Self-association of C3 and C6 epimers of hyodeoxycholate anions in aqueous medium: Hydrophobicity, critical micelle concentration and aggregation number

Abstract

© 2017 Elsevier B.V. Hyodeoxycholic acids anion (HD) and it's 3- and 6-epimers (3e-HD and 6e-HD) are suitable for biopharmaceutical application since they possess α equatorial i.e. β axial OH groups so their membranotoxicity is reduced. Self-association of stereoisomers 3e-HD and 6e-HD has not been studied so far. According to the capacity factor (k, RPHPLC), hydrophobicity decreases in the following series: HD > 3e-HD > 6e-HD. However, critical micelle concentration (CMC) is the lowest for the 6e-HD (10 mM, 25 °C) and the highest for 3e-HD (38 mM, 25 °C), which is contrary to expectations according to their hydrophobicity. Aggregation number (n) has the highest value for 6e-HD (8, 25 °C) and the lowest value for the stereoisomer 3e-HD (4, 25 °C). The change in demicellisation capacity factor (∆ Cp) decreases in the following series: 6e-HD (316 J mol− 1 K− 1) > HD (260 J mol− 1 K− 1) > 3e-HD (181 J mol− 1 K− 1). In the plane of ln k – ln CMC epimer 6e-HD is outliner related to the hydrophobic congeneric group. This suggests that, in formation of micelles of HD and 3e-HD, besides hydrophobic effect other interactions are neglected. However, in formation of 6e-HD micelle, beside hydrophobic effect significant interaction exists different from hydrophobic interaction (formation of hydrogen bonds between building units of the micelle).