A Combined Solid-State NMR and X-ray Powder Diffraction Study of a Stable Polymorph of Paclitaxel

Solid-state NMR (SSNMR) and X-ray powder diffraction (XRPD) allow a study of a novel and stable polymorph of paclitaxel (Taxol) with two molecules per asymmetric unit (Z‘) in the P212121 space group. The asymmetric unit volume is 2167 A3, about four times larger than that previously characterized in combined XRPD/SSNMR studies. The method, employing SSNMR constraints, allows the XRPD Rietveld analysis to establish many of the lattice details that otherwise would be unavailable. NMR structural constraints are provided by isotropic shifts and three-dimensional (3D) chemical shift tensors (CST), which are determined by ab initio quantum mechanical calculations. CST data give highly sensitive information on short-range structural features such as intra-atomic distances (particularly for proton positions that are undetermined with XRPD methods) and short-range valence angles that exhibit relatively poor sensitivity in reasonably large microcrystalline powders. Conversely, space group symmetry, unit cell volume...