Structural studies of five novel bile acid-4-aminopyridine conjugates

Synthesis and solid-state structural characterization of five bile acid amides of 4-aminopyridine (4-AP) are reported. Systematic crystallization experiments revealed a number of structural modifications and/or solvate/hydrate systems for these conjugates. Particularly, cholic acid conjugate exhibited five distinct structure modifications, including one anhydrous form, mono- and dihydrates, as well as ethanol and 2-butanol solvates. The obtained crystal forms were examined extensively with various analytical methods, including solid-state NMR, Raman, and IR spectroscopies, powder and single crystal X-ray diffraction methods, thermogravimetry, and differential scanning calorimetry. After releasing their crystal solvent molecules, the resulted non-solvated structure forms showed 50–75 °C higher melting points than corresponding bile acids, and thermal degradation occurred for all conjugates at about 300–330 °C. Moreover, the single crystal X-ray structure of the ursodeoxycholic acid-4-aminopyridine conjugate is reported.

► Five novel bile acid-4-aminopyridine conjugates were synthesized. ► Crystallization screening resulted in twelve different crystal modifications. ► SS-NMR, XRD, optical spectroscopy, and thermal analysis were used for analysis.