Lewis, Viliyana;
(2023)
Towards Magnetic Resonance Imaging for Detection of Nerve Agent Adducts.
Doctoral thesis (Eng.D), UCL (University College London).
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Abstract
Nerve agents are the deadliest class of chemical warfare agents known to mankind. Currently, detection techniques such as LC-MS are readily available, however real-life cases have shown that these detection methods take too long considering the severity of nerve agent poisoning. Magnetic Resonance Imaging (MRI) is a non-invasive technique which could offer an alternative approach to nerve agent detection and this thesis seeks to explore the possibility of such sensing using MRI. A range of analytical techniques were utilised to investigate binding of oxyanion analogues of nerve agent adducts to a Gd3+ metal centre in a chelate. Furthermore, amplification of the MRI signal of Gd3+−doped nanomaterials, based on porous silica nanoparticles was investigated using NMRR. Finally, inorganic ligands proposed to bind phosphotyrosine residues were synthesised and their binding to sarin- and cyclosarin-tyrosine adducts was tested using MRI. We discovered weak binding interactions between the contrast agent Gd3+‒DOTA and an excess of oxyanions, such as tyrosine, ibuprofen, and lysine. Interestingly, phosphate and phosphoserine showed a formation of a second hydration sphere instead, which led to increase in relaxivity. The addition of mesoporous silica nanoparticles (MSNs) incorporating Gd3+‒DOTA, to excess lysine resulted in significant increase in relaxivity, which resulted in amplification of the detection response (signal increased from 40 mM-1 s-1 to 59 mM-1 s-1). The final part of this project sought to directly observe interactions between nerve agent adducts (produced by Dstl) and Gd3+chelates, incorporating aromatic groups in their structure. We demonstrated that the presence of G-type nerve agent adducts causes a significant modulation of the MRI signal arising from Gd3+ chelates in very short timescales. In conclusion, this work offers a powerful alternative method for the detection of nerve agent poisoning which can easily be used by both – scientists at Dstl and healthcare professionals.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Eng.D |
| Title: | Towards Magnetic Resonance Imaging for Detection of Nerve Agent Adducts |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | Copyright © The Author 2023. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10176304 |
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