Synthesis and Gelling Abilities of Polyfunctional Cyclohexane-1,2-dicarboxylic Acid Bisamides: Influence of the Hydroxyl Groups.

New enantiomerically pure C16-alkyl diamides derived from trihydroxy cyclohexane-1,2-dicarboxylic acid have been synthesized from (-)-shikimic acid. The hydroxyl groups in these compounds are free or, alternatively, they present full or partial protection. Their gelling abilities towards several solvents have been tested and rationalized by means of the combined use of Hansen solubility parameters, scanning electron microscopy (SEM), and circular dichroism (CD), as well as computational calculations. All the results allowed us to account for the capability of each type of organogelator to interact with different solvents and for the main mode of aggregation. Thus, compounds with fully protected hydroxyl groups are good organogelators for methanol and ethanol. In contrast, a related compound bearing three free hydroxyl groups is insoluble in water and polar solvents including alcohols but it is able to gelate some low-polarity solvents. This last behavior can be justified by strong hydrogen bonding between molecules of organogelator, which competes advantageously with polar solvent interactions. As an intermediate case, an organogelator with two free hydroxyl groups presents an ambivalent ability to gelate both apolar and polar solvents by means of two aggregation patterns. These involve hydrogen bonding interactions of the unprotected hydroxyl groups in apolar solvents and intermolecular interactions between amide groups in polar ones.

Cyclobutane Scaffold in Bolaamphiphiles: Effect of Diastereoisomerism and Regiochemistry on Their Surface Activity Aggregate Structure.

Cationic bolaamphiphiles have been synthesized starting from meso cis- or chiral trans-1,2-difunctionalized cyclobutane derivatives. They include cis/trans pairs of diastereoisomers, of N- or C-centered bisamides. The goal of this work was to investigate the influence of stereochemistry and regiochemistry on their abilities as surfactants and self-assembly. Very large differences in surface coverage (2-fold), critical micellar concentration (cmc, up to 2 orders of magnitude), and aggregate structure (from lamellae to fibers) for the four molecules are remarkable due to regio- and stereochemistry differences. Computational calculations were carried out to rationalize the experimental findings and a new methodology has been developed to calculate the structure of these bolaamphiphiles at the surface. Although the four surfactants adopt a wicket-like conformation, for N-centered trans, the distance between polar heads is much larger than that for the other three molecules, as suggested by calculations. We have shown that the interplay between the regiochemistry and stereoisomerism, enhanced by rigidity of the cyclobutane ring, affects different physicochemical properties quite differently. That is, the cmc value is mainly governed by stereochemistry, with regiochemistry only modulating this value. On the other hand, regiochemistry definitely governs the morphology of the supramolecular aggregates (i.e., long fibers versus plates or spherical assemblies), with stereochemistry finely modulating their structural parameters. All these results must help in the rational design of new bolaamphiphiles with predictable properties and useful potential applications.

Studies on Cycloalkane-Based Bisamide Organogelators: A New Example of Stochastic Chiral Symmetry-Breaking Induced by Sonication.

Enantiomerically pure C16 -alkyl amides derived from cis and trans cycloalkane-1,2-dicarboxylic acids, respectively, have been synthesized and their behavior as organogelators has been investigated. These compounds include cis/trans diastereomeric cyclobutane and cyclohexane derivatives with the aim to explore the influence of the ring size as well as the relative configuration in their hierarchical self-assembly to form gels. High resolution 1 H NMR spectroscopy studies allowed the determination of the dynamics of the gelation process in [D8 ]toluene and the sol-gel transition temperature. The morphology and size of the aggregates have been investigated and results have shown that, in the case of cyclobutane derivatives, the cis/trans stereochemistry is not relevant for the gelation behavior and the properties of the soft-materials obtained, but it is remarkable for cyclohexane diamides, which are better organogelators. The four compounds produce chiral aggregates despite that two of them are meso achiral molecules. We show herein that this fact is an example of stochastic symmetry breaking induced by sonication. The self-assembly of these molecules has been modelled providing information and support about the structure and the chirality of the aggregates.

Efficient DNA Condensation Induced by Chiral ß-Amino Acid-Based Cationic Surfactants.

Four cationic chiral amino acid-based surfactants, cis- and trans-1 and cis- and trans-2, have been studied as DNA-condensing agents with enhanced properties and the absence of cell toxicity. The polar head of the surfactant is made of a cyclobutane ß-amino acid in which the amino group is a hydrochloride salt and the carboxyl group is involved in an amide bond, allowing the link with hydrophobic C12 (surfactant 1) or C16 (surfactant 2) chains. The ability of these surfactants to condense DNA was investigated using a dye exclusion assay, gel electrophoresis, and circular dichroism and compared with the well-studied dodecyltrimethylammonium bromide (DTAB) and cetyltrimethylammonium bromide (CTAB). The surfactant with the longest chain length and the trans stereochemistry (trans-2) was found to be the most efficient in condensing the DNA, including CTAB. Surfactant cis-2 was found to be less efficient, probably due to its poorer solubility. The ß-amino acid surfactants with the shorter chain length behaved similarly, such that the cis/trans stereochemistry does not seem to play a role in this case. Interestingly, these were also found to induce DNA condensation for the same concentration as trans-2 and CTAB but showed a lower binding cooperativity. Therefore, a longer alkyl chain only slightly improved the effectiveness of these surfactants. Further, atomic force microscopy revealed that they compact DNA into small complexes of about 55-110 nm in diameter.