Aqueous lyotropic liquid crystal (LLC) assemblies with bicontinuous cubic morphologies (Q-phases) have shown promise in applications ranging from selective chemical separations to ion transporting media, yet universal design criteria for amphiphiles that adopt these unique structures remain elusive. Recent reports have demonstrated that cationic gemini surfactants exhibit a tendency to form bicontinuous cubic LLCs as compared to single-tail amphiphiles; however, the universality of this surfactant design motif in stabilizing Q-phases remains untested. Herein, we report the modular synthesis of a new class of anionic gemini surfactants derived from aliphatic carboxylic acids and demonstrate their unexpectedly strong propensity to form gyroid LLC phases with unprecedented stability between 25 and 100 °C over amphiphile concentration windows up to 20 wt % wide. By systematically varying the alkyl spacer length and surfactant counterions (Na(+), K(+), and (CH(3))(4)N(+)), we identify molecular motifs that favor formation of technologically useful bicontinuous cubic LLC morphologies.

Network-phase lyotropic liquid crystals (LLCs) derived from the water-directed self-assembly of small molecule amphiphiles comprise a useful class of soft nanomaterials, with wide-ranging applications in structural biology and membrane science. However, few known surfactants enable access to these mesophases over wide temperature and amphiphile concentration phase windows. Recent studies have demonstrated that gemini ("twin tail") dicarboxylate surfactants, in which alkyl carboxylates are covalently linked near the headgroups by a hydrophobic bridge, exhibit increased propensities to form double gyroid network phase LLCs. We demonstrate herein that the lyotropic self-assembly behaviors of gemini dicarboxylates sensitively depend on the linker length, whereby odd-carbon linkers stabilize the double gyroid network LLC over unprecedented amphiphile concentration windows up to ∼45 wt % wide between T ≈ 22-80 °C. These self-assembly phenomena, which arise from the linker length-dependent preferred molecular conformations of these amphiphiles, will broaden the technological applications of these nanostructured LLCs.

Network phase aqueous lyotropic liquid crystals (LLCs) are technologically useful materials with myriad applications in chemistry, biology, and materials science, which stem from their structurally periodic aqueous and hydrophobic nanodomains (∼0.7-5.0 nm in diameter) that are lined with well-defined chemical functionalities. The exclusive observation of bicontinuous cubic network phase LLCs (e.g., double gyroid, double diamond, and primitive phases) has fueled speculations that all stable LLC network phases must exhibit cubic symmetry. Herein, we describe the self-assembly behavior of a simple aliphatic gemini surfactant that forms the first example of a triply periodic network phase LLC with the 3D-hexagonal symmetry P63/mcm (space group #193). This normal, tetracontinuous 3D-hexagonal network LLC phase HI(193) partitions space into four continuous and interpenetrating, yet non-intersecting volumes. This discovery directly demonstrates that the gemini amphiphile platform furnishes a rational strategy for discovering and stabilizing new, three-dimensionally periodic multiply continuous network phase LLCs with variable symmetries and potentially new applications.

Interactions between polypeptide chains containing amino acid residues with opposite absolute configurations have long been a source of interest and speculation, but there is very little structural information for such heterochiral associations. The need to address this lacuna has grown in recent years because of increasing interest in the use of peptides generated from D amino acids (D peptides) as specific ligands for natural proteins, e.g., to inhibit deleterious proteinprotein interactions. Coiled-coil interactions, between or among α-helices, represent the most common tertiary and quaternary packing motif in proteins. Heterochiral coiled-coil interactions were predicted over 50 years ago by Crick, and limited experimental data obtained in solution suggest that such interactions can indeed occur. To address the dearth of atomic-level structural characterization of heterochiral helix pairings, we report two independent crystal structures that elucidate coiled-coil packing between L-and D-peptide helices. Both structures resulted from racemic crystallization of a peptide corresponding to the transmembrane segment of the influenza M2 protein. Networks of canonical knobs-into-holes side-chain packing interactions are observed at each helical interface. However, the underlying patterns for these heterochiral coiled coils seem to deviate from the heptad sequence repeat that is characteristic of most homochiral analogs, with an apparent preference for a hendecad repeat pattern.D peptides | transmembrane peptides | racemic crystallization | racemic detergent | coiled coil P olypeptides comprising D-amino acid residues have been sources of growing interest for biological applications, often for functions that depend on recognition by specific natural proteins (1-3). D peptides offer identical versatility in terms of conformation and side-chain functionality relative to conventional peptides (composed of L-amino acid residues), but D peptides are impervious to the action of proteolytic enzymes, which should improve pharmacokinetic properties in vivo relative to those of conventional peptides. The engineering of D peptides to display defined protein-binding preferences is hindered, however, by the dearth of experimental information available for such complexes. Structural principles that are well-known to govern interactions between two L-polypeptide chains are not directly extensible to pairings between peptides of opposite chirality. Favorable heterochiral interactions (between L-and D peptides) that are analogous to homochiral associations between L peptides were postulated decades ago on the basis of geometrical considerations (4, 5). In a 1953 analysis of structural parameters governing coiled-coil formation between right-handed α-helices formed from L peptides, for example, Crick suggested that analogous assemblies should be accessible to pairs of right-and left-handed helices (4). In the same year, Pauling and Corey postulated that heterochiral peptide mixtures could form "rippled" β-sheet assemblies with backbo...