In Silico Structure-Guided Optimization and Molecular Simulation Studies of 3-Phenoxy-4-(3-trifluoromethylphenyl)pyridazines as Potent Phytoene Desaturase Inhibitors

A series of novel 3-phenoxy-4-(3-trifluoromethylphenyl)pyridazines 2–5 were designed, based on the structure of our previous lead compound 1 through the in silico structure-guided optimization approach. The results showed that some of these new compounds showed a good herbicidal activity at the rate of 750 g ai/ha by both pre- and post-emergence applications, especially compound 2a, which displayed a comparable pre-emergence herbicidal activity to diflufenican at 300–750 g ai/ha, and a higher post-emergence herbicidal activity than diflufenican at the rates of 300–750 g ai/ha. Additionally, 2a was safe to wheat by both pre- and post-emergence applications at 300 g ai/ha, showing the compound’s potential for weed control in wheat fields. Our molecular simulation studies revealed the important factors involved in the interaction between 2a and Synechococcus PDS. This work provided a lead compound for weed control in wheat fields.     

Synthesis and biological activity of novel 2-methyl-4-trifluoromethyl-thiazole-5-carboxamide derivatives

Nine novel 2-methyl-4-trifluoromethylthiazole-5-carboxamide derivatives were designed and synthesized utilizing ethyl 4,4,4-trifluoroacetoacetate as a starting material. Subsequently, the biological activity of the compounds was evaluated in the greenhouse. Results indicated that all of the compounds have some fungicidal and insecticidal activity but no herbicidal activity. Compound 1 has fungicidal activity with 90% control of tomato late blight at 375 g ai/ha, while two compounds 2F and 2H show insecticidal activity with 80 and 100% control, respectively, against potato leafhopper at 600 g ai/ha.     

Synthesis and bioactivity of novel (3-chloro-5-(trifluoromethyl)pyridin-2-yloxy)phenyl containing acrylate and acrylonitrile derivatives

Fifteen novel (3-chloro-5-(trifluoromethyl)pyridin-2-yloxy)phenyl containing Baylis-Hillman adduct derivatives were designed and synthesized. Evaluation of their biological activities showed that methyl 2-((3-(3-chloro-5-(trifluoromethyl)pyridin-2-yloxy)phenoxy)(phenyl)methyl)acrylate (2g) exhibited efficient broad-spectrum fungicidal activity, with 100% control of wheat powdery mildew and cucumber downy mildew and 98% control of cucumber anthracnose at 400 g ai/ha. Some of the other title compounds 2, 3 and two Baylis-Hillman bromide intermediates (11a, 11b) had moderate to good fungicidal activity.     

新型4,4-二甲基异噁唑-3-酮衍生物的合成及生物活性研究

以Baylis-Hillman加成物为起始原料,设计并合成了5个结构新颖的4,4-二甲基异唑-3-酮衍生物。所合成的化合物经IR、1HNMR和元素分析确证。生物活性测试结果表明,所合成的目标产物在2000gai/ha的剂量下均具有较好的除草活性。中间体1-(2,4-二氯苯基)-2-溴甲基丙烯酸乙酯具有杀虫活性,在600gai/ha的剂量下对朱砂叶螨防效为100%。     

Synthesis and herbicidal activity of 2-cyano-3-(2-fluoro-5-pyridyl)methylaminoacrylates

A series of 2-cyano-3-(2-fluoro-5-pyridyl)methylaminoacrylates were synthesized as herbicidal inhibitors of photosystem II (PSII) electron transport. 2-Fluoro-5-pyridinemethylamine was prepared from 2-amino-5-methylpyridine, subsequent reaction with 2-cyano-3,3-dimethylthioacrylates or 2-cyano-3-methoxyacrylates to yield these title compounds. All of these compounds were confirmed by ¹H NMR, IR, mass spectrum and elemental analyses. Their herbicidal activities were evaluated. All of the title compounds showed excellent herbicidal activities to amaranth pigweed and rape in post-emergence treatment. At the rate of 150 g/ha, one compound exhibited similar activity to Cl-analogue. The replacement of chlorine by fluorine group showed the same herbicidal activity.     

