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

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. © The Royal Society of Chemistry 2008.