Hexakis (3,6-anhydro) tetrakis (2A,B,D,E-O-butyl) cyclomalto hexaose as a promising biological cation cryptant: complexation and NMR study of interaction with membranes

Per anhydro α-cyclodextrin exhibits in vivo and in vitro cation complexation properties, especially for heavy metal cations. In order to enhance the selectivity for toxic cations, several alkyl derivatives were prepared by substitution at the C-2 position. Among the series of 3,6-an-hydro-α-cyclodextrin derivatives (from hexakis (3,6-anhydro) hexakis (2A,B,C,D,E,F-O-methyl) cyclomaltohexaose (M36) to hexakis (3,6-anhydro) tetrakis (2A,B,D,E-O-octyl) cyclomaltohexaose (O36) alkyl derivatives) hexakis (3,6-anhydro) tetrakis (2A,B,D,E-O-butyl) cyclomaltohexaose (B36) was found to be of special interest. The properties of B36 in aqueous solution and in the presence of synthetic membranes were studied by mass spectroscopy, 31P, 2H and 1H-NMR spectroscopy, by surface plasmon resonance using BIAcore, and via superficial pressure measurements. It was found that B36 exhibits a special affinity for lead compared to other heavy toxic cations (mercury, cadmium, uranyl), but a negligible affinity for physiological cations (sodium, calcium, potassium), i.e. a great selectivity. The surface-active properties of the soapy B36 solution in water (with DMSO < 5%) were determined by surface tension measurements. In terms of solubility, B36 is very soluble in methanol (30 mM), less in ethanol (2 mM), while poorly soluble in water (500 μM). However, the use of a ternary solvent system (methanol, ethanol, water) allowed the formation of a true gel. This, related with its amphiphilic properties and possibilities for peculiar interactions with membranes are shown by 31P and 2H-NMR spectroscopic studies.