Predicting the Crystal Structure of Decitabine by Powder NMR Crystallography: Influence of Long-Range Molecular Packing Symmetry on NMR Parameters

Abstract

Crystal structure determination in the absence of diffraction data still remains a challenge. In this contribution, we demonstrate a complete reconstruction of the crystal structure of decitabine exclusively from 1H and 13C solid-state NMR (ss-NMR) chemical shifts through comparison with the NMR parameters calculated for density functional theory-optimized, computer-generated crystal structure predictions. In particular, we discuss the previously unconsidered influence of long-range molecular packing symmetry on the NMR parameters and subsequent selection of the correct crystal structure. Symmetry operations considerably influenced the global molecular packing and unit cell parameters of the predicted crystal structures, while the conformations and short-range molecular arrangements were practically identical. Consequently, the NMR parameters calculated for NMR-consistent candidates were similar and barely distinguishable by the standard deviations of the experimental and calculated 1H and 13C chemical sh...