2 results for Doctoral, Approaches to Photoactivated Cytotoxins

  • Approaches to Photoactivated Cytotoxins

    Zibaseresht, Ramin (2006)

    Doctoral thesis
    University of Canterbury Library

    The synthesis and coordination chemistry of eleven bridging ligands, eight of which are new compounds, are described. These ligands are all based on the tridentate terpyridyl system. The other metal ion binding sites of these ligands contain pyridine/bipyridine/pyrazole rings or amine/azamacrocycles domains. In these ligands, the two metal ion binding sites are differentiated by the number of atoms in each site, the configuration of the binding site or the types of donor atom that are present. This binding site differentiation allows to use the different coordination properties of the binding sites to control the regiochemistry of the complexation, ensuring that the correct metal ion is incorporated at the correct binding site in the ligand. Many of the complexes synthesised are mono-ruthenium(II) complexes where Ru(II) ions are situated in the terpyridyl sites of the ligands. These include heteroleptic Ru(II) complexes of the type [Ru(ttp)(L)]2+, where ttp is 4'-(p-tolyl)-2,2':6',2ʺ- terpyridine, and L is the bridging ligand. Reactions of the Ru(II) complexes with a range of metal ions including Co(III) ion have been investigated. The Ru(II) complexes can be classified into three main categories depending on the type of ligands that have been employed: (1) Ru(II) complexes which can react with Co(III) ions to form heterodinuclear Ru(II)-Co(III) complexes; (2) Ru(II) complexes which react only with Ag(I) ions and no other common metal ions that we have tried; (3) Ru(II) complexes with no detectable ability to coordinate other common metal ions. Following standard cobalt chemistry, some heterodinuclear Ru(II)-Co(III) complexes of the type [(ttp)Ru(cymt)Co(X)2]3+, where X = NO2 -, Cl-, and OH-, have been successfully prepared from the corresponding Ru(II) complexes. In these heterodinuclear complexes, anions such as NO2 -, Cl-, or OH- can be readily attached to the Co(III) ions. However, attachment of a neutral species such as en ligands to the Co(III) ions in the complexes proved to be more difficult. Reactions of heterodinuclear Ru(II)-Co(III) complexes with en ligands result in removal of the cobalt ions from the complexes. This is may be a result of a significant difference in the overall charges between the complexes with anionic and the complexes with neutral ligands (3+ vs 5+). Higher overall charge of the complexes when protonable ligands such as monodentate en are present, may destabilize the complexes even more. A combination of NMR spectroscopy, ESI-MS, UV-vis spectroscopy, elemental analysis, and X-ray crystallography has been used to characterise the ligands and their complexes. The crystal structures of one new ligand and sixteen complexes are described.

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  • Approaches to Photoactivated Cytotoxins

    Kariyawasam, Janadari (2016)

    Doctoral thesis
    University of Canterbury Library

    Ruthenium(II)-cobalt(III) heterodinuclear systems are of interest as potential photoactivated cytotoxins. This thesis describes synthetic approaches to the preparation of ruthenium(II)-cobalt(III) heterodinuclear prodrug systems. The majority of work described in this thesis explores the coordination chemistry of amino alcohol ligands with cobalt(III), and use of the amino alcohol cobalt(III) complexes in safer synthetic approaches to nitrogen mustard complexes. This thesis presents the successful synthesis and characterisation of twenty four complexes and twenty three X-ray crystal structures. Twelve different cobalt(III) complexes of 2-((2-aminoethyl)amino)ethanol, L1, and its derivatives are presented in chapter 02, including ten that have been characterised by X-ray crystallographic methods. A reaction web has been developed for the interconversion of a number of these complexes. Chapter 03 presents the successful synthesis of ten new cobalt(III) complexes with series of more complicated amino alcohol ligands, including some that also include zinc(II) or manganese(II). The utilisation of these amino alcohol complexes for the synthesis of potentially bis-alkylating cobalt(III) nitrogen mustard complexes is also discussed, and a total of sixteen X-ray crystallographic studies are presented in this chapter. The synthesis and characterisation of new ruthenium complexes [Ru(4,4’-dmbpy)2(pytp)]2+ and [Ru(4,4’-decbpy)2(pytp)]2+ are presented in chapter 04, along with NMR experiments that examine the synthesis of ruthenium(II)-cobalt(III) complexes. The chemistry discovered in this project extends the coordination chemistry of these amino alcohol complexes and use of them as precursors for the synthesis of nitrogen mustard complexes with potential for use in photoactivated cytotoxins.

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