Synthesis of novel pyranoflavylium-based dyes as promising photosensitizers for antimicrobial photodynamic inactivation

Amino-substituted dyes have recently been described for their interesting photosensitizing properties in photodynamic therapy against bacterial growth. In the present study, two novel pyranoflavylium-based dyes namely 4′-dimethylamino-10-(4''-(dimethylamino)phenyl)pyranoflavylium (4′,4″N(Me)₂PyF) and 6-Bromo-4′-dimethylamino-10-(4''-(dimethylamino)phenyl)pyranoflavylium (6Br4′,4″N(Me)₂PyF) were synthesized through the reactions between salicylaldehyde and acetophenone derivatives to improve the photo-properties of 5-hydroxy-4′-dimethylaminoflavylium (5OH4′N(Me)₂F), a non-photoactivated flavylium salt previously reported due to the presence of a hydroxyl group in its structure. The presence of a pyranic ring with an additional dimethylaminophenyl group and the insertion of a bromine atom changed the spectroscopic properties of the parent flavylium, causing a red shift of the absorption band, higher molar extinction coefficient, and fluorescence emission. Both pyranoflavylium dyes showed appreciable singlet oxygen production, and phototoxicity studies demonstrated their photoactivable nature, leading to a reduction of >3log in cellular viability of S. aureus ATCC 29213 after 15 min of irradiation (22.5 J/cm²).

In conclusion, this study describes a chemical strategy to extend π-conjugation, converting a non-active flavylium dye into photoactivable ones. This approach could be further explored to develop novel solutions for antimicrobial photodynamic inactivation, potentially addressing issues related to antimicrobial resistance.