Selective Removal of Palmitic Acid from Langmuir Monolayers by Complexation with New Quaternary Ammonium β-Cyclodextrin Derivatives

Abstract

The in vivo toxicity of several cyclodextrins (CyDs) appears to involve binding to and extraction of membrane cholesterol, resulting in altered membrane permeability properties. To investigate whether selective binding to lipids other than cholesterol can be achieved, a series of new water-soluble β-CyD derivatives was synthesized and tested for the ability to extract a fatty acid versus cholesterol in a model system. Quaternary ammonium derivatives (β-CyD-N+(Me)2(CH2)nOH OH- (n = 2, 3: compounds 1−2) and β-CyD-N+(Me)2(CH2)nNMe2 OH- (n = 1−3: compounds 3−5)) were 400−600 times more effective than unmodified β-CyD in inducing desorption of palmitic acid from Langmuir monolayers but were completely ineffective hosts for cholesterol. The rates of desorption of palmitic acid induced by amino- and hydrazine-β-CyD derivatives [β-CyD-NH(CH2)6NH2 (compound 6) and β-CyD-NHNH2 (compound 7)] were ∼100 and 10 times faster, respectively, than that induced by unmodified β-CyD. A β-CyD dimer, bis(2,2‘-S-β-CyD)-di(2-mercaptoethyl) ether (8), and a thioglycerol derivative of β-CyD, 6-S-(2,3-dihydroxypropyl)thio-β-CyD (9), were moderately more effective than unmodified β-CyD in inducing both palmitic acid and cholesterol desorption from their respective pure lipid Langmuir monolayers.