Transition State Captured By Force

By stretching a polymer, researchers have caused it to isomerize to an energetically disfavored product and contract in size.

The unexpected product and size change, in addition to the use of force instead of the usual heat as a reaction driver, make the study unusual. The team also discovered that, mechanistically, the force stabilizes the reaction’s transition state—the elusive, highly unstable, and usually unobservable intermediary between reactant and product—enabling the researchers to trap it with a reactive snare.

The findings help advance the field of reaction dynamics, but they also could lead to practical applications, including new materials with properties that change when force is imposed and ways to forcibly control reaction yields and products.

Force has been used previously to set off reactions; theory has demonstrated how this occurs; and transition states have been observed, such as by femtosecond spectroscopy. But the new study is the first to combine a force-induced reaction to a disfavored product with trapping of a transition state and a theoretical understanding of how the process occurs.

Physical organic and materials chemist Stephen L. Craig of Duke University, theoretical chemist Todd J. Martinez of Stanford University, and colleagues carried out the study (Science 2010, 329, 1057).

“What they did is really great,” says Sergei Sheiko of the University of North Carolina, Chapel Hill, who specializes in the use of mechanical tension to activate specific chemical bonds in macromolecules. “From an experimental point of view, they trapped a diradical transition state that normally lasts for only the shortest of moments, which one can view as catching lightning in a bottle. And from a fundamental point of view, they demonstrated the unique power of force to direct a reaction pathway toward a thermodynamically less stable isomer.” Craig, Martinez, and coworkers show in the paper that heating gives a different result, yielding the more stable of two products.

The study began when Jeremy Lenhardt, a student in Craig’s group, found that if he exerted force on a polymer containing cis- and trans-substituted gem-difluorocyclopropane groups, the polymer shortened. He imposed the force through ultrasonication, which causes solvent velocity gradients similar to rapids in a river. Polymers are stretched by these gradients “just as a rope held between two rafts would be stretched as one raft reached the rapids,” Craig says.

Craig, Martinez, and coworkers found that force caused the cyclopropane groups to isomerize to their cis form, a reaction that shortens the polymer. Craig notes that “the behavior comes from pulling on the molecule hard enough to force it into a 1,3-diradical structure”—the transition state of the force-free isomerization reaction—which relaxes to the shorter cis-only product when the force is released.

The diradical transition state exists “for at least tens of thousands of bond vibrations, on the order of nanoseconds,” which is unusually long, Craig says. Lenhardt verified the transition state’s existence by trapping it with a radical reagent.

“This is a pretty exciting result,” says Jeffrey S. Moore of the University of Illinois, Urbana-Champaign, whose specialties include mechanochemistry, the effects of physical force on chemical processes. “The combination of experiment and theory shows us something remarkable about the way transient forces can modify the potential-energy surface” of the isomerization reaction, he says.

“For a long time, people have tried to use lasers to steer chemical reactions” into different paths, Moore says. The new study “demonstrates another way to modify reaction pathways,” he says, noting that the work could lead to the development of mechanically adaptive materials.

Associate research scientist Sergi Garcia-Manyes of Columbia University, whose interests include force effects on protein folding and unfolding, says the study demonstrates the use of sonication to change the nature of a reaction, captures a transition state, and uses simulations to show the molecular mechanisms involved. The approach could be used to adjust the isomeric composition of laboratory and industrial reaction products, he says.

“Hundreds of radicals can be generated along a single polymer chain under stress,” Craig notes. “So this reaction, or other reactions that generate reactive species, might be used to induce localized cross-linking and increased strength in highly stressed regions of a polymeric material that is susceptible to failure.”

In addition, “it should be possible to characterize new reactivity that results when structures that typically exist for very short periods of time—one or a few bond vibrations—are forced to exist for longer times,” Craig says. “One avenue we are pursuing right now is trapping multiple transition state structures or other high-energy species in proximity to each other and observing the reactions between species that result.”