Photoactive bile salts with critical micellar concentration in the micromolar range

Abstract

The aggregation behavior of bile salts is strongly dependent on the number of hydroxyl groups. Thus, cholic acid (CA), with three hydroxyls, starts forming aggregates at 15 mM, while deoxycholic, chenodeoxycholic or ursodeoxycholic acids, with two hydroxyls, start aggregating at 5-10 mM; for lithocholic acid, with only one hydroxyl group, aggregation is observed at lower concentration (2-3 mM). Here, the singular self-assembling properties of dansyl and naproxen derivatives of CA (3β-Dns-CA and 3β-NPX-CA, respectively) have been demonstrated on the basis of their photoactive properties. Thus, the emission spectra of 3β-Dns-CA registered at increasing concentrations (25-140 µM) showed a remarkable non-linear enhancement in the emission intensity accompanied by a hypsochromic shift of the maximum and up to three-fold increase in the singlet lifetime. The inflection point at around 50-70 µM, pointed to the formation of unprecedented assemblies at such low concentrations. In the case of 3β-NPX-CA, when the NPX relative triplet lifetime was plotted against concentration, a marked increase (up to two-fold) was observed at 40-70 µM, indicating formation of new 3β-NPX-CA assemblies at ca. 50 µM. An additional evidence supporting formation of new 3β-Dns-CA or 3β-NPX-CA assemblies at 40-70 µM was obtained from singlet excited state quenching experiments using iodide. Moreover, to address the potential formation of hybrid assemblies, 1:1 mixtures of 3β-Dns-CA and 3β-NPX-CA (2-60 µM, total concentration) were subjected to steady-state fluorescence experiments, and their behavior compared to that of the pure photoactive derivatives. A lower increase in the emission was observed for 3β-NPX-CA in the mixture, while a huge increase was experienced by 3β-Dns-CA in the same concentration range (up to 60 µM total). A partial intermolecular energy transfer from NPX to Dns, consistent with their reported singlet energies, was revealed, pointing to the formation of extremely fluorescent hybrid assemblies at 5-10 µM (total concentration). The morphology of the entities was investigated by means of confocal microscopy. At 90 µM, 3β-Dns-CA showed disperse assemblies in the µm range.

Bile Salts: Natural Surfactants and Precursors of a Broad Family of Complex Amphiphiles

“…Miranda and co-workers investigated the self-assembly of dansyl and naproxen derivatives of C. The aggregation of the two molecules was studied by following their optical properties to demonstrate that they self-assemble in photoactive aggregates at very low concentrations (micromolar range), and their photophysical properties show dramatic changes upon variations of concentration …”

“…Miranda and co-workers investigated the self-assembly of dansyl and naproxen derivatives of C. The aggregation of the two molecules was studied by following their optical properties to demonstrate that they self-assemble in photoactive aggregates at very low concentrations (micromolar range), and their photophysical properties show dramatic changes upon variations of concentration. 60 With the intention to develop new building blocks to be applied in the preparation of new biomaterials, our group has lately focused on the synthesis and self-assembly of molecules bearing amino acids. Again, the substitution in C-3 was considered in light of the remarkable effect it has on the selfassembly of the BSDs.…”

Wormlike reverse micelles in lecithin/bile salt/water mixtures in oil

“…The BSs are synthesized in the liver using cholesterol as starting material and act as solubilizers and emulsifiers of non-polar material, in particular cholesterol itself, lipids, fat-soluble vitamins, fatty acids and monoglycerides [5,6]. Moreover, they are widely used as starting materials in the preparation of synthetic derivatives by changing their amphiphilic structure and by introducing specific functionalities [9,13,14]. Due to the steroid rigidity and the peculiar distribution of hydrophobic and hydrophilic domains, these molecules are particularly attractive for the bottom up construction of complex nanostructures.…”

Twisted nanoribbons from a RGD-bearing cholic acid derivative

“…This results in ordered aggregates that can have different size and shape, such as globular, rod-or fiber-like and tubular, depending on the type of BA and on the experimental conditions [29][30][31][32][33]. In addition, synthetic derivatives of BAs showing a different hydrophilic-hydrophobic balance can provide complex supramolecular structures and self-assembly behavior that cannot be observed for the precursors [30,34]. Molecules that arrange into tubules are often observed.…”