Synthesis and insecticidal activity of anthranilic diamides with hydrazone substructure

A series of anthranilic diamides with a hydrazone substructure was synthesised and characterised using ¹HNMR, ¹³C NMR, IR and elemental analyses. The in vitro insecticidal activity of all the compounds was tested against Plutella xylostella. The results showed the synthesised compounds to possess good insecticidal activity. The LC₅₀ values of compounds VIIg, VIIl, VIIm, VIIn exhibited excellent insecticidal activities, with the LC₅₀ affording 7.92 mg L^?1, 12.01 mg L^?1, 0.62 mg L^?1 and 10.71 mg L^?1, respectively. These may prove to be useful as potential insecticidal agents.     

Design, synthesis, insecticidal evaluation and molecular docking studies of cis-nitenpyram analogues bearing diglycine esters

Based on the strategies of receptor structure-guided neonicotinoid design, a series of novel cis-nitenpyram analogues bearing diglycine esters were designed and synthesized. Preliminary bioassays indicated that the insecticidal spectra of the target compounds were expanded compared with our previous work, while all the target compounds presented excellent insecticidal activities against Nilaparvata lugens and Aphis medicagini at 100 mg/L. Among these analogues, 6b showed 100% mortality against Nilaparvata lugens (LC 50 = 0.163 mg/L) and 90% against Aphis medicagini at 4 mg/L. SARs suggested that the insecticidal potency of our designed cis-nitenpyram analogues was dual-controlled by the size and species of the ester groups. The molecular docking simulations revealed that the structural uniqueness of these analogues may lead to a unique molecular recognition and binding mode compared with the previously designed compounds. Introduction of the peptide bond gave rise to more significant hydrogen bonds between the nitenpyram analogues bonding with the amino acid residues of insect nAChRs. The docking results explained the SARs observed in vitro, and shed light on the novel insecticidal mechanism of these cis-nitenpyram analogues.     

<em>N</em>-Substituted 5-Chloro-6-phenylpyridazin-3(2<em>H</em>)-ones: Synthesis, Insecticidal Activity Against <em>Plutella xylostella </em>(L.) and SAR Study

A series of N-substituted 5-chloro-6-phenylpyridazin-3(2H)-one derivatives were synthesized based on our previous work; all compounds were characterized by spectral data and tested for in vitro insecticidal activity against Plutella xylostella. The results showed that the synthesized pyridazin-3(2H)-one compounds possessed good insecticidal activities, especially the compounds 4b, 4d, and 4h which showed > 90% activity at 100 mg/L. The structure-activity relationships (SAR) for these compounds were also discussed.     

Computational Investigations about the Effects of Hetero‐molecular Aggregation on Bioactivities: a Case of Neonicotinoids and Water

Molecular aggregation state of bioactive compounds plays a key role in bio‐interactive procedure. Diverse aggregation states of bioactive compounds contribute to different biological or chemical properties. Water‐bridge, as the simple hetero‐molecular aggregation, has been found bridging the binding between many bioactive compounds and their targets through hydrogen bonding network, e.g. in the recognition of neonicotinoids with insect nAChRs. To better understanding the roles of water‐bridge on bioactivities of compounds, an approach of hetero‐dimeric aggregation with water was proposed. Quantitative structure‐activity relationship (QSAR) and pharmacophore modeling investigations were applied on 19 neonicotinoids, as well as their aggregates with water. The aggregate‐based CoMSIA, PHASE and linear QSAR models presented better statistical significance and predictabilities than the monomer ones, which indicated that the bioactivities correlated with the aggregate properties and water bridged hydrogen bond of the active site. All results revealed the essential roles of water‐bridge in ligand recognition, which should be considered in future ligand design and optimization.     

