Crystal Structures of Two Important Pharmaceuticals Solved by 3D Precession Electron Diffraction Tomography,Organic Process Research & Development

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Crystal Structures of Two Important Pharmaceuticals Solved by 3D Precession Electron Diffraction Tomography
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2018-09-04 00:00:00 , DOI: 10.1021/acs.oprd.8b00149
Partha P. Das ₁ , Enrico Mugnaioli ₂ , Stavros Nicolopoulos ₁ , Camilla Tossi _{2,

3} , Mauro Gemmi ₂ , Athanasios Galanis ₁ , Gheorghe Borodi ₄ , Mihaela M. Pop ₅

Affiliation

The crystal structures of two important marketed pharmaceuticals, namely, ramelteon (RAM) and tolvaptan (TOL), were determined for the first time using 3D precession electron diffraction tomography (PEDT) on 500 nm-sized crystals. The results were compared with the same structures determined by single-crystal X-ray diffraction on subsequently grown 50–200 μm single crystals, indicating a good match of molecular conformation, crystal packing, and unit cell parameters. The X-ray crystal structures were used to validate the developed workflow of data acquisition and structure solution with electron diffraction. This study highlights that 3D PEDT alone is able to provide accurate crystal structures from pharmaceutical nanocrystals that will suffice for most practical applications when no larger crystals can be grown.

中文翻译：

3D旋进电子衍射层析成像法解决的两种重要药物的晶体结构

首次使用3D进动电子衍射断层扫描（PEDT）在500 nm大小的晶体上首次确定了两种重要的市售药物，即雷梅替尼（RAM）和托伐普坦（TOL）的晶体结构。将结果与随后生长的50–200μm单晶上通过单晶X射线衍射确定的相同结构进行了比较，表明分子构象，晶体堆积和晶胞参数具有良好的匹配性。X射线晶体结构被用于验证电子衍射的数据采集和结构解决方案开发的工作流程。这项研究突出表明，仅3D PEDT就能从药物纳米晶体中提供准确的晶体结构，当无法生长更大的晶体时，这将满足大多数实际应用。

更新日期：2018-09-04

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