Helices Based on Metal-ligand Interactions and Salt Bridges

As mentioned above one of the major disadvantages of H-bonded structures is their limited strength in polar solvents. Hence, most of the folding and structure building described above is limited to chloroform or even less polar organic solvents. The addition of more polar solvents such as DMSO, methanol or water normally immediately destroys the aggregates [48]. Therefore, to achieve stable structures in more polar solvents other interactions are needed. Perhaps the most widely used approach in the context of hybridization induced folding of unstructured molecules is the formation of metal helicates. Monomeric strands are designed with appropriate metal binding sites such as phenanthrolines or bipyri-dines. The addition of metal ions then can lead to the formation of double, triple or even quadruple-helical complexes. In general, the underlying monomeric li-gands are not structured, but the resulting metal helicates are well defined. The exact structure of the helicate is controlled by the complexation geometry of the templating metal ion. Besides the usual solution techniques, such as NMR, also structure determination in the solid state is often possible providing the ultimate proof for the hybridization induced folding; another great advantage compared to H-bonded assemblies, which are often difficult to fully characterize structurally. This vast area of research has been covered in several excellent review articles and will not be discussed here any further [49]. Just one interesting recent example should serve to illustrate this approach. Three bis-pyridylimine organic strands can wrap around two Fe(II)-ion to form a stable triple-helicate. This metal-helicate has the correct size and shape to interact with a DNA three-way junction (Fig. 4.16). As an X-ray structure showed the metal complex sits directly in the middle of the junction. The aromatic phenyl rings of the ligands allow for exten-

Fig. 4.16 Metal ions can form stable double and triple helices with appropriate ligands (A). Whereas the ligands themselves are normally not structured the metal helicates are. In this case a triple helix is built which can further interact with a DNA three-way junction (B: major groove side view) [50].

sive hydrophobic contacts with the thymine and adenine bases at the junction, whereas the overall cationic charge of the helicate provides additional long range electrostatic interactions with the negatively charged DNA. Furthermore, the threefold symmetry of the DNA junction exactly matches the threefold symmetry of the triple-helicate. The helicate is hence a perfect match in size and complementary interacting sites to fill the void in the core of the three-way junction [50].

Besides metal-ligand interactions, which in general are much stronger than other noncovalent interactions often approaching the strength of covalent bonds, also ion pair formation can be used to increase the stability of duplexes as had been shown above for zwitterionic dimers (Fig. 4.11). This approach was also used by Yashima [51] who designed meta-terphenyl dimers with either amidi-nium or carboxylates attached to the central aromatic ring of the terphenyl unit. Chiral groups attached to the amidinium cations were used to induce a defined helical twisting of the monomer. Nevertheless, this monomer exists in solution as a mixture of several conformers as indicated by multiple signal sets in the NMR in chloroform. Addition of the corresponding dicarboxylate resulted in a simplified spectrum of a single species indicating the formation of an ion paired duplex of considerable stability (K > 106 M-1). As ion pairs between amidinium or guanidinum cations and carboxylates are directional (in contrast to the interaction of spherical ions) [52], the two salt bridges bring the two strands together in a distinct orientation. The chiral twist of the terphenyl units of the diamidinium cation then induces a winding up of both strands in a right-handed double helical structure (Fig. 4.17). Without the chiral inductors a racemic mixture of right and left handed double helices would result. This double helical structure was con-

Fig. 4.17 Charge interactions can significantly improve the stability of supramolecular dimers as shown here for a helical meta-terphenyl heterodimer developed by Yashima et al. [51] (A: structure of the two monomers; B: schematic representation of heterodimerization).

firmed at least for the solid state by X-ray analysis. By using the enantiomer of the cation, the helical sense of the double helix can be reversed as could be shown by the mirror-image CD signals of the corresponding duplexes in solution. Due to the stronger electrostatic interactions relative to simple H-bonding, the double helical structure is also retained at least to ca. 70% in the more polar solvent DMSO.

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