Search Results (7)

Bulky NCN aryl-diamides featuring methyl groups in the benzyl positions were synthesized with the aim of creating a new class of meta-xylene-based trianionic pincer ligands where the common decomposition pathway of metal pincer complexes via C-H activation is prevented. Sterically demanding substituents on the ligands furthermore provide steric protection of the metal centre and can help prevent the dimerization of the complexes. While a double deprotonation of the ligands and the formation of a dilithium salt was straightforward, difficulties were encountered when attempting to deprotonate the ipso-CH proton on the central aryl ring to yield trianionic ligands. This stands in contrast to related pincer ligands without methyl groups in the benzylic positions. Experimental and theoretical investigations led to the conclusion that the challenges encountered when attempting the third deprotonation are likely caused by an interplay of increased electron density at the nitrogen atoms and steric hindrance. Both effects originate in the introduction of methyl groups in the benzylic positions, which make the targeted proton less accessible. These results provide further insight into the impact of methyl groups in the benzyl positions on both steric and electronic properties of NCN pincer ligands, which may find utility in coordination chemistry applications where metalation can be achieved by direct C-H activation rather than requiring triple deprotonation. Full article

The rice stem borer (RSB) Chilo suppressalis is a devastating rice pest with resistance to a number of insecticides. Recently, the new meta-diamide insecticide cyproflanilide has been considered an effective insecticide to control RSB. However, its resistance risk has not been reported. In the present study, we aimed to assess the resistance risk and evaluate the fitness cost after the RSB was exposed to cyproflanilide. After five generations of selection, the resistance level of RSB increased by 1.5-fold. When h² was 0.125, a 10-fold resistance increase in the LD₅₀ values was expected in fourteen and thirty-one generations at the selection intensity of 90% and 50%, respectively. The selected population (RSB-SEL) had significant differences in the developmental duration of eggs, 1st, 2nd, 3rd, and 6th instar larvae, and female pupae compared to the unselected population (RSB-UNSEL). Besides, the adult longevity was shortened, and the average pupal weight of males, the emergence rate, the sex ratio, the oviposition, the mean fecundity, and the full life cycle rate were decreased in RSB-SEL. The intrinsic rate of increase (r), the net reproductive rate (R₀), and the finite rate of increase (λ) of RSB-SEL were significantly lower than those of RSB-UNSEL, while the mean generation time (T) of RSB-SEL was significantly longer than that of RSB-UNSEL. Based on the results of the prediction of the generations required for a 10-fold resistance increase in the LD₅₀, a potential risk of resistance development exists in RSB after continuous and excessive use of cyproflanilide. These results will be useful in designing the dose of cyproflanilide to control C. suppressalis in field. Full article

Ionotropic γ-aminobutyric acid (GABA) receptors in insects, specifically those composed of the RDL (resistant to dieldrin) subunit, serve as important targets for commonly used synthetic insecticides. These insecticides belong to various chemical classes, such as phenylpyrazoles, cyclodienes, meta-diamides, and isoxazolines, with the latter two potentially binding to the transmembrane inter-subunit pocket. However, the specific amino acid residues that contribute to the high sensitivity of insect RDL receptors to these novel insecticides remain elusive. In this study, we investigated the susceptibility of seven distinct Drosophila melanogaster Rdl point mutants against four meta-diamide and isoxazoline insecticides: isocycloseram, fluxametamide, fluralaner, and broflanilide. Our findings indicate that, despite exhibiting increased sensitivity to fluralaner in vitro, the Rdl^I276C mutant showed resistance to isocycloseram and fluxametamide. Similarly, the double-points mutant Rdl^I276F+G279S also showed decreased sensitivity to the tested isoxazolines. On the other hand, the Rdl^G335M mutant displayed high levels of resistance to all tested insecticides. Molecular modeling and docking simulations further supported these findings, highlighting similar binding poses for these insecticides. In summary, our research provides robust in vivo evidence supporting the idea that the inter-subunit amino acids within transmembrane M1 and M3 domains form the binding site crucial for meta-diamide and isoxazoline insecticide interactions. This study highlights the complex interplay between mutations and insecticide susceptibility, paving the way for more targeted pest control strategies. Full article

