[Show abstract][Hide abstract] ABSTRACT: The cis- and trans-configurational isomers of are designed and investigated as chemodosimeters for CN(-) ions for the first time. The cis- reveals a NIR absorbance at 717 nm (vs. trans-, 620 nm), and such a configurational difference can be attributed to the acidity as well as position of the binding site (CH group). A probable sensing mechanism involving cyanide-driven carbanion electron-transfer oxidation is proposed.
Chemical communications (Cambridge, England). 10/2014;
[Show abstract][Hide abstract] ABSTRACT: Fipronil, which targets on GABAA receptors (GABAARs), is the first phenylpyrazole insecticide widely used in crops protection and public hygiene. However, its high toxicity on fishes deeply limited its applications. In the present study, a series of computational methods including the homology modeling, docking and molecular dynamics simulation studies were integrated to explore the binding difference of fipronil with GABAARs from fruitfly and zebrafish systems. It was found that, in zebrafish system, the H-bond between 6'Thr and fipronil exerted key effects on the recognition of fipronil, which was absent in fruitfly system. On the other hand, in fruitfly system, strong electrostatic interaction between 2'Ala and fipronil was favorable to the binding of fipronil, while was detrimental to the binding in zebrafish system. These findings marked the binding difference of fipronil with different GABAARs, which might be helpful in designing selective insecticides against pests instead of fishes.
Journal of agricultural and food chemistry. 10/2014;
[Show abstract][Hide abstract] ABSTRACT: The cis- and trans-configurational isomers 3 are designed and investigated as chemdosimeter for CN ions for the first time. The cis-3 reveals a NIR absorbance at 717 nm (vs trans-3, 620 nm), and such configurational difference can be attributed to the acidity as well as position of binding site (CH group). A probable sensing mechanism involving cyanide-driven carbanion electron transfer oxidation is proposed.
Chemical Communications 10/2014; · 6.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ninhydrin and heterocyclic ketene aminals (HKAs) are versatile building blocks in organic chemistry. Reactions of ninhydrin with HKAs initially produced the kinetic products indeno[1,2-b]pyrrol-4(1H)-one derivatives, which could further isomerize to thermodynamic counterparts indeno[2,1-b]pyrrol-8(1H)-ones. The isomerization showed a strong solvent dependency and occurred through a decomposition–reconstruction pathway. This is the first example of isomerization of ninhydrin-constructed products. The conversion between kinetic and thermodynamic control may be applicable to similar reactions involving ninhydrin or HKAs.
Annalen der Chemie und Pharmacie 08/2014; · 3.10 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Chinese Journal of Chemistry 04/2014; · 0.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Three series of novel azabridge neonicotinoid analogues were designed and Three series of novel azabridge neonicotinoid analogues were designed and synthesized, which were constructed by starting material A, glutaraldehyde and primary amine hydrochlorides (aliphatic amines, phenylhydrazines and anilines). Most of eight-membered azabridge compounds presented higher insecticidal activities than oxabridge compound B against cowpea aphid (Aphis craccivora) and brown planthopper (Nilaparvata lugens). Compared with imidacloprid, some azabridge compounds exhibited excellent insecticidal activity against brown planthopper. The crystal structures and bioassay indicated that changing bridge-atoms from O to N could lead to entirely different conformations, which might be the important influential factors of the bioactivities.
Journal of Agricultural and Food Chemistry 12/2013; · 3.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pharmacophore modeling, comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA) studies have been carried out on 5-(4-piperidyl)-3-isoxazolol (4-PIOL) analogs as GABAA receptor antagonists in this study. The best pharmacophore hypothesis generated by PHASE was ADHPR.6, which comprised a hydrogen bond acceptor (A), a hydrogen bond donor (D), a hydrophobic group (H), a positively charged group (P), and an aromatic ring (R). The pharmacophore model provided a good alignment for the further 3D-QSAR analyses, which presented a good R
2 value of 0.943, 0.930, and 0.916 for atom-based QSAR model, CoMFA model, and CoMSIA model, respectively. All QSAR models presented good statistical significance and predictivity, the corresponding Q
2 values for each 3D-QSAR model are 0.794, 0.569, and 0.637, respectively. Both pharmacophore and CoMSIA results showed that the hydrophobic sites are the key structural feature for GABAA receptor antagonists with high activities.