Synthesis and Insecticidal Evaluation of Chiral Neonicotinoids Analogs: The Laurel Wilt Case

Xyleborus sp beetles are types of ambrosia beetles invasive to the United States and recently also to Mexico. The beetle can carry a fungus responsible for the Laurel Wilt, a vascular lethal disease that can host over 300 tree species, including redbay and avocado. This problem has a great economic and environmental impact. Indeed, synthetic chemists have recently attempted to develop new neonicotinoids. This is also due to severe drug resistance to “classic” insecticides. In this research, a series of neonicotinoids analogs were synthesized, characterized, and evaluated against Xyleborus sp. Most of the target compounds showed good to excellent insecticidal activity. Generally, the cyclic compounds also showed better activity in comparison with open-chain compounds. Compounds R-13, 23, S-29, and 43 showed a mortality percent of up to 73% after 12 h of exposure. These results highlight the enantioenriched compounds with absolute R configuration. The docking results correlated with experimental data which showed both cation-π interactions in relation to the aromatic ring and hydrogen bonds between the search cavity 3C79 and the novel molecules. The results suggest that these sorts of interactions are responsible for high insecticidal activity.     

Synthesis,insecticidal activities,and SAR studies of novel piperazine-containing heterocyclic mono-/di-/tri-amide derivatives

Diamide compounds such as chlorantraniliprole, a famous anthranilic diamide insecticide targeting the insect ryanodine receptor (RyR), have received continuous attention in pesticide research during the past 15 years owing to their excellent insecticidal potentials. With the aim of discovering new heterocyclic pesticides used for crop protection, based on the structural information of compound M from the reported pharmacophore-based virtual screening for RyR insecticides and diamide compound, a series of new heterocyclic mono-, di-, and tri-amide derivatives containing piperazine moiety have been synthesized in this paper. The new compounds were identified and confirmed by melting point, ¹H NMR, ¹³C NMR and HRMS. Compound M was firstly validated for insecticidal activities, and the new synthesized compounds were all made comprehensive insecticidal evaluations against diamondback moth and oriental armyworm. The bioassay results showed that some of the compounds exhibit favorable insecticidal potentials, particularly some novel piperazine-containing heterocyclic mono-/di-/tri-amide derivatives such as 8g, 14a, 15a, 15g, 15i, 15j, 15k, 15l, and 15m could be used as new insecticidal leading structures for further study (e.g., towards diamondback moth, 15i-15m LC₅₀: 0.0022−0.0081 mg/L). The structure-activity relationships of the compounds discussed in detail provide useful guidance for further design and development of new insecticides.     

Synthesis,insecticidal activities and SAR studies of novel anthranilic diamides containing trifluoroethoxyl substituent and chiral amino acid moieties

Based on the structures of ryanodine receptors (RyRs) activators anthranilic diamide insecticidal agents and FKI- 1033, a series of 18 novel trifluoroethoxyl-containing chiral anthranilic diamides Ia–i and IIa–i were synthesized. Their insecticidal activities were evaluated systematically and the SAR was discussed.     

Synthesis,Insecticidal Assay and Molecular Docking Study of Novel Neonicotinoids N‐Oxide Analogues

Eight novel neonicotinoids N‐oxide analogues were designed and synthesized. All the compounds have been identified by ¹H NMR and HRMS. The N‐oxide analogues exhibit high insecticidal activity against cowpea aphids (Aphis craccivora) at 250 mg·L^?1. The influence of N‐oxide formation on the biological activity was elucidated by computational chemical study, and it indicated that the water bridge hydrogen bonding network was broken due to the influence of the O atom connected with the pyridine ring.     

Studies on the biological activity of gem-difluorinated 3,3-spirocyclic indole derivatives

The biological activities of a series of 3,3-spirocyclic indole derivatives containing CF₂, phosphine oxide,indole, and cyano functional groups were evaluated, and these derivatives were found to exhibit antiTMV, fungicidal, and insecticidal activities.     

Study on the Dynamic Difference between Single and Mixed Residues of Three Neonicotinoids in Brassica chinensis L.

