The synthesis of ligand systems and complexes thereof suitable for use as positron emission tomography (PET) agents is studied herein. The ligands 6,6’-(1,4-diazepane- 1,4-diyl)bis(3-aminobenzoate) (HPR), 6,6’-(piperazine-1,4-diyl)bis(3-aminobenzoate) (PipR.2HCl), 6,6’,6”-(1,4,7-triazonane-1,4,7-triyl)tris(3-aminobenzoate) (TACNR), 1,4-bis(2-amino-4-tolyl)- 1,4-diazepane (HPTol), 1,4-bis(2-amino-4-trifluoromethylphenyl)-1,4-diazepane (HPCF3 ), di-tert-butyl 4,4’-(1,4-diazepane-1,4-diyl)bis(3-aminobenzoate) (HPtButyl), 1,3-bis(2-amino- 4-tolyl)-1,3-diazacyclohexane (PipTol), 1,4,7-tris(2-amino-4-trifluoromethylphenyl)-1,4,7- triazacyclononane (TACNCF3), have been studied. Ni(II), Cu(II), and Zn(II) complexes of these ligands have been synthesised, DFT calculations have elucidated structural configuration, whilst x-ray crystal structures of NiHPtButyl, and CuTACNCF3 have been determined. EPR measurements of CuHPR have been taken. A series of triazine core compounds have been prepared for use as model compounds for targeting molecules. The compound Tz(EtGly)(BocGuan)Cl has been synthesised with the required arms to selectively bind to the integrin αvβ3. DO3A moieties have been added to these ligands, and mass spectra analysis of the coordination products with a series of metals has been determined. NO2A derived compounds 2,2’-(7-tosyl-1,4,7-triazonane-1,4-diyl)diaceticacid (TsTACNA2) and 2,2’-(7-(4-nitrophenyl)-1,4,7-triazonane-1,4-diyl)diacetic acid (NPhTACNA2) have been studied,with the x-ray crystallography of the copper complexes completed. Positron emmision tomography (PET) studies of the complexes have also been undertaken and show high levels of complexation at ng scales, with moderate stability in human serum. Glutaric acid functionalised compounds (2S,2’S)-2,2’-(1,4-diazepane-1,4-diyl)dipentanedioic acid (HPGlut), 2,2’,2”-(1,4,7-triazonane-1,4,7-triyl)tripentanedioic acid (TACNGlut), and 2,2’-(4,11-dimethyl-1,4,8,11-tetraazacyclotetradecane-1,8-diyl)dipentanedioic acid (DMiii iv CGlut) have been synthesised, with the copper complex of DMCGlut affording structural determination. The Mn(II) and Gd(III) complexes of the DMCGlut ligand system have been studied by xylenol orange UV titration for their metal-ligand binding ratio, with the Mn(II) system showing a 1:1 binding ratio, whilst the Gd(III) complex showed no binding at all. Synthesis of the trispyrazylborate analogue, tris(4-methyl-2-(2-pyridine)pyrazyl)borate (MeTpPy), was unsuccessful, however, the bis- (MeDpPy) and tetra- (MeQpPy) substituted analogues were successfully synthesised.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:571724 |
| Date | January 2012 |
| Creators | Hughes, Stephen |
| Publisher | Cardiff University |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://orca.cf.ac.uk/47610/ |
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