Antioxidant 3-hydroxyflavone analogues: Integrated experimental and theoretical insights into lead fluoro-sensing and...

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

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.

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.