Unprecedented Packing Polymorphism of Oxindole: An Exploration Inspired by Crystal Structure Prediction

Area of Science:

• Solid-state chemistry
• Materials science
• Crystallography

Background:

• Crystal polymorphism significantly impacts molecular physical properties.
• Determining a molecule's polymorphic landscape is challenging and time-consuming.
• Disappearing polymorphs present reproducibility issues in the pharmaceutical industry.

Purpose of the Study:

• To assess the solid-state landscape and thermodynamic stability of oxindole (OX).
• To validate crystal structure prediction (CSP) by comparing predicted structures with experimental data.
• To investigate the formation of novel polymorphs and understand disappearing forms.

Main Methods:

• Crystal structure prediction (CSP) was employed to model OX's solid-state landscape.
• Melt and solution crystallization experiments were conducted in bulk and nanoconfined environments.
• Predicted structures were compared with experimentally observed and novel polymorphs.

Main Results:

• CSP successfully predicted known oxindole polymorphs and identified potential new forms.
• Experimental crystallization reproduced known forms and yielded four previously undiscovered polymorphs.
• The study established a new record for packing polymorphism in rigid molecules.

Conclusions:

• The combined CSP and experimental approach enhances the understanding of molecular polymorphism.
• This methodology aids in reconstructing disappearing polymorphs and building comprehensive polymorphic landscapes.
• The findings offer valuable insights for pharmaceutical development and materials science.