Synthesis, spectroscopic properties and photodynamic activity of a novel Zn(II) phthalocyanine substituted by fluconazole groups

Abstract

A novel Zn(II) phthalocyanine derivative (ZnPcF) bearing four antifungal structures of fluconazole was synthesized by a two-step procedure starting from 4-nitrophthalonitrile. First, phthalonitrile-azole derivative was prepared by a nucleophilic ipso-nitro substitution reaction between 4-nitrophthalonitrile and fluconazole. The cyclotetramerization of phthalonitrile-azole with Zn(II) acetate in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) results in the formation of the ZnPcF as a mixtures of constitutional isomers with 27% yield. Absorption and fluorescence spectroscopic studies were analyzed in different media. The results show that ZnPcF is lowly soluble in polar solvents or in reverse micellar systems. However, addition of HCl produce an increase in the monomerization of ZnPcF in N,N-dimethylformamide (DMF)/water (10% v/v) and in benzene/benzyl-n-hexadecyldimethyl ammonium chloride (BHDC, 0.1 M)/water (W0=10). A value of 0.19 was calculated for the fluorescence quantum yield (fF) of this photosensitizer in DMF/water (10%)/HCl 1.2 mM. The photodynamic activity of ZnPcF was evaluated using 9,10-dimethylanthracene (DMA). An enhancement in the singlet molecular oxygen, O2(1Dg), production was obtained in acidified DMF/water or BHDC micellar system, which represent an appropriate system to induce monomerization of ZnPcF. Preliminary studies to evaluate the photodynamic activity of ZnPcF were tested against a typical yeast Candida albicans. These results indicated that ZnPcF is an interesting antifungal agent because it has antimycotic activity in dark and its efficiency increases in the presence of light due to the photodynamic inactivation caused by the photosensitizer moiety.