Experimental charge density of organic nanocrystals revealed by 3D electron diffraction

Abstract Charge density analysis is a cornerstone of quantum crystallography, offering deep insights into electron densities and chemical bonding in crystals, traditionally relying on high-resolution X-ray diffraction (XRD). Three-dimensional electron diffraction (3D ED) emerges as a powerful alternative, uniquely suited for micro- and nanocrystals and accurate hydrogen atoms localization due to a strong electron-matter interaction. This study presents a comprehensive experimental charge density analysis of L-alanine, urea, and L-tyrosine crystals using 3D ED. Incorporating dynamical scattering into multipole refinement allowed to model accurately electron density and simultaneously to reliably refine hydrogen positions and anisotropic displacements−beyond XRD limitations. Results align well with DFT and experimental XRD data, validating the approach. These findings establish 3D ED as a powerful and viable method for full charge density analysis for organic crystals, particularly in cases where conventional XRD is limited by small crystal size, difficulty in resolving hydrogen atoms, or reduced sensitivity to subtle electron density features.