Medicinal Chemistry Research 12/2013; · 1.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The neonicotinoids with a nitroconjugated system had excellent bioactivity, which could rival imidacloprid, and has been previously reported. However, the photodegradation and hydrolysis of this series of neonicotinoids was very quick according to our further investigation, which can't be developed as pesticide further. The approach to further enhance the conjugation was tried not only to increase the bioactivities but also improve the stability in water and in the sun. A substituted phenyl group was introduced into the furan ring of compound 3, thirteen novel neonicotinoids analogues with higher conjugation system were designed and synthesized. The target molecular structures have been confirmed based on satisfactory analytical and spectral data. All compounds presented significant insecticidal activities on cowpea aphid (Aphis craccivora), cotton aphid (Aphis gossypii) and brown planthopper (Nilaparvatalugens). The stability test exhibited that the stability of novel analogues in water and under the mercury lamp has been improved significantly compared with compound 3.
Journal of Agricultural and Food Chemistry 11/2013; · 3.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Ligands binding at the benzodiazepine site of GABAA receptor play important pharmacological roles in clinical application. In this study, ligand‐based pharmacophore modeling, 3D‐QSAR analysis, and Bayesian model studies have been performed on a set of 84 diverse ligands binding at the benzodiazepine site. The results showed the best pharmacophore hypothesis AADHR.4, which included two hydrogen acceptors (A), one hydrogen donor (D), one hydrophobic group (H), and one aromatic ring (R). Atom‐based 3D‐QSAR model was built, and it showed good statistical significance (R 2 = 0.936) and excellent predictive ability (Q 2 = 0.821). Moreover, Bayesian model was developed and used to identify the key molecular features which are good or bad for the ligand binding activity. All the results from the pharmacophore, 3D‐QSAR, and Bayesian modeling studies revealed that a hydrogen‐bond donor (e.g., N‐H) and a hydrophobic group (e.g., Br) are critical structural features for the ligands binding at the benzodiazepine site.
Chemical Biology & Drug Design 01/2013; 81(5). · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Twenty nine novel N-4-methyl-1,2,3-thiadiazole-5-carbonyl-N′-phenyl ureas were designed and synthesized, and their structures were confirmed by proton nuclear magnetic resonance (1H NMR), infra red spectroscopy (IR) and high-resolution mass spectroscopy (HRMS). Compounds V-9, V-11, V-12, V-15, V-19, V-21, V-22 and V-24 exhibit excellent activity against Culex pipiens pallens. Compounds V-12 and V-22 present good insecticidal activity against Plutella xylostella L. Their median lethal concentrations (LC50) are 164.15 and 89.69 mg·L−1, respectively. Compound V-11 also has potential wide spectrum of fungicide activity. Its median effective concentrations (EC50) detected from 3.82 µg·mL−1 against Physalospora piricola to 31.60 µg·mL−1 against Cercospora arachidicola. Compounds V-15 and V-24 show outstanding induction activities as same as positive controls TDL and ningnanmycin, furthermore V-24 has the highest induction activity of 41.85%±4.43%. To elucidate the structure activity relationship in these compounds, a 3D-QSAR model has been built. The established model showed a reliable predicting ability with q2 values of 0.643 and r2 values of 0.982.