Synthesis and biological activity of ethyl 2-(5-methyl-3-arylisoxazole-4-carboxamido)-4-alkylthiazole-5-carboxylate

A series of novel ethyl 2-(5-methyl-3-arylisoxazole-4-carboxamido)-4-alkylthiazole-5-carboxylates I-1-6 were synthesized. The structures of all target compounds were characterized by ¹H NMR, ¹³C NMR, IR, MS and elemental analyses. Their fungicidal and herbicidal activities were evaluated. The results of preliminary bioassays show that the title compounds I-4 possess 20–50% inhibition against most of the tested plants at the dosage of 150 g ai/ha, while the title compounds I-1-5 possess 32–58% inhibition against FusaHum graminearum, Thanatephorus cucumeris, Botrytis cinereapers and Fusarium oxysporum in vitro at the concentration of 100 mg/L.     

Discovery of novel 3-{[(5,5-dimethyl-4,5-dihydroisoxazol-3-yl)sulfonyl]methyl}benzo[d]isoxazole analogs as promising very long chain fatty acids inhibitors

Very long chain fatty acids (VLCFAs) are one of the most principal and promising targets for herbicides discovery. In order to explore and find novel VLCFAs inhibitors with higher herbicidal activity and improved crop safety, a variety of new 3-{[(5,5-dimethyl-4,5-dihydroisoxazol-3-yl)sulfonyl]methyl}benzo[d]isoxazole derivatives were reasonably designed and synthesized. The results of greenhouse experiments indicated that several compounds exhibited good herbicidal activity against Digitaria sanguinalis, Echinochloa crus-galli, and Setaria faberii at rates of 150 g ai/ha. Compounds g4 and h1 displayed promising herbicidal activity against D sanguinalis and E crus-galli at rates of 75 g ai/ha, which is better than commercial pyroxasulfone and S-metolachlor. Moreover, compound h1 displayed higher activity against E crus-galli, D sanguinalis, and S faberii than pyroxasulfone and S-metolachlor even at a rate of 37.5 and 18.75 g ai/ha. Furthermore, both of the compounds g4 and h1 were much safer to these tested crops, especially to rice, wheat and rape, at the rate of 150 g ai/ha than pyroxasulfone. Therefore, h1 may act as a new lead structure for novel herbicides discovery.     

4-(7-甲氧基-2,2-二甲基-2,3-二氢苯并呋喃-5-基)-2-苄亚氨基噻唑的合成与生物活性

呋喃酚经醚化、傅克酰化、α-溴代、噻唑环化和亚胺化等反应合成了16种4-(7-甲氧基-2,2-二甲基-2,3-二氢苯并呋喃-5-基)-2-苄亚氨基噻唑新化合物.化合物的结构经1H NMR、质谱和元素分析等确证.杀虫活性实验结果表明,化合物2a和2i在500 mg/L对棉红蜘蛛死亡率分别为53.10%和67.71%,杀菌活性实验结果表明,化合物2a和2k在25 mg/L对油菜菌核病菌抑制率分别为57.9%和59.8%,除草活性实验结果表明,2l在2250 g.ai/ha浓度下对苘麻、刺苋、藜具有一定的除草活性.     

High-performance liquid chromatographic method for the disposition of mazindol and its metabolite 2-(2-aminoethyl)-3-(p-chlorophenyl)-3-hydroxyphthalimidine in mouse brain and plasma

A high-performance liquid chromatographic method was developed for the analysis of the appetite suppressant mazindol and its metabolite 2-(2-aminoethyl)-3-(p-chlorophenyl)-3-hydroxyphthalimidine (Met) in mouse brain and plasma. The two compounds were quantified by measuring Met after two different sample pretreatments. For mazindol determination, the treatment involved the hydrolysis of mazindol to Met, by incubating the sample at 80 °C for 15 min at pH 10.6 followed by liquid-liquid extraction procedure while for the determination of Met, the hydrolysis step was omitted. The obtained Met was analyzed by HPLC after its derivatization with the fluorescent reagent 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride (DIB-Cl). The separation was performed on an ODS column with mobile phase consisted of a mixture of acetonitrile-methanol-0.1 M acetic acid (46:4:50, v/v/v) containing tetrahydrofuran (6%). The effluent was monitored at excitation and emission wavelengths of 330 and 445 nm, respectively. Calibration curves of mazindol and Met ranged from 0.1 to 25 ng/ml and from 0.5 to 250 ng/g in spiked mouse plasma and brain tissue, respectively. The method is highly sensitive with the limits of detection for Met on column of 2.8 and 3.5 fmol in plasma and brain, respectively, at a signal-to-noise ratio of 3. The intra- and inter-day precisions were less than 4.5 and 9.7%, in plasma and less than 8.8 and 7.2% in brain, respectively. The developed method was applied for the monitoring of mazindol and Met levels in mouse plasma and brain tissue regions after single intraperitoneal administration of mazindol, 0.5 mg/kg.     

