Synthesis, characterization and photodynamic antitumor activity of amine-modified zinc (II) phthalocyanines

Abstract

In order to reduce the intramolecular charge-transfer (ICT) effect of amine groups on the photophysical properties of zinc (II) phthalocyanine (ZnPc), tertiary amines were covalently connected with ZnPc ring via ethyl p-hydroxybenzoate or diethyl 5-hydroxyisophthalate. Six new tertiary amine-modified ZnPcs were therefore synthesized and characterized. Meanwhile, the corresponding quaternary ammonium ZnPcs were also synthesized. The effects of different substitution ways (mono-substitutions, symmetrical tetra-substitutions, or asymmetric tetra-substitutions) and the numbers of different substitutions on the photophysical and physicochemical properties of these ZnPcs were studied. All twelve ZnPcs had relatively high singlet oxygen quantum yields (ΦΔ = 0.32–0.68) and fluorescence quantum yields (ΦF = 0.23–0.40), where the amine-containing substituents did not show obvious ICT effect. All ZnPcs showed effective phototoxicity towards breast cancer cells (IC50 = 63–366 nmol/L). Among them, three tetra-substituted ZnPcs containing quaternary ammonium groups (4aN, 4bN and 4cN) showed the best in vitro anticancer photodynamic activities with IC50 = 64–76 nmol/L, which owned to their relatively high cellular uptake. The tumor inhibition rate of 4aN on H22 tumor-bearing mice reached 87% (4aN dose: 3 nmol/g; light dose: 685 nm, 135 J/cm2).