The devil is in the detail: a rare H-bonding motif in new forms of docetaxel

DOI: 10.1021/cg400814a

Authors: Liana Vella-Zarb (Max Planck Institute for Solid State Research; Durham University) , Robert E. Dinnebier (Max Planck Institute for Solid State Research) , Ulrich Baisch (Newcastle University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Crystal Growth & Design , VOL 13 (10) , PAGES 4402-4410

State: Published (Approved)
Published: September 2013
Diamond Proposal Number(s): 6749

Abstract: Docetaxel is a semisynthetic analog of the taxane paclitaxel, pivotal for the treatment of various types of cancer. Minor differences in its chemical structure give docetaxel a slightly better water solubility profile when compared to paclitaxel. An understanding of the hydrogen-bonding network in docetaxel is therefore imperative if an explanation for its improved solubility over its predecessor is to be sought. New crystalline forms for solvated (ethanol), hydrated, and anhydrous docetaxel are reported. The crystal structures were determined by single crystal synchrotron and laboratory powder X-ray diffraction experiments on crystalline materials resulting from polymorph screening tests in various solvents. Variable-temperature experiments were carried out over ranges between 20 and 130 °C, with subsequent loss of crystal water at 70 and 90 °C. The resulting structures are discussed in terms of their intermolecular interactions, molecular conformations, and packing motifs. A rare hydrogen-bonding motif, observed between carbamate and tetracyclic ether groups, was found in the packing of all phases of docetaxel. Subtle but significant changes in structural hydrogen bonding motifs are discussed and their differences supported and visualized by Hirshfeld surface calculations and related two-dimensional fingerprint plots.

Subject Areas: Chemistry, Medicine, Biology and Bio-materials


Instruments: I19-Small Molecule Single Crystal Diffraction

Added On: 11/09/2013 12:03

Discipline Tags:

Non-Communicable Diseases Health & Wellbeing Cancer Biochemistry Chemistry Organic Chemistry Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Single Crystal X-ray Diffraction (SXRD)