Multiple insecticides’ residues after the mixed application of several neonicotinoids cause combined pollution and bring new challenges to food safety and pest control during agricultural production. In this study, three neonicotinoid insecticides, namely imidacloprid (IMI), acetamiprid (ACE), and thiamethoxam (TMX), were mixed and evenly sprayed on Brassica chinensis L. in the field. Then, the insecticides’ residues were dynamically monitored to determine the differences in their rates of dissipation and final residues after 10 days. The results showed that the dissipation kinetics of neonicotinoids still conformed to the first-order kinetic model for binary or ternary application of neonicotinoid mixtures, with all determination coefficients (R²) being above 0.9 and the dissipation half-life (DT₅₀) being 2.87–6.74 d. For treatment groups with five times the recommended dosages (IMI 300 g·hm⁻², ACE 900 g·hm⁻², and TMX 600 g·hm⁻²), mixed insecticides had a slower dissipation rate, and the DT₅₀ values of mixtures were longer than those of single insecticides. Moreover, the final insecticide residues with mixed application were higher than those of single compounds at 10 d after spraying. Thus, mixed applications of neonicotinoids may increase food safety risks as they increase the final insecticide residues in Brassica chinensis L., and care should therefore be taken when considering the combined use of such compounds.     

Design,synthesis, and insecticidal activities of novel diamide derivatives with alpha-amino acid subunits

A series of diamide derivatives containing α-amino acids were designed and synthesized. These compounds were evaluated for their insecticidal activities against Plutella xylostella, Mythimna separate, Myzus persicae, and Tetranychus cinnabarinus. Most of the title compounds containing an l -phenylglycine skeleton were endowed with good activities at the concentration of 500 mg·L⁻¹. Compounds ( R)-A6 showed a potential value for further optimization as an insecticidal lead with the LC₅₀ value of 86.8 mg·L⁻¹.     

Synthesis and Biological Activities of 3‐Substituted Analogues of Tenuazonic Acid

A series of tenuazonic acid analogues in which the acetyl group was replaced with electron‐withdrawing substituents have been synthesized with the aim of obtaining molecules with various bioactivities. Substituents such as cyano, sulfonyl, and amido were introduced at the 3‐position of the pyrrolidine‐2,4‐dione nucleus of tenuazonic acid. 3‐Cyano and sulfonyl pyrrolidine‐2,4‐dione compounds ( 2 and 6 ) were prepared via a Dieckmann cyclization as key step. 3‐Amido pyrrolidine‐2,4‐dione compounds ( 9 ) were prepared by a microwave‐assisted amidation reaction from corresponding 3‐carboxylate derivative. The target compounds were evaluated; their herbicidal, fungicidal, and insecticidal activities, and the preliminary bioassay data showed that some 3‐cyanopyrrolidine‐2,4‐diones 2 gave good insecticidal activity, whereas some 3‐amido compounds 9 exhibited moderate to strong fungicidal activity against Pythium dissimile at 20 mg/L.     

Synthesis and biological activity of permethrin analogs containing various substituents in position <Emphasis Type="Italic">2</Emphasis> of the cyclopropane ring

A number of permethrin derivatives having various substituents (Me, Et, Pr, Ph, PhCH₂, PhCH₂CH₂) in position 2 of the cyclopropane ring were synthesized and assayed for insecticidal activity against typhoid flies, rice weevils, and black bean aphid and juvenile hormone activity against flour beetle chrysalises. The examined compounds showed a weak insecticidal activity. Some derivatives were found to exert knockdown effect analogous to that of commercial pyrethroid tetramethrin; however, unlike permethrin, they exhibited pronounced juvenile hormone activity.     

The Raman OH stretching bands of liquid water

In this work, from the discussion on water structure and clusters, it can be deduced that the OH stretching vibration is closely related to local hydrogen-bonded network for a water molecule, and different OH vibrations can be assigned to OH groups engaged in various hydrogen bonding. At ambient condition, the main local hydrogen bonding for a molecule can be classified as DDAA (double donor–double acceptor), DDA (double donor–single acceptor), DAA (single donor–double acceptor) and DA (single donor–single acceptor) and free OH vibrations. As for water at 290 K and 0.1 MPa pressure, the OH stretching region of the Raman spectrum can be deconvoluted into five sub-bands, which are located at 3014, 3226, 3432, 3572, and 3636 cm⁻¹, and can be assigned to ν_DAA-OH, ν_DDAA-OH, ν_DA-OH, ν_DDA-OH, and free OH₂ symmetric stretching vibrations, respectively.     

