Green Electrochemical Complexation of Fluconazole, Itraconazole, Voriconazole, Ketoconazole and Clotrimazole with Silver, Copper and Zinc Cations

Abstract

Electrochemical complexation of azole antifungal drugs fluconazole (FCZ), itraconazole (ITZ), ketoconazole (KTZ), voriconazole (VCZ) and clotrimazole (CTZ) with silver, copper and zinc cations was carried out galvanostatically in an undivided electrolytic cell equipped with a sacrificial anode and a stainless steel cathode under green conditions. In this work, we synthesized twenty different complexes of these drugs by a simple method in water (containing a strong acid)/ethanol mixtures with high yield (average 67%) and purity. The effective synthetic parameters, including the applied current, electricity consumption, acid concentration, cell voltage, energy consumption and cell design were optimized. Our results indicate that the applied current and acid concentration have no significant effects on the yield and purity of azole complexes. But these factors have a significant effect on cell voltage and energy consumption in such a way that by increasing the applied current or decreasing the acid concentration, the cell voltage and energy consumption increase. The Fourier-transform infrared spectroscopy (FTIR), field emission scanning electron microscopy (FE-SEM) and energy dispersive X-ray (EDX) techniques have been used for the characterization of synthesized complexes. In addition, cyclic voltammetry analysis has been used to investigate the reaction mechanism. This method provides an efficient and green strategy for the complexation of azole drugs in one step without the need for metal salts.