The Devil is in the Detail: A Rare H‑Bonding Motif in New Forms of Docetaxel

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

The Devil is in the Detail: A Rare H‑Bonding Motif in New Forms of Docetaxel

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

Furosemide Cocrystals: Structures, Hydrogen Bonding, and Implications for Properties

In this paper, we report the crystal growth of four cocrystals of furosemide (4-chloro-2-[(2-furanylmethyl)­amino]-5-sulfamoylbenzoic acid), a loop diuretic drug used for the treatment of hypertension and edemas, prepared with <i>p</i>-aminobenzoic acid, nicotinamide, and isonicotinamide as coformers. We present four new crystal structures and elucidate the intermolecular interactions present in the cocrystals. The structures display interesting supramolecular chemistry: a number of different synthons, as well as short strong hydrogen bonds with partial proton transfer and indications of proton disorder. Using powder X-ray diffraction, solid state NMR, and thermal analysis, we provide evidence for the preparation of bulk samples of two compositions, namely, the 1:1 cocrystal of furosemide and <i>p</i>-aminobenzoic acid and 2:1 cocrystal of furosemide and isonicotinamide, highlighting the general necessity of such multitechnique approaches to characterize organic solids (including cocrystals and solvates) prepared by grinding methods. Finally, we correlate the structural features reported for the first time in this work with the previously published pharmacologically relevant properties (solubility and intrinsic dissolution rate) of the furosemide cocrystals

Systematic and Controllable Negative, Zero, and Positive Thermal Expansion in Cubic Zr_1–<i>x</i>Sn_<i>x</i>Mo₂O₈

We describe the synthesis and characterization of a family of materials, Zr_1–<i>x</i>Sn_<i>x</i>Mo₂O₈ (0 < <i>x</i> < 1), whose isotropic thermal expansion coefficient can be systematically varied from negative to zero to positive values. These materials allow tunable expansion in a single phase as opposed to using a composite system. Linear thermal expansion coefficients, α_l, ranging from −7.9(2) × 10^–6 to +5.9(2) × 10^–6 K^–1 (12–500 K) can be achieved across the series; contraction and expansion limits are of the same order of magnitude as the expansion of typical ceramics. We also report the various structures and thermal expansion of “cubic” SnMo₂O₈, and we use time- and temperature-dependent diffraction studies to describe a series of phase transitions between different ordered and disordered states of this material