Synthetic access to tetracationic benzoporphyrins and their role as photosensitizers towards gram-negative Escherichia coli

Nowadays population face an episode where bacteria are becoming resistant to antibiotics, and it is crucial to find out alternatives and new molecules to fight these microorganisms. Photodynamic inactivation of microorganisms has been pointed out as an alternative to conventional therapies. This is an approach that involves the light activation of a photosensitizer which in the presence of molecular oxygen (³O₂) leads to the generation of cytotoxic species, namely singlet oxygen (¹O₂). Among the several photosensitizer agents available, porphyrins and related macrocycles have been highlighted as the most advantageous and effective due to their characteristic photochemical and photophysical features.

This work describes the synthesis and characterization of benzoporphyrins derivatives bearing triazolyl groups and also of the analogues with pyridyl units under Heck coupling conditions. The benzoporphyrin derivatives containing pyridyl groups were further quaternized with iodomethane and 1-iodopentane to evaluate the influence of alkyl chain size on their photoinactivation ability. The biological studies towards Gram-negative bioluminescent Escherichia coli showed that the tetracationic benzoporphyrins can efficiently inactivate this bacterium. However, the pentylated derivative showed to be more efficient in E. coli inactivation when compared to the methylated porphyrin, probably due to its larger alkyl chain, which promotes better bacterial membrane binding.