Chiral groups attached to the end of quinoline-derived oligoamide foldamers give rise to chiral helical induction in solution. Using various chiral groups, diastereomeric excesses ranging from 9% to 83% could be measured by NMR and circular dichroism. Despite these relatively weak values and the fact that diastereomeric helices coexist and interconvert in solution, the right-handed or left-handed helical sense favored by the terminal chiral group could be determined unambiguously using X-ray crystallography. Assignment of chiral induction was performed in an original way using the strong tendency of racemates to cocrystallize, and taking advantage of slow helix inversion rates, which allowed one to establish that the stereomers observed in the crystals do correspond to the major stereomers in solution. The sense of chiral helical induction was rationalized on the basis of sterics. Upon assigning an Rs or Ss chirality to the stereogenic center using a nomenclature where the four substituents are ranked according to decreasing sizes, it is observed that Rs chirality always favors left-handed helicity and Ss chirality favors right-handed helicity (P). X-ray structures shed some light on the role of sterics in the mechanism of chiral induction. The preferred conformation at the stereocenter is apparently one where the bulkiest group should preferentially point away from the helix, the second largest group should be aligned with the helix backbone, and the smallest should point to the helix.

No abstract

The introduction of an R asymmetric center in an aromatic oligoamide that adopts stable helical conformations leads to a significant shift of the equilibrium between the right-handed and left-handed helices in solution: the R-P and R-M helices are diastereoisomers. However, these two species were found to cocrystallize in 1:1 proportions. Thus the chiral induction observed in solution is switched off in the solid state. This phenomenon represents an original and unexpected means to control handedness in helical oligomers.

No abstract

CommunicationsMolecular machines can convert energy into controlled molecular motions of large amplitude. Selective protonation of an oligoamide strand leads to an extension of the initial helical conformation to a linear structure, which then refolds into another helix. For more information see the following communication by Huc and co-workers.

The unambiguous elucidation of a new folded structure in solution may prove to be a very challenging task. The NMR protocols developed for solving the solution structures of alpha-peptides have been applied to aliphatic beta- and gamma-peptides but are not directly applicable to aromatic oligomers. In particular, the string of spin systems in an aromatic sequence cannot be reconstituted solely from correlations between protons. For aromatic oligomers, it is shown that the assignment of a large part of the 13C NMR spectrum through HMBC and HSQC experiments allows to unambiguously assign proton NMR spectra and in turn to interpret NOE correlations. This has been implemented both with quinoline- and pyridine-derived oligoamide foldamers, and should be applicable to a wide range of oligomers including various combinations of monomers. The NOE correlations allow the unambiguous solution structure elucidation of helical conformations of oligoamides derived from pyridine and quinoline monomers showing that, in these series, the solution structures correspond very well to the structures observed in the solid state.

Synthetic helical foldamers are of significant interest for mimicking the conformations of naturally occurring molecules while at the same time introducing new structures and properties. In particular, oligoamides of aromatic amino acids are attractive targets, as their folding is highly predictable and stable. Here the design and synthesis of new amphipathic helical oligoamides based on quinoline-derived amino acids having either hydrophobic or cationic side chains are described. Their structures were characterized in the solid state by single-crystal X-ray diffraction and in solution by NMR. Results of these studies suggest that an oligomer as short as a pentamer folds into a stable helical conformation in protic solvents, including MeOH and H(2)O. The introduction of polar proteinogenic side chains to these foldamers, as described here for the first time, promises to provide possibilities for the biological applications of these molecules. In particular, amphipathic helices are versatile targets to explore due to their importance in a variety of biological processes, and the unique structure and properties of the quinoline-derived oligoamides may allow new structure-activity relationships to be developed.

The synthesis of various 1,8-diaza-4,5-dialkoxy-2,7-anthracene dicarboxylic acid derivatives and their incorporation into cyclic and helically folded aromatic oligoamides are reported. The ability of the diaza-anthracene monomers to undergo photoaddition or head-to-tail photodimerization was investigated in the solid state and in solution. Quantitative conversion of a monomer diester to the corresponding head-to-tail photodimer could be achieved in the solid state without protection from oxygen. The formation of an emissive excimer between two diaza-anthracene units appended at the end of a helically folded oligomer was demonstrated. Intramolecular photodimerization was not observed in this compound, possibly due to the low thermal stability of the head-to-head photoadduct. A cyclic oligoamide composed of two diaza-anthracene and two pyridine units was shown to adopt a flat conformation and to form columnar stacks in the solid state. Longer, noncyclic oligoamides composed of one or two diaza-anthracene units were shown to adopt helical conformations that exist preferentially as double helical dimers.