Trifluoroacetyl neonicotinoid insecticides with enhanced hydrophobicity and effectiveness

Neonicotinoids with nitro- or cyanoimino substituents are extensively utilized as plant-mobile (systemic) insecticides controlling the piercing-sucking insect pests. This investigation considers structural features of neonicotinoids with trifluoroacetyl pharmacophores, which may confer enhanced hydrophobicity and effectiveness. Fifteen trifluoroacetyl neonicotinoid analogues [=NC(O)CF(3) and =CHC(O)CF(3)] are therefore prepared to evaluate the hydrophobicity index, toxicity to houseflies (Musca domestica), and binding affinity to the Musca nicotinic receptor. The =NC(O)CF(3) and =CHC(O)CF(3) compounds showed a higher hydrophobicity than that of nitro- or cyanoimino analogues. The intrinsic insecticidal activities (defined by intrathoracic injection with a synergist pretreatment) of test compounds were well-correlated to their target site potencies. Although nitro or cyano neonicotinoids were not toxic via the topical application route in the absence of a synergist, trifluoroacetyl analogues exhibited excellent insecticidal activity under the same condition. Accordingly, the increased hydrophobicity of trifluoroacetyl neonicotinoids presumably improves the penetrability of compound into insect integument and insecticidal effectiveness.