N-杂环甲基2-(4-杂芳氧基苯氧基)丙酰胺的合成及除草活性

以2-(4-羟基苯氧)丙酸为原料,设计合成了16个新的手性N-杂环甲基2-(4-杂芳氧基苯氧基)丙酰胺化合物,其化学结构经核磁共振、色谱-质谱、红外光谱及元素分析确证.初步生物活性测定结果表明,合成的化合物在2.25×103g/ha剂量时对单子叶杂草马唐(Digitaria sanguinalis)、稗草(Echinochloa crus-galli)及狗尾草(Setaria viridis)等均具有90%以上的活性;进一步活性及作物安全性测试表明,化合物(R)-(+)-N-[(6-氯吡啶-3-基)甲基]-2-[4-(3-氯-5-三氟甲基吡啶-2-基氧基)苯氧基]丙酰胺(2b)的除草活性高于噁唑酰草胺,且对水稻茎叶处理安全,同时对水稻田主要杂草千金子的活性远高于氰氟草酯;化合物的除草活性与立体构型有关,R构型为活性构型.     

Indium-HI-mediated one-pot reaction of 1-(2-arylethynyl)-2-nitroarenes to 2-arylindoles

While 1-(2-arylethynyl)-2-nitroarenes were reduced to 2-(2-arylethynyl)anilines in the presence of indium and InCl₃ in THF/H₂O (v/v = 5/1) at 50 °C, 1-(2-arylethynyl)-2-nitroarenes were reductively cyclized to 2-arylindoles with good yields in the presence of indium and aqueous HI in benzene.     

Synthesis of 4-hydroxy-3-[(E)-2-(6-substituted-9H-purin-9-yl)vinyl]coumarins as lipoxygenase inhibitors

The synthesis of 4-hydroxy-3-[(E)-2-(6-substituted-9H-purin-9-yl)vinyl] coumarins has been achieved from the reactions of 4-hydroxycoumarin with 2-(6-substituted-9H-purin-9-yl)acetaldehydes in DMF under heating. The new compounds showed significant lipoxygenase inhibitory activity (e.g., 6a: IC₅₀ = 6.25 μM).     

Design,synthesis and herbicidal activity of novel cyclic phosphonates with diaryl ethers containing pyrimidine

Abstract

Thirteen novel cyclic phosphates were rationally designed and synthesized by introducing diary ethers containing pyrimidine. All the target compounds were characterized by ¹H, ¹³C, ³¹P NMR and HRMS. The test of herbicidal activity indicated that most of the compounds showed good herbicidal activities against Amaranthus retroflexus. The compounds IA-2 (1-(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)propyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate) and IA-3 ((5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)(phenyl)methyl-2-((4,6-dimethoxypyrimidin-2-yl)oxy)benzoate) exhibited remarkable post-emergency herbicidal activity against the tested monocotyledonous weed at the dosage of 112.5?g ai/ha.     

Determination of manganese by flame atomic absorption spectrometry after its adsorption onto naphthalene modified with 1-(2-pyridylazo)-2-naphthol (PAN)

A system for determination of manganese, after preconcentration with 3% (w/w) 1-(2-pyridylazo)-2-naphthol (PAN), adsorbed on microcrystalline naphthalene is proposed. An amount of 200 mg of this complexing mixture is placed in a glass column and conditioned with a NH₄Cl/NH₄OH buffer solution (pH 9.5). The aqueous sample, containing manganese, is treated with an ammonium tartrate solution, then with a hydroxylammonium chloride solution and, finally, with a buffer solution. The resulting solution is passed through the column containing microcrystalline naphthalene modified with 1-(2-pyridylazo)-2-naphthol (PAN) where Mn(II) is retained. The column is first washed with deionized water and then with 10.0 ml of dimethylformamide to dissolve the Mn(II)-PAN/naphthalene complex. Manganese is determined by air-acetylene flame atomic absorption spectrometry. About 1 μg of manganese can be concentrated from 200 ml of aqueous sample, allowing a preconcentration factor of 20, a limit of quantification of 5 ng ml⁻¹ and R.S.D. of 3.8%. The accuracy was ascertained using certified reference materials, including samples of urine and glass. Water samples were also analysed and the results are in good agreement with those obtained by graphite furnace atomic absorption spectrometry.     