Synthesis,insecticidal activities,and molecular docking studies of 1,5‐disubstituted‐1,3,5‐hexahydrotriazine‐2‐(N‐nitro)imines

A series of novel neonicotinoids analogs were designed by modifying the pharmacophore of imidacloprid to 1,3,5‐hexahydrotriazine conjugated to nitroimine (?NNO₂) and introducing the phenyl or arylmethyl at the 5‐position, and their insecticidal activities were evaluated. Introducing a heterocyclic methyl at 5‐position increased the insecticidal activities, whereas other phenyl, phenylmethyl or phenylethyl substituents were unfavorable to activities. Molecular docking study was also performed to clarify the interactions of the most potent analog 1‐((6‐chloropyridin‐3‐yl)methyl)‐5‐(3‐pyridylmethyl)‐1,3,5‐hexahydrotriazine‐2‐(N‐nitro) imine ( 7s ) with the target nicotinic acetylcholine receptor, which explained the structure‐activity relationships observed in vitro, and revealed further possibilities for insecticide development. J. Heterocyclic Chem., (2011).     

Charge‐transfer complexes of N‐methyl‐and N‐ethyl­carbazole with 3,5‐di­nitro­benzo­nitrile

In the two title compounds, N‐methyl­carba­zole–3,5‐di­nitro­benzo­nitrile (1/1), C₁₃H₁₁N·C₇H₃N₃O₄, (I), and N‐ethyl­carba­zole–3,5‐di­nitro­benzo­nitrile (1/1), C₁₄H₁₃N·C₇H₃N₃O₄, (II), the donor and acceptor mol­ecules are stacked alternately to form one‐dimensional columns. In (I), the N‐methyl group of the donor is nearly eclipsed with respect to one of the nitro groups of the neighboring acceptor in a column, whereas the N‐ethyl group is anti with respect to the cyano group of the neighboring acceptor in (II).     

Conformation and coordination of β-diketonates in mixed-ligand copper(II) chelates of 1,2-diamines. Theoretical approach and experimental verification. Crystal structure of [bis(N,N′-dimethyl-1,2-diaminoethane) bis(3-cyano-2,4-pentanedionate)copper(II)]dihydrate

The reaction of the bis(2,4-pentanedionato)copper(II), Cu(acac)₂, and its substituted derivatives (Cu(NC-acac)₂, Cu(O₂N-acac)₂, and Cu(tfac)₂), with 1,2-diaminoethane (en), 1,2-diaminopropane (pn) and certain N-substituted derivatives of 1,2-diaminoethane, enR, is reported. The reaction products were found to depend on the reaction conditions, the extent of N-substitution of the diamine and the nature of the β-diketonate anion, β⁻. The [Cu(enR)β₂] addition compounds are not always sufficiently stable and in most instances the tetragonal species [Cu(enR)₂β₂] prevail as the final product. The 1,2-diamine molecules in [Cu(enR)₂β₂] form chelate rings attaining the gauche conformation while the β-diketonato anions essentially confer electrical neutrality. Density functional theory (DFT) calculations suggest that the active sites of the β-diketonato anion and its conformation depend on their ability to create hydrogen bonds and on the substituents in 3-position. The Fukui indices of chemical reactivity favor the carbonyl oxygens as binding sites of most anions while in the case of the 3-cyano-2,4-pentanedionato anion, NC-acac⁻, bonding through the cyano nitrogen is envisaged with the S(E, Z) conformer having the lowest energy. These findings are in accord with experimental data and further proof is given by single crystal X-ray diffraction analysis of the structure of [Cu(MeenMe)₂(NC-acac)₂] · 2H₂O (MeenMe denoting N,N′-dimethyl-1,2-diaminoethane). In this compound the NC-acac⁻ attains the S(E, Z) conformation and interacts with the square-planar entity [Cu(MeenMe)₂]²⁺ through the cyano nitrogen, while intermolecular hydrogen bonding involving the water molecules leads to supramolecular structure.     

