Interactions of organometallic ruthernium arene anticancer complexes with DNA

Organometallic Ru(II) arene complexes of the type [(n6- arene)Ru(en)Cl]+(arene = p-cymene (1) or biphenyl (2), en = ethylenediamine),1 are toxic to cancer cells, including cisplatinresistant cell lines. A possible target for these complexes is DNA and we are therefore investigating the kinetics and thermodynamics of binding to DNA including the nature of any structural distortions. Such knowledge maybe incorporated into design concepts for this class of anticancer agents and assists the exploration of structureactivity relationships.
We have studied reactions of complex 1 or 2 with the singlestranded DNA d(CGGCCG) and duplex d(CGGCCG)2, and the 14- mer duplex d(ATACATGGTATCATA)• d(TATGTACCATGTAT) by HPLC, ESI-MS, 1D and 2D 1H and 15N NMR spectroscopy. These studies2 show that the arene ligand plays a major role in distorting the duplex either via steric interactions (1) or via intercalation (2), and provide a structural basis for understanding their biological effects. The time dependence of reactions of 15N-1 or 15N-2 with V has also been studied.