SOME OBSERVATIONS ON THE SYNTHESIS OF POLYSUBSTITUTED ZINC PHTHALOCYANINE SENSITIZERS FOR PHOTODYNAMIC THERAPY

The syntheses and properties of a number of polysubstituted zinc phtha locyanines are described which are suitable as sensitisers for photody namic therapy. Zinc phthalocyanine tetrasulphonic acid itself a useful photosensitiser, has been used to prepare tetrasulphonamides by conve rting it to the tetrasulphonyl chloride and reacting this with various amino compounds. This has afforded lipophilic and water-soluble anion ic and neutral tetra-sulphonamido derivatives. Chlormethylation of zin c phthalocyanine under carefully defined conditions followed by reacti on with pyridine affords a water-soluble cationic dye with an average of two methylenepyridinium groups per molecule. Hydrolysis of zinc pht halocyanine tetracarboxyamide could not be carried out to completion t o afford the tetracarboxylic acid, and the resultant product had an av erage composition corresponding to a dicarboxylic acid-dicarboxyamide structure. Visible absorption spectroscopic properties and singlet oxy gen sensitising efficiencies of the dyes (measured relative to methyle ne blue) are described All the dyes ave photocytotoxic in vitro and sh ow anti-tumour photoactivity in vivo. Copyright (C) 1997 Elsevier Scie nce Ltd.