Approaches to Photoactivated Cytotoxins
Degree GrantorUniversity of Canterbury
Degree NameDoctor of Philosophy
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.