Approaches to Photoactivated Cytotoxins

Abstract

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.