Technology

3D ED / MicroED crystal structure analysis

At SPERA PHARMA, we have added the latest 3D ED/MicroED (Three-Dimensional Electron Diffraction/Microcrystal Electron Diffraction) to our conventional X-ray analysis lineup, paving the way for a new chapter in crystal structure analysis.

Features of 3D ED/MicroED Structural Analysis

• ◆ Capable of analyzing extremely small crystals (under 1μm) that are difficult to analyze using conventional single-crystal X-ray diffraction equipment.
• ◆ Analysis of crystalline powder is capable.
• ◆ Determination of each crystal structure in mixtures is capable.

Analysis Utilizing the Features of 3D ED/Micro ED

【3D-Molecular Structure Analysis】

• ◆ Capable of structural analysis of compounds that are difficult to obtain in sufficient quantities or difficult to prepare single-crystal, such as natural products.
• ◆ Capable of analyzing mixtures, allowing for the structural analysis of each component even in a crude product before purification.
• ◆ Allows the determination of absolute configuration clearer than conventional single-crystal X-ray diffraction.

【Crystal Structure Analysis】

• ◆ By adding 3D ED/MicroED analysis data to powder X-ray diffraction (PXRD) charts which have been pattern recognized only, it becomes possible to distinguish crystal polymorphs with crystallographic evidence. This also helps in understanding and identifying pseudo-polymorphic situations.
• ◆ Enables crystal structure analysis of compounds that are difficult to obtain single crystals that can be analyzed by X-ray crystallography, facilitating the determination of the crystal structure of development compounds in pharmaceutical, agrochemical, or chemical companies.
• ◆ Capable of analyzing mixtures, allowing application to the preparation process of salts and co-crystals.
• ◆ Capable of discriminating salt or cocrystal clearer than conventional single-crystal X-ray diffraction, because of the high sensitivity of hydrogen atom.

Potential Applications of 3D ED/MicroE

• ◆ Facilitates structure determination even for trace impurities, contributing to pharmaceutical process development.
• ◆ Accelerates ADMET/metabolite research by enabling easier structural determination of trace metabolites.
• ◆ Contributes to the generation of initial structures in computational chemistry by accelerating 3D molecular structure analysis.
• ◆ By conducting synthetic experiments in parallel, it enables rapid structural determination of intermediates, especially enhancing research efficiency for synthesizing complex compounds.
• ◆ By measuring the fine powder obtained by grinding, it can contribute to the mechanochemistry field.
• ◆ By analyzing the ground tablets, the crystal form and molecular structure in the tablets can be confirmed.
• ◆ Molecular structures can be easily determined even in mixtures, accelerating Diversity-oriented synthesis and contributing to drug discovery by expanding the chemical space.
• ◆ The structure of the organometallic complex can be easily determined, accelerating catalyst design and reaction development and contributing to process chemistry.

Example of 3D ED/Micro ED analysis

• 　Selexipag (Uptravi^®)

SPERA PHARMA not only offers 3D ED/MicroED structural analysis services as part of its lineup but also provides strong support for our customer’s research and development from various angles.