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

在许多工业部门中，准确测定有机晶体结构中氢的位置对于合理的产品设计是必不可少的。虽然晶体学一直是结构测定的黄金标准，但许多感兴趣的材料不能以单晶形式生产，并且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的中子方法在这一领域的应用也受到限制。该项目主题位于EPSRC的未来制造和医疗保健主题之内。它已经展示了NEXAFS如何与密度泛函理论（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。这种质子和氢位置的NEXAFS细化是确定由小有机分子形成的晶体结构中的氢位置的一种全新的方法，并且随着高通量NEXAFS的出现，它也将在实验上变得简单。它克服了X射线衍射晶体学的局限性，因为它不需要晶体和中子方法，因为它不需要deuteration.The拟议的博士项目将使用高通量近环境压力NEXAFS设施在钻石光源的高通量C，N和O K边缘NEXAFS测量结晶样品库专注于不同的供体/受体氢键对的方案。在利兹和钻石在2019/20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代表性晶体结构的库。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细化的准确性。

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.