Quinine and Quinidine Derivatives as Photosensitizers for Photodynamic Inactivation of Bacterial Pathogens

This study reports the synthesis and characterization of 5-azoniabenzo[<i>no</i>]tetraphene derivatives of <i>Cinchona</i> alkaloids with potential applications in antimicrobial photodynamic therapy (aPDT). These compounds exhibit absorption maxima at 430-441 nm, as well as in the UV-A (340-342 nm) and UV-C (270-275 nm) regions, with fluorescence emission peaks ranging from 519 to 534 nm. At nontoxic concentrations of 2 μg mL^-1 and upon irradiation with blue light (418 nm), these compounds demonstrated potent bactericidal activity depending on the light dose. <i>Staphylococcus aureus</i> was eradicated after 5 min of irradiation (50 J cm^-2) with the isomer of 7<i>R</i>,2'<i>S</i> configuration (<b>QN-1</b>) as a photosensitizer. Gram-negative bacteria exhibited reduced sensitivity, with <i>Acinetobacter baumannii</i> requiring an energy dose of 150 J cm^-2 for effective killing, whereas <i>Proteus mirabilis</i> showed no significant reduction after exposure to 200 J cm^-2. The differences in sensitivity are attributed to the structure of the cell envelopes, which influence the uptake of the photosensitizer: the compounds accumulated intracellularly in Gram-positive bacteria but remained extracellular in Gram-negative rods. It is suggested that the aPDT mechanism involves a combination of oxidative pathways for <b>QN-1</b> and <b>QD-1</b> as photosensitizers and a Type II mechanism when <b>QN-2</b> was applied.