Supramolecular Double Helices from Small C₃-Symmetrical Molecules Aggregated in Water

Abstract

Supramolecular fibers in water, micrometers long and several nanometers in width, are among the most studied nanostructures for biomedical applications. These supramolecular polymers are formed through a spontaneous self-assembly process of small amphiphilic molecules by specific secondary interactions. Although many compounds do not possess a stereocenter, recent studies suggest the (co)existence of helical structures, albeit in racemic form. Here, we disclose a series of supramolecular (co)polymers based on water-soluble benzene-1,3,5-tricarboxamides (BTAs) that form double helices, fibers that were long thought to be chains of single molecules stacked in one dimension (1D). Detailed cryogenic transmission electron microscopy (cryo-TEM) studies and subsequent three-dimensional-volume reconstructions unveiled helical repeats, ranging from 15 to 30 nm. Most remarkable, the pitch can be tuned through the composition of the copolymers, where two different monomers with the same core but different peripheries are mixed in various ratios. Like in lipid bilayers, the hydrophobic shielding in the aggregates of these disc-shaped molecules is proposed to be best obtained by dimer formation, promoting supramolecular double helices. It is anticipated that many of the supramolecular polymers in water will have a thermodynamic stable structure, such as a double helix, although small structural changes can yield single stacks as well. Hence, it is essential to perform detailed analyses prior to sketching a molecular picture of these 1D fibers.

Elucidating dynamic behavior of synthetic supramolecular polymers in water by hydrogen/deuterium exchange mass spectrometry

“…Recently, we found that double helices are present in the sample next to other supramolecular structures. 47 We hypothesize that the formation of a double helix stabilizes the interactions between the BTAs, which would prevent them from moving into the solvent and therefore a slowing down of the H/D exchange of the core amides can occur.…”

“…We recently elucidated that BTA (1) forms a double helical structure in water. 47 In contrast, diacetylene bis-urea amphiphile (BU [2]) forms fibrous bundles, 48 and the two benzotrithiophenes (BTT-5F [3] and BTT [4]) form single fibers (Scheme 1). 13 BTT-5F (3) polymerizes via an isodesmic mechanism, whereas all other monomers polymerize via a cooperative mechanism.…”

Higher-order interfiber interactions in the self-assembly of benzene-1,3,5-tricarboxamide-based peptides in water

“…Recent studies have reported that, upon closer examination, at least some nanofibers in aqueous solutions comprise two smaller fibers, either twisted or parallel. 28,29 Furthermore, several studies have reported the formation of more complicated structures (e.g., nanoribbons or triple helices) during the self-assembly of BTAbased molecules in organic solvents or their mixtures with water. [30][31][32] In water, stepwise self-assembly into clearly defined double helical nanorods was reported only for BTA-based Aucontaining metalloamphiphiles.…”

Emergence, evidence, and effect of junction clustering in supramolecular polymer materials

“…96 Very recently, Meijer, Böttcher, and coworkers utilized cryo-TEM with advanced cryo-electron tomography analysis to study details of the structure of another supramolecular polymer in water. 157 In this analysis method, multiple views from different directions…”

“…158 However, employing the cryo-electron tomography analysis they realized that these units can form micrometer-long, double helix structures with a pitch size that is tunable by the choice of the tail compositions. 157 Another microscopy technique that is widely used for studying supramolecular polymer materials is fluorescence microscopy including confocal microscopy and high-resolution fluorescence microscopy such as stochastic optical reconstruction microscopy (STORM). 159 Hamachi and coworkers studied the self-assembly of peptide-based and lipid-like gelators into nanofibers and further the self-sorting of these nanofibers by in situ imaging of a confocal microscope.…”