Ruthenium metallopharmaceuticals

The well-developed synthetic chemistry of ruthenium, particularly with ammine, amine and imine ligands, provides for many approaches to innovative new metallopharmaceuticals. Advantages of utilizing ruthenium am(m)ine complexes in drug development include, (1) reliable preparations of stable complexes with predictable structures; (2) the ability to tune ligand affinities, electron transfer and substitution rates, and reduction potentials; and (3) an increasing knowledge of the biological effects of ruthenium complexes. Many Ru(II) and Ru(III) am(m)ine complexes selectively bind to imine sites in biomolecules. Collectively, these lend ruthenium complexes to redox-activation and photodynamic approaches to therapy as well as the development of radiopharmaceuticals containing one of several radionuclides of ruthenium. Ruthenium red and the related Ru360 strongly inhibit calcium ion uptake in the mitochondria. A number of ruthenium compounds with anticancer activity appear to penetrate tumors through a transferrin-mediated process and bind to cellular DNA following intracellular activation by reduction. Ruthenium complexes exhibit both nitric oxide release and scavenging functions that can affect vasodilation and synapse firing. Simple ruthenium complexes are unusually effective in suppressing the immune response by inhibiting T cell proliferation.