Homo- and Hetero-dinuclear Arene-Linked Osmium(II) and Ruthenium(II) Organometallics: Probing the Impact of Metal Variation on Reactivity and Biological Activity

Dinuclear metallodrugs offer much potential in the development of novel anticancer chemotherapeutics as a result of the distinct interactions possible with bio-macromolecular targets and the unique biological activity that can result. Herein, we describe the development of isostructural homo-dinuclear Os-II-Os(II)and hetero-dinuclear Os-II-Ru(II)organometallic complexes formed from linking the arene ligands of [M(eta(6)-arene)(C2O4)(PTA)] units (M=Os/Ru; PTA=1,3,5-triaza-7-phosphaadamantane). Using these complexes together with the known Ru-II-Ru(II)analogue, a chromatin-modifying agent, we probed the impact of varying the metal ions on the structure, reactivity and biological activity of these complexes. The complexes were structurally characterised by X-ray diffraction experiments, their stability and reactivity were examined by using(1)H and(31)P NMR spectroscopy, and their biological activity was assessed, alongside that of mononuclear analogues, through MTT assays and cell-cycle analysis (HT-29 cell line). The results revealed high antiproliferative activity in each case, with cell-cycle profiles of the dinuclear complexes found to be similar to that for untreated cells, and similar but distinct profiles for the mononuclear complexes. These results indicate these complexes impact on cell viability predominantly through a non-DNA-damaging mechanism of action. The new Os-II-Os(II)and Os-II-Ru(II)complexes reported here are further examples of a family of compounds operating via mechanisms of action atypical of the majority of metallodrugs, and which have potential as tools in chromatin research.