The real-time monitoring of nuclear motion within molecules has been possible since the 1980s thanks to ultrafast spectroscopy. However, optical spectroscopy lacks element specificity. Time-resolved X-ray and electron diffraction, and X-ray spectroscopy offer element selectivity, initially limited to heavy atoms due to their efficient scattering and absorption of hard X-rays. Soft X-ray spectroscopy extends this capability to light elements crucial in organic and biochemistry. Chirality plays a vital role in various fields, and distinguishing enantiomers is key. Circular dichroism (CD) spectroscopy is commonly used, but extending this to core-level spectroscopies offers element-specific enantiomer identification during chemical reactions. Simulations show that the dichroic response of an element varies depending on electronic coupling, distance from the chiral center, and local geometry. This allows distinguishing identical but non-equivalent atoms. The study combines ISRS with ultrafast circularly polarized soft X-ray absorption spectroscopy at the carbon K-edge to visualize the response of specific carbon atoms in a racemic Ibuprofen (IBP) mixture subjected to low-frequency coherent vibrations. The ISRS triggers low-frequency modes, modulating C K-edge absorption, while polarization control adds enantiomeric selectivity.

Previous research on ultrafast spectroscopy and its application to molecular dynamics is reviewed, highlighting the limitations of optical methods and the advancements in time-resolved X-ray and electron diffraction techniques. The literature on time-resolved X-ray absorption spectroscopy and its application to various systems (metal molecular complexes, biomolecules, solids) is discussed. Studies using both table-top setups and large-scale facilities are examined. The existing methods for detecting enantiomers, specifically circular dichroism (CD) spectroscopy and its time-resolved variants, are reviewed, along with the limitations of extending these methods to core-level spectroscopies. Theoretical studies on X-ray CD signals of organic molecules and their dependence on various factors are also discussed, showing the potential for distinguishing identical atoms in different chemical environments. Existing literature on the vibrational spectroscopy of Ibuprofen, including Raman and infrared studies, is also reviewed.

The experimental setup uses the EIS-TIMEX end-station of the FERMI FEL. The sample, a racemic mixture of Ibuprofen, is photoexcited with laser pulses (4.7 eV) resonant with the IBP absorption, generating low-frequency modes via ISRS. The resulting molecular motion is probed with circularly polarized soft X-ray pulses from the FEL, tuned to the carbon K-edge. Steady-state C K-edge absorption spectra are recorded using both left and right circularly polarized light. Time-resolved studies are performed by scanning the pump-probe delay and recording the transmitted soft X-ray intensity. The sample preparation involves dissolving IBP in ethanol and depositing it onto a silicon nitride membrane. The membrane undergoes hydrophilization to ensure uniform sample coverage. Quantum chemical calculations are performed using RASSCF(6/6) and RASSCF(9/8)/cc-pVDZ levels of theory to compute the C K-edge energies and oscillator strengths, simulating the absorption and CD spectra. Time traces are fitted using a damped sinusoidal function to extract frequencies and damping constants. The experimental setup is described in detail, including the generation and control of the pump and probe pulses, sample preparation, and data acquisition and analysis.

The steady-state C K-edge absorption spectra show clear differences between left and right circularly polarized light, indicating a dichroic response. The calculated and experimental C K-edge CD spectra show good agreement, confirming that inequivalent carbon atoms exhibit a differential dichroic response. Time-resolved transmission signals exhibit periodic modulations reflecting Raman-induced processes. The frequencies extracted from the fit agree well with calculated and measured low-frequency Raman peaks, while the damping times correlate with spectral widths in the steady-state Raman spectrum. The differences between signals with different probe energies and circular polarizations demonstrate the ability to distinguish between identical elements in different chemical environments. This technique combines element- and enantiomer-selectivity, visualizing the response of specific atoms within a given enantiomer to molecular deformations.

The results demonstrate a novel approach to identify atoms most affected by molecular deformations in a specific enantiomer. The method's ability to probe ground-state molecular interactions with element and enantiomer selectivity offers unprecedented insight into molecular reactivity. Comparison with existing techniques like vibrational optical activity (VOA) highlights the advantages of this approach in terms of signal strength and element specificity. The findings have implications for understanding enantiomer-specific chemical reactivity and could guide the design of bioactive molecules. The use of isotopic labeling to modify vibrational behavior while preserving electronic properties is proposed as a future research direction.

This study demonstrates a novel approach for element- and enantiomer-selective visualization of molecular motion using a combined ISRS and ultrafast circularly polarized soft X-ray absorption spectroscopy. This technique offers unprecedented insights into molecular dynamics, particularly in chiral systems, and opens new avenues for understanding chemical reactivity at the atomic level. Future work could explore the application of this method to other systems and reactions, and investigate the use of isotopic labeling to further enhance selectivity.

The study is limited to a specific chiral molecule, Ibuprofen. The relatively low signal-to-noise ratio in the time-resolved CD signal may limit the precision of the obtained results. The data analysis relies on a simplified model that assumes damped sinusoidal behavior, and the validity of this model may need further evaluation. The current setup could be limited by the FEL repetition rate and available photon energy range.