Mn(III) porphyrins as photosensitizers: structural, photophysical and anticancer studies

Herein, we synthesized, characterized and explored the photo-triggered anticancer activity of five Mn(III) porphyrins Mn1-Mn5, viz. (diaqua)meso-(tetraphenylporphyrinato)manganese(III) propionate, [Mn(III)TPP(H₂O)₂]⁺(C₃H₅O₂^-) or Mn1; (diaqua)meso-tetrakis(4-methylphenylporphyrinato)manganese(III) propionate, [Mn(III)TMeP(H₂O)₂]⁺(C₃H₅O₂^-) or Mn2; (diaqua)meso-tetrakis(4-methoxyphenylporphyrinato)manganese(III) propionate, [Mn(III)TMP(H₂O)₂]⁺(C₃H₅O₂^-) or Mn3; (diaqua)meso-tetrakis(4-fluorophenylporphyrinato)manganese(III) propionate, [Mn(III)FTPP(H₂O)₂]⁺(C₃H₅O₂^-) or Mn4 and (diaqua)meso-tetrakis(4-chlorophenylporphyrinato)manganese(III) propionate, [Mn(III)ClTPP(H₂O)₂]⁺(C₃H₅O₂^-) or Mn5, which remain virtually unexplored as photodynamic therapy (PDT) agents like other paramagnetic metalloporphyrins. These Mn(III) porphyrins, bearing different para-substituents on their meso-phenyl rings and two water molecules as axial ligands, were characterized using spectroscopic techniques and structurally through single-crystal X-ray diffraction, revealing an octahedral MnN₄O₂ geometry. Binding studies demonstrated a strong affinity of the metalloporphyrins for human serum albumin (HSA), indicating their potential for biological applications. The visible light-assisted generation of reactive oxygen species (ROS) by these Mn(III) porphyrins was confirmed via 1,3-diphenylisobenzofuran (DPBF) titration, identifying singlet oxygen (¹O₂) as one of the primary ROS. Photoredox activity under visible light, displayed by the Mn(III) porphyrins in the presence of ascorbic acid involving +3 and +2 oxidation states of manganese, further underscores the photochemotherapeutic potential of Mn1-Mn5. The ROS generation ability was further validated intracellularly in HeLa cells using Mn4 with the help of 2',7'-dichlorofluorescein diacetate (DCFDA) assay under visible light irradiation (λ = 400-700 nm). Furthermore, among the five Mn(III) porphyrin complexes (Mn1-Mn5) evaluated for photo-triggered anticancer activity using MTT assays, Mn4 exhibited superior photocytotoxicity, with a half-maximal inhibitory concentration (IC₅₀) of 4.93 ± 0.7 μM against HeLa cancer cells under visible light irradiation and negligible dark toxicity (IC₅₀ > 50 μM). These results suggest that both type-I and type-II ROS generation pathways contribute to the observed photocytotoxicity. This study highlights the potential of paramagnetic metalloporphyrins, particularly Mn(III) porphyrins, in anticancer application by demonstrating their effectiveness as photosensitizers for photodynamic cancer therapy.