Shafrira Greenberg

THE EFFECT OF SUBSTITUENTS ON PHTHALOCYANINE PHOTOCYTOTOXICITY

Phthalocyanine (Pc) dyes are a class of photosensitizers that are being considered for use in the photodynamic therapy of cancer. A final choice for the most useful drug demands phototoxicity screening of various structurally related Pc dyes, such as those with different substituents at the peripheral benzene rings. Using the colony forming ability of Chinese hamster cells as an endpoint, the photobiological activity for ZnPc was found to be the highest for the unsubstituted compound, followed in decreasing order by the 2,9,16,23‐tetrahydroxy‐, 2,9,16,23‐tetrasulfonated‐, and 2,9,16,23‐tetraneopentoxy‐Pc derivatives. This effect could be correlated with the uptake rate of the respective Pc derivatives by the cells, but it is unrelated to the apparent lipophilicity of these compounds, or, alternatively, to their ability to photogenerate singlet oxygen. The first synthesis of a metal‐free tetrahydroxy Pc is described.

SYNTHESIS AND PHOTOCYTOTOXICITY OF SOME NEW SUBSTITUTED PHTHALOCYANINES

Abstract Some new, ring‐substituted phthalocyanines have been synthesized and underwent preliminary testing for photodynamic activity using the colony forming ability of Chinese hamster cells in culture as an endpoint. Using 4‐(3‐N, N‐diethylaminopropyl)phthalonitrile as a precursor, the previously unknown metal‐free 2,9,16,23‐tetra‐(3‐N, N‐diethylaminopropyl)phthalocyanine was prepared and converted to its zinc (II) and its cationic water‐soluble 2,9,16,23‐tetramethylammonium zinc (II) iodide derivatives. Other new phthalocyanine derivatives tested, include a 2,9,16,23‐tetra(2‐hydroxymethyl‐2‐methyIbutoxy)phthalocyaninato zinc (II) and 2,3,9,10,16,17,23,24‐octahydroxyphthalocyaninato zinc (II) derivatives. Boron tribromide cleavage of the newly prepared and fully characterized 2,3,9,10,16,17,23,24‐octamethoxyphthalocyanine gave the unstable metal‐free octahydroxyphthalocy‐anine, which could only be characterized by ultraviolet‐visible, NMR and IR spectroscopy.

The syntheses of a monosubstituted and an unsymmetrical tetrasubstituted phthalocyanine using binuclear phthalocyanines

Abstract The syntheses of 2-hydroxyphthalocyanine and 2-hydroxy-9,16,23-tri- tert -butylphthalocyanine have been accomplished.

Substituted Phthalocyanines as Photodynamic Sensitizers

The phthalocyanine dyes have recently been suggested for use in the photodynamic therapy of cancer.1,2 Their superior attributes, such as the very intense light absorption in the wavelength range preferred for photodynamic therapy (600–700 nm), the lack of toxicity and selective localization of some dyes of this group in experimental tumors, the high efficiency to photosensitize killing of mammalian cells in culture, and finally the ability to induce necroses of transplanted tumors in animals3,4 have made this suggestion very attractive.