By Carol Clark
The National Science Foundation has awarded $20 million to Emory University’s Center for Selective C-H Functionalization, which brings together scientists from leading research universities across the country working to revolutionize the field of organic synthesis.
“We believe that C-H functionalization will have a huge impact on the development of new drugs and other fine-chemical products, by breaking new ground for organic synthesis, and making it faster, simpler and greener,” says Huw Davies, professor of chemistry at Emory and the director of the Center for Selective C-H Functionalization, or CCHF.
“The center is at the forefront of a major paradigm shift in organic chemistry,” Davies adds. “We’re not just driving new methods of synthesis, we’re building new models for teaching and research.”
Most of the synthetic products of modern daily life – from our coffee cups and clothes to medications – are derived from organic synthesis. Chemists start with simple, bulk chemicals that are readily accessible, like petroleum and plant extracts. These bulk materials are converted into commodity chemicals and then into finer chemicals through step-by-step transformations. These steps eventually lead to more elaborate structures like plastic, nylon and drugs.
“The challenge, and the art, of organic synthesis is controlling the reaction at each stage of the process,” Davies says. “You want to modify just one reactive site at a time.”
"Our approach could lead to the kind of paradigm shift that would require rewriting the organic chemistry textbooks," Davies says.
Traditionally, organic chemistry has focused on the division between reactive, or functional, molecular bonds and the inert, or non-functional bonds carbon-carbon (C-C) and carbon-hydrogen (C-H). The inert bonds provide a strong, stable scaffold for performing chemical synthesis on the reactive groups. C-H functionalization flips this model on its head.
“We are designing tools to make the scaffolding functional,” Davies says. “We ignore the reactive groups and do synthesis at the inert C-H sites. We can now get reactions to occur at these sites.”
Ultimately, the CCHF aims to open new chemical space for exploration. “It’s like a farmer being able to grow crops in the desert, or in Antarctica,” Davies explains. “C-H functionalization represents a whole new way for chemists to synthesize materials in what were once barren sites. It opens the possibility for materials that are completely different from anything we’ve known.”
C-H functionalization is also more efficient, stripping out steps from the linear process of traditional organic synthesis, and reducing unwanted byproducts. “Every organic chemical has multiple C-H bonds, like the branching of a tree,” Davies says. “That makes it possible to have convergence, a tremendously fast and powerful way to join two compounds together and build new molecules.”
Emory competed with more than 50 other universities to win a $1.5 million NSF grant in 2009, which funded phase one of the CCHF. “The work of the center is right in the middle of my scientific passion,” says Davies, whose lab developed a rhodium catalyst that can selectively activate C-H bonds.
In addition to the Davies lab, the Emory CCHF team includes chemists Simon Blakey and Cora MacBeth, and computer scientist Jamal Musaev, director of Emory’s Cherry Emerson Center for Scientific Computation. World-class investigators of C-H activation from Stanford, the University of Illinois at Urbana-Champaign and the Scripps Research Institute round out the center’s inaugural team.
“Organic chemistry tends to be incredibly competitive, with people mostly working in isolation,” Davies says. “But we all recognized the grand challenge before us, and developed the trust needed to become an effective team.”
The CCHF recently expanded to include a total of 25 scientists from 15 universities, representing the most comprehensive group of top experts in C-H functionalization ever assembled. The center has also forged alliances with companies in a range of industries, from pharmaceuticals to farming, that are eager to tap sustainable methods for the synthesis of fine chemicals. The collaboration has been prolific, resulting in 25 published papers so far.
“We are changing the field by working together,” says Davies, who holds weekly video-conferencing sessions that unite the center’s far-flung members. “We’re pulling together the range of expertise needed to go beyond our individual research programs and develop broad applications of C-H functionalization.”
Graduate students serve as liaisons, bridging labs and specialties. Felicia Fullilove, a PhD candidate in the Davies lab, is collaborating with a chemical engineer at the Scripps Research Institute, where she will spend some time this fall.
“It’s great experience to venture outside of our group and bounce ideas off of someone with a different perspective,” Fullilove says. “It’s changed the way I think about chemistry. Most big science problems now require more of a team effort, so it’s important to learn how to communicate across specialties.”
Fullilove especially appreciated the chance to travel with a CCHF team to Washington DC, to help make the case for the $20 million grant to move the center into its second phase. “We had to make presentations and answer some tough questions before a panel,” she says. “I learned a lot by seeing the inner workings of the grant process.”
The CCHF is now poised to help C-H functionalization enter the mainstream of organic chemistry, Davies says. “We will keep building on the synergy and trust we’ve created,” Davies says. “Collaboration will help us to make advances faster.”
Many hurdles remain, he adds, before C-H functionalization can be fully optimized for broad applications. “Our goal is to make available a suite of chemical transformations for bond formation that are predictable, general and utilitarian,” Davies says. “It’s going to be an incredibly difficult thing to achieve completely, but even if we partially achieve it, that will be a huge advance for chemistry and for society. Today, more than ever, new products and materials need to be made efficiently, and in an environmentally sustainable way.”
Take a video tour of the Huw Davies lab at Emory
NSF Center aims to simplify drug synthesis