A Terminal Modification Strategy for Enhancing the Difference in Photoregulated Activity of Azobenzene–Tolfenpyrad Hybrids

Photopharmacology provides a strategy for green pesticide design. Starting from tolfenpyrad, azobenzene-modified photochromic ligands ABT1–6 were synthesized. ABT6 showed high bioactivity and photoisomerization efficiency but limited trans / cis activity difference. To enhance this, terminal phenyl modifications yielded ABT7–15, which displayed amplified photoregulatory activity differences across pests. Notably, ABT14 exhibited a 4.8-fold photoinduced activity enhancement against Culex pipiens pallens larvae and a 6.6-fold photoinduced activity reduction against Aphis craccivora, while ABT11 achieved a 35-fold reduction against Tetranychus cinnabarinus . Molecular docking and binding free energy calculations indicated stronger cis -isomer binding to the target via multiple hydrogen bonds. Molecular orbital analysis revealed a minimal HOMO–LUMO gap difference (0.05 eV) between isomers, suggesting activity differences arise from conformational changes in charge distribution rather than energy variations. This work demonstrates a rational design approach for high-performance photoresponsive pesticides.