Chemical Intuition

Thomas E. Smith '88

Thomas E. Smith ’88

By Jennifer Weeks ’83

Of all widely taught undergraduate courses, few have reputations as fearsome as organic chemistry, the study of carbon and its myriad compounds. College students almost universally speak of “orgo” as a killer class that separates real scientists from dabblers and is a make-or-break for anyone considering medical school. But Thomas E. Smith ’88, professor of chemistry at Williams, says it doesn’t have to be that way.

“At many schools organic chemistry is taught in an enormous class, and the goal is to move students through as fast as possible,” says Smith, one of five national winners of a Henry Dreyfus Teacher-Scholar Award from the Camille & Henry Dreyfus Foundation in 2008. “The easy way to do that is to make it all about memorization and screen people out who can’t keep up. But that’s not what we want to accomplish.”

In Smith’s view, high school and introductory college chemistry cover fairly predictable material. “Up to this point in their chemistry studies, students are accustomed to seeing a lot of equations and may assume that if they know where to plug the numbers in, they can turn the crank and they’re done,” he says.

Orgo, however, is dramatically different. Carbon’s chemical properties give it a propensity to combine with other elements in numerous forms. There are more than 6 million known organic compounds, many of which are extremely large and complex. Mastering organic chemistry takes more than memorizing formulas.

Chemists classify organic compounds with similar structures into so-called functional groups, such as alcohols and ethers. Once students learn the fundamental principles of how various classes of organic chemicals behave, Smith tries to help them develop chemical intuition. “It’s key to recognize the relationship between chemical structure and chemical reactivity,” says Smith. “Much of the work in orgo involves learning about the reactivity of these functional groups—understanding that electron-rich substances react with electron-poor substances, and vice versa.”

Smith and his colleagues use three-dimensional molecular models to help students comprehend organic compounds’ physical shapes. “Organic chemistry has a visual quality that separates it from other chemistry fields,” says Smith, who studied art history as a Williams senior and might have pursued architecture if chemistry hadn’t beckoned. Today he’s still thinking about structures—they’re just invisible to the naked eye. “I’m a nano-architect,” he says with a laugh.

With enough chemical facility, students can make assumptions about unfamiliar substances. On exams, Smith often includes a full-page diagram of a huge organic molecule like Vancomycin (a potent antibiotic drug used to treat stubborn bacterial infections) and asks students how it is likely to react with other substances. “Their initial reaction is, ‘Oh my god, I’ve never seen anything like this.’ But if they look deeper, they see key features of the molecule and start to realize that they can understand it,” he says.

Organic chemicals are building blocks of modern pharmaceuticals as well as plastics, petrochemicals, synthetic fabrics and other staples of industrialized life. “You can see the relationship between a molecule’s structure and its reactivity played out in medical research,” says Smith. Medicines produce biological responses based on how they react with different receptors in the human body—a function of their molecular shapes. Smith has spent a lot of time studying those relationships. He was an American Cancer Society postdoctoral fellow at Harvard after receiving his Ph.D. from Stanford, and he has received research grants from the National Institutes of Health, the American Chemical Society, Pfizer and the National Science Foundation.

Currently Smith’s lab includes four Williams students and one postdoctoral researcher, whom he hired to provide some continuity on research projects while undergraduates cycle through. The group is studying tools for producing synthetic versions of natural compounds with cancer-inhibiting properties. He doesn’t expect that new drugs will come directly out of his lab, but this work—in scientific parlance, methods development—could make applied pharmaceutical research at other institutions more efficient.

Smith brings this research perspective back into the classroom by teaching a course on medicinal chemistry. “I want to show students that they don’t have to be doctors to have an impact on human health—they can contribute as chemists or statisticians or in the pharmaceutical industry,” he says.

Or by making orgo a portal instead of a barrier.