Newswise — Part of almost all the top 200 brand-name drugs is a nitrogen-containing ring-shaped structure that chemists call an "N-heterocycle." Manufacturing these drugs depends on the ability to synthesize N-heterocycles, but most synthesis reactions take a long time and produce toxic waste byproducts.

A University of Illinois at Chicago research group may have found a faster, cleaner, "greener" way to streamline these chemical reactions, and the National Institutes of Health has just awarded the team a five-year, $1.48 million grant to prove its effectiveness.

"Hopefully it will reduce the cost of doing business," said Tom Driver, assistant professor of chemistry, whose laboratory is leading the research effort. "I can't compete with a pharmaceutical company in inventing new materials, but what I can do is invent new tools for them to use. We're interested in making the synthesis of drugs a lot easier."

Driver and his coworkers have devised a chemical reaction that creates a carbon-nitrogen bond, such as in the N-heterocycle, using an azide, a chemical that powers the airbags in cars.

"You need a particular type of starting point that has to be energetic, because the bonds we're trying to functionalize are quite stable," he said. Since the azide contains three nitrogen atoms, he said, after it gives up one, "the only byproduct in our reaction is nitrogen gas, which is green and non-toxic."

Driver's reaction reduces the number of steps needed to synthesize the N-heterocycle molecules. He compares the process to a better way of cooking a feast.

"You can do it using 15 to 20 pots and pans, which you've then got to clean up. But if you can make that feast in a way that uses just one or two pots and pans, that would be fantastic."

Driver's laboratory has already published four research papers describing the reaction.

"This is a brand new reaction -- no one's ever done it before," he said. "We've demonstrated that what we're proposing works. Now, basically, we want to flesh it out in more detail and invent new reactions."

The NIH is also interested in using Driver's reaction to alter certain chemotherapy drugs that cancer cells have developed a way to pump out of themselves.

"We want to learn how to clog the pumps and turn them off," Driver said, so that standard chemotherapy drugs remain lethal to the cancer cells. A key obstacle is that "between our blood and brain, these pumps exist as well," which helps keep the chemotherapy drugs from being too neurotoxic.

Driver's team is trying to figure out how small molecules interact with the pump, which scientists at pharmaceutical companies can use in designing chemotherapeutics.

"We're interested in mechanism," said Driver. "Our reaction can be employed to ease the synthesis of these quite complex small molecules.

"We're not only going to be interested in the invention of new reactions, but also demonstrating its applicability in the synthesis of complex functional, important small molecules."