Chirality, the property of an object being different from its mirror image, is a fundamental concept in chemistry, biology, and medicine. The two mirror-image forms of a molecule, known as enantiomers, can exhibit vastly different biological activity, with profound consequences in areas such as biochemistry and drug development. More recently, chirality has also emerged as a topic of growing interest in physics and materials science, driven by the coupling between electronic spin and chiral structure, with novel applications in spintronics and quantum information science. Despite its central importance across disciplines, directly observing and tracking molecular chirality at specific stereocenters and during chemical reactions remains a major scientific challenge.
The CHIRAX project addresses this challenge by exploiting the capabilities of modern X-ray spectroscopy to probe chirality with unprecedented elemental and chemical specificity. By taking advantage of recent advances in light sources—such as third- and fourth-generation synchrotrons and X-ray free electron lasers (XFELs) capable of delivering extremely bright and ultrashort X-ray pulses—CHIRAX develops and implements new experimental approaches to access the chiral centers of molecules.
A central focus of CHIRAX is X-ray natural circular dichroism (XNCD), a technique that measures the difference in absorption of left- and right-circularly polarized X-rays by chiral molecules. While circular dichroism is routinely used in the ultraviolet and visible ranges, its extension to the X-ray regime is extremely challenging because the signals are extremely weak in isotropic samples such as liquids. However, XNCD offers a key advantage: it enables chirality to be probed at specific atomic sites within a molecule. This capability would be transformative for studies of complex molecules containing multiple stereocenters and, when combined with time-resolved techniques, could allow the direct tracking of stereochemical changes during chemical reactions
In addition, CHIRAX is pioneering several novel experimental X-ray techniques for probing chirality. These include X-ray helical dichroism, which utilizes X-ray beams carrying orbital angular momentum, and nonlinear X-ray spectroscopies. CHIRAX has demonstrated hard X-ray transient grating spectroscopy (of achiral samples), and is developing cross polarization X-ray transient grating as a probe of chirality. In parallel, the project pursues optical–X-ray sum-frequency generation (ox-SFG) and difference-frequency generation (ox-DFG), nonlinear techniques in which optical (ultraviolet) and X-ray pulses are overlapped in the sample to generate signals at new frequencies that are sensitive to the chirality of the sample. Theoretical studies indicate that tuning the optical and X-ray photon energies across electronic resonances provides signal enhancements that encode detailed information about chiral structure and electronic coupling.
Overall, CHIRAX leverages state-of-the-art X-ray methodologies to develop new element-specific spectroscopies for studying chiral molecular systems of chemical, biological, and technological importance.
