Structure-Property Relationships in Sodium Muricholate Derivative (Bile Salts) Micellization: The Effect of Conformation of Steroid Skeleton on Hydrophobicity and Micelle Formation-Pattern Recognition and Potential Membranoprotective Properties

It is known that beta-muricholic acid anions prevent membrane toxicity of hydrophobic bile acids, which are being used in therapy for solubilization of the cholesterol type bile stone. Better knowledge of these derivative micelles is very important for understanding their physiological and pharmacological effects. beta-Axial (a) oriented hydroxyl group from the steroid skeleton decreases the hydrophobic surface of the convex side of the steroid skeleton. Therefore, the critical micellization concentration (CMC) for steroid surfactants with beta-aOH group should increase, but in the case of OH groups of different orientations forming H-bonds in the hydrophobic phase of the micelle, it has the opposite effect; the CMC decreses, and aggregation is more favored. The set of muricholic acids (MCs) is composed by alpha-MC, beta-MC, gamma-MC, and omega-MC, where alpha-MC and beta-MC have beta-axialOH groups. The aggregation numbers (n) are determined using the MoroiMatsuokaSugioka thermodynamic method. CMC, enthalpy of demicellization, and Delta C-p are determined by isothermal titration calorimetry (ITC). This report pioneers in the study of MC derivatives micellization. Micelles of beta-MC and gamma-MC belong to the linear congeneric group (LCG) and their micelles above 85 mM have constant aggregation numbers n = 45. Micelles of alpha-MC and omega-MC are outliers in relation to the LCG, their aggregation number constantly increases; at 85 mM n = 6.8 (alpha-MC) and 6.5 (omega-MC). In micelles of derivatives beta-MC and gamma-MC, there is a low probability for the existence of hydrogen bonds. A micelle of alpha-MC probably has hydrogen bonds in its hydrophobic domain.