Metal ions ligand-modified duplexes

To put in perspective the binding of metal ions to ligand-modified nucleic acid duplexes, we summarize the conclusions of these reviews on metal binding to DNA duplexes and emphasize those conclusions that are relevant for the influence of metal coordination on the secondary structure of DNA. These studies have been the prologue of today s efforts to use DNA or its synthetic analogues as scaffold for transition metal ions. 

When one or several isolated 2PA ligands were introduced in LNA DNA duplexes, addition of 1 equiv of Ni, Zn, or Cu per 2PA ligand significantly increased the duplex stability with respect to that of the metal-free duplexes (121). A similar increase in stability was observed upon addition of 1 equiv of Ni or Cu to 2PA-modified PNA DNA duplexes (137). The effect of Ni was larger than that of Cu for both types of duplexes. In the case of Zn, 2 equiv of metal ions were necessary to measure reversible melting transitions for PNA DNA duplexes, which was attributed to the low-binding constant of 2PA for Zn + (137). 

It is conceivable that an interstrand complex can be created by coordination of a metal ion to the 2PA situated on the PNA or LNA strand and to a nucleobase or phosphodiester group from the opposite, non-modified DNA strand in the nucleic acid duplex. Molecular modeling of LNA DNA duplexes showed that a [3 -I-1] 2PA-M -P04R2 coordination mode can be realized by coordination of a 2PA ligand from one strand and a phosphodiester from either the same strand or from the opposite strand of the LNA DNA duplex (121). This model was supported by data obtained for 2PA-modified PNA DNA duplexes showing that (a) the... 

Recent studies of bipyridine-modified PNA duplexes have shown that several positively charged and nonsquare-planar complexes also can be incorporated in duplexes (16). The UV-vis and EPR spectroscopic studies showed that the 10 bp PNA duplexes that contained two or three adjacent pairs of bpy ligands contained one or two octahedral [M(bpy)3] complexes (M = Ni, Cn), respectively (16). The melting curves of the bpy-modified PNA duplexes in the presence of metal ions showed low hypochromicity, suggesting that the octahedral complexes interfere with the stacking of the base pairs. Addition of 3 equiv of Ni " " to the PNA duplexes that contained three pairs of bpy did not lead to conversion of the two tris-bpy complexes into three bis-bpy complexes, which is likely due to the electrostatic repulsion. 

The rich coordination chemistry of transition metal ions has been used not only to create metal-ligand complexes that play the role of alternative nucleo-base pairs within nucleic acid duplexes, but also to influence the secondary structure adopted by the nucleic acid, for example, hairpin, duplex, or triplex, and to create connectors for such nucleic acid structures. In this context, oligonucleotides that contain terminal ligands can lead to structures distinct from those accessible by using centrally-modified oligonucleotides, such as cyclic structures or hairpins (Fig. 3). 

During the creation of synthetic duplexes, transition metal ions were introduced as key organizational elements. One early example made use of Cu(II) and modified DNA bases to form artificial DNA (Figure 9.4a). Another common approach takes advantage of the tendency of linear multi-dentate ligands to twist in a helical fashion."... 

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