30 Years of Atomic Force Microscopy: IBM Scientists Trigger and Observe Reactions in an Individual Molecule

Once again, IBM scientists are opening the eyes of the world to objects that exist only at the atomic scale.

In a new paper appearing today in the peer-reviewed journal Nature ChemistryIBM 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.

The Bergman cyclisation is a fascinating rearrangement reaction with
implications beyond organic chemistry. It has now been shown that a reversible
Bergman cyclisation action in a single molecule sitting on an ultra thin NaCl film
can be directly imaged using atomic force microscopy.
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.

The Bergman cyclisation Diyne from model to image. 
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.

IBM scientist Bruno Schuler
Professor Peña adds, “This work suggests the great potential of this technique to discover unexpected new reactions. In conventional solution chemistry, after so many decades of rigorous research, the chances of finding new important reactions are quite limited. Compared to this, single-molecule chemistry by tip manipulation is in its infancy, and I expect extremely exciting discoveries in the near future.”

The next steps for the team will be to synthesize large custom-designed molecules and molecular networks with the tip that cannot be made by any other means. The team is also interested in exploring new applications for molecules, such as molecular logic devices based on single-electron transfer. 

Bruno Schuler, IBM postdoc and first author of the paper, adds, “The molecules we have investigated here are promising building blocks for molecular logic devices. We can envision forming networks with covalent bonds established between these radicals. Moreover, the switching of the molecules, effecting its transport and magnetic properties, might be useful functions for such devices in the future.”

Prof. Robert Bergman shared his excitement on the paper with IBM scientists via email commenting, "When we first reported this reaction I had no idea that it would be biologically relevant, or that the reaction could someday be visualized at the molecular level."

Read the paper here: Reversible Bergman cyclization by atomic manipulation,” Nature Chemistry, AOP 25 Jan 2016, doi: 10.1038/nchem.2438

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