Hydrophobic nanoprecipitates formed by benzoylphenylureas and β-cyclodextrin inclusion compounds: synthesis, characterization and toxicity against aedes aegypti larvae

Abstract

The aim of this work was to synthesize and characterize the inclusion compounds formed by the complexation of β-cyclodextrin (βCD) with insecticides from the class of benzoylphenylureas (BPUs), named novaluron (NOV) and diflubenzuron (DIF), beyond evaluate their larvicidal activity against Aedes aegypti larvae. Solid state characterization by FTIR showed changes in the main peaks of BPUs and βCD, suggesting the formation of inclusion compounds in solid phase. DTA and TGA thermal analysis showed changes in temperatures of BPUs decomposition as result of molecular interactions. 1H NMR experiments allowed to observe the occurrence of interactions in solution through changes in chemical shifts of BPUs aromatic hydrogens. However, the presence of H–H intermolecular correlations in 2D ROESY was found only for the DIF/βCD complex, suggesting different topology for each complex. Such hypothesis was corroborated by thermodynamic analysis using ITC, which showed different profile of titration curves, beyond endothermic and exothermic interactions for NOV/βCD and DIF/βCD complexes, respectively. DLS titrations of BPUs or BPUs/βCD DMSO solutions in aqueous solution demonstrated that the spontaneously formed hydrophobic nanoprecipitates (HNPs) have different profile of sizes depending on the BPU/βCD system, corroborating also with the hypothesis about the existence of different topologies for each complex. Finally, the HNPs of inclusion compounds showed to be more efficient than free BPUs, allowing proposing a new insecticide formulation.