Mirror symmetry breaking and chiral amplification in foldamer-based supramolecular helical aggregatesw

There are numerous examples of achiral or dynamically racemic molecules that generate chirality in one-, two-, or threedimensional crystals, polymers, liquid crystal or supramolecular assemblies. Such systems are particularly attractive for investigating asymmetric induction (i.e. mirror symmetry breaking) and chiral amplification. These conglomerate forming systems typically yield a stochastic mixture of leftand righthanded entities. Ideal examples are achiral molecules that crystallize to form equal numbers of enantiomorphous conglomerate crystals from solution. However, under certain conditions, slight and often unperceived, chiral imbalances can be amplified to homochirality. The generation of chirality in supramolecular systems generally involves helical self-assembly and requires a chiral influence in the form of a chiral solvent, a chiral additive (e.g. the sergeant in the sergeant-and-soldiers principle), polarized light or a clockwise/counter-clockwise vortex or spin coating direction. There are unsurprisingly few examples of undirected chirogenesis. For example, Fukushima, Aida and co-workers recently reported the synthesis of polymeric ortho-phenylenes with a helical conformation. In solution, the helices rapidly interconvert, but form conglomerate crystals with observed mirror symmetry breaking enhanced by stirring. Lehn and co-workers have observed the induced chirality of a helical oligopyridinedicarboxamide molecular strand using chiral solvation with either diethyl D-tartrate or diethyl L-tartrate. A related alternating pyridine/pyridazine strand, 1, has a propensity to fold into a helical lock-washer motif with twelve heterocycles per turn with an outside diameter of about 25 Å, and undergoes hierarchical self-assembly into helical fibers in dichloromethane and pyridine (Scheme 1). A predominance of fibers bearing one helicity over the other (i.e. mirror symmetry breaking) was observed in preliminary TEM images of a dichloromethane gel. Herein, we describe a more detailed investigation of the chirality in this supramolecular system. A key observation was the gradual increase of the CD signal with time starting from a dilute sonicated sample of 1 in CH2Cl2 (Fig. 1a).w This induced chirality is believed to be governed by an autocatalytic secondary nucleation process, where the conformationally labile foldamer preferentially feeds one of two possible ‘conglomerate’ supramolecular fibers. In this case, ‘lockwasher’ stacking decreases the conformational flexibility of 1 and facilitates helical growth and chiral amplification where optimal p–p stacking between aromatic rings is only possible when two (or more) foldamers of the same chirality interact (Scheme 1). This is analogous to crystallization-induced deracemization (i.e. an ‘asymmetric transformation of the second kind’). In an example of mirror symmetry breaking during the formation of J-aggregates from amphiphilic dye monomers, it was suggested that ‘‘the presence of some heredity mechanism from a seeding aggregate nucleus transfers its chirality to the majority of the later-formed aggregates’’. In our case, the biased growth mechanism is thought to be initiated by the Scheme 1 (a) Structure of foldamer 1 (R: -S-nPr). (b) Lock-washer cartoon representation of 1 (M-helicity). (c) Homochiral lock-washer stacking (P-helicity).