Synthesis, spectroscopic, and cellular properties of a-pegylated cis-A2B2- and A3B-types ZnPcs

Abstract

A series of pegylated cis-A2B2- or A3B-type ZnPcs, substituted on the rx-positions with tri(ethylene glycol) and hydroxyl groups, were synthesized from a new bis-phthalonitrile. A clamshell­ type bis-phthalocyanine was also obtained as a byproduct. The hydroxyl group of one ZnPc was alkylated with 3-dimethylaminopropyl chloride to afford a pegylated ZnPc functionalized with an amine group. All mononuclear ZnPcs were soluble in polar organic solvents, showed intense Q absorptions in DMF, and had fluorescence quantum yields in the range 0.10-0.23. The clamshell-type bis-phthalocyanine adopts mainly open shell conformations in DMF, and closed clamshell conformations in chloroform. All ZnPcs were highly phototoxic to human carcinoma HEp2 cells, particularly the amino-ZnPc mainly protonated under physiological conditions, which showed the highest phototoxicity (ICso = 0.5 ~ at 1.5 J/cm2) and dark cytotoxicity (ICso = 22 I-lM), in part due to its high cellular uptake. The ZnPcs localized in multiple organelles, including mitochondria, lysosomes, Golgi and ER