Development of optimised MRI contrast agents for copper(I) click reactions

Aloraibi, Farah K. M.

Abstract

This research has been focused on synthesising three gadolinium(III) 1,4,7-triacetic acid-1,4,7,10-tetraazacyclododecane (DO3A) macrocyclic complexes (Gd6, Gd7, Gd8) as potential T1 MRI contrast agents. Alkyne derivativised chelators were synthesised with three different alkyne pendent arms (propargyl, propargyl acetamide and butyne) which are suitable for Cu(I) catalysed cycloaddition ‘click’ chemistry with azide derivatives to form 1,2,3-triazole rings.
Triazole formation with benzyl azide was used as “proof of concept” to form chelators and gadolinium complexes (Gd6, Gd7, Gd8) that could be assessed for their properties as MRI contrast agents. One of the complexes was then selected for conjugation with an azide derivative of a thymidine DNA base (AZT, a clinically approved drug molecule) to link via the triazole group and demonstrate the widespread utility of this approach.
Relaxivity measurements were carried out on the synthesised gadolinium(III) complexes to evaluate their potential as MRI contrast agents with Gd8 showing the highest T1relaxivity result. Therefore, Gd8 (relaxivity, 5.74 mM-1 s-1) was conjugated with the DNA base derivatives (3’-Azido-3’-deoxythymidine, AZT) to give the desired product in an 89% yield with a relaxivity of 4.33 mM-1 s-1 indicating the potential of these compounds for future in vivo applications in MRI studies.

Citation

Aloraibi, F. K. M. Development of optimised MRI contrast agents for copper(I) click reactions. (Thesis). University of Hull. https://hull-repository.worktribe.com/output/4224113

• Thesis Type: Thesis
• Deposit Date: Apr 12, 2022
• Publicly Available Date: Feb 24, 2023
• Keywords: Chemistry
• Public URL: https://hull-repository.worktribe.com/output/4224113
• Additional Information: Department of Chemistry, The University of Hull
• Award Date: Apr 1, 2017