Design, Synthesis, Characterization and Biological Applications on Ruthenium and Gold Compounds

In search of new metal-based anticancer compounds, Ru(III/II) complexes have deserved special attention not only because of their good antitumour activity in screening studies, but also because of their cancer-cell specific targeting properties. The need of more biological and chemical evidence in the reactivity of Ru(III/II) systems has encouraged, the synthetic, spectroscopic, structural and biological studies of two novel bis(arylimino)pyridine Ru(III) chloride compounds containing the ligands, 2,6-bis(2,4,6-trimethylphenyliminomethyl)pyridine and 2,6bis(2,6-diisopropylphenyliminomethyl)pyridine is described in this chapter. The bis(arylimino)pyridine ligands were synthesized by condensation of 2,6pyridinedicarboxaldehyde with 2,4,6-trimethylaniline or 2,6-diisopropylaniline and further characterized in the solid state through monocrystal X-ray diffraction analysis and other standard characterization techniques. The Ru(III) compounds, with general formula [RuCl3(L)]x(H2O), where L=L1=2,6-bis(2,4,6trimethylphenyl-iminomethyl)pyridine, L2=2,6-bis(2,6-isopropylphenylimino methyl)pyridine and x=0 or 1, named RuL1 and RuL2 respectively, were structurally determined on the basis of analytical and spectroscopic (IR, UV-Vis, ESI-MS, EPR) studies. A complete assignment of the H NMR resonances of the two paramagnetic compounds was made in deuterated dmf by oneand twodimensional techniques. These new compounds are intended to constitute a series of new anticancer Ru(III) and Ru(II) compounds with improved cytostatic properties; likely to be modified in a desirable manner due to the relatively facile ligand modification of the bis(imino)pyridines and their molecular architecture. Although the ligands by themselves are moderately cytotoxic in selected cell lines (EVSA-T and MCF-7), the anticancer activity of the [Ru(L)Cl3]xH2O compounds is significant for a broad range of cancer celllines tested in vitro (IC50 values = 4 ∼ 17 μM). Finally, reaction of RuL1 with the DNA model base, 9-ethylguanine (9EtGua) was found to produce in a redox reaction, the species trans-[Ru(II)(L1)(9EtGua)2(H2O)](ClO4)2 (abbreviated as RuL1-2(9EtGua)) which was fully characterized by conventional methods in solution and also in the solid state, by X-ray crystallography. The structure comprises the as yet unknown transbis(purine)-Ru(II) unit. “We especially need imagination in science. It is not all mathematics, nor all logic, but it is somewhat beauty and poetry” Maria Montessori, physician, educator, philosopher (1870-1952) * Some of the results presented in this chapter have been published Garza-Ortiz, A.; Maheswari, P. U.; Siegler, M.; Spek, A. L. and Reedijk, J., Inorg. Chem. 47 (2008) 6964-6973. 4