Chinese Journal of Chemistry 10/2012; 30(10). · 0.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A novel fluorescent probe for peroxynitrite, PN(600), was rationally designed on the basis of a unique fluorophore assembly approach. PN(600) is a green-emitting coumarin derivative. Upon oxidation by peroxynitrite, PN(600) is transformed into a highly fluorescent red-emitting resorufin derivative via an orange-emitting intermediate. This three-channel signaling capability enables PN(600) to differentiate peroxynitrite from other reactive oxygen and nitrogen species, including hypochlorite and hydroxyl radical. Moreover, PN(600) is membrane-permeable and compatible with common TRITC filter sets and displays low cytotoxicity. Therefore, PN(600) is a promising candidate for in vitro peroxynitrite imaging.
Journal of the American Chemical Society 09/2012; · 10.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Chinese Journal of Chemistry 02/2012; 30(2). · 0.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The structure-based design and synthesis of a series of novel neonicotinoid analogues are described. The novel neonicotinoid analogues were designed based upon the reaction of enamine derivatives with electron-withdrawing β-substituents with electrophilic thiocyanogen reagents. These compounds were characterized by spectroscopic methods. Bioassays indicated that some of the synthesized compounds exhibited excellent bioactivity against cowpea aphids (Aphis craccivora). The LC₅₀ values of compounds 7, 9,12, 13, 15, 17, 19, 20 and commercial imidacloprid were 0.01567, 0.00974, 0.02494, 0.01893, 0.02677, 0.01778, 0.0220, 0.02447 and 0.03502 mmol L⁻¹, respectively, which suggested that they could be used as leads for future development of new insecticides.
[Show abstract][Hide abstract] ABSTRACT: On the basis of research of the proposed modes of action between neonicotinoids and insect nicotinic acetylcholine receptor (nAChR), a series of phenylazoneonicotinoids were designed and synthesized to further promote the π-π interaction between molecule and amino acid residues. The target compounds have been identified on the basis of satisfactory analytical and spectral ((1)H NMR, (13)C NMR, HRMS, and X-ray) data. The preliminary results revealed that tiny differences in substitutes resulted in different configurations and great bioactivity variations. Some compounds with electron-donating groups on positions 2 and 6 of the phenyl ring presented higher insecticidal activity than imidacloprid against cowpea aphids ( Aphis craccivora ). The impressive crystal structure of the excellent insecticidal activity compound 9q clearly proved that the functional electronegative pharmacophore was approximately vertical to the methyleneimidazolidine plane. The differences in the mode of interaction on nAChR of typical compounds 9h and 9q remain unclear.
Journal of Agricultural and Food Chemistry 09/2011; 59(19):10615-23. · 3.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A series of novel imidazopyrazinone derivatives were synthesized and evaluated with regard to their ability to inhibit dipeptidyl peptidase IV (DPP-IV) in vitro. Of these compounds (2R)-4-oxo-4-[2-(3-carbamoylbenzyl)-hexahydro-3-oxoimidazo [1,5-a]pyrazin-7(8H)-yl]-1-(2,4,5-trifluorophenyl)butan-2-amine fumaric acid (17h, IC(50)=78 nM) was shown to effectively inhibit the activity of the dipeptidyl peptidase IV enzyme. Molecular docking studies were also performed to illustrate the binding mode of compounds 15c and 17h. Favorable interactions were identified from the binding of inhibitor 15c with DPP-IV. By analogy to the binding mode of compound 15c, it seems that the introduction of a substituted benzyl moiety onto the imidazopyrazinone could remarkably improve the inhibitory activity of compound 17h.
