A2B2-type porphyrins enhanced by N-donor units: Synthesis optimization and photodynamic efficiency towards S. aureus

Antimicrobial photodynamic therapy (aPDT) is a promising alternative or complementary strategy to traditional antimicrobial treatments. This approach relies on the light activation of a photosensitizer (PS) to generate reactive oxygen species (ROS) that destroy microorganisms. This study described the synthesizes of a series of Zn(II) complexes and free-base trans-A₂B₂-type porphyrins, modified with nitrogen-based donor moieties directly attached to the porphyrin core via CN bonds. The functionalization of the porphyrin macrocycle was strongly dependent on the nature of the porphyrin template (H₂BPP, ZnBPP or ZnBr₂BPP) as well as the structure of the nitrogen-based reagent (carbazole, 3,6-dimethoxy-9H-carbazole, 10H-phenoxazine, 10H-phenothiazine and bis(4-methoxyphenyl)amine). Both series of derivatives were effectively incorporated into polyvinylpyrrolidone (PVP) formulations, allowing them to overcome their low water solubility. The photodynamic activity of the PVP-based formulations obtained was assessed towards the Gram-positive Staphylococcus aureus, with and without the coadjuvant KI. The biological assays revealed that the new PVP-PS formulations were generally highly effective in the photoinactivation of S. aureus in the presence of KI. Principal component analysis (PCA), used to examine relationships between variables and identify key factors, showed that iodine (I₂) formation was the most influential factor of the photosensitizing activity of PVP-based formulations. The results showed that trans-A₂B₂-type porphyrins modified with N-donor units through CN bond have a high potential to develop novel and efficient porphyrin-based PS to be used in the photodynamic inactivation of bacterial strains.