University of Sussex
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Development of NMR tools to investigate aggregation phenomena

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posted on 2023-06-08, 16:19 authored by Rebecca Emily Joyce
Chemistry and biology are full of examples of aggregation phenomena; from the useful applications in drug molecule stabilisation and tissue engineering, to the negative effects of causing diseases such as Alzheimer's and Parkinson's. NMR is a useful tool for probing aggregation as it can provide detail at the atomic scale; however, the molecular size of the aggregates can lead to poor resolution and spectral broadening, issues which require some development to solve. The research detailed in this thesis aims to develop NMR tools to investigate aggregation phenomena from two angles; firstly, to directly monitor aggregation using diffusion-ordered NMR spectroscopy and secondly to probe the effects of aggregates on biomimetic constructs using NMR techniques. To achieve the first aim, diffusion-ordered NMR Spectroscopy in conjunction with a size-exclusion chromatography stationary phase was developed for the purpose of monitoring aggregation in a time-resolved manner. The size-exclusion stationary phases, commonly used to separate molecules of different sizes, such as proteins from salts, in liquid chromatography methods, provide an additional perturbation of the diffusion profile of molecules of different sizes when added to NMR samples for diffusion-ordered spectroscopy analysis. The development of this method and a selection of applications are detailed within two chapters of the thesis. These studies have been published in Journal of Magnetic Resonancei and Journal of Physical Chemistry Cii. A complementary study of the interactions between aggregates and biological structures such as biomimetic cell membranes using NMR methods such as time-resolved 31P NMR and the implementation of paramagnetic shift reagents is discussed in the final two chapters. Changes in chemical shift caused by additional interactions between the shift reagent and the solvent are fully investigated and the method is applied to the study of membrane permeation by amyloid-ß oligomers.


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University of Sussex

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