Leana Travaglini

Sugar-Bile Acid-Based Bolaamphiphiles: From Scrolls to Monodisperse Single-Walled Tubules.

The introduction of a mannose residue on carbon 3 of lithocholic acid gives rise to an asymmetric and rigid bolaamphiphilic molecule, which self-assembles in water to form elongated tubular aggregates with an outer diameter of about 20 nm. These tubular structures display a temporal evolution, where the average tube diameter decreases with time, which can be followed by time-resolved small-angle X-ray scattering experiments. Cryogenic transmission electron microscopy images collected as a function of time show that at short times after preparation tubular scrolls are formed via the rolling of layers, after which a complex transformation of the scrolls into single-walled tubules takes place. At long time scales, a further evolution occurs where the tubules both elongate and become narrower. The observed self-assembly confirms the tendency of bile acids and their derivatives to form supramolecular aggregates with an ordered packing of the constituent molecules. It also demonstrates that scrolls can be formed as intermediate structures in the self-assembly process of monodisperse single-walled tubules.

Between peptides and bile acids: self-assembly of phenylalanine substituted cholic acids.

Biocompatible molecules that undergo self-assembly are of high importance in biological and medical applications of nanoscience. Peptides and bile acids are among the most investigated due to their ability to self-organize into many different, often stimuli-sensitive, supramolecular structures. With the aim of preparing molecules mixing the aggregation properties of bile acid and amino acid-based molecules, we report on the synthesis and self-association behavior of two diastereomers obtained by substituting a hydroxyl group of cholic acid with a l-phenylalanine residue. The obtained molecules are amphoteric, and we demonstrate that they show a pH-dependent self-assembly. Both molecules aggregate in globular micelles at high pH, whereas they form tubular superstructures under acid conditions. Unusual narrow nanotubes with outer and inner cross-section diameters of about 6 and 3 nm are formed by the derivatives. The diasteroisomer with α orientation of the substituent forms in addition a wider tubule (17 nm cross-section diameter). The ability to pack in supramolecular tubules is explained in terms of a wedge-shaped bola-form structure of the derivatives. Parallel or antiparallel face-to-face dimers are hypothesized as fundamental building blocks for the formation of the narrow and wide nanotubes, respectively.

Tailoring Supramolecular Nanotubes by Bile Salt Based Surfactant Mixtures

An approach for tailoring self-assembled tubular structures is described. By controlling the relative composition of a two-component surfactant mixture comprising the natural bile salt lithocholate and its bolamphiphilic derivative, it was possible to finely tune the nanotube cross-section of the mixed tubular aggregates that self-associated spontaneously in aqueous solution at pH 12. The diameter was found to vary up to 50% when the stoichiometric ratio of the two bile salts was changed. The tuning of supramolecular nanochannels with such remarkable precision is of significant interest for technological applications of these materials.

Twisted nanoribbons from a RGD-bearing cholic acid derivative

In light of the biomedical interest for self-assembling amphiphiles bearing the tripeptide Arg-Gly-Gly (RGD), a cholic acid derivative was synthesized by introducing an aromatic moiety on the steroidal skeleton and the RGD sequence on the carboxylic function of its chain 17-24, thus forming a peptide amphiphile with the unconventional rigid amphiphilic structure of bile salts. In aqueous solution, the compound self-assembled into long twisted ribbons characterized by a very low degree of polydispersity in terms of width (≈25nm), thickness (≈4.5nm) and pitch (≈145nm). It was proposed that in the ribbon the molecules are arranged in a bilayer structure with the aromatic moieties in the interior, strongly involved in the intermolecular interaction, whereas the RGD residues are located at the bilayer-water interface. The nanostructure is significantly different from those generally provided by RGD-containing amphiphiles with the conventional peptide-tail structure, for which fibers with a circular cross-section were observed, and successfully tested as scaffolds for tissue regeneration. From previous work on the use of this kind of nanostructures, it is known that features like morphology, rigidity, epitope spacing and periodicity are important factors that dramatically affect cell adhesion and signaling. Within this context, the reported results demonstrate that bile salt-based peptide surfactants are promising building blocks in the preparation of non-trivial RGD-decorated nanoaggregates with well-defined morphologies and epitope distributions.

Crystal structure of a lithium salt of a glucosyl derivative of lithocholic acid

The crystal structure of a Li(+) salt of a glucosyl derivative of lithocholic acid (lithium 3α-(α-d-glucopyranosyl)-5β-cholan-24-oate) has been solved. The crystal belongs to the orthorhombic system, P212121 spatial group, and includes acetone and water in the structure with a 1:1:2 stoichiometry. Monolayers, having a hydrophobic interior and hydrophilic edges, are recognized in the crystal structure. Li(+) is coordinated to three hydroxyl groups of three different glucose residues, with two of them belonging to the same monolayer. A fourth molecule, located in this monolayer, is involved in the coordination of the cation through the carboxylate ion by an electrostatic interaction, thus completing a distorted tetrahedron. All Li(+)-oxygen distances values are very close to the sum of the ionic radius of Li(+) and van der Waals radius of oxygen. Each steroid molecule is linked to other five steroid molecules through hydrogen bonds. Water and acetone are also involved in the hydrogen bond network. A hierarchical organization can be recognized in the crystal, the helical assembly along 21 screw axes being left-handed.