A novel approach to refinement of proton positions in organic crystal structures

在许多工业部门中，准确确定有机晶体结构中氢的位置对于合理的产品设计至关重要。虽然晶体学一直是确定结构的金标准，但许多感兴趣的材料不能以单晶形式生产，粉末衍射方法在定位氢的能力方面受到限制。需要对样品进行氘化处理的中子法在该领域的应用也受到限制。该项目主题属于EPSRC的“制造未来”和“医疗保健”主题。研究表明，NEXAFS可以与密度泛函理论（DFT）计算相结合，以确定氢键长度，其精度可与高分辨率x射线衍射和中子衍射方法相媲美。这种NEXAFS对质子和氢位置的改进是一种从根本上确定小有机分子形成的晶体结构中氢位置的新方法，随着高通量NEXAFS的出现，它在实验上也将是直接的。它克服了x射线衍射晶体学的局限性，因为它不需要晶体，也克服了中子方法的局限性，因为它不需要氘化。拟议的博士项目将使用钻石光源的高通量近环境压力NEXAFS设备，对不同供体/受体氢键对的晶体样品库进行高通量C， N和O k边缘NEXAFS测量。在2019/20年在利兹大学和戴蒙德大学接受培训后，博士生将进行这些研究，从剑桥晶体学数据库中选择具有代表性的晶体结构库。在可能的情况下，将通过高分辨率x射线和中子衍射的额外分析来验证所得晶体结构精化的准确性。

Accurate determination of hydrogen positions within organic crystalline structures is essential for rational product design in many industrial sectors. While crystallography has been the gold standard for structure determination, many of the materials of interest cannot be produced in single crystal form and powder diffraction methods are limited in their ability to locate hydrogens. Neutron methods which require deuteration of the sample are also limited in application for this field. The project theme sits within the Manufacturing the Future and Healthcare themes of EPSRC.It has been shown how NEXAFS can be combined with Density Functional Theory (DFT) calculations to determine hydrogen bond lengths with accuracy comparable to high-resolution X-ray diffraction and neutron diffraction methods. Such NEXAFS refinement of proton and hydrogen positions is a radically novel way of determining the hydrogen positions in crystal structures formed by small organic molecules, and with the advent of high-throughput NEXAFS it will also be experimentally straightforward. It overcomes limitations of X-ray diffraction crystallography because it does not require crystals and those of neutron methods because it does not require deuteration.The proposed PhD project will use the High-Throughput Near-Ambient Pressure NEXAFS facility at Diamond Light Source for a programme of high-throughput C, N and O K-edge NEXAFS measurements on crystalline sample libraries focused on different donor/acceptor hydrogen bond pairs. After training at Leeds and Diamond in 2019/20 the PhD student will perform these studies, choosing libraries of representative crystal structures from the Cambridge Crystallography database. Where possible, the accuracy of the resulting crystal structure refinement will be validated through additional analysis with high-resolution X-ray and neutron diffraction.