Tetrakis(thiadiazole)porphyrazines. 8. Singlet oxygen production, fluorescence response and liposomal incorporation of tetrakis(thiadiazole)porphyrazine macrocycles [TTDPzM] (M = MgII(H2O), ZnII, AlIIICl, GaIIICl, CdII, CuII, 2HI)

Abstract

The photoactivity for the generation of singlet oxygen, ¹O₂, the key cytotoxic agent in the anticancer treatment known as photodynamic therapy (PDT), and the fluorescence response of the highly electron-deficient tetrakis(thiadiazole)porphyrazines of formula [TTDPzM] (M = Mg^II(H₂O), Zn^II, Al^IIICl, Ga^IIICl, Cd^II, Cu^II, 2H^I) were examined (c ≅ 10⁻⁵ M) in dimethylformamide (DMF) and/or in DMF preacidified with HCl (DMF/HCl; [HCl] = 1–4 × 10⁻⁴ M). The singlet oxygen quantum yield (Φ_Δ) of all the compounds was determined by using a widely employed procedure based on the selective oxidation of the 1,3-diphenylisobenzofuran (DPBF), modified in part as reported. The list of the Φ_Δ values indicates excellent photosensitizing properties for the series of compounds carrying “closed shell” metal ions, with values measured in DMF/HCl respectful of the “heavy atom effect” for the first four lighter centers, increasing in the order Mg^II < Al^III < Zn^II < Ga^III. Data of Φ_Δ concerning the unmetalated species [TTDPzH₂], present in solution in the form of the corresponding anion [TTDPz]²⁻, and the Cd^II and Cu^II complexes are also presented and discussed. Extensive discussion is also developed on the fluorescence quantum yield values Φ_F, with data on the Mg^II and Al^III compounds in DMF/HCl (0.44 and 0.53, respectively) indicative of promising perspectives for applications in fluorescence imaging techniques. The Φ_F data of the studied porphyrazine series, Φ_F^Pz, correlate linearly with those of the homologous phthalocyaninato complexes, Φ_F^Pc, suggesting a closely similar behaviour between the two classes of compounds. The incorporation of [TTDPzZn] into liposomes was successfully achieved following the detergent depletion method (DDM) from a mixed micellar solution by means of gel-filtration. Retention of [TTDPzZn] (∼40%) in its photoactive monomeric form into liposomes is proved by absorption and fluorescence spectra, this proposing the Zn^II complex as a promising candidate for use in PDT.