Carrier-free self-assembled baicalein derivative nanoparticles: pH-responsive antibacterial agent for controlling plant diseases caused by Xanthomonas spp.

Plant bacterial diseases caused by Xanthomonas threaten global crop production and food security, whereas conventional bactericides exhibit poor stability and limited efficacy against biofilms. In this work, a series of baicalein derivatives (X1–X32) containing a tertiary amine-functionalized piperidine moiety are designed and synthesized. All compounds form carrier-free nanoscale assemblies in water and exhibit superior in vitro antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas axonopodis pv. citri (Xac), and Xanthomonas campestris pv. mangiferaeindicae (Xcm) compared to thiodiazole copper (TC). Among them, X28 self-assembles into uniform, nearly spherical nanoparticles in aqueous solution, initiated by hydrophobic effects and stabilized by van der Waals interactions and π–π stacking. X28 nanoparticles (NPs) display pH-responsive disassembly under weakly-acidic conditions in vitro. At 200 µg mL⁻¹, they show superior in vivo protective and curative efficacies (52.9%–78.4%) against the corresponding bacterial diseases compared to TC (21.7%–59.3%). Additionally, they exhibit favorable foliar wettability, photostability, and biosafety. Mechanistic studies demonstrate that X28 NPs significantly inhibit biofilm formation and partially eliminate mature biofilms, and reduce bacterial motility, colonization, and pathogenicity. These findings demonstrate that X28 NPs serve as a promising and eco-friendly agrochemical for the efficient and sustainable control of plant bacterial diseases. Rational molecular functionalization of natural baicalein with a pH-responsive piperidine moiety, combined with carrier-free self-assembly, constructs a multifunctional antibacterial system with favorable agricultural performance. X28 nanoparticles self-assemble driven by hydrophobic interactions, van der Waals forces and π–π stacking, undergo pH-responsive disassembly in acidic infection microenvironments, and exert multi-target antibacterial action against Xanthomonas spp. by suppressing biofilm formation, motility and pathogenicity. X28 nanoparticles exhibit superior in vivo control efficacy over commercial bactericide thiodiazole copper, along with excellent foliar wettability, photostability and biosafety, offering a feasible strategy for developing high-efficiency agrochemicals.