Synthesis of Novel Functionalised Zinc Phthalocyanines Applicable in Photodynamic Therapy

The synthesis of several new phthalonitriles 3, 9, 14, 25, 33, and 36, functionalised with carboxyl groups, including two examples of amino acid derivatives is described. All new phthalonitriles were converted into their corresponding phthalocyaninatozinc compounds. The phthalocyanines, 2,3,9,10,16,17,23,24-octa(1-carboxyethyloxy)phthalocyaninatozinc (5), 2,9,16,23-tetra(2-amino-2-carboxyethyl)phthalocyaninatozinc (11), 2,9,16,23-tetra(1-carboxy-2-hydroxyethylaminocarbonyl)phthalocyaninatozinc (16), 1,8,15,22-tetra(carboxybutyl)phthalocyaninatozinc (27), 2,3,9,10,16,17,23,24-octa(carboxyalkyl)phthalocyaninatozinc (39), and the nonidentically substituted 9,10,16,17,23,24-hexa(carboxyalkyl)-2-[4-(N-succinimidyloxycarbonyl)butyl]phthaloyaninatozinc (41) are all sufficiently soluble in water. The nonidentically-substituted compounds are important due to their selective binding to tumor-selective antibodies. UV/Vis-spectroscopy was used to investigate the effect of more or less sterically-demanding substituents in the periphery of the phthalocyanines towards aggregation. The phototoxicity towards cancer cells of some of the new compounds was investigated in several in-vitro experiments.