THE EFFECT OF ACCEPTOR GROUP VARIATION ON THE SOLVATOCHROMISM OF DONOR-ACCEPTOR FLUOROPHORES

Abstract The absorption and emission characteristics of five hydroxytetrahydrochrysenes substituted with acceptor groups (nitro, cyano, methylketone, 1° amide and methyl ester) (THC-NO₂, THC-CN, THC-COCH₃, THC-CONH₂ and THC-CO₂CH₃, respectively) were investigated in an extensive set of solvents. The order of absorption and fluorescence bathochromicity are: THC-NO₂ > THC-COCH₃ > THC-CN ≥ THC-CO₂CH₃ > THC-CONH₂ and THC-NO₂ >> THC-COCH₃ > THC-CO₂CH₃ > THC-CN > THC-CONH₂, respectively. The emission spectra of these compounds are sensitive to the solvent polarity (E_T[30] scale) in the order: THC-NO₂ > THC-COCH₃ > THC-CO₂CH₃ > THC-CONH₂ > THC-CN. The response of the emission maxima of these compounds to the solvent polarity and hydrogen-bond donor/acceptor properties (π*/α/β and acity/basity scales) was also determined. The emission energies of THC-NO₂ were most sensitive to π*, β, acity, and basity of the solvent; those of the amide were least sensitive to the solvent π*, β, and basity. The ground- and excited-state dipole moments were determined by semiempirical molecular orbital calculations and the absorption/fluorescence solvent-shift method, respectively. THC-NO₂ had the largest ground- and excitedstate moments. The ester and amide had the smallest ground- and excited-state moments, respectively. In general, unsatisfactory results were obtained for correlations of the emission and absorption energies, fluorescence solvatochromism and the ground- and excited-state dipole moments with the Hammett substituent constants of the five acceptor groups. Acceptable correlations were obtained for the absorption and emission energies and the fluorescence solvatochromism with the substituent constants if the cyano compound was excluded.     

Fluoride binding to an organoboron wire controls photoinduced electron transfer

We demonstrate that the rates for long-range electron transfer can be controlled actively by tight anion binding to a rigid rod-like molecular bridge. Electron transfer from a triarylamine donor to a photoexcited Ru(bpy)₃²⁺ acceptor (bpy = 2,2′-bipyridine) across a 2,5-diboryl-1,4-phenylene bridge occurs within less than 10 ns in CH₂Cl₂ at 22 °C. Fluoride anions bind with high affinity to the organoboron bridge due to strong Lewis base/Lewis acid interactions, and this alters the electronic structure of the bridge drastically. Consequently, a large tunneling barrier is imposed on photoinduced electron transfer from the triarylamine to the Ru(bpy)₃²⁺ complex and hence this process occurs more than two orders of magnitude more slowly, despite the fact that its driving force is essentially unaffected by fluoride addition. Electron transfer rates in proteins could potentially be regulated via a similar fundamental principle, because interactions between charged amino acid side chains and counter-ions can modulate electronic couplings between distant redox partners. In artificial donor-bridge-acceptor compounds, external stimuli have been employed frequently to control electron transfer rates, but the approach of exploiting strong Lewis acid/Lewis base interactions to regulate the tunneling barrier height imposed by a rigid rod-like molecular bridge is conceptually novel and broadly applicable, because it is largely independent of the donor and the acceptor, and because the effect is not based on a change of the driving-force for electron transfer. The principle demonstrated here can potentially be used to switch between conducting and insulating states of molecular wires between electrodes.     

Tröger's base scaffold in racemic and chiral fashion as a spacer for bisdistamycin formation. Synthesis and DNA binding study

‘Head-to-head’ oligo-N-methylpyrrole peptide dimers linked by a methano[1,5]diazocin scaffold are presented in racemic as well as chiral fashion. Their DNA binding activities were assayed on calf thymus DNA, poly(dA-dT)₂, and poly(dC-dG)₂ by NMR and ECD spectroscopies, and fluorescence probe displacement assay. The presented dimers prefer AT sequences, but show higher affinity to poly(dC-dG)₂ than distamycin A. The (4R,9R) configuration of methanodiazocin bridge was found to be better suited for interaction with ct-DNA and poly(dA-dT)₂ than (4S,9S) configuration.