Glycosylated zinc(ii) phthalocyanines as efficient photosensitisers for photodynamic therapy. Synthesis, photophysical properties and in vitro photodynamic activity

Abstract

Treatment of 3- or 4-nitrophthalonitrile with 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose or 1,2:3,4-di-O-isopropylidene-α-D-galactopyranose in the presence of K₂CO₃ gave the corresponding glycosubstituted phthalonitriles. These precursors underwent self-cyclisation, or mixed-cyclisation with the unsubstituted phthalonitrile, to afford the tetra- or mono-glycosylated zinc(II) phthalocyanines, respectively. As shown by absorption spectroscopy, these compounds were not significantly aggregated in organic solvents, giving a weak to moderate fluorescence emission. Upon irradiation these compounds could sensitise the formation of singlet oxygen in DMF, with quantum yields in the range of 0.40–0.66. The in vitro photodynamic activities of these compounds against HepG2 human hepatocarcinoma and HT29 human colon adenocarcinoma cells were also studied. The mono-glycosylated phthalocyanines exhibited significantly higher photocytotoxicity compared with the tetra-α-glycosylated analogues, having IC₅₀ values down to 0.9 μM. The tetra-β-glycosylated counterparts were essentially inactive. The lower photocytotoxicities of the tetra-glycosylated phthalocyanines are in line with their lower cellular uptake and/or higher aggregation tendency as reflected by weaker intracellular fluorescence, and lower efficiency at generating intracellular reactive oxygen species. For the mono-glycosylated phthalocyanines, the higher uptake can be attributed to their hydrophilic saccharide units, which increase the amphiphilicity of the macrocycles.