Synthesis and study of dinuclear cobalt(III)-platinum(II) complexes as potential anti-cancer pro-drugs.

Type of content
Theses / Dissertations
Publisher's DOI/URI
Thesis discipline
Chemistry
Degree name
Doctor of Philosophy
Publisher
University of Canterbury
Journal Title
Journal ISSN
Volume Title
Language
English
Date
2016
Authors
Tavakolinia, Fatemeh
Abstract

The aim of this project was to develop [Co(μ-OH)₂Pt] prodrugs that can undergo bio-reduction in hypoxic cells within solid tumours. This thesis describes synthetic methods to produce heterodinuclear [Co(μ-OH)₂Pt] complexes. Purification methods and characterisation of this class of complexes are also discussed. The formation of [{Co(μ-OH)nM}m] complexes (M = transition metals) by reaction between equilibrium mixtures of cis- and trans-[Co(en)₂(OH)(OH₂)]²⁺ and different metal ions was studied using ¹³C NMR spectroscopy, in order to gain a better understanding of the reactions that may be occurring in solution. This involved monitoring the effect of the added metal ions on the position of the cis-trans equilibrium of the Co complex. This work is described in chapter 2. In chapter 3, the synthesis and characterisation of [Co(μ-OH)₂Pt] complexes is discussed. Formation of [Co(μ-OH)₂Pt] complexes has been confirmed, following separations on ion exchange resins. These complexes proved to be rather labile and this led to insurmountable difficulties when attempting to isolate these complexes in pure form. Problems associated with purification of [(en)₂Co(μ-OH)Pt(L)] and [(tren)Co(μ-OH)Pt(L)] (L = chda, (NH₃)₂) complexes led us to synthesise a new class of [Co(μ-OH)₂Pt] complexes, bearing a nitrilotriacetate ligand, as many reported anticancer drugs in literature are neutral (chapter 4). Both characterisation and biological assessment of these complexes was hindered by their low solubility. However, NMR studies at high temperature in DMSO again demonstrated the lability of these complexes. In summary, [Co(μ-OH)₂Pt] complexes can be made, but they proved to be very labile and they do decompose. The direction of this research should be changed in future in order to produce a less labile [Co(μ-OH)₂Pt] system. We speculate that this may be possible by incorporating a bulky group to reduce ligand exchange on platinum. In chapter 5, a conclusion for synthesis of dinuclear [Co(μ-OH)₂Pt] complexes and the future work for this study are discussed. Chapter 6 describes the synthesis and characterisation of organotin complexes which can be potential anticancer drugs. The experimental work of the thesis is explained in chapter 7.

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