Toxicity Assessment of Brazilian Brown Propolis-Cu ²⁺ Complex with Enhanced Visible-Light Absorption and Antimicrobial Properties

In this study, we synthesized and characterized a novel Propolis-Cu (II) complex to enhance its photophysical and antimicrobial properties. The complex was characterized using UV-vis spectroscopy, FTIR, and scanning electron microscopy (SEM), revealing a distinct absorption profile and significantly enhancing Cu²⁺ absorption bands at 800-900 nm. FTIR reveals molecular interactions via carbonyl inhibition, and SEM indicate morphological changes with distinct crystalline structure formation. Although the Cu-PRO exhibits a significant decrease in antioxidant activity compared to propolis extract, the complex still retains considerable activity, which could be beneficial in future therapeutic applications. The antimicrobial activity of the Cu-PRO was significantly enhanced compared to pure propolis. While propolis alone exhibited strong activity against <i>Escherichia coli</i> (MIC = 12.5 μg·mL^-1) and good activity against <i>Listeria monocytogenes</i> (50.0 μg·mL^-1), the complex demonstrated an enhanced bactericidal action against <i>Staphylococcus aureus</i> at lower concentrations (50.0 μg·mL^-1) and good inhibitory activity against <i>Salmonellagallinarum</i> (50.0 μg·mL^-1) but not in <i>E. coli</i> and <i>L. monocytogenes</i>. Critically, toxicological assessment in <i>Drosophila melanogaster</i> revealed a chronic and dose-dependent toxicity profile, with lethal effects emerging only at doses >2.5 mg·mL^-1, in longer exposure, and a cumulative reduction in LC₅₀ over time (7.92 → 3.64 mg·mL^-1 in 6 days). However, toxicity was expressively lower than free Cu²⁺ salts, attributed to propolis-mediated chelation reducing free Cu²⁺ bioavailability and antioxidant activity, possibly mitigating oxidative stress. The complex's improved antimicrobial properties against <i>S. aureus</i> and <i>S. gallinarum</i>, coupled with modulated toxicity, position it as a promising candidate for therapeutic applications; particularly, its enhanced visible-light absorption in 800-900 nm falls into the therapeutic window of Photodynamic Therapy (PDT). We speculate that the results presented here highlight the potential of this complex as an innovative approach for combined therapies. Future studies are focusing on exploring its mechanisms of action and potential for light-assisted therapies, such as PDT where it can be used to simultaneously promote wound healing and combat infections.