Towards the synthesis of novel chelates for technetium-99m imaging

Abstract

Abstract This thesis details the synthesis of tetradentate ligand systems for use with technetium-99m with a focus on sulphur donors. The synthesis of a series of S4 tetradentate ligands is detailed (Chapter 3). The ligands with general formula Me2PS(CH2)2S(CH2)nS(CH2)2PSMe2 where n = 2 – 4 (3.1 – 3.3). The ligands were reacted with technetium-99m, [ReO2(py)4]Cl and [ReOCl3(PPh3)2] unfortunately evidence for complexation was not obtained. In order to gain an understanding of the coordination chemistry of the ligands 3.1 – 3.3 were successfully complexed to Cu(I), Ag(I) and Pd(II) centres, the compounds and structures are discussed in chapter 3. The synthesis of ligands containing 1-methyl-2H-imidazole-2-thione units, which act as S donors is featured in chapter 4. Challenges met during the synthesis of the S4 and N2S2 ligands are discussed. P2S2 (4.12 and 4.16) ligands were synthesised by the reaction of the imidazole unit with 1,3-propanebis(phenyldihydroxymethylphosphine) dichloride. This led to the subsequent synthesis of an analogous P2O2 (4.17) ligand using 1-ethyl-2H-imidazolin-2-one. The P2S2 and P2O2 chelates were reacted with PdCl2 to produce Palladium(II) complexes. Reactions with [ReOCl3(PPh3)2] were also completed and although pure samples were not isolated, there is evidence that [ReO2L]+ complexes were synthesised. The synthesis of a tetradentate phosphine oxime (P2N2) ligand system is the focus of chapter 5. The synthetic challenges encountered during the proposed synthesis are detailed along with alternative synthetic routes. The synthesis of analogous P2N2 compounds is also reported. Whilst evidence for the target chelate (5.2) was obtained its synthesis could not be fully confirmed.