Cholic acid dimers as invertible amphiphilic pockets: synthesis, molecular modeling, and inclusion studies

Abstract

Two dimers of cholic acid were synthesized through simple covalent linkers. The dimers form invertible molecular pockets in media of different polarity; hydrophobic pockets are formed in water and hydrophilic pockets are formed in organic media. Fluorescence studies show that pockets formed by these dimers can serve as invertible hosts for the hydrophobic guest pyrene and the hydrophilic guest coumarin 343. The molecular pocket also enhances dissolution of the weakly soluble cresol red sodium salt in organic media. Molecular modeling was performed to better understand the host–guest complexation process of the invertible amphiphilic pockets. The calculated free energy changes indicate that the two dimers form the most stable complexes with coumarin 343 at a host to guest ratio of 2:2, whereas the host to guest ratio differs in the formation of complexes with pyrene for the two dimers. The dimer with the shorter, less flexible linker seems to form host–guest complexes that are more stable in both water and organic solvents.

Bile Acid Oligomers and Their Combination with Antibiotics To Combat Bacterial Infections

“…HRMS m / z : calculated for C 52 H 90 N 3 O 8 + [M + H] + 884.6738, found 884.6722; calculated for [M + Na] + 906.6490, found 906.6542. The 1 H NMR and 13 C NMR spectra were consistent with that reported in the literature …”

“…The specific conformational flexibility by the cholic acid dimer 9a was recently described by Zhu and co-workers by studying the behavior of three guest molecules of different polarity. Using molecular modeling, it was suggested that the molecular conformations and interactions with the guest molecule may depend on the length and the functionality of the linker between the two cholic acid moieties in the dimer …”

“…Using molecular modeling, it was suggested that the molecular conformations and interactions with the guest molecule may depend on the length and the functionality of the linker between the two cholic acid moieties in the dimer. 23 The complete SAR study also demands the analysis for the necessity of two cholic acid moieties along with the appropriate linker containing free amine. The need of cholic acid scaffold to adopt specific conformation leading to the biological activity was confirmed by synthesizing analogue 22 wherein one of the cholic acid moiety was replaced by palmitoyl group.…”

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

“…In another work, the same group investigated the self-assembly of the bis-cholic acid compound and that of an analogous dimer bearing a tertiary amine that was synthesized by reducing the carboxylic functions to hydroxyl groups that were then converted to mesylates, which finally reacted with n -butylamine. The compounds act as invertible amphiphilic pockets, allowing the complexation of hydrophobic molecules in water and of hydrophilic ones in nonpolar solvents …”

“…The compounds act as invertible amphiphilic pockets, allowing the complexation of hydrophobic molecules in water and of hydrophilic ones in nonpolar solvents. 90 Yang et al synthesized a novel dimeric derivative characterized by two units of DC, a spacer bearing an amide, and a carboxylic function. 91 The compound in alkaline aqueous solutions forms gels consisting of a randomly oriented network of fibers.…”