Complexes of fluconazole with sodium p-sulfonatocalix[n]arenes: characterization, solubility and antifungal activity†
Abstract
Aiming at providing new formulations capable of improving the biopharmaceutical properties of fluconazole, we studied the formation of host–guest complexes of this antifungal agent with water-soluble sodium p-sulfonatocalix[4]arene and sodium p-sulfonatocalix[6]arene. The formation of inclusion complexes was first investigated using 1H NMR spectroscopy and TGA experiments. The complexes' stoichiometry, apparent binding constants (Ka) and the complexed populations (%pbound), were determined, using 1H NMR data. The topology of the complexes were assessed by 1D ROESY experiments, and the data were corroborated by semi-empirical and DFT calculations. The activity of the fluconazole-calix[n]arene complexes against clinically relevant fungal species was investigated. Finally, the effect of complexation on the solubility of fluconazole was investigated using the phase-solubility method of Higuchi and Connors.