SYNTHESES AND PHOTODYNAMIC ACTIVITIES OF NOVEL TRISULFONATED ZINC PHTHALOCYANINE DERIVATIVES

The synthesis of water-soluble, unsymmetrical, trisulfonated zinc phth alocyanines (ZnPcS3) as single products of the ring expansion of boron tri(4-sulfo) subphthalo cyanine (SubPc) is reported. The novel, water -soluble trisulfo-SubPcB(OH) was prepared via hydrolysis of the tris(4 -chlorosulfonyl)SubPcB(Br) which in turn was obtained from the condens ation of 4-(chlorosulfonyl)phthalonitrile with BBr3 in 1-chlorobenzene . A number of ZnPcS3 analogues were prepared via the reaction of S(3)S ubPcB(OH) with different diiminoisoindoline derivatives of increasing hydrophobicity. The reaction proceeds at relative low temperature with acceptable yields. Metalation of free base Pc's with zinc acetate dih ydrate afforded the corresponding zinc complexes. Photodynamic activit ies were measured against the EMT-B mouse mammary tumor cell line and compared to those of the known ZnPcS3 and ZnPcS4. Added (t-Bu)benzo an d (t-Bu)naphtho groups increased the in vitro cell photoinactivation e fficacy of the ZnPcS3, whereas addition of a fourth sulfobenzo or bulk y diphenylpyrazino group decreased the activity of the parent molecule . The (t-Bu)naphthotrisulfobenzoporphyrazine induced the best in vivo photodynamic tumor control which, combined with its good solubility an d broad absorption spectrum, renders this compound an interesting dye for photodynamic applications in medicine.