European journal of medicinal chemistry 11/2010; 45(11):4953-62. · 3.27 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: One nicotinic acetylcholine receptor non-alpha subunit was cloned from the pond wolf spider, Pardosa pseudoannulata, an important predatory enemy of some insect pests with agricultural importance, such as the green peach aphid Myzus persicae. The subunit shows high amino acid identities to insect beta1 subunits (74-78%), and was denoted as Ppbeta1. Although high identities are found between Ppbeta1 and insect beta1 subunits, amino acid differences are found within loops D, E and F, important segments contributing to ligand binding. The effects of amino acid differences within these loops were evaluated by introducing loops of insect or spider beta1 subunits into rat beta2 subunit and co-expressing with insect alpha subunit. The corresponding regions of rat beta2 chimera beta2(Mpbeta1) (beta2 with loops D, E and F from M. persicae beta1 subunit Mpbeta1) were replaced by loops D, E and F of Ppbeta1 singly or together to construct different chimeras. When these chimeras were co-expressed with insect Nlalpha1, it was found that the replacement of loops D, E and F of beta2(Mpbeta1) by that of Ppbeta1 resulted in a right-ward shift of the imidacloprid dose-response curves, reflecting increases in EC(50), compared to Nlalpha1/beta2(Mpbeta1). By contrast, the influences on ACh potency were minimal. The further study showed that R81Q, N137G and F190W differences, within loops D, E and F respectively, contributed mainly to these sensitivity changes. This study contributes to our understanding of the molecular mechanism underlying selectivity of neonicotinoids against insects over spiders.
[Show abstract][Hide abstract] ABSTRACT: Molecular aggregation state of bioactive compounds plays a key role in its bio-interactive procedure. In this article, based on the structure information of dimers, the simplest model of molecular aggregation state, and combined with solvational computation, total four descriptors (DeltaV, MR2, DeltaE(1), and DeltaE(2)) were calculated for QSAR study of a novel insect-growth regulator, N-(5-phenyl-1,3,4-oxadiazol-2-yl)-N'-benzoyl urea. Two QSAR models were constructed with r(2) = 0.671, q(2) = 0.516 and r(2) = 0.816, q(2) = 0.695, respectively. It implicates that the bioactivity may strongly depend on the characters of molecular aggregation state, especially on the dimeric transport ability from oil phase to water phase.
Journal of Computational Chemistry 07/2009; 31(3):586-91. · 3.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Acetylcholinesterase (AChE) and its mutation recently emerged as a significant research area, due to its resistance against organophosphate and carbamate insecticides. Residue G265, which is always a conservative residue, mutated to A265 is the most frequent mutant of AChE in Drosophila populations. However, only this mutation caused a 'butterfly effect' that gives high insecticidal resistance. Herein, the models of sensitive strain (Dm-S) and the resistance strain (Dm-R) were constructed, to give a total of 2000 ps molecular dynamics simulation and to reveal the insecticidal resistance mechanism, with implied, the active gorge of Dm-R was much less flexible than that of Dm-S. The "back door" channel was widened to accelerate the detoxication against insecticides by the conformation changing of W83 and I161. All the distances (S238-H480, S238-G150, S238-G151, Y71-M153) in Dm-R became smaller than those in Dm-S, which may deeply influence the binding between the insecticides and DmAChE.
Journal of Molecular Modeling 04/2009; 15(10):1229-36. · 1.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate whether free cyclooctatetraene dianion (COT2−) is aromatic, quantum chemistry methods were used to optimize its structure. Based on the optimized structures, the natural population analysis (NPA) charge, bond order, delocalization energy, nucleus-independent chemical shift (NICS), and harmonic oscillator model of aromaticity (HOMA) values were computed by DFT-B3LYP method with basis set 6-311++G**, which shows that COT2− is not aromatic as it is not planar and has different bond lengths and bond orders, smallest delocalization energy and positive NICS values. To further confirm the finding, the changes of NICS and energy against ring distortion angle were scanned. The COT2− has positive NICS values all along the angle from 180° to 120° while other aromatic systems always have negative values. The energy scanning suggests that COT2− should have the weakest capability to maintain its planar structure. All the calculations strongly indicate that COT2− is not aromatic. This study also suggests that NICS scan might be a good approach to judge aromaticity.
Chinese Journal of Chemistry 01/2009; 27(10):1914-1918. · 0.92 Impact Factor