Researchers have used probe microscopy techniques to drive and then watch a chemical reaction proceed in both directions at a single-molecule level (Nat. Chem. 2016, DOI: 10.1038/nchem.2438). Leo Gross of IBM Research Zurich and coworkers there and at the University of Santiago de Compostela used scanning tunneling microscopy (STM) to push a molecule to react and atomic force microscopy (AFM) to image atomic-level details of that molecule as it formed radical intermediates and a final product.
The technique could allow chemists to initiate radical reactions by manipulating molecules at an atomic level, the researchers say. They note that the approach could be useful not only for making new chemical reactions possible but also for assembling functional molecules for molecular electronic devices and other applications.
The team chose to study a version of the Bergman cyclization, a molecular rearrangement discovered by Robert G. Bergman of the University of California, Berkeley, in 1972, while at California Institute of Technology. In the reaction, an enediyne forms a diradical intermediate that then takes on two hydrogens to form a cyclized product. Some anticancer drugs, such as calicheamicin, work by cleaving DNA through the reaction.
In 2003, Felix R. Fischer and Michael F. Crommie of UC Berkeley used AFM to observe an enediyne cyclize by a similar reaction mechanism (Science 2013, DOI: 10.1126/science.1238187 and C&EN, June 3, 2013, page 7). In that work, the researchers heated the molecule to make the reaction occur.
In the new study, Gross and coworkers used voltage pulses from an STM probe to break first one and then another C–Br bond in the tricyclic compound 9,10-dibromoanthracene to form mono- and then diradical intermediates. The salt surface on which the researchers ran the reaction stabilized the radicals, allowing for AFM imaging. They then used another voltage pulse to convert the diradical to a bicyclic diyne.
The overall process is a ring-opening retro-Bergman reaction with an extra monoradical step that is not actually part of the Bergman mechanism. The researchers also demonstrated the reversible nature of the reaction by jolting the diyne to re-form the diradical intermediate.
The IBM study “is a real breakthrough,” says Wolfram Sander of Ruhr University Bochum, a chemist who studies reaction intermediates. The ability to visualize and push the system in both reaction directions “is a great achievement,” he says.
Peter Chen of the Swiss Federal Institute of Technology (ETH) Zurich, also a reactive intermediates expert, notes that the technique “allows the chemist to initiate the reaction of a single molecule and then see the bonding changes in that very same molecule—not quite directly, but as close to directly as one can possibly imagine. This corresponds to the state of the art of what can be achieved” with probe microscopy today.