QSPR study of the effect of steroidal hydroxy and oxo substituents on the critical micellar concentration of bile acids

Measurements of the fluorescence intensity of 1,6-diphenylhexatriene (DPH) as a probe molecule allowed the determination of critical micellar concentrations (CMCs) for 30 bile acid (BA) molecules belonging to three linear congeneric groups, with three (Group I) and two (Group II) oxygen atoms from OH or oxo groups bound to the steroid skeleton, and glyco conjugated cholic acid and glyco conjugated cholic acid derivatives (Group III). The CMC values are related to the structure of the steroid nucleus by constructing novel molecular descriptors with 2D and 3D characteristics of topological descriptors. Namely, with conventional topological descriptors (first-order connectivity index, third-order connectivity index, Wiener-index, Balaban-index, molecular topological index, cluster count, etc.) BA molecules from the same congeneric group have identical values, so that these descriptors cannot be used to form a new model for the given congeneric group.The linear regressions (models) obtained in this work for each congeneric group relate the CMCs to this new descriptor. Statistical parameters of these models, as well as their predictivity, indicate the significance of the obtained equations, that is that the micelle formation is influenced not only by the number of OH and oxo groups in the steroid nucleus but also by their steric environment.

Research highlights▶ The descriptor d0.25 has characteristics of both 2D and 3D topological descriptors. ▶ Descriptor d0.25 explains variance within the congeneric groups of tested bile acid. ▶ The descriptor d0.25 is in a good correlation with the bile acids CMC values.