Investigating rotational disorder by inexpensive multi-temperature X-ray diffraction experiments

柏林自由大学建立了一个独特的单晶衍射仪测量装置。它结合了a）一个用于多温度测量的低温恒温器，30 K，B）可透过X射线的真空圆筒和c）CCD区域检测。购买装置并重建衍射仪装置。它的功能为这个应用程序提供了基础。旋转无序是晶体学中的基本兴趣，并且有强烈的迹象表明它与多晶型晶体结构的稳定性有关，这是制药工业中的重要课题。本项目的主要目的是使用合适的化合物了解导致这种疾病发生的条件。多温度实验是表征连续旋转无序的关键。解决这个科学问题需要在30至300 K的宽温度范围内对同一样品进行多个样品的衍射实验;应更新X射线源，以减少这些测量的持续时间，并能够研究较小的样品。实验数据将评估特殊的差异电子密度图，使旋转无序的准确表征。同时，分子动力学模拟和QM/MM计算将进行补充实验。我们的最终目标是提供更好的建模工具来处理小分子晶体学中的无序。新的测量设置将允许在未来研究一系列其他固态研究问题。为了使技术实施以及开展拟议的研究，我们申请了2/3 TV-L E13博士学位三年。

A unique single-crystal diffractometer measurement setup had been established at the Free University Berlin. It combined a) a cryostat for multi-temperature measurements to approx. 30K, b) a vacuum cylinder permeable for X-rays and c) CCD-area detection. The setup was purchased and the diffractometer setup rebuild. Its functionality provides the foundation for this application. Rotational disorder is of fundamental interest in crystallography and there are strong indications that it is relevant for the stability of polymorphic crystal structures, an important topic in the pharmaceutical industry. Establishing an understanding of the conditions that lead to the occurrence of such disorder using suitable compounds is the main aim of this project. Multi-temperature experiments are vital to characterize continuous rotational disorder. Answering this scientific question requires carrying out diffraction experiments of several samples in a wide temperature range of 30 to 300 K on the same specimen; the X-ray source should be updated to reduce the duration of these measurements and to enable the study of smaller samples. Experimental data will be evaluated with special difference electron-density maps that allow accurate characterization of rotational disorder. In parallel, molecular dynamics simulations and QM/MM computations will be performed to complement the experiments. We ultimately aim to provide better modeling tools to deal with disorder in small-molecule crystallography. The new measurement setup will subsequently allow to study of a range of other solid-state research questions in the future. To enable the technical implementation as well as to carry out the proposed research we apply for a 2/3 TV-L E13 PhD position for three years.