From Original Ferrocene-Based Small-Molecule Design to Multifunctional Supramolecular Bactericides: Their Efficient Applications in Controlling Biofilm-Associated Bacterial Infections

Abstract

Conventional bactericides struggle with biofilm barriers and inefficient deposition on hydrophobic leaves, resulting in undesirable control of plant bacterial diseases. To overcome these challenges, an innovative ferrocene-based small-molecule (FccA8R) is conceived, featuring biofilm disruption capabilities. Further optimizing FccA8R with seven-membered oligosaccharide-involved host–guest supramolecular strategy creates two kinds of biocompatible multifunctional supramolecular nanospheres (FccA8R@β-CD and FccA8R@HP-β-CD). This manipulation efficiently eradicates mature biofilm barriers while enhancing droplet retention on hydrophobic leaves. At a concentration of 56.64 µg mL⁻¹, the two materials remove Xanthomonas-biofilms by 76.32–76.83%, notably surpassing that of single FccA8R (57.96%). Their versatility extends to the enhanced inhibition of bacterial motility, extracellular enzymes secretion, and exopolysaccharides production, all reducing the bacterial virulence. In vivo pot experiments, FccA8R@β-CD and FccA8R@HP-β-CD demonstrate workable control efficacies of 48.91–52.03% against rice bacterial blight at 200 µg mL⁻¹, superior to the commercial thiodiazole-copper-20%SC (36.42%) and FccA8R-0.1%Tween (39.54%). Furthermore, these supramolecular assemblies disclose broad-spectrum bactericidal efficacy (71.45–73.19%) against kiwifruit canker, significantly higher than thiodiazole-copper-20%SC (43.05%) and FccA8R-0.1%Tween (57.24%). Besides, supramolecular bactericides are safe for plants and non-target organisms like zebrafish and earthworms. Briefly, this research builds a key foundation for creating green bactericides from small-molecule conception to eco-friendly supramolecular assemblies, realizing the prevention of bacterial diseases and environmental safety.