Selective detection and quantitation of organic molecule crystallization by second harmonic generation microscopy

Area of Science:

• Crystallization science
• Nonlinear optics
• Pharmaceutical science

Background:

• Crystallization is crucial in pharmaceutical development.
• Early detection of crystal formation and growth kinetics is challenging.
• Chiral crystals require specialized detection methods.

Purpose of the Study:

• To apply Second Order Nonlinear Optical Imaging of Chiral Crystals (SONICC) for early-stage crystal detection.
• To characterize nucleation and growth kinetics of chiral crystals.
• To demonstrate SONICC's sensitivity and applicability to pharmaceutical compounds.

Main Methods:

• Utilized Second Harmonic Generation (SHG), a nonlinear optical effect.
• Employed SONICC for imaging noncentrosymmetric ordered domain structures.
• Studied model systems: griseofulvin and chlorpropamide.

Main Results:

• SONICC achieved low detection limits, outperforming macroscopic and optical microscopy techniques by 8 and 5 orders of magnitude, respectively.
• Enabled selective detection of crystal formation at early stages.
• Successfully monitored individual crystal growth, nucleation rate, and macroscopic crystallization kinetics simultaneously in amorphous griseofulvin.

Conclusions:

• SONICC is a highly sensitive technique for early detection of chiral crystal formation.
• SONICC provides detailed insights into crystallization kinetics.
• SONICC has significant potential for pharmaceutical research and development.