Synthesis and in Vitro Photodynamic Activity of Oligomeric Ethylene Glycol–Quinoline Substituted Zinc(II) Phthalocyanine Derivatives

Abstract

A new series of zinc(II) phthalocyanine derivatives have been synthesized and characterized. These macrocycles exhibited a sharp absorption band in the red visible region in DMF, which indicated that they were dissolved well and almost did not aggregate in this solvent. Compared with the unsubstituted zinc(II) phthalocyanine, all these phthalocyanines have a red-shifted Q-band (at 678-699 vs 670 nm) and exhibit a relatively weaker fluorescence emission and a higher efficiency at generating singlet oxygen. The monosubstituted photosensitizers also exhibit high photocytotoxicity toward HepG2 human hepatocarcinoma cells with IC50 values as low as 0.02-0.05 μM (λ = 670 nm, 80 mW·cm(-2), 1.5 J·cm(-2)). The high photodynamic activities of these compounds are in accordance with their low aggregation tendency and high cellular uptake. Their structure-activity relationship was assessed by determining the photophysical properties, cellular uptake, and in vitro photodynamic activities of this series of compounds. As shown by confocal microscopy, monosubstituted phthalocyanines can target the mitochondria and lysosomes of the cells, and tetrasubstituted phthalocyanines tend to target the lysosomes of the cells.