The crystal structure of orthocetamol solved by 3D electron diffraction.

Orthocetamol is a regioisomer of the well-known pain medication paracetamol and a promising analgesic and an anti-arthritic medicament itself. However, orthocetamol cannot be grown as single crystals suitable for X-ray diffraction, so its crystal structure has remained a mystery for more than a century. We report here the ab-initio structure determination of orthocetamol obtained by 3D electron diffraction, combining a low dose acquisition method and a dedicated single electron detector for recording the diffracted intensities. The structure is monoclinic, with a pseudo-tetragonal cell that favors multiple twinning on a scale of a few tens of nanometers. The successful application of 3D electron diffraction to orthocetamol introduces a new gold standard of total structure solution in all cases where X-ray diffraction and electron microscope imaging methods fail.

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