Halogen Modulation: Novel Fluoropyridylphenylurea Derivatives as Potent Molluscicides Unveiling Snail‐Killing Mechanisms

Abstract Pomacea canaliculata is an invasive species that poses significant threats to agriculture and human health. The development of environmentally friendly molluscicides is crucial for its management. In this study, we synthesized 17 fluoropyridylphenylurea derivatives using a halogen modulation strategy to explore their potential as molluscicides. Compounds L‐1 and L‐2 demonstrated notable molluscicidal activity, with LC 50 values of 1.377 mg/L and 1.001 mg/L, respectively. Among these, L‐2 exhibited superior efficacy while causing minimal harm to other aquatic organisms, particularly fish. The molluscicidal mechanism of L‐2 was investigated using Tandem Mass Tags (TMT)‐labeled quantitative proteomic analysis and non‐targeted metabolic analysis. These analyses revealed that L‐2 significantly affected the liver metabolism of P. canaliculata by disrupting the transaminase, gluconeogenesis, and glycolysis pathways. This metabolic disruption is likely a contributing factor to the mortality observed in the snails. Our findings suggest that compound L‐2 is a promising molluscicide, offering high efficiency and minimal environmental impact. These insights could guide future research and development in molluscicide applications.