Amphiphilic fluralaner pro-pesticides with enhanced systemicity on plants and reduced honeybee toxicity

Fluralaner, as a broad-spectrum and highly effective pesticidal molecule, is severely limited from agricultural application due to its high toxicity to honeybees. Herein, novel pro-pesticides were prepared by covalently linking fluralaner to polyethylene glycol and long-chain fatty acids, respectively, and were subsequently self-assembled into regular nano-micelles to reduce the toxicity of fluralaner to honeybees. The results showed that the obtained pro-pesticides self-assembled into nano-micelles without using any adjuvants, and the prepared nano-micelles showed spherical morphology, a low polydispersity index, strong negative charges, good surface activity and excellent maximum retention on hydrophobic leaves because of the amphiphilic structure. The toxicity of fluralaner prodrug molecules coupled with different fragments against Apis mellifera was more than 50 times lower than that of fluralaner. The solubility of compound E1 was increased by 68.4 times and was systemically distributed in all parts of Chinese flowering cabbage (Brassica rapa var. parachinensis; abbreviation: CS) seedlings. Therefore, the self-assembly nanotechnology of this prodrug conjugate is expected to improve the effective utilization rate of pesticides and reduce the toxicity of pesticides to the ecology and environment.