Nanofibers and lyotropic liquid crystals from a class of self-assembling beta-peptides.

Lyotropic liquid-crystalline (LC) phases, in other words, LC phases induced by the presence of a solvent, form through the assembly of large anisometric particles, such as rigid polymers, viruses, or inorganic rods, as a result of excluded volume interactions (Onsager theory). Small molecules can form lyotropic LC phases if they undergo self-assembly to generate anisometric nanostructures. Aqueous LC phases are commonly observed for small molecules that have clearly segregated hydrophilic and lipophilic segments, such as detergents and lipids. For such “globally amphiphilic” molecules it is believed that hydrophobically induced association of the lipophilic segments drives the assembly that underlies LC formation. Chromonic LCs are formed from a distinct class of small molecules that self-assemble in water but do not display a simple segregation of hydrophilic and lipophilic segments (they are non-globally amphiphilic). It is difficult to understand how the self-assembly of chromonic molecules (i.e., molecules that form chromonic LCs) is related to the nature and internal organization of lipophilic surfaces because these molecular properties cannot readily be altered in an incremental fashion. Here we describe a class of oligomers that, like the chromonic molecules, are not globally amphiphilic but nevertheless form LC phases in water. The intrinsic modularity of these oligomers allows rational and systematic modification of lipophilic or hydrophilic components, which enables us to define key features that are required for LC formation. Short oligomers of b-amino acids (b-peptides) are attractive for systematic study of assembly processes leading to LCs because b-peptides can display a diverse range of functionalized side chains, and these oligomers fold into compact and stable conformations that orient the side chains in predictable ways. The most widely studied b-peptide secondary structure is the 14-helix, which is defined by i, i 2 C=O···H N hydrogen bonds (14-membered ring) between backbone amides and contains approximately three residues per helical turn. The high stability of the 14-helix, in combination with ready manipulation of b-peptide sequence, permits considerable control over the nanopatterning of chemical functionality in three dimensions. Here we exploit these features by designing b-peptide oligomers that fold into helical nanostructures and are decorated with functional groups in patterns that either do or do not confer global amphiphilicity on the 14-helix. As described below, this sequence-based patterning strategy has led to the discovery of b-peptide oligomers that are non-globally amphiphilic and exhibit liquid crystallinity in aqueous solution. Our initial experiments focused on sequence isomers A and iso-A (Figure 1). The latter has a repeating triad motif containing trans-2-aminocyclohexanecarboxylic acid (ACHC), bhomophenylalanine (bhPhe), and bhLys residues; the lipophilic–lipophilic–hydrophilic ACHC-bhPhebhLys sequence repeat pattern in iso-A leads to a globally amphiphilic nanostructure. In contrast, the sequence of A does not lead to global segregation of lipophilic and hydrophilic side chains in the 14-helix, but rather to a distribution of lipophilic and hydrophilic side chains around the entire periphery of the helix (Figure 1). The helix from A is defined as non-globally amphiphilic. Since global amphiphilicity of bpeptides has previously been associated with liquid crystallinity, we expected iso-A but not A to form a LC phase in water. Surprisingly, however, strong birefringence was observed for aqueous solutions containing A 6.5 wt%, (36 mm, Figure 2), but no birefringence was detected for solutions of iso-A up to the solubility limit > 10 wt% (57 mm, Figure 2). Inspection of the birefringent domains at high magnification shows an absence of optical textures characteristic of higher ordered mesophases such as smectics and cholesterics; these observations lead us to conclude that the mesophase is likely nematic. The unexpected ability of the non-globally amphiphilic helix to form an LC phase is [*] V. M. Yuwono, Prof. J. D. Hartgerink Department of Chemistry and Bioengineering Rice University 6100 Main Street MS60, Houston, TX 77005 (USA) Fax: (+1)713-348-4201 E-mail: jdh@rice.edu