Seeing real-time atomic motion in enantiomers

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A team of researchers led by EPFL has demonstrated the real-time visualization of specific atomic motions within enantiomers –mirror-image molecules. The method can lead to significant advancements in fields such as biology, chemistry, and drug development.

Chiral molecules are species whose mirror images cannot be superimposed, like our left and right hands. Known as “enantiomers” these come in mixtures of equal amounts of both, called “racemic mixtures”. Distinguishing between enantiomers is critical in biology and drug development, as Nature is homochiral and the two enantiomers can have vastly different effects on living organisms – thalidomide being a tragic example.

Researchers from Italy, France and Switzerland have now made a breakthrough in the study of molecular motion, which can help distinguish enantiomers. The team has developed a new technique that allows for the real-time visualization of specific atomic motions within a given enantiomer in a racemic mixture.

The research was led by the group of Professor Majed Chergui at EPFL, Riccardo Mincigrucci and Claudio Masciovecchio at ELETTRA (Trieste, Italy), and Jeremy Rouxel at the Jean Monnet University (St Etienne, France).

The technique, called “impulsive stimulated Raman scattering (ISRS) pump/Carbon K-edge absorption probe spectroscopy”, combines ultrafast laser pulses and X-ray absorption spectroscopy to detect the motion of specific nuclei in molecules. Using this approach, the researchers observed the low frequency motions of molecules, which are important in the process of drug docking. They were also able to achieve element-specific selectivity within a molecule, solving a longstanding problem of detecting light elements in organic molecules.

"This work demonstrates that the low frequency motions of molecules can be visualized in real-time and with enantiomeric selectivity," says Professor Chergui. "This is crucial for biology and because Nature is homochiral and it is the low frequency motions that are involved in docking of drugs".

Funding

Swiss National Science Foundation (NCCR:MUST)

European Research Council

National Science Foundation

US Department of Energy

Université de Lyon

Fédération de Recherche André Marie Ampère (FRAMA)

National Social Fund–National Operative Research Program and Innovation

References

R. Mincigrucci, J. R. Rouxel, B. Rossi, E. Principi, C. Bottari, S. Catalini, J. S. Pelli-Cresi, D. Fainozzi, L. Foglia, A. Simoncig, A. Matruglio, G. Kurdi, F. Capotondi, E. Pedersoli, A. Perucchi, F. Piccirilli, A. Gessini, M. Giarola, G. Mariotto, M. Oppermann, S. Mukamel, F. Bencivenga, M. Chergui, C. Masciovecchio. Element- and enantiomer-selective visualization of molecular motion in real-time. Nature Communications 24 January 2023. DOI: 10.1038/s41467-023-36047-5