Volume 2, Issue 12
Change Agent
Organic chemistry depends on catalysts to spur the transformation of molecules during chemical synthesis. Like the catalytic reactions that are his specialty, UC Berkeley chemist Dean Toste is an agent of change. Toste develops new catalysts that could someday transform some forms of chemical synthesis, perhaps even streamlining drug discovery and pharmaceutical production.
While completing his PhD at Stanford, F. Dean Toste received the Nobel Laureate Signature Award of the American Chemical Society, the highest honor a chemistry graduate student can receive.
"Our catalytic reactions are less like the difficult transformations people often associate with organic chemistry and much more like cooking," Toste says.
Chemists employ catalysts to accelerate the rate of chemical reactions. These catalysts provide a pathway between the reactants and the end product that requires far less energy than the transformation would take on its own. During the last several decades, metal catalysts have emerged as a powerful tool for organic synthesis in the pharmaceutical and materials science. These highly reactive metals enable transformations that may not be possible using traditional methods. The problem, Toste explains, is that the metals are often in low-oxidation states, making them incredibly sensitive to air and moisture.
"It's a double-edged sword," he says. "You add a lot of reactivity but the reactions become so sensitive that they react with the environment around them. That limits the catalysts' practical utility."
The pharmaceutical industry already uses metal catalysts when it's seeking out new possible medicines during drug discovery. The high reactivity requires chemists to purify the solvents involved in the process and remove the air from the reaction vessels. Toste's novel metal complexes and catalytic reactions negate the need for those steps.
"Medicinal chemists might use our catalysts to make the discovery phase much easier, but our reactions may also be able to further streamline the production of drugs," says Toste, who has won numerous awards from pharmaceutical companies for his basic research successes.
One of the novel catalysts in action, catalyzing a reduction in an open test tube. (courtesy the researchers)
For example, Cytochrome P-450 is a high oxidation state metal enzyme that the human body uses to make cholesterol, steroids, and lipids. Toste and his colleagues have engineered catalysts based on Cytochrome P-450 that are non-oxidative.
"We took something that nature uses for oxidation and reversed it so now it does reduction," he says. "Since it's already oxidized, it isn't sensitive to the environment. You can just drop it into your flask and stir it up."
Along with the benefits of being tolerant of air and moisture, the catalysts coming from Toste's lab promise to have less impact on the environment. The reactions primarily are additions to the molecular product, or isomerizations, in which the organization of the atoms is changed but not the constituency of the molecule.
"Nearly everything you put in ends up in the final product, so the waste stream becomes very small." Toste says.
The researchers are also developing catalysts based on gold. Most of us think of gold as an inert substance that's perfect "for a wedding band," Toste says, the fact that gold is a low oxidation-state metal makes it interesting as a catalyst, but it's historically been very difficult to demonstrate very many useful reactions based on the element. Recently though, the Berkeley researchers have developed myriad gold complexes that work well as "open-flask" catalysts.
"Even if we don't discover the groundbreaking fundamental reaction that produces a new drug for pennies, we hope in the future that our catalysts could lead someone to those kinds of opportunities."