School of Molecular Sciences, University of Western Australia, Perth, WA, 6009, Australia.
Department of Chemistry and iNano, Aarhus University, 8000, Aarhus C, Denmark.
Angew Chem Int Ed Engl. 2019 Jul 22;58(30):10255-10259. doi: 10.1002/anie.201905085. Epub 2019 Jun 24.
The observation of an unusual crystal habit in the common diuretic drug hydrochlorothiazide (HCT), and identification of its subtle conformational chirality, has stimulated a detailed investigation of its crystalline forms. Enantiomeric conformers of HCT resolve into an unusual structure of conjoined enantiomorphic twin crystals comprising enantiopure domains of opposite chirality. The purity of the domains and the chiral molecular conformation are confirmed by spatially revolved synchrotron micro-XRD experiments and neutron diffraction, respectively. Macroscopic inversion twin symmetry observed between the crystal wings suggests a pseudoracemic structure that is not a solid solution or a layered crystal structure, but an unusual structural variant of conglomerates and racemic twins. Computed interaction energies for molecular pairs in the racemic and enantiopure polymorphs of HCT, and the observation of large opposing unit-cell dipole moments for the enantiopure domains in these twin crystals, suggest a plausible crystal nucleation mechanism for this unusual crystal habit.
在常用利尿剂氢氯噻嗪（HCT）中观察到一种不寻常的晶体形态，并确定其微妙的构象手性，这激发了对其晶体形态的详细研究。HCT 的对映异构体构象解析为一种不寻常的结构，由具有相反手性的对映纯域组成的连生对映体孪晶。通过空间旋转同步加速器微 X 射线衍射实验和中子衍射分别证实了域的纯度和手性分子构象。在晶体翼之间观察到的宏观反转双轴对称表明存在假外消旋结构，它不是固溶体或层状晶体结构，而是外消旋和对映体孪晶的一种不寻常结构变体。计算了 HCT 的外消旋和对映纯多晶型物中分子对的相互作用能，以及在这些孪晶中观察到的对映纯域的大相反单位细胞偶极矩，这表明了这种不寻常晶体形态的一种合理的晶体成核机制。
