Double-stranded Hybrids Based on Aryl-aryl Interactions and Hydrophobic Contacts

Besides H-bonds and ion pair formation also aromatic and hydrophobic contacts have been used to drive the aggregation of unstructured monomeric strands into folded and structured supramolecular oligomers. Even though these types of interactions even increase in strength in polar and aqueous solvents they are much more difficult to deliberately use. For example, it is much more difficult to control the specificity of a supramolecular interaction based on hydrophobic contacts as any hydrophobic residues will tend to stick together (see also Chapter 3) [48]. Hence, often such unspecific hydrophobic or aromatic interactions are combined with specific H-bonds or charge interactions to control the hybridization specificity. One nice example which combines aromatic edge-to-face stacking interactions with H-bonds was provided by Hunter [53] and coworkers. A series of amide oligomers derived from isophthalic acid and a bisaniline derivative were synthesized. Concentration dependent NMR studies in chloroform revealed that these oligomers form dimers with a zig-zag structure (Fig. 4.18). The stability increased with increasing chain length with some indication of positive cooperativ-ity. The complexation induced changes in chemical shift of both amide and aryl hydrogens were monitored by NMR dilution experiments in chloroform. Upon complexation the amide hydrogens shift downfield, whereas the aromatic hydrogens of the bisaniline shift upfield indicating aromatic edge-to-face interactions which bring them into the shielding cone of the isophthalic acid. The NMR dilution and titration experiments of complementary but different oligomers were

Fig. 4.18 A molecular zipper based on aromatic interactions and H-bonds as developed by Hunter et al.

also used for the determination of association constants and their correlation with the numbers of hydrogen bonds. A two-hydrogen-bonded complex has an association constant Ka of 18 M_1, which increases to a value of 240 for a four-hydrogen-bonded complex and 55 000 for the six-hydrogen-bonded complex. All experiments were measured in a mixture of chloroform and methanol (95:5). This nonlinear increase in complex stability with increasing number of H bonds indicates a positive cooperativity [54]. However, the stability of the dimers is significantly depending on the solvent. Increasing the content of methanol significantly destabilizes the complexes. This suggests that even though aromatic interactions occur the main driving force for association is arising from the H bonds.

A way to increase the specificity of hybridization based on aromatic interactions alone is to use the alternating stacking of electron-rich and electron-poor aro-matics as shown by Iverson [55]. Flexible oligomers with alternating electron rich dialkoxynaphthalene units (Dan) and electron poor naphthalenetetracarbox-ylic diimides (Ndi) adopt stable structures via intramolecular stacking even in aqueous solvents. The dominant driving force for folding in this case is the de-solvation of the aromatic surfaces upon their mutual interaction in water. However, the electrostatic complementarity of the aromatic rings determines the extent of stacking (face-centered vs. off-centered or edge-to-face-stacking) leading to the formation of a defined and well structured foldamer. These so called aedamers are described in more detail in Chapter 3. The same stacking interaction can also be used to construct stable heteroduplexes in water. Oligomers of either Dan or Ndi alone do not fold intramolecularly. However, upon mixing these two types of oligomers stable heteroduplexes result (Fig. 4.19). The stability of these

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