First images of hydrogen bonds

To stare at the structure of molecules is what chemists do. The technology that will allow them to do it better will have a huge impact on this area. For example, scientists from China reported on the first visualization of hydrogen bonds using atomic force microscopy (AFM).


In May, Felix Fisher and his colleagues at the University of Berkeley in California used AFM to capture molecules before and after chemical transformation. These amazing images show the formation of covalent bonds in a cyclization reaction.


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In the most recent study on molecular vizualization, Xiaohui Qiu and his colleagues at the National Center for Nano-Science and Technology, China, did one more step. They used the same non-contact AFM as Fischer, but instead of seeing covalent bonds with it, she set it up to see weaker interactions.

AFM can be used in two modes. In contact mode, the tip of a cantilever made of silicon or silicon nitride moves along the surface of the sample. The deflection caused by the repulsive force on the surface is processed, resulting in an image of the surface. In the non-contact mode, the cantilever oscillates with a resonant frequency above the sample surface. Weak van der Waals forces reduce the resonant frequency of the cantilever. This change in frequency can be processed to produce an image with atomic precision.

Hydrogen bonds are fundamental to the most important molecules in nature. These bonds are responsible for connecting two strands of the DNA double helix and many enzymes work as catalysts using them. These intermolecular bonds occur when hydrogen bound to a highly electronegative atom reacts with another negatively charged atom.

Despite its ubiquity, says Qiu, "the nature of hydrogen bonds is still under discussion." It has long been believed that this coupling is an electrostatic interaction, but it was recently suggested that it has the characteristics of a chemical coupling, as shown by X-ray diffraction experiments.

See connections

Qiu chose to study 8-hydroxyquinoline (8hq), because this molecule is flat, with the exception of one hydrogen bond outside the plane of the structure, which can improve its visibility. However, he was not sure that the contrast from this hydrogen bond would be strong enough to be observed. “We did not expect to see the hydrogen bonds between the 8hq molecules in our AFM due to the very low electron density in the immediate vicinity of these weak bonds,” he says.

For many years, the older method of microscopy, scanning tunneling microscopy (STM), had a higher resolution than AFM. In 2011, scientists combined the STM with density functional theory to visualize hexamers formed using hydrogen bonds between methanol molecules adsorbed on the surface of gold, albeit with poor resolution. But in 2009, Leo Gross from IBM created a technique to attach a carbon monoxide molecule to the tip of a cantilever in AFM, which significantly improved the resolution of the method. This technique was used in the new study, with which Gross was very impressed. “Very constructive work,” he says.

The results only confirm that AFM can be used to study the nature of hydrogen bonds. They have not yet advanced the discussion about the nature of these relationships. “Direct observation of hydrogen bonds agrees well with the concept we all learned in school: an electropolar hydrogen atom connects two electronegative atoms X and Y, which we denote as X – H ··· Y,” says Qiu. “The problem now is to better understand what causes the contrast in these hydrogen bonds,” says Gross.

Qiu hopes that, just as chemists use NMR and mass spectroscopy to study molecules every day, they will also use AFM. Gross looks at it more skeptically, since sample preparation is complex and the need for qualified personnel makes this method less attractive. But if these limitations are overcome, few of the chemists will miss the chance to see the molecules that they manipulate every day.

Publication in the journal Science: J Zhang et al, Science, 2013. DOI: 10.1126 / science.1242603