| Summary: | In this thesis the biological activity and aqueous solution chemistry of half-sandwich Os<sup>11</sup> arene complexes of the type [(η<sup>6</sup>-arene)Os(XY)C1] is explored, and it is demonstrated that these properties can be tuned by careful choice of XY chelating ligand (N,N-, O,O- and N,O-chelates) to achieve cancer cytotoxicity comparable to carboplatin. The osmium complexes containing N,N-chelates hydrolyse more slowly than their ruthenium analogues and the p<i>K</i><sub>a</sub> of the resulting water is more acidic. Efforts to increase the rates of hydrolysis and the resulting p<i>K</i><sub>a</sub> led to replacement of the neutral N,N-chelating ligand by an anionic O,O-chelate. This was successful in that hydrolysis is more rapid and the p<i>K</i><sub>a</sub> of the coordinated water has increased by ca 0.8 units. However, these complexes are deactivated by formation of the inert and thermodynamically stable hydroxo-bridged dimers. Attempts to tune the stability of complexes containing XY = O,O-chelate, by replacing the 6-membered O,O-chelate with 5-membered analogues, was partially successful for the development of active complexes, but was unsuccessful in preventing hydroxo-bridged dimer formation. Within the class of N,N- and N,O-chelated complexes the choice of donor group is important. Replacing amine N-donor groups with the Π-acceptor pyridine, reduced both the rate of hydrolysis and p<i>K</i><sub>a</sub> or coordinated water, and increased the overall stability of the complex. This was especially the case for complexes containing N,O-chelates, which displayed aqueous chemistry in between that of the parent compounds containing neutral N,N-or anionic O,O-chelates. Within this group of osmium arene complexes, [(η<sup>6</sup>-arene)Os(N,O)C1], active cytotoxic complexes were obtained, and the first X-ray crystal structures of osmium bound to either G or A nucleobases is reported. This work shows that a wide range of reactivity can be obtained for complexes of the form [(η<sup>6</sup>-arene)Os(XY)C1]<sup>n+</sup> by careful choice of the XY chelating ligand, and this knowledge has allowed complexes with cancer cell cytotoxicity to be designed.
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