In introductory organic chemistry courses, students learn about reaction mechanisms, often by drawing neat arrows connecting one intermediate state to the next until ending with a final product. Observing these proceedings in reality, however, is much more difficult.
Now, a team of international researchers has made a device that captures the real-time dynamics of a classic chemical reaction at the single molecule level (Sci. Adv. 2018, DOI: 10.1126/sciadv.aar2177). Developed by Xuefeng Guo at Peking University, Kendall N. Houk at UCLA, and Deqing Zhang at the Institute of Chemistry, Chinese Academy of Sciences, the method could illuminate the mechanism of important chemical and biological processes.
The device consists of two graphene arrays that flank a single molecule covalently secured to each array through amide linkers. The molecule, 9-fluorenone, contains a carbonyl group situated astride three fused rings. The team submerged the device in a solution containing a catalyst and the reagent hydroxylamine, which reacts with 9-fluorenone’s carbonyl group. The reaction changes the electrical charge of 9-fluorenone, so the team could follow the nucleophilic addition reaction by monitoring current conducted by the graphene arrays.
To map the device’s electrical signals to molecular intermediates, the group turned to theory. They calculated rates for each step of the reaction, allowing them to assign lifetimes to reaction intermediates and then match those calculations to experimental data. Using this approach, they identified a reversible transition between the reactant and a new intermediate for the reaction.
Unlike existing single-molecule methods, such as fluorescence microscopy-based ones, this new technique doesn’t rely on adding complex fluorescent labels to the molecule being studied. Also a key advantage of the graphene device is that researchers can monitor reactions with microsecond time resolution, says Peng Chen of Cornell University, who was not involved in the work. “Microsecond time resolution is possible but challenging,” for optical methods, he adds.
“This study presents a powerful and elegant combination of molecular electronics, quantum chemistry and single-molecule chemical physics,” says David Millar of the Scripps Research Institute California. “Chemical reaction kinetics are directly revealed at the single-event level, providing a textbook-like clarity.”