Accuracy of the Crystal Structure of Sofosbuvir Polymorphs Obtained by Powder X-Ray Diffraction

The paper is devoted to the crystal structure refinement of two polymorphs of the active pharmaceutical ingredient sofosbuvir that is used to treat hepatitis C. The refinement is based on the powder X-ray diffraction data obtained from a synchrotron radiation source of the Kurchatov Institute Research Center. The Rietveld refinement of the structures was carried out using soft constraints. The effect of the model used to calculate optimal bond lengths and angles on the quality of the diffractogram description is demonstrated. Geometry is optimized using quantum chemical calculations with periodic boundary conditions, and it is shown that calculations using the PBE functional lead to a noticeable overestimation of bond lengths at the phosphorus atom. A noticeably better result is achieved using the SCAN hybrid functional. To verify and determine the accuracy of the obtained structures, standard deviations between experimental atomic positions and those optimized by quantum chemical calculations (RMSCD), as well as the HUW parameter (half uncertainty window), are calculated.