Anyfanti Goulielmina, Husanu Elena, Andrusenko Iryna, Marchetti Danilo, Gemmi Mauro
Electron Crystallography, Istituto Italiano di Tecnologia (ITT), Viale Rianaldo Piaggio 34, Pontedera 56025, Italy.
IUCrJ. 2024 Sep 1;11(Pt 5):843-848. doi: 10.1107/S2052252524007383.
The antipsychotic drug olanzapine is well known for its complex polymorphism. Although widely investigated, the crystal structure of one of its anhydrous polymorphs, form III, is still unknown. Its appearance, always in concomitance with forms II and I, and the impossibility of isolating it from that mixture, have prevented its structure determination so far. The scenario has changed with the emerging field of 3D electron diffraction (3D ED) and its great advantages in the characterization of polyphasic mixtures of nanosized crystals. In this study, we show how the application of 3D ED allows the ab initio structure determination and dynamical refinement of this elusive crystal structure that remained unknown for more than 20 years. Olanzapine form III is monoclinic and shows a similar but shifted packing with respect to form II. It is remarkably different from the lowest-energy structures predicted by the energy-minimization algorithms of crystal structure prediction.
抗精神病药物奥氮平因其复杂的多晶型现象而广为人知。尽管已进行了广泛研究，但其无水多晶型之一（III型）的晶体结构仍不清楚。它总是与II型和I型同时出现，且无法从该混合物中分离出来，这使得至今仍无法确定其结构。随着三维电子衍射（3D ED）这一新兴领域的出现及其在纳米晶体多相混合物表征方面的巨大优势，情况发生了变化。在本研究中，我们展示了3D ED的应用如何实现对这种20多年来一直未知的难以捉摸的晶体结构进行从头算结构测定和动力学精修。奥氮平III型为单斜晶系，相对于II型显示出相似但有位移的堆积方式。它与晶体结构预测的能量最小化算法所预测的最低能量结构有显著不同。
