Sulfonated phthalocyanines: Photophysical properties, in vitro cell uptakeand structure-activity relationships

Aluminium phthalocyanines sulfonated to a different degree (AlPcSn) and con sisting of various isomeric species were studied by spectroscopic technique s to determine their tendencies to form dimers and aggregates. These charac teristics were compared with the cell-penetrating properties of the species , using the Ehrlich ascites mouse tumor cell line, to arrive at structure-a ctivity relationships. AlPcSn preparations consisting of the least number o f isomeric species exhibited the highest tendency to form dimers and aggreg ates, whereas the more complex preparations, consisting of many isomeric pr oducts, 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 ext racellular environment. Among the purified, single isomeric AlPcSn the amph iphilic disulfonated AlPcS2a, enriched in positional isomers featuring sulf onate groups on adjacent phthalic subunits, showed the best membrane-penetr ating properties. Even higher cell uptake was observed for the AlPcS2mix re flecting a combination of optimal lipophilicity and a low degree of aggrega tion. Similarly, in the case of AlPcS4, the pure isomeric compound showed l ess cell uptake than the mixed isomeric preparation of similar hydrophobici ty, reflecting the higher degree of aggregation invoked by its symmetrical structure. Our data indicate that mixed sulfonated phthalocyanine preparati ons may exert higher photodynamic efficacy in biological applications as co mpared to the pure isomeric constituents. (C) 1998 John Wiley & Sons, Ltd.