With an ageing baby-boomer population in the Western World, cancer is becoming a significant cause of death. The prevalence of cancer and all associated costs, both in human and financial terms, drives the search for new therapeutic drugs and treatments. Platinum anticancer agents, such as cisplatin have been highly successful but there are several disadvantages associated with their use. What is needed are new compounds with different mechanisms of action and resistance profiles. What needs to be recognised is that there are many other metals in the periodic table with therapeutic potential. Here we have highlighted metal complexes with activity and illustrate the different approaches to the design of anticancer complexes.

Platinum(II)-based DNA intercalators where the intercalating ligand is 1,10-phenanthroline or a phenanthroline derivative and where the ancillary ligand is either achiral (e.g. ethylenediamine) or chiral (e.g. diaminocyclohexane) show a range of cytotoxicities with a defined structure–activity relationship. The most cytotoxic are those that contain methylated-phenanthroline ligands and 1S,2S-diaminocyclohexane (S,S-dach) as the ancillary ligand. We have developed a new purification method using Sep-Pak® C-18 reverse phase columns, which means these metal complexes can be made faster and cheaper compared to published methods. Platinum(II)-based complexes containing imidazole, pyrrole and β-alanine subunits, that are capable of recognising specific DNA base-pair sequences have also been synthesised. These include linear or hairpin polyamide ligands that can recognise DNA sequences up to seven base-pairs in length and contain single platinum centres capable of forming monofunctional adducts with DNA. We have now synthesised and characterised, by ¹H and ¹⁹⁵Pt NMR, ESI-MS and elemental analysis, the first dinuclear platinum(II) DNA sequence selective agent. Finally, using ¹H NMR we have examined the encapsulation of our platinum(II)-based DNA intercalators by cucurbit[6]uril (CB[6]). Encapsulation by CB[6] was found to not significantly change the cytotoxicity of five platinum(II)-based DNA intercalators, indicating it may have utility as a molecular carrier for improved drug delivery.