Novel Porphyrazine Derivatives show Promise for Photodynamic Therapy despite Restrictions in Hydrophilicity

Complexing of ligands to photosensitizers (Ps) has gained popularity by enhancing solubility, cell‐surface recognition and tissue specificity for applications in Photodynamic Therapy (PDT) and fluorescence‐based diagnostics. Here we report on nine carbohydrate‐functionalized porphyrazine (Pz‐galactopyranose/methyl‐ribose) derivatives bearing either H₂, Zn(II) or Ni(II) cores for potential use in PDT. Derivatives proved soluble only in organic solvents; dichloromethane (DCM) and tetrahydrofuran (THF). Derivatives were subsequently solubilized using DCM‐based PEG‐DSPE₅₀₀₀‐PBS encapsulation for biological studies due to THF cytotoxicity. Absorption spectra analyses viewed no correlation between core ion, carbohydrate type and peripheral position though encapsulation efficiency (%EE) followed a general order of Zn(II) (60–92%) > H₂ (5–34%) > Ni(II) (4–21%). As such, phototoxicity of Zn(II)Pz derivatives were far superior to H₂Pz and Ni(II)Pz counterparts following 631.4 nm excitation of MCF‐7 breast cancer cells. Variation was attributed to persistent aggregation and low %EE when regarding the absorption properties recorded. It is therefore believed that revision of the encapsulation method for H₂Pz and Ni(II)Pz derivatives would render improved phototoxicity. Zn(II)Pz derivatives show promise as agents for PDT of cancer.