Antioxidant 3-hydroxyflavone analogues: Integrated experimental and theoretical insights into lead fluoro-sensing and toxicity mitigation in living systems.

BACKGROUND

Lead (Pb2+) toxicity represents a major public health challenge, underscoring the need for advanced detection and remediation strategies.

RESULTS

We introduce two synthetic 3-hydroxyflavone (3-HF) analogues: 3',4'-methylenedioxy-3-hydroxyflavone (1) and 4'-N,N-dimethyl-3-hydroxyflavone (2) as multifunctional "sense-and-treat" agents for Pb2+. These probes detect Pb2+ via a characteristic excited-state intramolecular proton transfer (ESIPT) fluorescence response, demonstrating excellent sensitivity with detection limits of 1.8 μM for (1) and 4.9 μM for (2), and high selectivity over competing ions such as Hg2+ and Cd2+. Density functional theory (DFT) calculations confirm that Pb2+ chelation at the 3-hydroxy-4-carbonyl motif induces the observed fluorescence shift. The probes enabled real-time fluorescence mapping of Pb2+ in live mice hepatocytes with minimal cytotoxicity (>90 % cell viability). Furthermore, probe (1) mitigated Pb2+-induced oxidative stress in vivo by sequestering Pb2+ into a less reactive complex, restoring redox homeostasis and tissue integrity.

SIGNIFICANCE: This study advances the understanding of 3-HF-metal interactions, establishing 3-HF analogues as a promising integrated platform for comprehensive lead toxicity management. These findings have direct applications in environmental monitoring, clinical toxicology, and public health.