Scientists can now identify mirror-image molecules more easily, thanks to a new technique. This is crucial for drug development among other things as the two variants can have different impacts on the human body. In the academic journal Nature Photonics, researchers from the Paul Scherrer Institute PSI, EPF Lausanne (EPFL), and the University of Geneva present the innovative technique.
At the Swiss Light Source SLS at PSI, researchers have successfully shown that enantiomers can be distinguished from one another using helical X-ray light. Enantiomers are molecules that are mirror images of each other. Separating such molecules is relevant in biochemistry and toxicology, as well as in drug development. Image Credit: Paul Scherrer Institute/Benedikt Rösner.
Like human right and left hands, certain molecules may be found in two forms that are physically similar yet mirror reflections of one another - these are called chiral molecules and enantiomer is the name given to their two mirror images. In biological molecules, chirality is particularly important as it can have a variety of physiological effects.
Separating enantiomers from one another is therefore crucial in biochemistry, toxicology, and drug development in order to, for example, ensure that only the desired version enters a drug. Now, scientists from PSI, EPFL, and the University of Geneva have created a novel technique called helical dichroism in the X-Ray domain that improves the separation of enantiomers from one another.
Circular dichroism (CD) is the currently used technique to distinguish between enantiomers. This method involves shining a certain type of light through the sample, known as circularly polarized light. The enantiomers absorb this light to varying degrees. The analytical chemistry, biochemical research, pharmaceutical, and food sectors all employ CD extensively.
However, in CD, the signals are quite weak: the difference in light absorption between the two enantiomers is only a little under 0.1%. Although there are several methods for boosting the signals, these only work when the sample is present in the gas phase. However, the majority of chemistry and biochemistry research is done in liquid solutions, mostly water.
The new technique, however, makes use of a phenomenon known as helical dichroism, or HD. Instead of the polarization of the light, the effect that underlies this phenomenon is curving into a helical form of the wavefront.
The scientists were able to demonstrate effectively for the first time that enantiomers could also be separated from one another using helical X-Ray light at the Swiss Light Source SLS at PSI. At the cSAXS beamline of SLS, they demonstrated this on a sample of the chiral metal complex iron-tris-bipyridine in powdered form, which the University of Geneva researchers had made available.
Compared to what CD can produce, the signal researchers were able to acquire was many orders of magnitude greater. HD is suitable as a precondition for applications in chemical analysis as it can be utilized in liquid solutions.
For this experiment, it was essential to produce X-Ray light with the ideal characteristics. The so-called spiral zone plates, a unique kind of diffractive X-Ray lens that the researchers used to send the light through before it reached the material, allowed them to do this.
“With the spiral zone plates we were able, in a very elegant way, to give our X-ray light the desired shape and thus an orbital angular momentum. The beams we create in this way are also referred to as optical vortices,” adds Benedikt Rösner, a PSI researcher, who created and made the spiral zone plates for this experiment.
Helical dichroism provides a completely new kind of light-matter interaction. We can exploit it perfectly to distinguish between enantiomers.
Jérémy Rouxel, Study First Author and Researcher, Ecole Polytechnique Fédérale de Lausanne
The Swiss National Science Foundation’s National Centre of Competence in Research Molecular Ultrafast Science and Technology (NCCR MUST), the German Academic Exchange Service (DAAD), and the European Research Council’s ERC Advanced Grant DYNAMOX made it feasible to conduct the study.
Journal Reference:
Rouxel, J. R., et al. (2022) Hard X-ray helical dichroism of disordered molecular media. Nature Photonics. doi.org/10.1038/s41566-022-01022-x.