Complexes with mixed chloride and heterocyclic ligands

Several RuII complexes of the type cis-[RuII(L)2Cl2] (where L is a bidentate heteroaromatic ligand) have also been prepared and are currently investigated for their anti-tumor properties on the basis of their similar reactivity as compared to cisplatin.

Figure 19.4 Complexes with chlorides and heterocyclic ligands. (a) ci's-[RuII(bpy)2Cl2], (b) cis-[RuII(azpy)2Cl2], (c) mer-[RuII(terpy)Cl3]^

Figure 19.4 Complexes with chlorides and heterocyclic ligands. (a) ci's-[RuII(bpy)2Cl2], (b) cis-[RuII(azpy)2Cl2], (c) mer-[RuII(terpy)Cl3]^

The complex «'s-[Run(bpy)2Cl2] (bpy = 2,2'-bipyridine; Figure 19.4a) has been tested on different cell lines but is mostly inactive as anti-tumor agent.27 In contrast, one of the isomers (the one with C2 symmetry) of the cis-[Run (azpy)2Cl2] (azpy = 2-phenylazopyridine; Figure 19.4b) exhibits a high cyto-toxicity that is comparable or even better than that of cisplatin against several fast-growing cell lines.27,42,43 The higher activity of «'s-[Run(azpy)2Cl2] as compared to cis-[RuII(bpy)2Cl2] seems to be due to a higher flexibility of the azpy ligand which allows an easier substitution of the chloride ligands and thus the binding of the complex to two bases.42

Another example is the complex mer-[RuII(terpy)Cl3]1_, where terpy is the tridentate ligand 2,2':6',2"-terpyridine (Figure 19.4c). This complex presents a high cytotoxic activity that seems to be related to the possibility of interstrand DNA cross-links formation.27,44 Indeed, this complex is able to form a number of interstrand cross-links which is almost identical to that formed under the same conditions by cisplatin. This cross-linking should be favored, as compared to the case of the «'s-[Run(L)2Cl2] compounds, thanks to the presence of the three chloride ligands that should increase the probability of adduct formation and decrease the hindrance resulting from a biadduct formation.

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