Selective removal of palmitic acid from Langmuir monolayers by complexation with new quaternary ammonium beta-cyclodextrin derivatives

The in vivo toxicity of several cyclodextrins (CyDs) appears to involve bin ding to and extraction of membrane cholesterol, resulting in altered membra ne permeability properties. To investigate whether selective binding to lip ids other than cholesterol can be achieved, a series of new water-soluble b eta -CyD derivatives was synthesized and tested for the ability to extract a fatty acid versus cholesterol in a model system. Quaternary ammonium deri vatives (beta -CyD-N+(Me)(2)(CH2)(n)OH OH- (n = 2, 3: compounds 1-2) and be ta -CyD-N+(TMe)(2)(CH2)(n)NMe2 OH- (n = 1-3: compounds 3-5)) were 400-600 t imes more effective than unmodified beta -CyD in inducing desorption of pal mitic acid from Langmuir monolayers but were completely ineffective hosts f or cholesterol. The rates of desorption of palmitic acid induced by amino- and hydrazine-beta -CyD derivatives [beta -CyD-NH(CH2)(6)NH2 (compound 6) a nd beta -CyD-NHNH2 (compound 7)] were similar to 100 and 10 times faster, r espectively, than that induced by unmodified beta -CyD. A beta -CyD dimer, bis(2,2 ' -S-beta -CyD)di(2-mereaptoethyl) ether (8), and a thioglycerol de rivative of beta -CyD, 6-8-(2,3-dihydroxypropyl)thio-beta -CyD (9), were mo derately more effective than unmodified beta -CyD in inducing both palmitic acid and cholesterol desorption from their respective pure lipid Langmuir monolayers.