Determination of critical micellar concentrations of two monoketo derivatives of cholic acid

Abstract

Critical micellear concentrations (CMC) were determined for two novel promoters of membrane permeability-7-monoketocholic acid (7-MKC) and 12-monoketocholic acid (12-MKC), using two non-invasive (1H NMR relaxation experiment and conductometry) and two invasive (spectral shift and partition coefficient of the probe molecule) methods. Studies by the former methods suggest the different aggregation abilities of the investigated bile acid derivatives. In an aqueous solution, 7-MKC has a somewhat lower CMC value (43 mM) than 12-MKC (50 mM). Further, it was found that, in addition to primary micelles, 7-MKC forms also secondary micelles. In the experiments with probe (hydrophobic) molecules, the aggregation properties of investigated bile acids did not differ in water, whereas the presence of urea altered the aggregation of 7-MKC. Based on the CMC value, 7-MKC is more hydrophobic than 12-MKC. The apparent hydrophobicity of 7-MKC is a consequence of the formation of secondary micelles, shifting the monomer equilibrium to the direction of primary micelles, which is manifested as a decrease in the CMC value. © 2009 Elsevier B.V. All rights reserved.