Thermodynamic properties on quaternary aqueous solutions of chlorides charge-type 1-1*2-1*2-1: XCl + MgCl2 + CaCl2 + H2O with (X ≡ Na; NH4)

In this investigation, the quaternary aqueous solutions of chlorides charge-type 1-1*2-1*2-1 with a cation (Na⁺; NH₄⁺; Mg²⁺; Ca²⁺) have been studied using the hygrometric method at 298.15 K. The water activities of the systems NH₄Cl + MgCl₂ + CaCl₂ + H₂O and NaCl + MgCl₂ + CaCl₂ + H₂O are measured at total molalities from 0.60 mol kg⁻¹ to saturation for different ionic-strength fractions NH₄Cl or NaCl, y = 0.20, 0.50, 0.80, and z ratio ionic-strength for other solutes, with z = 0.20, 0.50 and 0.80 for each y. The obtained data allow the deduction of osmotic coefficients.     

Nitro group photoreduction of 4-(2-nitrophenyl)- and 4-(3-nitrophenyl)-1,4-dihydropyridines

The photoprocesses of nifedipine, a 4-(2-nitrophenyl)-1,4-dihydropyridine, and nimodipine and nitrendipine, two 3-nitrophenyl Hantzsch-type analogues, were studied by steady-state and time-resolved methods. The intramolecular photoreduction of nifedipine into its nitrosophenyl product takes place within a few ns. The quantum yield of conversion is Φ_red = 0.3 and does not depend significantly on the oxygen concentration and solvent properties. Formation of the fully reduced 4-(2-aminophenyl)-1,4-dihydropyridine as minor product is indicated by fluorescence spectroscopy. The photoreduction of nimodipine and nitrendipine is inefficient, Φ_red = 0.002 in acetonitrile, but markedly enhanced in the presence of donors such as triethylamine (TEA) and 2-propanol, e.g. for TEA Φ_red is up to 0.03. The triplet states of nimodipine and nitrendipine were characterized. They react intermolecularly with TEA and 2-propanol, forming radicals as intermediates and eventually several reduction products.     

2-[2-(烷氧羰基苯氧羰基)苯氧基]-4,6-二甲氧基嘧啶类化合物的合成及其除草活性研究

为了寻找高效、安全、经济的除草活性化合物, 设计并合成了9个新的2-[2-(烷氧羰基苯氧羰基)苯氧基]-4,6-二甲氧基嘧啶类化合物, 其化学结构经IR, ¹H NMR, LC/MS和元素分析确证. 初步生物活性测定结果表明, 该类化合物在有效成份2250 g/ha剂量时, 对苘麻(Abutilon theophrasti)、稗草(Echinochloa crus-galli)、狗尾草(Setaria viridis)等都具有良好的除草活性, 抑制率达90％以上. 其中5b, 5e, 5h在187.5 g/ha剂量时, 仍具有良好的除草活性, 抑制率达90％以上.     

Evaluation of V, Ir, Ru, V-Ir, V-Ru, and W-V as permanent chemical modifiers for the determination of cadmium, lead, and zinc in botanic and biological slurries by electrothermal atomic absorption spectrometry

