TALP, a new method for solving crystal structures of pharmaceutical and molecular compounds by powder diffraction

Abstract

Powder diffraction is a powerful tool for solving crystal structures of ionic and molecular compounds when no single crystals are available. The recent development of direct-space methods allows the resolution of complex structures of molecular compounds, despite the limited d-spacing resolution of the data for these materials and especially organic molecules. This paper describes the new direct-space multisolution method TALP and its application. It combines random or rotation function- assisted search algorithms with fast least square minimizations of atomic coordinates. Diffraction intensities are determined by a three-step procedure and the molecular model is defined in terms of atomic coordinates, distance restraints and free rotation bonds. TALP has solved structures containing thirteen torsion angles and more than one independent molecule in the asymmetric unit from laboratory powder diffraction data and calculated molecular models. By way of example, the step-by-step TALP redetermination of the known structure of (S)-ibuprofen is presented.

Keywords: Powder diffraction, X-ray diffraction, synchrotron radiation, structure determination, crystal structure, molecular
compounds, pharmaceuticals.