Anticancer activity of multinuclear arene ruthenium complexes coordinated to dendritic polypyridyl scaffolds

The rational development of multinuclear arene ruthenium complexes (arene = p-cymene, hexamethylbenzene) from generation 1 (G¹) and generation 2 (G²) of 4-iminopyridyl based poly(propyleneimine) dendrimer scaffolds of the type, DAB-(NH₂)_n (n = 4 or 8, DAB = diaminobutane) has been accomplished in order to exploit the ‘enhanced permeability and retention’ (EPR) effect that allows large molecules to selectively enter cancer cells. Four compounds were synthesised, i.e. {(p-cymene)RuCl₂}₄G¹] (1), {(hexamethylbenzene)RuCl₂}₄G¹] (2), {(p-cymene)RuCl₂}₈G²] (3), and {(hexamethylbenzene)RuCl₂}₈G²] (4), by first reacting DAB-(NH₂)_n with 4-pyridinecarboxaldehyde and subsequently metallating the iminopyridyl dendrimers with (p-cymene)RuCl₂]₂ or (hexamethylbenzene)RuCl₂]₂. The related mononuclear complexes (p-cymene)RuCl₂(L)] (5) and (hexamethylbenzene)RuCl₂(L)] (6) were obtained in a similar manner from N-(pyridin-4-ylmethylene)propan-1-amine (L). The molecular structure of 5 has been determined by X-ray diffraction analysis and the in vitro anticancer activities of the mono-, tetra- and octanuclear complexes 1–6 studied on the A2780 human ovarian carcinoma cell line showing a close correlation between the size of the compound and cytotoxicity.