School of Pharmacy, University of Reading, Whiteknights, P.O. Box 224, Reading, RG6 6AD, UK.
C4X Discovery, Manchester One, 53 Portland Street, Manchester, M1 3LD, UK.
J Pharm Sci. 2018 Aug;107(8):2042-2047. doi: 10.1016/j.xphs.2018.04.010. Epub 2018 Apr 18.
Crystal structure determination from powder diffraction data (SDPD) using the DASH software package is evaluated for data recorded using transmission capillary, transmission flat plate, and reflection flat plate geometries on a selection of pharmaceutical compounds. We show that transmission capillary geometry remains the best option when crystal structure determination is the primary consideration and, as expected, reflection flat plate geometry is not recommended for SDPD because of preferred orientation effects. However, the quality of crystal structures obtained from transmission plate instruments can be excellent, and the convenience factor for sample preparation, throughput, and retrieval is higher than that of transmission capillary instruments. Indeed, it is possible to solve crystal structures within an hour of a polycrystalline sample arriving in the laboratory, which has clear implications for making small-molecule crystal structures more routinely available to the practicing laboratory medicinal chemist. With appropriate modifications to crystal structure determination software, it can be imagined that SDPD could become a rapid turn-around walk-up analytical service in high-throughput chemical environments.
使用 DASH 软件包从粉末衍射数据（SDPD）中确定晶体结构，评估了在一系列药物化合物上使用传输毛细管、传输平板和反射平板几何形状记录的数据。我们表明，当晶体结构确定是主要考虑因素时，传输毛细管几何形状仍然是最佳选择，并且由于择优取向效应，反射平板几何形状不建议用于 SDPD。然而，从传输板仪器获得的晶体结构的质量可以非常好，并且在样品制备、通量和检索方面的便利性因素高于传输毛细管仪器。实际上，有可能在多晶样品到达实验室后的一个小时内解决晶体结构问题，这对使小分子晶体结构更常规地提供给实践实验室药物化学家具有明显的意义。通过对晶体结构测定软件进行适当的修改，可以想象 SDPD 可能成为高通量化学环境中的快速周转现场分析服务。
