Bile Acid Derived Adaptive Dendrons And Anion Receptors

Abstract

Chapter 1. Bile acid derived adaptive dendrons Bile acids are naturally occurring rigid, chiral molecules with unique facial amphiphilicity making it an attractive build block for designing supramolecular systems. Synthesis of bile acid derived chiral dendrimers with acetates protecting the peripheral hydroxyl groups has already been reported by our group (Figure 1). These dendrons did not survive an attempted deprotection of the acetates, as the dendritic linkages were ester linkages. To keep the facial amphiphilicity of bile acid fragments intact, we have worked on two different synthetic strategies. Bile acid derived dendritic components having chloroacetate functional group were synthesized and the α-halo ketone was reacted with a bile acid carboxylate to generate a dendritic species with free hydroxyl group having a glyocolate spacer (Figure 2). At the same time we also were able to protect bile acid hydroxyl group as its corresponding benzyl ether and after dendron synthesis, benzyl groups were removed by hydrogenolysis to give bile acid derived dendritic components with free hydroxyl groups and simple ester linkages (Figure 2). Dye solubilization ability of these dendrons was tested. We observed that some of these structures had the ability to solubilize both a polar dye in a nonpolar solvent and/or a nonpolar dye in a polar solvent. We carried out different extraction techniques (liquid-liquid, solid-liquid) and transport experiments to establish that these dendrons can act as both as normal and inverse micellar mimics. Depending upon the polarity of the medium, this dendron (Figure 2, right) can adopt different conformation and hence this is described as an “adaptive dendron” (Figure 3). Chapter 2. Bile acid derived anion receptors We discovered that the self-condensation of 3α-chloroacetyloxy cholic acid produced a “cholaphane” with free hydroxyl groups in just two step from naturally occurring bile acid. This cyclic dimer (Figure 4) is an inside-out cyclodextrin analog having a polar interior and nonpolar outer surface. The structure of this molecule was confirmed by X-ray crystallography (Figure 5). This molecule showed a remarkable ability to bind two fluoride ions in its cavity (K1 = 1900 M-1 and K2 = 250 M-1 in CHCl3). The pair of doublets from the glycolate methylene hydrogen spacers were found to collapse to a singlet and they again reappear as a pair of doublets with increase in the concentration of fluoride. This anomalous behaviour of gylcolate methylene spacers were rationalized by MP2 calculation at the 6-31+G* level which showed that upon interaction with fluoride, electron density on C-H hydrogen decreased while that on the other geminal hydrogen increased. Detailed NMR study and interaction of fluoride with different acyclic compounds enabled us to determine the mode of fluoride binding. Based on the NMR data and calculation results, fluoride binding models were proposed involving O-H…F- and C-H…F- interactions. When the binding affinity of cyclic dimer was examined for other anions, this molecule showed weak affinity to chloride ions (K ~ 100 M-1) whereas for other bigger anion (HSO4-, H2PO4-) it showed no binding. Similar interactions were utilized to generate bile acid based tripodal geometry where those receptors were able to bind anions weakly (K ~ 100-200 M-1 for fluoride, chloride and bisulphate).