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

Abstract

A new series of di-alpha-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).2H(2)O 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-alpha-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 IC(50) values as low as 0.06 muM. 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.