Highly photocytotoxic glucosylated silicon(IV) phthalocyanines. Effects of peripheral chloro substitution on the photophysical and photodynamic properties.

Two novel glucoconjugated silicon(IV) phthalocyanines (compounds 3 and 4) have been prepared and examined for their photophysical and biological properties. With two axial 1,2:5,6-di-O-isopropylidene-alpha-d-glucofuranose substituents linked to the silicon center through the tetraethylene glycol chain, both compounds are highly soluble and remain nonaggregated in N,N-dimethylformamide. The dichloro-substituted phthalocyanine 4 exhibits a weaker fluorescence emission and higher efficiency to generate singlet oxygen compared with the nonchlorinated counterpart 3 as a result of the heavy atom effect. Both compounds are highly photocytotoxic against HT29 human colorectal carcinoma and HepG2 human hepatocarcinoma cells, particularly the nonchlorinated phthalocyanine 3, of which the IC50 values are as low as 6 nM. The lower photodynamic activity of the chlorinated derivative (IC50 = 17-21 nM) can be attributed to its higher aggregation tendency in the biological media, leading to a lower efficiency to generate reactive oxygen species inside the cells. Fluorescence microscopic studies have also revealed that compound 3 has a high and selective affinity to the lysosomes, but not the mitochondria, of HT29 cells.