Taking Crystal Sponges into the Nanoscale Using 3D Electron Diffraction

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In the crystal sponge method (CSM), noncrystalline molecules are ordered bound in a porous crystal to allow collection of single crystal X-ray diffraction (SCXRD) data of both the host and the analyte. This protocol has huge promise but is hindered by a lack of suitable sponge materials that can be isolated as large single crystals, and difficulties in inducing the ordered, high occupancy guest loading required for data collection. Herein, we propose to apply the CSM to 3D electron diffraction (3DED), a technique that allows analysis of ~100 nanometres nanocrystals, which will remove the requirement for time-consuming growth of large crystals, open up many new potential sponges for analysis, minimise issues with sponge activation and analyte diffusion, lower analyte detection limits, mitigate for crystal stability issues, and allow much more rapid analysis. We shall downsize existing crystal sponges (CSs) and perform a crystallographic comparison of data collected on analytes by SCXRD vs 3DED, including key parameters of the diffusion time and required quantities of the analyte. Secondly, we shall exploit the applicant’s recent discovery of a new class of sponge, BTB-MOF-24, to develop a series of new CSs with related structures through isoreticular expansion. We will compare 3DED to SCXRD for the data acquisition by these sponges. By gaining fine control over pore size and geometry, we will elucidate design criteria to control hostguest interactions and ensure ordered analyte binding for excellent data quality. Finally, we will apply these sponges to the structural analysis of complex lipids, biologically relevant molecules, but difficult to analyse due to their flexibility and chirality, and use these analytes as exemplars of the power of 3DED compared to SCXRD. Ultimately, by signposting the efficacy of 3DED and developing design rules for preparing new CSs, we will reinvigorate Taking Crystal Sponges into the Nanoscale Using 3D Electron Diffraction