Vibrational circular dichroism (VCD) spectroscopy appears as a useful method for characterizing optically active substances in the solid state. This is particularly important for active pharmaceutical ingredients. However, measurement and interpretation of the spectra bring about many difficulties. To assess the experimental and computational methodologies, we explore an anti-inflammatory drug, naproxen. Infrared (IR) and VCD spectra of the pure compound and its cocrystals with alanine and proline were recorded, and the data were interpreted by quantum chemical simulations based on a cluster model and density functional theory. Although unpolarized IR spectroscopy can already distinguish pure ingredients from cocrystals or a mixture, the VCD technique is much more sensitive. For example, the naproxen carboxyl group strongly interacts with the zwitterionic alanine in the cocrystal via two strong hydrogen bonds, which results in a rather rigid structure crystallizing in the chiral P212121 Sohncke group and its VCD is relatively strong. In contrast, the d-proline and (S)-naproxen cocrystal (P21 group) involves a single hydrogen bond between the subunits, which together with a limited motion of the proline ring gives a weaker signal. Solid-state VCD spectroscopy thus appears useful for exploring composite crystal structures and interactions within them, including studies of pharmaceutical compounds.

• Keywords
• alanine, cocrystals, density functional theory, naproxen, proline, solid state, spectra modeling, vibrational circular dichroism,
• MeSH
• Alanine chemistry   MeSH
• Anti-Inflammatory Agents, Non-Steroidal chemistry   MeSH
• Circular Dichroism * methods   MeSH
• Crystallization MeSH
• Models, Molecular MeSH
• Naproxen * chemistry   MeSH
• Proline chemistry   MeSH
• Spectrophotometry, Infrared MeSH
• Stereoisomerism MeSH
• Vibration MeSH
• Hydrogen Bonding MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Alanine MeSH
• Anti-Inflammatory Agents, Non-Steroidal MeSH
• Naproxen * MeSH
• Proline MeSH

Protein fibrils are involved in a number of biological processes. Because their structure is very complex and not completely understood, different spectroscopic methods are used to monitor different aspects of fibril structure. We have explored circularly polarized luminescence (CPL) induced in lanthanide compounds to indicate fibril growth and discriminate among fibril types. For hen egg-white lysozyme and polyglutamic acid-specific CPL, spectral patterns were obtained and could be correlated with vibrational circular dichroism (VCD) spectra and thioflavin T fluorescence. The CPL spectra were measured on a Raman optical activity spectrometer, and its various polarization modes are discussed. The experiments indicate that the induced CPL is sensitive to more local aspects of the fibril structure than VCD. For CPL, smaller amounts of the sample are required for the analysis, and thus this method appears to be a good candidate for future spectroscopic characterization of these peptide and protein aggregates.

• Publication type
• Journal Article MeSH