Studies building on existing research into the development of in vivo oxidant sensors which could be used as magnetic resonance (MR) imaging agents for the early detection of oxidative stress have been carried out. A series of N₂S₂ copper macrocyclic systems have been synthesised building on previous studies. The compounds have been modified at various positions to further enhance the suitability of these species as magnetic resonance imaging agents. The modifications include the introduction of oxo and sulfur based pendant arms at the nitrogen donor atoms, the introduction electron withdrawing and electron donating groups at various positions on the ring and the use of softer donor atoms to produce an S₄ and S₃N system. The stability and suitability of the complexes were challenged using a number of techniques including spectrophotometric titrations, cyclic voltammetry and T₁ relation NMR. The stability of the copper centre of the macrocycles was challenged with a biologically relevant sequestration agent (bovine serum albumin). It was found that 5 coordinate copper macrocycles are the most stable. The electrochemical reversibility of the complexes was tested using cyclic voltammetry to identify which compounds were capable of redox reversibility. A sulfur based pendant arm complex (compound 52) showed promise. Studies using ascorbate and hypochlorite demonstrate that this compound will survive chemical reduction and re-oxidation returning an acceptable percentage reversibility. To assess the potential of all of the complexes for use as imaging agents, the effect of the complexes on the T₁ relaxation time was tested over a range of concentrations. This was compared with a Gd-DTPA control and original parent complex (compound 2). The modifications made very little difference to the T₁ relaxation times.Although the relaxivity is low the studies indicates that the modified complexes may have some viability for use and warrant further investigation.
|Date of Award||5 Jun 2015|
- University Of Strathclyde
|Sponsors||University of Strathclyde|
|Supervisor||John Reglinski (Supervisor) & Mark Spicer (Supervisor)|