Synthesis and photodynamic activity of zinc(II) phthalocyanine derivatives bearing methoxy and trifluoromethylbenzyloxy substituents in homogeneous and biological media

E. INÉS YSLAS; V. RIVAROLA; E.N. DURANTINI

BIOORGANIC & MEDICINAL CHEMISTRY.

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2005 vol. 13 p. 39 - 46

0968-0896

Two zinc(II) phthalocyanines bearing either four methoxy (ZnPc 3) or trifluoromethylbenzyloxy (ZnPc 4) substituents have been synthesized by a two-step procedure starting from 4-nitrophthalonitrile. Absorption and fluorescence spectroscopic studies were analyzed in different media. These compounds are essentially non-aggregated in the organic solvent. Fluorescence quantum yields (/F) of 0.26 for ZnPc 3 and 0.25 for ZnPc 4 were calculated in tetrahydrofuran (THF). The photodynamic activity of these compounds was compared in both THF containing photooxidizable substrates and in vitro on Hep-2 human larynx-carcinoma cell line. The production of singlet molecular oxygen, O2(1Dg), was determined using 9,10-dimethylanthracene yielding values of 0.56 for both sensitizers. Under these conditions, the addition of b-carotene (Car) suppresses the O2(1Dg)-mediated photooxidation. In biological medium, no dark cytotoxicity was found for cells incubated with 0.1lM of phthalocyanines 3 and 4 for 24 h. However, under similar conditions 0.5lM of ZnPc 4 was toxic (70% cell survival). The uptake into Hep-2 cells was evaluated using 0.1lM of sensitizer, reaching values of 0.05nmol/106 cells after 3h of incubation at 37C. The cell survival after irradiation of the cultures with visible light was dependent upon both light exposure level and intracellular sensitizer concentration. A higher photocytotoxic effect was found for ZnPc 3 with respect to 4 (32%/70% cell survival after 15min of irradiation). Also, these studies were performed treating the cells with 0.5lM of ZnPc 3. In this case, an increase in the uptake (0.28nmol/106 cells) was observed, which is accompanied by a higher photocytotoxic activity (20% cell survival). These results show that even though both sensitizer present similar photophysical properties in homogeneous medium, the photodynamic behavior in cellular media can significantly be changed.