Some observations on the synthesis of polysubstituted zinc phthalocyanine sensitisers for photodynamic therapy

The syntheses and properties of a number of polysubstituted zinc phthalocyanines are described which are suitable as sensitisers for photodynamic therapy. Zinc phthalocyanine tetrasulphonic acid itself a useful photosensitiser, has been used to prepare tetrasulphonamides by converting it to the tetrasulphonyl chloride and reacting this with various amino compounds. This has afforded lipophilic and water-soluble anionic and neutral tetra-sulphonamido derivatives. Chlormethylation of zinc phthalocyanine under carefully defined conditions followed by reaction with pyridine affords a water-soluble cationic dye with an average of two methylenepyridinium groups per molecule. Hydrolysis of zinc phthalocyanine tetracarboxyamide could not be carried out to completion to afford the tetracarboxylic acid, and the resultant product had an average composition corresponding to a dicarboxylic acid-dicarboxyamide structure. Visible absorption spectroscopic properties and singlet oxygen sensitising efficiencies of the dyes (measured relative to methylene blue) are described All the dyes ave photocytotoxic in vitro and show anti-tumour photoactivity in vivo. Copyright (C) 1997 Elsevier Science Ltd.