Detection of Hydrogen Atoms Using Only 3D ED/MicroED and Contribution to Structure Determining Salts or Cocrystals

In this study, we elucidate the crystal structures of three pharmaceuticals using only three-dimensional (3D) ED/MicroED, thereby unambiguously determining whether they were salts or cocrystals based on hydrogen position identification. The analysis targets in this study were indomethacin nicotinamide cocrystals, ensitrelvir fumaric acid cocrystals, and bisoprolol hemifumarate Form I. 3D ED/MicroED analysis revealed that all crystals had residual electron density in key segments, which could be clearly identified as hydrogen atoms, allowing the determination of whether the crystals were salts or cocrystals.