Osmium arene

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). 

Fig. 25. (a) General aqueous reactivity of osmium(II)-arenes the formation of an hydroxido-bridged dimer can play a major role in the aqueous chemistry of osmium(II)-arenes, especially if the chelate XY is an 0,0-bidentate ligand (b) molecular structures of the osmium-arene anticancer agents 26-30. 

Fig. 26. Bar charts relate the influence of different chelates in [Os(r 6-arene)Cl(XY)]n+ (XY = NJV- N,0- or 0,0-) on cytotoxicity, stability with respect to hydroxido-dimer formation, hydrolysis rates, and pKa of the aqua adduct for osmium-arene complexes. Shading indicates the range in observed values. Adapted from Ref. (III).

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... 

The University of Edinburgh (former employer of Peter J. Sadler) has filed patent applications relating to the ruthenium-arene, and platinum diazido complexes and University of Warwick for osmium-arene complexes under study in the Peter J. Sadler laboratory. 

A good example of how to tune a family of oganometallic complexes all the way from a lack of cytotoxic activity to IC50 values comparable to those of cisplatin and carboplatin is the newly developed series of osmium arene organometallic complexes. 

Once the ruthenium or osmium arene organometallic complex is activated with the formation of the aqua species, [Ru/Os(r 6-arene)(OH2)(X)(Y)] (Chart 3), the metal becomes a potential centre for nucleophilic attack by biomolecules. The binding of Run/Osn arene complexes to nucleobases is of special interest, since DNA could be the ultimate target for this class of organometallic complexes. A number of studies have confirmed this postulate [86, 87] and investigated in detail such interactions [53, 54, 72, 88-93]. DNA interactions of Ru and Os arene complexes have recently been reviewed [94],... 

Peacock AFA, Parsons S, Sadler PJ (2007) Tuning the hydrolytic aqueous chemistry of osmium arene complexes with N,O-chelating ligands to achieve cancer cell cytotoxicity. J Am Chem Soc 129 3348-3357... 

E3.5 Molecular and crystal structures of ruthenium and osmium arene clusters... 

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