A novel semi-rigid latent chromophore E1, containing an amide subunit activated by an adjacent semi-rigid intramolecular hydrogen-bonding (IHB) unit, was designed for the detection of fluoride ion by the ‘naked-eye’ in CH₃CN. Comparative studies on structural analogs (E2, E3, and E4) provided significant insight into the structural and functional role of the amide N–H and IHB segment in the selective recognition of fluoride ions. The deprotonation of the amide N–H followed by the enhancement of intramolecular charge transfer (ICT) induced the colorimetric detection of E1 for fluoride ion. Copyright © 2015 John Wiley & Sons, Ltd.

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.

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.

A series of novel phthalic diamide derivatives containing 1,2,3-triazole moiety were synthesized using one-pot click chemistry approach and characterized by ¹H NMR and HRMS. The insecticidal activity against armyworm (Mythimna separata), Tetranychu scinnabarinus and cowpea aphid (Aphis craccivora) was evaluated. Compounds 4II-a and 4II-i showed 50% insecticidal activity against armyworm (Mythimna separata) at the concentration of 4 mg/L and one-third of the compounds had moderate activity against Tetranychus cinnabarinus at 500 mg/L.

Ligands binding at the benzodiazepine site of GABA_A 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 (R² = 0.936) and excellent predictive ability (Q² = 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.

For a novel potential commercial chiral pesticide, an independent study on the fate characteristics and residues of each stereoisomer is essential if the application rates for the pesticide and human exposure are to be reduced. The absorption and translocation behavior of a chiral insecticide, cycloxaprid, in plants treated by root immersion and blade smearing was studied using ¹⁴C-labeling tracer techniques. With the root treatment, total absorption of (1R;8S)-cycloxaprid (RS) (12.39%) was much greater than that of (1S;8R)-cycloxaprid (SR) (3.31%) at 192 h after treatment (HAT). The mass concentrations (RS/SR) of cycloxaprid in the roots, cotyledons, leaf 1, leaf 2, and leaf 3 were 37.0/16.8, 8.3/2.8, 11.7/6.5, 5.1/4.8, and 8.0/4.7 mg kg^-1 (fresh weight), respectively, at 192 HAT at an initial concentration 1.6 mg kg^-1. With the foliar application treatment, no significant difference was observed between the total absorption of RS (3.11%) and SR (4.03%) at the end of the treatment. Both acropetal and basipetal transport of absorbed ¹⁴C occurred and more than 71.83% of absorbed RS and 82.42% of SR remained in the treated leaf. Stereoselective absorption was observed during root uptake but not during foliar absorption. Chirality 25:686–691, 2013. © 2013 Wiley Periodicals, Inc.

To support the metabolism and toxicology study of cis-neonicotinoids, radio or stable isotope was introduced into different sites of the key intermediate 2-chloro-5-((2-(nitromethylene)imidazolidin-1-yl)methyl)pyridine (6-Cl-PMNI). [³H₂]- and [¹⁴C]-label were successively prepared from initial materials NaB³H₄ and [¹⁴C]-nitromethane, respectively. Similarly, [D₂]-6-Cl-PMNI was prepared from NaBD₄ in four steps, with 52.6% overall isotopic yield, and dual-labeled [D₂, ¹³C]-target was obtained from NaBD₄ and [¹³C]-nitromethane, affording overall isotopic yield of 42.5%. Moreover, [¹⁴C₂] was introduced from [U-¹⁴C]-ethylenediamine dihydrochloride in three steps, with a 58.3% overall chemical yield. Finally, typical labeled cis-neonicotinoids paichongding and cycloxaprid were prepared and characterized. The methods were proved to have good generality in the synthesis of other cis-neonicotinoids, and all results would be useful in metabolism studies of new cis-neonicotinoids. Copyright © 2012 John Wiley & Sons, Ltd.

Paichongding, a novel neonicotinoids pesticide with excellent insecticidal activity against imidacloprid-resistant brown planthopper, has been sold in the Chinese market as new pesticide. [¹⁴C]Paichongding was proposed as a tracer to support the further study to elucidate the metabolism of the commercialized pesticide. This paper describes an efficient synthesis of [¹⁴C]paichongding in five radiochemical steps from [¹⁴C]nitromethane (1). Then the four diastereoisomers (a, b, c, and d) were separated by preparative chiral HPLC and characterized by HPLC and HPLC-LSC. This methodology could be utilized in the syntheses of other ¹⁴C-labeled nitromethylene neonicotinoids derivatives. Copyright © 2011 John Wiley & Sons, Ltd.

Paichongding and Cycloxaprid are two novel neonicotinoids with good industrialization prospects for their high activity against imidacloprid-resistant pest. In this paper, the radiosynthesis of [³H₂]-Paichongding and [³H₂]-Cycloxaprid was achieved using a NaB³H₄ reduction. The title compounds were obtained with chemical purities of 98.7 and 98.4%, and radiochemical purities of 97.3 and 98.6%, respectively. The labeled compounds could be used as radiotracers for further study of metabolism and toxicology. Copyright © 2011 John Wiley & Sons, Ltd.

A series of {[1-(arylmethyl)piperidin-4-yl]oxy}-(trifluoromethyl)-pyridine derivatives were designed and synthesized on the basis of the ketanserin (1) framework, a prototypic mammalian 5-HT_2A receptor antagonist, and the structure–activity relationship (SAR) was also discussed. The result of the bioassay showed that most of the title compounds inhibited the insect growth and exhibited moderate-to-good growth regulating activity against the armyworm Pseudaletia separataWalker. Furthermore, the SAR study revealed that, when the determinant feature, interacting with mammalian 5-HT_2A receptor, was preserved, a simplified ArCH₂ group greatly contributed to insect growth inhibitory activities. It was also found that the substituted position of the CF₃ group at the pyridine ring played a key role, and that the introduction of 1-[bis(4-fluorophenyl)methyl]piperazine, an equivalent of the benzoylpiperidine moiety of ketanserin, resulted in bioactivities similar to those of the title compounds, which were in agreement with the model of ketanserin analogues binding to mammalian 5-HT₂ receptors.