Sulfonated phthalocyanines: photophysical properties, in vitro cell uptake and structure–activity relationships

Aluminium phthalocyanines sulfonated to a different degree (AlPcS_n) and consisting of various isomeric species were studied by spectroscopic techniques to determine their tendencies to form dimers and aggregates. These characteristics were compared with the cell-penetrating properties of the species, using the Ehrlich ascites mouse tumor cell line, to arrive at structure–activity relationships. AlPcS_n preparations consisting of the least number of isomeric species exhibited the highest tendency to form dimers and aggregates, whereas the more complex preparations, consisting of many isomeric products, showed more consistent monomeric features in aqueous environments. Uptake in cells was shown to correlate well with the overall hydrophobicity of the preparation and inversely with its degree of aggregation in the extracellular environment. Among the purified, single isomeric AlPcS_n the amphiphilic disulfonated AlPcS_2a, enriched in positional isomers featuring sulfonate groups on adjacent phthalic subunits, showed the best membrane-penetrating properties. Even higher cell uptake was observed for the AlPcS_2mix reflecting a combination of optimal lipophilicity and a low degree of aggregation. Similarly, in the case of AlPcS₄, the pure isomeric compound showed less cell uptake than the mixed isomeric preparation of similar hydrophobicity, reflecting the higher degree of aggregation invoked by its symmetrical structure. Our data indicate that mixed sulfonated phthalocyanine preparations may exert higher photodynamic efficacy in biological applications as compared to the pure isomeric constituents. © 1998 John Wiley & Sons, Ltd.