Comprehensive Application of XFEL Microcrystallography for Challenging Targets in Various Organic Compounds

Area of Science:

• Crystallography
• Materials Science
• Biophysics

Background:

• Growing demand for structure determination from small crystals.
• Limitations of three-dimensional electron diffraction (3D ED) regarding crystal thickness and data quality.
• 3D ED struggles with certain challenging crystal types, including pharmaceuticals and organic materials.

Purpose of the Study:

• To present serial X-ray crystallography (SX) with X-ray free electron lasers (XFELs) for small, thin crystal structure determination.
• To demonstrate the effectiveness of XFEL-based SX for challenging samples.
• To evaluate the data quality and utility of XFEL crystallography for organic compounds.

Main Methods:

• Application of serial X-ray crystallography (SX) using X-ray free electron lasers (XFELs).
• Utilizing small (μm or less) and thin (hundreds of nm or less) crystals dispersed on a substrate.
• Employing two-dimensional (2D) scanning of the substrate with XFEL exposures and sample rotation for efficient data collection.
• Indexing patterns using lattice parameters obtained from 3D ED.

Main Results:

• Successful data collection and indexing for small, thin crystals, including pharmaceuticals and organic materials.
• Demonstrated superior data quality from SX compared to 3D ED for challenging crystal orientations.
• 2D scanning with XFEL pulses provided sample distribution and insights into crystal grain properties.

Conclusions:

• XFEL-based SX is a powerful tool for structure determination of small organic crystals.
• This method overcomes limitations of 3D ED for difficult-to-study samples.
• XFEL crystallography enables efficient and high-quality structure analysis of novel compounds.