The meta-diamide (m-diamide) insecticide, Broflanilide, was characterized by its high efficiency, low toxicity and lack of cross-resistance with traditional GABA receptors. In accordance with the principles of drug molecular design, easily derivable sulfur with diverse bioactivities was introduced while leading with the parent Broflanilide. Twelve novel m-diamide target compounds containing sulfide derivatives were synthesized through exploration guided by the literature. Their structures were confirmed by melting points, ¹H NMR, ¹³C NMR and HRMS. Insecticidal activity assessments revealed that most target compounds A–D exhibited 100% lethality against Plutella xylostella (P. xylostella) and Aphis craccivora Koch (A. craccivora) at 500 mg·L⁻¹. Notably, for P. xylostella, compounds C-2, C-3, C-4 and D-2 demonstrated 60.00–100.00% insecticidal activity even at a concentration as low as 0.625 mg·L⁻¹. As determined by structure–activity relationship (SAR) analysis, compounds with R₁ = CH₃ and R₂ = Br (B-1, C-2 and D-2) and sulfoxide compound C-3 contained 100.00% lethality against A. craccivora at 500 mg·L⁻¹, surpassing the lethality when leading with the parent Broflanilide in terms of efficacy. Consequently, it can be inferred that the sulfoxide compound (C-3) requires further investigation as a potential active molecule for new insecticides. These explorations provide valuable references for future research on the synthesis and insecticidal activities of sulfide-containing m-diamide compounds. Full article

Spodoptera litura is a damaging and notorious insect pest of agricultural crops that has developed resistance to various insecticides. Broflanilide is a novel pesticide with a unique mode of action that displays high efficiency against lepidopterous larvae. We here determined the baseline susceptibility of a laboratory strain of S. litura to broflanilide and 10 other popular insecticides. Furthermore, we measured susceptibility and cross-resistance using three common insecticides in 11 field-collected S. litura populations. Broflanilide caused the highest toxicity among all tested insecticides, with the laboratory strain and all field-collected populations showing high susceptibility. Moreover, no cross-resistance was detected between broflanilide and the other tested insecticides. We subsequently evaluated the sublethal effects of broflanilide and found that treatment with the 25% lethal concentration (LC₂₅) prolonged the development duration in the larvae, reduced the pupation rate and pupae weight, and decreased egg hatchability. Finally, the activities of three detoxifying enzymes were measured in S. litura after treatment with the LC₂₅ dose. The results suggested that enhanced cytochrome P450 monooxygenase (P450) activity could be involved in broflanilide detoxification. Overall, these findings demonstrate the strong toxicity and significant sublethal effects of broflanilide in S. litura and suggest that increased P450 activity may be associated with broflanilide detoxification. Full article

The Aphis gossypii is an important pest that can damage cotton plants and can cause a huge economic loss worldwide. Chemical control is a main method to manage this pest, but the cotton aphid resistance to insecticides has become a severe problem in the management of the cotton aphid. It is important to introduce a novel insecticide for rotational application with other insecticides. Broflanilide, as a meta-diamide insecticide with a special mode of action, showed high efficiency against lepidopterous larvae. However, we found that broflanilide possessed high insecticidal activity against the sap-sucking pest A. gossypii. The susceptibility of A. gossypii to broflanilide from 20 field populations in main cotton planting areas of China in 2021 was determined by the leaf-dipping method. LC₅₀ values of broflanilide to A. gossypii ranged from 0.20 μg mL⁻¹ to 1.48 μg mL⁻¹. The susceptible baseline of A. gossypii to broflanilide was established with the LC₅₀ value of 0.41 μg mL⁻¹ and might be used to calculate the resistance ratio (RR) of cotton aphid population in broflanilide resistance monitoring. The RR value of field populations in China was from 0.49 to 3.61 in 2021. It suggested that the broflanilide may be a potential agent in the resistance management of A. gossypii to insecticides. These results are significantly useful for the rational chemical control of cotton aphids. Full article

Herein, we describe novel pentafluorosulfanyl (SF₅) group-containing meta-diamide insecticides. For the facile preparation of the SF₅-based compounds 4a–d, practical synthetic methods were applied. Among newly synthesized compounds, 3-benzamido-N-(2,6-dimethyl-4-(pentafluoro-λ⁶-sulfanyl)phenyl)-2-fluorobenzamide 4d showed (i) a high insecticidal activity, (ii) an excellent selectivity to insects, and (iii) good levels of water solubility and log P values. In this study, we demonstrated that the pentafluorosulfanyl moiety could serve as an attractive functionality for the discovery of a new scope of crop-protecting agents. Full article