Synthesis, Characterization, and In Vitro Photodynamic Activity of Novel Amphiphilic Zinc(II) Phthalocyanines Bearing Oxyethylene-Rich Substituents

Abstract

Three novel zinc(II) phthalocyanines substituted with one or two 3,4,5-tris(3,6,9-trioxadecoxy)benzoxy group(s) have been prepared and spectroscopically characterized. These compounds are highly soluble and remain nonaggregated in N , N -dimethylformamide. Upon excitation, they exhibit a relatively weak fluorescence emission and high efficiency to generate singlet oxygen compared with the unsubstituted zinc(II) phthalocyanine. These amphiphilic photosensitizers formulated with Cremophor EL are highly photocytotoxic against HT29 human colon adenocarcinoma and HepG2 human hepatocarcinoma cells. The mono- α -substituted analogue 4 is particularly potent with IC 50 values as low as 0.02 μ M. The higher photodynamic activity of this compound can be attributed to its lower aggregation tendency in the culture media as shown by absorption spectroscopy and higher cellular uptake as suggested by the stronger intracellular fluorescence, resulting in a higher efficiency to generate reactive oxygen species inside the cells.