Tumor-pH-value responsive non-peripheral substituted phthalocyanines: Synthesis, investigation of photophysical and photochemical properties

Abstract

Cancer is one of the diseases with the highest mortality rate worldwide. Although PDT has recently produced encouraging outcomes, there are still many areas that need to be improved. The first of these is the negative consequences faced by patients treated with the PDT method when exposed to sunlight. For this reason, a new PDT method has been developed in recent years, and it is aimed at using photosensitizer molecules that can be active in acidic conditions. Since the pH values of tumor tissues are more acidic than normal tissues, preparing molecules that act effectively in acidic conditions will allow for more effective results in treating cancer with PDT. In this context, within the scope of this study, 3-(4-propionylphenoxy)phthalonitrile (1) and its nonperipheral tetra-substituted phthalocyanine derivatives [(2), (3), and (4)] were prepared. With these phthalocyanine derivatives, the novel compounds (5), (6), and (7) were synthesized for the first time. The aggregation tendencies of newly synthesized phthalocyanines (5-7) were investigated in solvent media. The effects of pH changes upon UV-Vis and fluorescence spectra were performed. The electronic and emission spectra of synthesized phthalocyanine derivatives are highly sensitive to pH changes. Formation constant (LogK) values of mono- and di-protonated phthalocyanine forms were calculated by the Henderson-Hasselback equation. The mono- and di-protonated species' equilibrium constants (logK1 and logK2) were calculated as similar to 5.0. This value may be promising for pH-sensitizing photosensitizers. Also, the photophysical and photochemical properties of synthesized metallophthalocyanine derivatives (2) and (5) were studied at different pH values. The singlet oxygen quantum yield of (2) and (5) was calculated to be 0.78 and 0.81 in DMSO, respectively. When pH = 6.4, that is, tumor-pH-values, this value for (5) has increased to 0.92. The newly synthesized phthalocyanines are suitable photosensitizers for PDT applications, especially with high singlet oxygen quantum yield at pH 6.4.