Effects of peripheral chloro substitution on the photophysical properties and in vitro photodynamic activities of galactose-conjugated silicon(IV) phthalocyanines

A series of silicon(IV) phthalocyanines with two axial isopropylidene- protected galactose moieties and one, two, or eight chloro group(s) on the periphery of the macrocycle have been synthesised and spectroscopically characterised. The photophysical properties and in vitro photodynamic activities of these compounds have been studied and compared with those of the nonchlorinated analogue. All the compounds, with the exception of the octachlorinated counterpart which has a limited solubility, are essentially nonaggregated in N,N-dimethylformamide. The fluorescence quantum yield decreases and the singlet oxygen quantum yield increases as the number of chloro substituent increases, which is in accord with the heavy-atom effect. The non-, mono-, and dichlorinated phthalocyanines formulated with Cremophor EL are all photodynamically active against HT29 human colon adenocarcinoma and HepG2 human hepatocarcinoma cells with IC₅₀ values ranging from 0.03 to 1.05 μm. The photocytotoxicity as well as the efficiency to generate intracellular reactive oxygen species decrease along this series because of the increase in aggregation tendency upon chloro substitution. The nonchlorinated analogue exhibits the highest potency and can target the lysosomes of HT29 cells, whereas the monochlorinated counterpart is not localised in the lysosomes. © 2008 Wiley-VCH Verlag GmbH & Co. KGaA.