Solid-State NMR, X-ray Diffraction, and Thermoanalytical Studies Towards the Identification, Isolation, and Structural Characterization of Polymorphs in Natural Bile Acids

Combined solid-state NMR, powder, and single crystal X-ray diffraction, as well as thermoanalytical studies were performed towards the identification, isolation, and structural characterization of polymorphs present in commercial samples of six natural bile acids. The C-13 {H-1} cross-polarization (CP) magic angle spinning (MAS) NMR technique was used as a primary tool to identify the mixture of polymorphs present in the natural bile acids obtained from commercial sources. A detailed study including selective crystallization of each polymorphic form of the bile acids in different solvents and mixture of solvents was carried out, and their spectral patterns were compared with the mode of packing and number of molecules present in an asymmetric unit. These studies were strongly supported by other complementary techniques such as powder/single crystal X-ray diffraction and differential scanning calorimetric (DSC) experiments. While a few single crystal X-ray structures are solved in order to confirm the correct polymorphic form, most of the powder X-ray diffraction data were compared with the simulated X-ray patterns obtained from previously reported single crystal structures. Detailed analyses using multiple experimental techniques provided useful insights towards the mode of packing which is responsible for unique spectral patterns in the solid state.