Advanced crystallisation methods for small organic molecules

Area of Science:

• Materials Science
• Crystallography
• Organic Chemistry

Background:

• Spectroscopic techniques are insufficient for full characterization of molecular materials.
• Single crystal X-ray diffraction (SCXRD) provides atomic-level structural elucidation, including absolute stereochemistry.
• Obtaining high-quality crystals for SCXRD is a major bottleneck in sample preparation.

Purpose of the Study:

• To review advanced methods for crystallizing small organic molecules for SCXRD.
• To highlight recent developments in crystalline material sample preparation.
• To guide researchers in selecting appropriate techniques for analytical challenges.

Main Methods:

• Summary of classical crystallization methods.
• Inclusion complexation using "crystalline sponges" and tetraaryladamantane chaperones.
• High-throughput crystallization using "under-oil" approaches like microbatch and ENaCt.

Main Results:

• Detailed review of inclusion complexation and high-throughput crystallization techniques.
• Presentation of representative examples for each advanced method.
• Discussion of the advantages and limitations of each technique.

Conclusions:

• Advanced crystallization methods are essential for overcoming SCXRD sample preparation challenges.
• Inclusion complexation and high-throughput methods offer novel solutions for obtaining suitable crystals.
• Selection of the appropriate technique depends on the specific analytical requirements.