. "It gives you a powerful linking reaction." By adding azides and alkynes to the molecules in an organogel, Díaz and his colleagues were able to thermally stabilize gels that normally would be liquid at room temperature, while keeping other properties unchanged.

While this is the first application of click reactions to gelled materials, materials scientists in general have embraced click chemistry even faster than other chemists, says Finn. Díaz led the way there, too, being one of two postdocs in the Finn lab (along with Dr. Sreenivas Punna) to pioneer the application of the azide-alkyne reaction to making new adhesive materials in 2002-2003. (To read about that effort, see: Díaz et al J. Polym. Sci. Part A: Polym. Chem. 2004, 42, 4394-4403, or go to: http://dx.doi.org/10.1002/pola.20330).

Díaz first came to the institute to work with Finn for a semester in 2000 while he was a graduate student at La Laguna University in the Canary Islands. He later returned, in 2002, to pursue postdoctoral research with Finn. Now Diaz is going back to Spain in a month to take a faculty position at the Autonomic University of Madrid. He won a prestigious Ramón y Cajal scholarship to support his first five years of research.

Asked about the success of his projects at Scripps Research, Díaz points to two things. First is his background in synthetic organic chemistry, which has given him the tools he needs to modify molecules. (In fact, in addition to the materials science project, Díaz had several focusing on pure organic synthesis.) The second key, says Díaz, has been working with others at Scripps Research—especially Finn, his mentor. "I owe a lot to M.G.—scientifically and otherwise," he says. "I learned to have fun with experiments."

Finn, for his part, reflects the praise back. "I deserve very little credit for any of David's work," Finn says. "The gels project was his idea, his design, and most definitely his execution—he is an outstanding researcher. Around his efforts have 'gelled' a remarkable collection of leading materials scientists who are now our collaborators, including Professors Craig Hawker at the University of California, Santa Barbara, Curt Frank at Stanford University, Jeff Koberstein at Columbia University, Joel Schneider at the University of Delaware, and Hugh Brown at the University of Wollongong, Australia."

Send comments to: mikaono[at]scripps.edu