Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.755339
Title: Design, synthesis and applications of multi-functional MRI contrast agents for bio-imaging
Author: Ali, Adil Hussein
ISNI:       0000 0004 7428 3349
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2018
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Abstract:
Multimodal imaging agents have the potential to be detected in both MRI and optical imaging experiments allowing for visualisation of biological systems from the cellular level up to the whole body. This thesis reports a series of second generation MRI contrast agents with monometallic and heteronuclear Ln-DO3A based complexes for different bio-imaging techniques. Herein, a series of novel dual-mode optical / MR imaging agents have been synthesised using Ir(III) and Pt(II) as emissive metals. Mono-gadolinium Ir(ppy)2GdL1 with q = 2 exhibits r1 = 7.5 mM-1 s-1 and two photon excitation at 850 nm gives rise to emission in the range 500-600 nm suggesting that it may be suitable for investigating in vitro CA co-localisation. The slow tumbling and presence of multinuclear Gd(III) units in IrGdL6L1 gives a ~3 fold increase in relaxivity cf. mono-gadolinium GdL1. The photophysical properties of the Ir(III) core complex are tuned to optimise the imaging probe by modifying the (N^C) cyclometallated or the (N^N') ancillary ligand. The water soluble dual-mode PtGdL10 with q = 1 gives r1 = 4.0 mM-1 s-1 and displays interesting emission characteristics in both its monomer and excimer forms. A number of europium-based carbonate sensors have been prepared, exploiting the inner-sphere water molecule displacement by bidentate carbonate anions. Incorporating a carbonate independent luminescent Re(I) core enables a ratiometric determination of carbonate ions in vitro. RepyEuL1 exhibits log K = 2.33 for NaHCO3, with a clear change in photoluminesence colour from green to yellow on binding carbonate. The Re(I) emission was tuned by OMe and CF3 substitution around the pyridine of regular pyridine-2-yl-1H-1,2,3-triazol-1-yl (pyta) or using the inverse triazole-4-yl ligand (tapy) for the complexation. High molecular weight CAs FeGdL1 and CoGdL1 have been synthesised. These multinuclear complexes show a three-fold enhancement in relaxivity cf. mono GdL1 parent complex at 400 MHz, 9.4 T. Finally, a new CA (GdL8) based on Gd-DO3A with a N-methylsulfonamide pendant arm was produced, which has a changeable hydration number, allowing pH to be reported in the range 6 to 8 reversibly. GdL8 exhibits a blood brain barrier permeability with pH response in in vivo cerebral stroke studies.
Supervisor: Lowe, Mark ; Cullis, Paul Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.755339  DOI: Not available
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