Micellization parameters (number average, aggregation number and critical micellar concentration) of bile salt 3 and 7 ethylidene derivatives: Role of the steroidal skeleton II

Abstract

© 2015 Elsevier B.V. Background Bile salts are steroidal biosurfactants. Micellar systems of bile salts are not only important for solubilization of cholesterol, but they also interact with certain drugs thus changing their bioavailability. Methods The number-average aggregation numbers (n¯) are determined using the Moroi-Matsuoka-Sugioka thermodynamic method. Critical micellar concentrations were determined by spectrofluorometric method using pyren and by surface tension measurements. Results Micelles of ethylidene derivatives possess the following values for n¯: 7-Eth-D (n¯=11 (50 mM)-n¯=14.8 (100 mM)); 12-Ox-7-Eth-L (n¯≈8.8, without concentration dependence) and 7,12-diOx-3-Eth-Ch (n¯≈2.9, without concentration dependence). In the planes n¯-ln k and ln CMC-ln k derivative 7-Eth-D is outlier in respect to hydrophobic linear congeneric groups. Conclusion Gibbs energy of formation for 7-Eth-D anion micelles in addition to the Gibbs energy of hydrophobic interactions consists excess Gibbs energy (G^E) from hydrogen bond formation between building blocks of micelles. Gibbs energy of formation for 7,12-diOx-3-Eth-Ch and 12-Ox-7-Eth-L anion micelle is determined by the Gibbs energy of hydrophobic interactions. Relative increase in hydrophobicity and aggregation number for ethylidene derivatives is larger when ethylidene group is introduced from the C7 lateral side of steroidal skeleton then it is when ethylidene group is on C3 carbon. General significance Position of outlier towards hydrophobic congeneric groups from n¯-ln k and ln CMC-ln k planes indicates the existence of excess Gibbs energy (G^E) which is not of hydrophobic nature (formation of hydrogen bonds). For the bile salt micelles to have G^E (formation of secondary micelles) it is necessary that steroidal skeleton possesses C3-α-(e)-OH and C12-α-(a)-OH groups.