DESIGN AND SYNTHESIS OF MOLECULAR UMBRELLAS

This paper describes the design and synthesis of a series of conjugate s derived from cholic acid, spermidine, and 5-(dimethylamino)-1-naphth alenesulfonyl (dansyl), which effectively shield the dansyl moiety fro m water. Direct coupling of cholic acid to both terminal amino groups of spermidine, and attachment of the environmentally-sensitive dansyl moiety to the remaining secondary amine, yields a ''molecular umbrella '' (Ia) whose fluorescent properties (lambda(max) and emission intensi ty) reflect a nonpolar microenvironment in water and one that is relat ively polar in intermediate dimethoxyethane/water mixtures. Comparison of Ia with analogous ''single-walled'' (II) and ''no-walled'' (III) u mbrellas further indicates that a minimum of two walls is necessary in order to have ''umbrella-like'' properties. Examination of the fluore scent properties of a related double-walled umbrella, bearing a flexib le (2-hydroxyethyl)-carbamate moiety at the C-3 position of the sterol (Ib), reveals that ''umbrella-like'' properties are present even when facial amphiphilicity is not rigorously maintained; however, the mole cule's ability to shield the fluorophore, as judged by its relative em ission intensity, is diminished. ''Methyl-capping'' of the (2-hydroxye thyl)carbamate (i.e., Ic) enhances the umbrella's ability to provide a hydrophobic shelter in water. A tetra-walled analogue of Ia, bearing four cholic acid units (i.e., IV), has been synthesized and its dansyl group found to have reduced exposure toward water. The potential util ity of molecular umbrellas in the area of drug delivery is briefly dis cussed.