Discovery of Oxyacanthine Dihydrochloride Monohydrate Polymorphs from Obfuscated Samples by Microcrystal Electron...

Area of Science:

• Pharmaceutical Science
• Natural Product Chemistry
• Crystallography

Background:

• Over 50% of pharmaceuticals originate from natural products.
• Accurate structural characterization is vital for drug development and quality control.
• Mislabeled samples pose significant challenges in pharmaceutical analysis.

Purpose of the Study:

• To identify and characterize polymorphic crystal structures of oxyacanthine dihydrochloride monohydrate.
• To demonstrate the utility of Microcrystal Electron Diffraction (MicroED) in analyzing complex natural product derivatives.
• To assess the conformational differences and thermodynamic stability of identified polymorphs.

Main Methods:

• Microcrystal Electron Diffraction (MicroED) for structural determination.
• Analysis of crystal structures, energies, and packing diagrams.
• Comparison of conformational differences in tetrahydroisoquinoline rings.

Main Results:

• Two distinct polymorphic crystal structures of oxyacanthine dihydrochloride monohydrate were identified.
• Polymorphs differed in the conformation of a tetrahydroisoquinoline ring (half-chair/half-boat vs. distinct half-boat).
• Thermodynamic analysis favored transformation into the distinct half-boat conformation.

Conclusions:

• MicroED is an efficient tool for structural analysis of natural product-derived pharmaceuticals.
• The study identified and characterized polymorphs from mislabeled samples, aiding quality control.
• Integrating MicroED into pharmaceutical pipelines improves accuracy and efficiency in drug analysis.