Synthesis and in vitro photodynamic activities of di-α-substituted zinc(ii) phthalocyanine derivatives

Abstract

A new series of di-α-substituted zinc(II) phthalocyanine derivatives have been prepared by mixed cyclisation of the corresponding 1,4-disubstituted phthalonitriles or naphthalonitriles with an excess of unsubstituted phthalonitrile in the presence of Zn(OAc)₂·2H₂O and 1,8-diazabicyclo[5.4.0]undec-7-ene. Having a large hydrophobic macrocyclic core substituted with two hydrophilic triethylene glycol chains or glycerol moieties, these compounds are amphiphilic in nature. They are highly soluble and remain non-aggregated in DMF as shown by the intense and sharp Q-band absorption. Compared with the unsubstituted zinc(II) phthalocyanine, these di-α-substituted analogues exhibit a red-shifted Q band (at 689–701 nm), a relatively weaker fluorescence emission, and a higher efficiency to generate singlet oxygen. Upon illumination, these compounds are highly cytotoxic towards HT29 human colorectal carcinoma and HepG2 human hepatocarcinoma cells with IC₅₀ values as low as 0.06 μM. The high photocytotoxicity of these compounds can be attributed to their high cellular uptake and low aggregation tendency in the biological media, leading to a high efficiency to generate reactive oxygen species inside the cells.