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<p>An extensive crystallization of olaparib with various coformers using mechanochemical grinding and slow evaporation method resulted in the discovery of three new solvates and one cocrystal. The solvates of the drug with benzene, ethyl acetate and tetrahydrofuran are isostructural in the monoclinic, centrosymmetric space group symmetry <i>P</i>2<sub>1</sub>/<i>n</i>. The change in the molecular conformation of the drug, by flipping of the conformationally flexible functional groups, in the solid state, is of significance, in the cocrystal, which crystallizes in the space group <i>P</i>2<sub>1</sub>/<i>c</i>. The analysis of the crystal-chemistry, corroborated by analysis of the pairwise intermolecular interaction energies and the molecular electrostatic potential maps suggest that the origin of unfolding of the conformation of the drug in the cocrystal is <i>via</i> strong I···O halogen bonds, supported by F···O and F···N fluorine bonds, while forming strong drug-coformer stacks, instead of drug-drug stacks, as in the case of solvates.</p>

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Structural chemistry of isostructural solvates and a cocrystal of the anti-cancer drug olaparib

  • 期刊论文

  • 发表日期：

    2025年12月1日

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  • Ipsha Shruti,
  • Somnath Dey,
  • Rampal Vishwakarma,
  • Shubham Som,
  • Deepak Chopra

摘要

An extensive crystallization of olaparib with various coformers using mechanochemical grinding and slow evaporation method resulted in the discovery of three new solvates and one cocrystal. The solvates of the drug with benzene, ethyl acetate and tetrahydrofuran are isostructural in the monoclinic, centrosymmetric space group symmetry P21/n. The change in the molecular conformation of the drug, by flipping of the conformationally flexible functional groups, in the solid state, is of significance, in the cocrystal, which crystallizes in the space group P21/c. The analysis of the crystal-chemistry, corroborated by analysis of the pairwise intermolecular interaction energies and the molecular electrostatic potential maps suggest that the origin of unfolding of the conformation of the drug in the cocrystal is via strong I···O halogen bonds, supported by F···O and F···N fluorine bonds, while forming strong drug-coformer stacks, instead of drug-drug stacks, as in the case of solvates.