A combined experimental and computational study of the substituent effect on the photodynamic efficacy of amphiphilic Zn(ii)phthalocyanines

Abstract

Zinc(II)phthalocyanines (Zn(II)Pc) have shown promising applications in photodynamic therapy due to their high quantum yield of singlet oxygen generation; however, optimization of their overall properties are required before their clinical application as photosensitizers (PSs). The photosensitization efficiency of photoprobes is strongly influenced by the nature of the conjugated moieties and often it can be efficiently tuned by variation in the substitution pattern. Through this study we examined how the structural design of amphiphilic carbohydrate-based Zn(II)Pcs affects their photophysical properties, binding affinity to human serum albumin (HSA) and photodynamic activity against human cancer melanoma cells. The replacement of oxygen with sulfur at non-peripheral positions of low-symmetry Zn(II)Pcs contributes to the bathochromic shift of maximum absorption, which is relevant for the activation of the PS in deeper tissues. Moreover, this modification also influences the overall flexibility of the macrocyclic core and results in different behaviour towards HSA. Density functional theory calculations have been carried out to substantiate the effect of the peripheral environment on the photophysical characteristics and geometry of the molecules.