Chemist Mariia Sapova has solved a decades-old problem in the analysis of chiral molecules. This now finally allows for the reliable determination of the structure and stereochemistry of metal-ligand environments in systems relevant to biology and chiral catalysis.
A molecule can exist in two versions that are each other's mirror images, like your left and right hands. Although they are constructed identically, they do not fit together perfectly. This is crucial when dealing with other molecules. The mirror image of a molecule can smell different, and when used as a drug, the mirror image can even be dangerous. It is therefore important to be able to quickly and unambiguously determine which form newly created molecules have.
Left- or right-handed
A very powerful approach to come to an unambiguous determination makes use of the difference in absorption of left- and right-handed circularly polarized light, so-called Vibrational Circular Dichroism (VCD) spectroscopy. Comparison of experimentally recorded spectra with theoretically predicted spectra then allows to determine whether the molecule is left- or right-handed. However, for many biological systems and chiral catalysts this approach was found to fail completely, thus inhibiting any assignment at all.
In a collaboration between the theoretical chemistry group of Luuk Visscher (Vrije Universiteit Amsterdam) and the experimental spectroscopy group of Wybren Jan Buma (University of Amsterdam), Mariia Sapova (Vrije Universiteit Amsterdam) now reports in Angewandte Chemie International Edition a radically different approach to analyse experimental VCD spectra . The newly developed theoretical approach explains enhanced vibrational circular dichroism (eVCD) and enables its reliable application. This technique amplifies the molecule's signal by attaching a metal atom. The experiments demonstrating this amplified signal have been known for 20 years, but no one has been able to properly interpret them until now.
Mirror image form
Sapova demonstrated what caused the problem in the calculations required to interpret the signal. Together with her co-researchers Chandan Kumar and Sahar Ashtar-Jafari, she then developed a method that circumvents this problem. This allows scientists to unambiguously determine for the first time which mirror image form is involved.
Medicine
Many metalloproteins are key to vital biological pathways (cytochrome-c, myoglobin, carbonic anhydrase, etc.). eVCD studies that are now possible will increase our understanding of the structure and function of biological molecules with attendant improvements in human health and the prevention of disease. eVCD moreover paves the way for testing the purity of drugs easier and more reliable in the future.