Thermodynamic study on complexation of long-chain fatty acid anions with α-cyclodextrin in water

Abstract

The interaction of five long alkyl-chain (≥C13) fatty acid anions (A−) with native α-cyclodextrin (α-CD) in water was systematically examined using the isothermal titration calorimetry. The A− comprised biologically relevant myristate, palmitate, stearate, oleate and linoleate anion. The obtained heat data at several temperatures were treated simultaneously allowing the estimation of a thermodynamically consistent temperature dependence of the equilibrium constant as well as the enthalpy for the sequential formation of the inclusion complexes of 1:1 and 1:2 stoichiometry (A−:α-CD). The formation of 1:1 complex was found remarkably strong with binding constant value up to 2⋅105, the 1:2 complexes are generally by one order of magnitude less stable. Thermodynamic quantities for complexation are discussed in terms of their temperature dependence and structural features such as alkyl chain length and dehydrogenation. Using present data the binding mode of α-CD to diacylphospholipids and triacylglycerides bearing identical alkyl moieties was successfully proposed. The detailed knowledge on A−/α-CD interaction thus allows precise modeling of equilibrium process in complex matrices used as drug delivery systems or cell membrane mimics.