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Taking Crystal Sponges into the Nanoscale Using 3D Electron Diffraction

Project description

Improved method to analyse the structure of non-crystalline molecules

Understanding the structure of non-crystalline molecules is a major challenge, especially regarding flexible and complex compounds such as lipids. With the support of the Marie Skłodowska-Curie Actions programme, the CrySpED project will introduce a novel approach to this that involves combining the crystal sponge method with 3D electron diffraction (3DED). Unlike traditional methods that require large crystals, 3DED allows analysing nanocrystals of around 100 nm in size, making the process faster. Researchers will also develop new sponge materials with tailored pore sizes to improve how molecules bind and organise within them. The proposed research should help overcome current limitations in molecular analysis, offering a powerful tool for studying complex molecules with greater precision.

Objective

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

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2024-PF-01

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Coordinator

UNIVERSITY OF GLASGOW
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 276 187,92
Address
UNIVERSITY AVENUE
G12 8QQ Glasgow
United Kingdom

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Region
Scotland West Central Scotland Glasgow City
Activity type
Higher or Secondary Education Establishments
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Total cost

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