Atomic Force Microscopy: Trigger and Observe Reactions in an Individual Molecule
In a new paper appearing in Nature Chemistry, IBM researchers, in collaboration with CiQUS at the University of Santiago de Compostela, have observed a fascinating molecular rearrangement reaction known as a Bergman cyclisation – which was first described in 1972 by American chemist Robert George Bergman. The paper will be featured on the cover of the March issue.
Professor Diego Peña, a chemist at the University of Santiago de Compostela and co-author of the paper, explains the significance: “At first the rearrangement was simply considered a curiosity, but in the late 1980s it was discovered that the mechanism of action for some anticancer drugs, which are based on this reaction. This naturally attracted a lot of attention from the scientific community, and now it's a very popular reaction in organic chemistry.”
The secret to imaging the Bergman reaction is a technique known as atomic force microscopy (AFM), which makes use of a nanosized-sharp tip to measure tiny forces between the tip and the sample.
The AFM was first demonstrated in 1986 by IBM scientists Gerd Binnig, Christoph Gerber, and Calvin Quate of Stanford University. Binnig, who is solely listed on the first patent, was quoted in IEEE Spectrum Magazine in 2004 saying that the idea for the AFM came to him subconsciously while he was lying on the couch. Not long afterwards Binnig and his colleague, the late Heinrich Rohrer, received the Nobel Prize for the scanning tunneling microscope (STM), the predecessor of the AFM.
Studying Individual Bonds With Advanced Tip
More recently, IBM scientists in Zurich have modified the tip of their AFM with a single carbon monoxide molecule. This diatomic molecule, which is less than one nanometer long, produces images so clear that scientists are able to study the sample’s chemical nature based on the minute differences between individual bonds.
The IBM team, led by Gerhard Meyer and Leo Gross, first published their technique in 2009 in the journal Science by producing a stunning image of the flat molecule pentacene.
Over the next several years, they worked on refining the technique and pushing its limits beyond what they ever expected.
Gross comments, “One main differentiator of our technique, with respect to other established techniques, is that we measure single molecules. Another advantage is that we can use the tip to initiate chemical reactions of individual molecules and we can follow the reactions and study their products at the atomic scale.”
A few years later the team produced a string of breakthroughs in 2012, including the ability to measure the electric field produced by a single molecule, a demonstration of bond-order discrimination and in 2013, the exact measurement of adsorption geometries.
During this period of notable publications, the team began receiving requests from scientists around the world, including a professor at Aberdeen University, who proposed in 2009 to use their technique to identify a species of bacterium collected from the deepest place on Earth. This pressure-tolerant bacterium — called Dermacoccus abyssi — produced a chemical compound which could not be recognised. Using their technique, IBM scientists successfully imaged and identified it as cephalandole A, a molecule previously isolated from a Taiwanese orchid.
With their latest work, the team has found another application for their technique: the ability to induce chemical reactions, like the Bergman cyclisation.
“Working at low temperatures and on special, inert surfaces like the two-atom-thick layers of salt that we used in our paper, we are able to stabilize reactive intermediates that under normal conditions are too short-lived to be studied in detail. Not only can we form highly reactive intermediates using the tip to create and cleave bonds within the molecule, we can even switch between different reaction intermediates.
Remarkably, we can change almost all important properties of these molecules by switching them, affecting their reactivity, structure and their optical, electronic and magnetic behavior,” said Gross.
As reported in Nature Chemistry this is the first time that a reversible Bergman cyclization has been demonstrated.