本项目针对目前微量未知化合物例如药物杂质、代谢产物以及中药化学成分结构鉴定的难题，拟设计和制备系列金属有机骨架材料(MOFs)作为“晶体海绵”，以其为载体，通过溶剂交换和分子吸附，使待测微量化合物有序排列在骨架内预留的空腔中，进而利用单晶X射线衍射(SCD)测定该化合物结构，实现不依赖目标分析物必须为单晶的结构分析；并以上述技术为基础，将待测微量化合物经色谱分离，而后收集微量洗脱馏分，置换进入晶体海绵，最后进行X射线衍射分析，从而构建LC-MOFs-SCD联用的新技术平台。研究中将探讨不同金属离子和有机配体组成对晶体海绵稳定性的影响及其与客体相互作用类型，通过改变材料孔径设计适合不同分子的“晶体海绵”，本项目还将着重研究极性溶剂在该方法中的适用性，以解决HPLC与SCD联用问题。本研究的完成将为LC-SCD联用方法的建立奠定重要基础。

Structure elucidation has been a great challenge in the fields of drug impurity profiling, drug metabolites analysis and nature product investigation. The aim of this work is to design and develop MOFs as crystalline sponges to absorb target molecules, and the guests can be oriented in the crystal pores and analyzed by X-ray diffraction, which overcomes the intrinsic limitations of X-ray single-crystal diffraction, and the crystallization step becomes unnecessary. Based on this strategy, mixtures can be separated by chromatographic process and each fraction is collected and directly treated with crystalline sponge, and then analyzed by X-ray diffraction, thus developing a new platform named LC-MOFs-SCD which combines HPLC separation and crystalline sponge method for X-ray crystallographic analysis. The influence of different metal ions and organic ligands on the stability of MOFs will be discussed as well as the interaction between guest molecules and crystalline sponges. We will also develop different crystalline sponges appropriate for different molecules of various sizes by adjusting the pore size of the MOFs. The application of hydrophilic solvent in this method will also be studied in order to achieve the successful combination of HPLC with SCD. This study will provide an important basis for the development of LC-SCD.