Probing chirality of crystals using electron paramagnetic resonance (EPR) spectroscopy

One of the most challenging tasks in analytical chemistry is the determination of the chirality (identification of an enantiomeric composition) in solids mainly because of the strict requirements of the pharmaceutical industry for enantiomerically pure drugs. Although there are a few methods available to accomplish enantio‑differentiation in solids, for example: X-ray diffraction (XRD), Thermogravimetric analysis (TGA), CD spectroscopy, and low-frequency (LF) Raman spectroscopy, this is still very challenging. In this work, we have developed a new method to measure the chirality of crystals, based on electron paramagnetic resonance (EPR) spectroscopy of chiral crystals doped with Cu2+ as the EPR active ion. Here, we demonstrate our approach using a model system of l- and DL-Histidine crystals doped with Cu2+. We show that EPR measurements of the Cu2+-doped Histidine crystals can accurately determine the chirality and enantiomeric composition of the crystals. We present a very preliminary example of this technique, and we hope that in the future it will be possible to refine and develop this method for many other chiral organic crystal systems.