Osmium anticancer complexes

We have recently extended our interest to the analogous halfsandwich osmium-arene complexes and are exploring the chemical and biological properties of [Os(r 6-arene)(XY)Z]ra 1 complexes (Fig. 25) (105). Both the aqueous chemistry and the biological activity of osmium complexes have been little studied. Third-row transition metals are usually considered to be more inert than those of the first and second rows. Similar to the five orders of magnitude decrease in substitution rates of Pt(II) complexes compared to Pd(II), the [Os(ri6-arene)(L)X]"+ complexes were expected to display rather different kinetics than their Ru(II)-arene analogs. A few other reports on the anticancer activity of osmium-arene complexes have also appeared recently (106-108). 

In line with expectations of kinetic inertness for third-row transition metals, little interest has been vested in the development of osmium anticancer drugs, as ligand-exchange rates did not seem favorable on the timescale of cellular processes. Our work, however, shows that the kinetic lability of such complexes can be timed to such extent that anticancer activity comes within range. We have demonstrated how rational chemical design can thus be applied to osmium-arene complexes resulting in specific... 

Hartinger, C. G., Phillips, A. D. Nazarov, A. A. Polynuclear Ruthenium, Osmium and Gold Complexes. The Quest for Innovative Anticancer Chemotherapeutics. Cwrr. Top. Med. Chem. 11, 2688-2702 (2011). 

The application of organometallic complexes of the other group 8 elements, iron and osmium, in anticancer drug design has until recently been almost exclusively focused on iron, with the ferrocenyl derivative of tamoxifen (ferrocifen) being the most prominent example (104). Organometallic osmium compounds have been little explored in this respect. 

Consequently, organometallic ruthenium(II) and osmium(II) arene complexes have recently attracted interest as anticancer agents [51]. The presence of a 7i-bonded arene in Ru11 (and Os11) complexes can have a dramatic influence on their chemical reactivity. There is a delicate balance between electron donation from the arene into the empty Ru 4d orbitals and back-donation from the filled 4d6 orbitals into vacant arene orbitals. This is influenced by the donor-acceptor power of the arene (e.g. hexamethylbenzene as a strong donor, in contrast to biphenyl which may act as acceptor) and by the other ligands on Ru11 which can influence the... 

Fig. 7 Examples of ruthenium(II)-arene and osmium(II)-arene paullone complexes with high in vitro anticancer activity...

---