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Durham e-Theses
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New gadolinium contrast agents for MRI

Elemento, Elisa (2008) New gadolinium contrast agents for MRI. Doctoral thesis, Durham University.



A collaboration between Bracco Imaging S.p.A. and Durham University allowed the work described in this thesis on the design and synthesis of new contrast agents for MRI. Significant enhancements in the relaxivity of contrast agents for MRI can be gained by increasing the complex rotational correlation time ((_TR)). Incorporating a Gd(^111) ion within a ligand structure possessing a suitably large dendritic framework, inspired the first part of this project. Thus, the periphery of a Gd-DOTA derivative was adorned with carbohydrate containing wedges. The symmetry of the mono- aqua tetra-substituted structure places the gadolinium-water vector at the centre of any tumbling motion, allowing a coherent tumbling of the macromolecule and an optimization of its rotational correlation time. The carbohydrates ensured high water solubility and favoured a large second sphere hydration contribution to the relaxivity. An increase in the hydration around the metal centre and a rapid exchange of the water molecules with the bulk solvent can also significantly increase the contrast agent efficacy, by efficiently transmitting the paramagnetic effect from the Gd(^111) to the solvent. In a second part of the work, the development was undertaken of diaqua systems based on the seven-membered heterocycle 6-amino-6-methyl- perhydro-1,4-diazepin (AMPED). The three N-positions were substituted with different phosphinate and carboxylate groups and lanthanide complexes (Eu(^111), Gd(^111), Yb(^111)) prepared and studied by multinuclear NMR methods The alkylation of the amino groups with chiral 1,5-dicarboxylate pendant arms led to complex diastereisomers, possessing different water exchange rates. The individual water exchange rates of each isomer were determined, and differed by a factor of six. Furthermore, the periphery of the isomer possessing a faster water exchange rate was adorned with carbohydrate containing wedges, and the relaxation properties studied.

Item Type:Thesis (Doctoral)
Award:Doctor of Philosophy
Thesis Date:2008
Copyright:Copyright of this thesis is held by the author
Deposited On:08 Sep 2011 18:28

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