Exploring Naproxen Cocrystals Through Solid-State Vibrational Circular Dichroism.

Area of Science:

• Solid-state chemistry
• Spectroscopy
• Pharmaceutical science

Background:

• Vibrational circular dichroism (VCD) is valuable for analyzing optically active solids, crucial for active pharmaceutical ingredients (APIs).
• Interpreting VCD spectra of solid-state compounds presents challenges.
• Naproxen, an anti-inflammatory drug, was chosen to evaluate VCD methodologies.

Purpose of the Study:

• To assess experimental and computational methods for solid-state VCD spectroscopy.
• To investigate the VCD spectra of naproxen and its cocrystals with alanine and proline.
• To correlate VCD signals with specific structural features and intermolecular interactions.

Main Methods:

• Infrared (IR) and VCD spectroscopy were used to analyze pure naproxen, naproxen-alanine cocrystals, and naproxen-proline cocrystals.
• Quantum chemical simulations employing a cluster model and density functional theory (DFT) were utilized for spectral interpretation.
• Analysis focused on distinguishing pure compounds from cocrystals and understanding hydrogen bonding interactions.

Main Results:

• VCD spectroscopy demonstrated higher sensitivity than IR spectroscopy in differentiating pure naproxen from its cocrystals.
• The naproxen-alanine cocrystal exhibited strong VCD signals due to a rigid structure formed by two strong hydrogen bonds.
• The naproxen-proline cocrystal showed weaker VCD signals, attributed to a single hydrogen bond and restricted proline ring motion.

Conclusions:

• Solid-state VCD spectroscopy is a powerful tool for examining composite crystal structures and interactions.
• The technique is particularly useful for studying pharmaceutical compounds and their solid forms.
• VCD provides detailed insights into the structural nuances influenced by intermolecular forces in cocrystals.