Pharmacophore model for neonicotinoid insecticides

An effective prediction pharmacophore model （RMS = 0.634, Correl = 0.893, Weight = 1.463, Config = 11.940） was successfully obtained by 3D-QSAR based on a series of nAChR （nicotinic acetylcholine receptors） agonists, which consists of a hydrogen- bonding acceptor, a hydrogen-bond donor, a hydrophobic aliphatic and a hydrophobic aromatic centre. This pharmacophore model may provide theoretical basis for designation and development of higher active insecticides.

Insights into Free and Conjugated Forms of Neonicotinoid Insecticides in Human Serum and Their Association with Oxidative Stress

Following exposure,neonicotinoid insecticides(NEOs)can be metabolized by both Phase Ⅰ and Phase Ⅱ reactions catalyzed by human cytochrome P450 enzymes.However,toxicities of parent NEOs and their metabolites are still unclear,and little is known about biotransformation rates and pathways of NEOs in humans.In this study,98 serum samples collected in China were analyzed for free,conjugated and total forms of six parent NEOs(i.e.,acetamiprid(ACE),imidacloprid(IMI),clothianidin(CLO),thiacloprid(THD),thiamethoxam(THM),and dinotefuran(DIN))and four metabolites(i.e.,N-desmethyl-acetamiprid(N-dm-ACE),1-methyl-3-(tetrahydro-3-furylmethyl)(DIN-U),5-hydroxy-imidacloprid(5-OH-IMI),olefin-imidacloprid(Of-IMI)).NEOs and their metabolites were detected in all serum samples,and the total median concentrations of free,conjugated,and total forms of 10 NEOs were 2.04,2.01,and 5.12 ng/mL,respectively.Conjugated forms of NEOs accounted for only half(53%)of the total forms of NEOs.Based on the profiles of Phase Ⅰ and Phase Ⅱ metabolites of NEOs in serum,it was found that age is a determinant in Phase Ⅰmetabolism of DIN and Phase Ⅱ metabolism of IMI.The Phase Ⅱmetabolites of NEOs are associated with oxidative DNA damage,and the conjugated forms of IMI,DIN,and 5-OH-IMI in serum were significantly positively correlated with oxidative stress.Overall,the amount of NEOs present in conjugated forms in human serum was determined to document the existence of a considerable proportion of free forms of these insecticides.

Occurrence, variations, and risk assessment of neonicotinoid insecticides in Harbin section of the Songhua River, northeast China

Neonicotinoid insecticides(NNIs)have been intensively used and exploited,resulting in their presence and accumulation in multiple environmental media.We herein investigated the current levels of eight major NNIs in the Harbin section of the Songhua River in northeast China,providing the first systematic report on NNIs in this region.At least four NNIs in water and three in sediment were detected,with total concentrations ranging from 30.8 to 135 ng L^(-1) and from 0.61 to 14.7 ng g^(-1) dw,respectively.Larger spatial variations in surface water NNIs concentrations were observed in tributary than mainstream(p<0.05)due to the intensive human activities(e.g.,horticulture,urban landscaping,and household pet flea control)and the discharge of wastewater from many treatment plants.There was a significant positive correlation(p<0.05)between the concentrations of residual imidacloprid(IMI),clothianidin(CLO),and S4NNIs in the sediment and total organic carbon(TOC).Due to its high solubility and low octanol-water partition coefficient(Kow),the sediment-water exchange behavior shows that NNIs in sediments can re-enter into the water body.Human exposure risk was assessed using the relative potency factor(RPF),which showed that infants have the highest exposure risk(estimated daily intake(SIMIeq EDI):31.9 ng kg^(-1) bw$d^(-1)).The concentration thresholds of NNIs for aquatic organisms in the Harbin section of the Songhua River were determined using the species sensitivity distribution(SSD)approach,resulting in a value of 355 ng L^(-1) for acute hazardous concentration for 5%of species(HC5)and 165 ng L^(-1) for chronic HC5.Aquatic organisms at low trophic levels were more vulnerable to potential harm from NNIs.

Design,synthesis,and insecticidal bioactivities evaluation of pyrrole-and dihydropyrrole-fused neonicotinoid analogs containing chlorothiazole ring

Chlorothiazole ring, as a substituted heterocycle, frequently occurred in structures of various insecticides, and brought positive effect on bioactivity. In purpose to find novel neonicotinoids, a series of pyrrole- and dihydropyrrole-fused neonicotinoid analogs containing chlorothiazole ring were synthesized for the first time. Results of the following biological assays showed that compounds Sa-c achieved good insecticidal activity against Aphis craccivora, and compound Sh exhibited good activity against Nilaparvata lugens.

Synthesis and insecticidal activities of novel bridged-neonicotinoids

A series of novel bridged-neonicotinoid analogues were designed and synthesized, which were constructed by starting material 8 with cyclopentenone or cyclohexenone in the presence of catalyst aluminium chloride. All of the compounds were characterized and confirmed by^1H NMR,^（13）C NMR, HRMS and IR. The bioassay tests showed that compounds 5 and 6a showed higher bioactivities than imidacloprid against Aphis craccivora.

Adsorption behavior of imidacloprid pesticide on polar microplastics under environmental conditions:critical role of photo-aging

The photo-aging behavior of microplastics(MPs)in natural environment has become a global concern.The ultraviolet radiation has enough energy to change the polymer structure and physicalchemical properties of MPs.Less attention has focused on the interactions of the photo-aged polar and biodegradable MPs with organic pollutants.This work investigated the structural properties of aged polar polyamide(PA)MPs and biodegradable polylactic acid(PLA)MPs exposed to ultraviolet irradiation and their adsorption behavior and mechanism for neonicotinoid insecticide imidacloprid(IMI).The results showed that the MPs had extensive changes in surface morphology and chemical properties after photo-aging.The C–N bond of PA MPs was disrupted to form more carbonyl groups.The oxygen-containing functional groups on the surface of aged PLA MPs were broken and generated relatively smaller molecules.The adsorption capacity of IMI on PA MPs decreased by 19.2%,while the adsorption capacity of IMI on PLA MPs increased by 41.2%after photo-aging.This depended on the natural structure of the MPs and their ability to absorb ultraviolet light.The electrostatic interactions,hydrogen bonds,van der Waals interactions,and polar-polar interactions were the main adsorption mechanisms of IMI on MPs.High initial solution pH and low ionic strength favored the adsorption of IMI by altering charge distribution on the MPs surface.The formation of the humic acid-IMI complexes decreased the concentration of IMI in the water phase and further decreased the adsorption on MPs.These results are enlightening for a scientific comprehension of the environmental behavior of the polar MPs.

Synthesis and insecticidal activities of 1,8-naphthyridine derivatives

1,8-Naphthyridines（NAP） are biological important scaffolds in bioactive molecules design. By hybrid of NAP with neonicotinoid core structure, nine novel NAP derivatives were synthesized and subjected to insecticidal activities evaluation. Some of the compounds showed excellent insecticidal activity against cowpea aphids（Aphis craccivora） with LC_（50） values ranging from 0.011 mmol/L to 0.067 mmol/L. The results indicated that 1,8-naphthyridine can be used as insecticidal structure for further modification.