Permanent modifiers (V, Ir, Ru, V-Ir, V-Ru, and W-V) thermally coated on to platforms of pyrolytic graphite tubes were employed for the determination of Cd, Pb, and Zn in botanic and biological slurries by electrothermal atomic absorption spectrometry (ETAAS). Conventional Pd + Mg(NO₃)₂ modifier mixture was also used for the determination of analytes in slurries and digested samples. Optimum masses and mass ratios of permanent modifiers for Cd, Pb, and Zn in slurry sample solutions were investigated. The 280 μg of V, 280 μg of V + 200 μg of Ir, 280 μg of V + 200 μg of Ru or 240 μg of W + 280 μg of V in 0.2% (v/v) Triton X-100 plus 0.5% (v/v) HNO₃ mixture was found as efficient as 5 μg of Pd + 3 μg of Mg(NO₃)₂ modifier mixture for obtaining thermal stabilization, and for obtaining best recoveries. Optimization conditions of analytes, such as pyrolysis and atomization temperature, characteristic masses and detection limits, and atomization and background peak profiles were studied with permanent and 5 μg of Pd + 3 μg of Mg(NO₃)₂ conventional modifiers and compared with each other. The permanent V-Ir, V-Ru, and W-V modifiers remained stable for approximately 250-300 firings when 20 μl of slurries and digested samples were delivered into the atomizer. In addition, the mixed permanent modifiers increase the tube lifetime by 50-95% when compared with untreated platforms. The characteristic masses and detection limits of analytes (dilution factor of 125 ml g⁻¹) obtained with V-Ir based on integrated absorbance as example for 0.8% (m/v) slurries were 1.0 pg and 3 ng g⁻¹ for Cd, 18 pg and 17 ng g⁻¹ for Pb, and 0.7 pg and 4 ng g⁻¹ for Zn, respectively. The results of analytes obtained by employing V-Ir, V-Ru, and W-V permanent modifier mixtures in botanic and biological certified and standard reference materials were in agreement with the certified values of reference materials.     

Nanoelectrospray with ion-trap mass spectrometry for the determination of beta-casomorphins in derived milk products

beta-Casomorphins (b-CMs) are bioactive peptides derived from casein with opioid agonist effects similar to morphine. The use of electrospray (ESI) with quadrupole ion-trap mass spectrometry (QIT-MS) for these compounds in two matrices, cheese and milk, was examined. It was compared to a liquid chromatography (LC) coupled to mass spectrometry (LC-MS), and a “soft” ionisation technique, NanoMate, with selected ion monitoring (SIM), which are unreliable for the determination of trace casomorphins in derived milk products. b-CM mass fragmentation pathways were done for the four most common b-CMs: β-casomorphin (1-5) bovine (b-CM-5), β-casomorphin (1-7) bovine (b-CM-7), [D-Ala2, D-Pro4,Tyr5]-β-casomorphin (1-5) amide (b-CM-10) and β-casomorphin (1-5) amide [D-Ala2,Hyp4,Tyr5] (b-CM-11). The major product ions obtained in QIT-MS were used to construct fragmentation pathways for b-CMs. The different collision energies using automated nanoelectrospray ion source NanoMate and conventional LC in QIT-MS were studied. Calibration data for b-CMs, using spiked milk or cheese samples (10 g or 10 mL), were: NanoMate/MS (25-1000 μg/L), r² = 0.998; NanoMate/MS² (5-1000 μg/L), r² = 0.9992; NanoMate/MS³ (2.5-1000 μg/L), r² = 0.9998. Reproducibility data (% RSD, N = 5) for NanoMate/MSⁿ mode ranged between 2.0 at 500 μg/L and 7.0 at 10 μg/L.     

Antibacterial and antifungal activity of metal(II) complexes of acylhydrazones of 3-isatin and 3-(N-methyl)isatin

Cobalt(II), nickel(II), copper(II) and zinc(II) complexes of 2-thiophenecarbonyl hydrazone of 3-isatin (H₂L¹) and 2-furoic hydrazones of 3-isatin (H₂L²) and 3-(N-methyl)isatin (HL³), with general composition [M(L)₂] · nX, where X is ethanol or/and water, were synthesised and characterised. The molecular structure of HL³ showed that it crystallised in the keto form, which is also the more abundant tautomer for the three hydrazone ligands in solution. The three ligands behave as κ²-O,N donors in the cobalt(II) and zinc(II) complexes. The X-ray crystal structure of pseudotetrahedral [Zn(HL¹)₂] · 1.75MeOH confirmed the O,N coordination mode of the two monodeprotonated ligands in their keto forms. Secondary interactions of zinc ions with the O atoms of each isatin keto residue provoke a substantial distortion towards a square pyramidal form. The interaction of the isatin keto residues is stronger in the three nickel(II) complexes where the three acylhydrazones can be considered as κ³-O,N,O donors.