Photogenerate Singlet Oxygen Research Articles

The effect of substituents on phthalocyanine photocytotoxicity.

AbstractPhthalocyanine (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.

The Role of Molecular Oxygen in the Photodynamic Effect of Phthalocyanines

Phthalocyanines are a class of mammalian cell photosensitizers which may be useful in photodynamic therapy for cancer. Chloroaluminum phthalocyanine tetrasulfonate was incubated with Chinese hamster cells in culture and exposed to white light at different concentrations of oxygen. The ability of the cells to form colonies served as an end point for the photobiological effect of the dye. The efficiency of photoinactivation of the sensitized cells decreased with decreasing oxygen concentration. Very little photoinactivation was observed when the atmosphere equilibrated with the cells was oxygen-free nitrogen. At an oxygen partial pressure of 2.5 mm Hg, photoinactivation was reduced by 50% compared to ambient atmosphere. In an attempt to understand the nature of the interaction between excited dyes and oxygen, the ability of several phthalocyanines to photogenerate singlet oxygen was measured. Thus phthalocyanines containing paramagnetic ions (copper, iron, vanadyl) do not generate 1O2 in contradistinction to diamagnetic metals (zinc and aluminum). The latter are efficient photosensitizers, while the former have little if any photobiological activity. In spite of this correlation, singlet oxygen may not be the intermediate involved in cytotoxicity. The reasons are discussed.