A recent study published in the journal Angewandte Chemie has demonstrated a novel method for determining the structure of Levocetirizine, a pharmaceutical compound used to treat allergies. Traditionally, X-ray crystallography has been the standard technique for determining molecular structures, but this method requires large, well-diffracting single crystals, which are often difficult to obtain.
The research team, led by Durga Prasad Karothu and Panče Naumov, employed a technique called 3D-electron diffraction/micro-crystal diffraction (3D ED/MicroED) to overcome the limitations of traditional methods. Instead of using X-rays, electron beams from an electron microscope were used to diffract the crystals. This approach allowed for the analysis of sub-micro to nanometer-sized crystals, which are typically more accessible than larger single crystals.
The team obtained crystals of Levocetirizine dihydrochloride by grinding commercially available tablets. Using 3D ED/MicroED, they were able to determine the crystal structure of the drug with high precision. Moreover, they employed a special evaluation process called dynamical refinement, which enabled them to unambiguously determine the absolute configuration of Levocetirizine. The absolute configuration refers to the precise spatial arrangement of all atoms within the molecule.
This study highlights the significance of understanding the molecular geometry and crystal structure of pharmaceutical compounds. Different crystal structures or the formation of cocrystals with additives can significantly impact a drug’s properties, such as its bioavailability, solubility, stability, and tabletability. By utilizing techniques like 3D ED/MicroED, researchers can gain valuable insights into the structures of pharmaceutical compounds, even when traditional crystallographic methods are challenging or not feasible.