Using X-rays to identify liquid mirror molecules

Innovative methods for research, biochemistry and pharmacy

Using left- or right-handed X-ray light, the mirror forms of chiral molecules can also be identified in the liquid phase. (Credit: Kyoto University)

Using left- or right-handed X-ray light, the mirror forms of chiral molecules can also be identified in the liquid phase. (Credit: Kyoto University, Stephan Thürmer [Source])

Sugars, amino acids, drugs - chiral molecules that come in two mirror forms are everywhere. Researchers in the AQUACHIRAL project at the Fritz-Haber-Institut (FHI) have used PETRA III to study hair-thin liquid jets of these molecules. Using a new method, they can now for the first time distinguish their components in liquid form – and more effectively than ever before, as the team reports in the journal Physical Chemistry Chemical Physics.

Chiral molecules occur very frequently in nature. Sugar, for example, consists of chiral molecules, as do many amino acids; our bodies are also made up of these building blocks. Chirality means that such molecules occur chemically in two forms whose geometric structures behave like image and mirror image. They have the same mass and the same components, but they are not identical. If one form is mirrored, it fits exactly on the other, but simply placed on top of each other, the two forms do not fit. The prototype for this sort of mirror symmetry are our own hands, and the greek word for hand, cheir, gave the phenomenon its name. Chirality is also called handedness.
Despite their symmetry, chiral molecules can have very different properties. Take, for example, carvone: one form smells like mint, the other like caraway. Chirality is particularly important in the manufacturing of pharmaceuticals, because seven of the ten most common drugs contain chiral molecules. However, usually only one of the two forms has the desired effect, while the other is just dead weight and potentially compromises the drug's effectiveness. Thus, to produce efficient and safe drugs, it is important to identify and use the correct form.

However, due to their similarity, it is not always easy to distinguish between the two. Regarding biological processes, it is particularly important to be able to make such distinctions in aqueous environments, as the latter can affect chemical reactivity. Researchers of the AQUACHIRAL project have now found a way to accomplish this by exploiting X-rays from a synchrotron. For the experiment, liquid fenchone was examined, which occurs in fennel-based oils and other essential oils. The researchers generated a very fine liquid fenchone jet – the diameter of a hair – and irradiated it with soft X-rays from DESY's PETRA III at beamline P04. “X-rays are high-energy photons”, explains Bernd Winter who leads the AQUACHIRAL project funded by the European Research Council ERC. “When such photons hit the liquid jet, electrons are emitted that carry information about the molecular form that exists in the liquid.”

What is new about this method is the type of radiation used. It adapts to the 'handedness' of the chiral molecules, i.e. the different forms. The two ‘handed’ forms can best be identified by using circular X-rays, which are also 'handed'. "In a sense, there are left-handed and right-handed molecules," says Uwe Hergenhahn, a research associate at the Fritz-Haber-Institut's Molecular Physics Department, "and we then irradiate them with X-rays that also turn right or left, like a screw." From the flight angles of the electrons that are created in this way, one can deduce the handedness of the molecule. "This type of circular X-ray light, which goes back to Louis Pasteur and others, had been known for some time. But the PETRA III synchrotron creates even stronger radiation with much more accurate results than ever before," explains Florian Trinter, PostDoc at FHI and associated Beamline Scientist at beamline P04.

This method is an important step for better analyses of biological and organic chiral molecules, which in the future may also provide more reliable results in biochemistry and pharmacy. Now that it has become possible to perform these experiments on liquids, the AQUACHIRAL project team would next like to study molecules in the environment in which they occur in living organisms, for instance in water.

Scientists from Fritz-Haber-Institut, the University of California in Berkeley, Lawrence Berkeley Laboratory, the Universität of Frankfurt/Main, Helmholtz-Zentrum Berlin, Kyoto University, Synchrotron Soleil, the University of Nottingham and DESY participated in this research.

(from DESY News)

Photoelectron circular dichroism in angle-resolved photoemission from liquid fenchone; Marvin N. Pohl, Sebastian Malerz, Florian Trinter, Chin Lee, Claudia Kolbeck, Iain Wilkinson, Stephan Thürmer, Daniel M. Neumark, Laurent Nahon, Ivan Powis, Gerard Meijer, Bernd Winter und Uwe Hergenhahn; Physical Chemistry Chemical Physics, 2022; DOI: 10.1039/d1cp05748k