Discovery of novel phenoxypyridine as promising protoporphyrinogen IX oxidase inhibitors.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is a significant target for the discovery of novel bleaching herbicides. Starting from the active fragments of several known commercial herbicides, a series of PPO inhibitors with diphenyl ether scaffolds were designed and synthesized by substructure splicing and bioisosterism methods. The greenhouse herbicidal activity and the PPO inhibitory activity in vitro were measured. The results showed that the novel synthesized compounds have good PPO inhibitory activity, and the IC50 value against corn PPO ranges from 0.032 ± 0.008 mg/L to 3.245 ± 0.247 mg/L. Among all target compounds, compound P2 showed the best herbicidal activity, with a half inhibitory concentration (IC50) of 0.032 ± 0.008 mg/L. In addition, the molecular docking results showed that the benzene ring part of compound P2 can form a π-π stacking with PHE-392, and the trifluoromethyl group and ARG-98 form two hydrogen bonds. Crop safety experiments and cumulative concentration analysis experiments indicated that compound P2 can be used for weed control in rice, wheat, soybean and corn. Therefore, compound P2 can be selected to develop potential lead compounds for novel PPO inhibitors.

Production of 1,3-propanediol and lactic acid from crude glycerol by a microbial consortium from intertidal sludge.

OBJECTIVES: To select a microbial consortium from intertidal sludge and evaluate its ability to convert crude glycerol from biodisel to high value-added products such as 1,3-propanediol (1,3-PDO) and lactic acid (LA). RESULTS: A microbial consortium named CJD-S was selected from intertidal sludge and exhibited excellent performance for the conversion of crude glycerol to 1,3-PDO and LA. The composition of CJD-S was determined to be 85.99% Enterobacteriaceae and 13.75% Enterococcaceae by 16S rRNA gene amplicon high-throughput sequencing. In fed-batch fermentation with crude glycerol under nonsterile conditions, the highest concentrations of 1,3-PDO and LA were 41.47 g/L and 45.86 g/L, respectively. CONCLUSIONS: The selected microbial consortium, CJD-S, effectively converted crude glycerol to 1,3-PDO and LA under nonsterile conditions and can contribute to the sustainable development of the biodiesel industry.

[Network pharmacological analysis and experimental study of Pulsatilla chinensis against inflammatory injury caused by pneumonia in mice infected with influenza virus FM_1].

Network pharmacology and the mouse model of viral pneumonia caused by influenza virus FM_1 were employed to explore the main active components and the mechanism of Pulsatilla chinensis against the inflammatory injury of influenza virus-induced pneumonia. The components and targets of P. chinensis were searched from TCMSP, and the targets associated with influenza virus-induced pneumonia were searched from GeneCards. The common targets between P. chinensis and influenza virus-induced pneumonia were identified with Venn diagram established in Venny 2.1. The herb-component-disease-target(H-C-D-T) network was constructed by Cytoscape 3.7.2. The above data were imported into STRING for PPI network analysis. Gene Ontology(GO) enrichment and KEGG pathway enrichment were performed with DAVID. BALB/cAnN mice were infected with the influenza virus FM_1 by nasal drip to gene-rate the mouse model of pneumonia. Immunohistochemistry was adopted to the expression profiling of inflammatory cytokines in the lung tissues of mice in the blank group, model group, and P. chinensis group 1, 3, 5, and 7 days after infection. The pathological changes of lung and trachea of mice in blank group, model group, and P. chinensis group were observed with light microscope and scanning electron microscope at all the time points. The network pharmacological analysis indicated that 9 compounds of P. chinensis were screened out, with a total of 57 targets, 22 of which were overlapped with those of influenza virus-induced pneumonia. A total of 112 GO terms(P<0.05) were enriched, including 81 terms of biological processes, 11 terms of cell components, and 20 terms of molecular functions. A total of 53 KEGG signaling pathways(P<0.05) were enriched, including TNF signaling pathway, influenza A signaling pathway, NF-κB signaling pathway, MAPK signaling pathway and other signaling pathways related to influenza/inflammation. In the P. chinensis group, the expression of TNF-α and IL-1 in the lung tissue was down-regulated on the 3 rd day after infection, and that of IL-6 in the lung tissue was down-regulated on the 5 th day after infection. Light microscopy and scanning electron microscopy showed that P. chinensis significantly alleviated the pathological damage of lung and trachea compared with the model group. This study reflects the multi-components, multi-targets, and multi-pathways of P. chinensis against influenza virus-induced pneumonia. P. chinensis may reduce the production of proinflammatory cytokines and mediators and block the pro-inflammatory signaling pathways to alleviate viral pneumonia, which provides reference for future research.

The Role of the NOD1/Rip2 Signaling Pathway in Myocardial Remodeling in Spontaneously Hypertensive Rats.

BACKGROUND Chronic hypertension changes the function and structure of the heart and blood vessels. This study aimed to explore the role of the NOD1/Rip2 (nucleotide-binding oligomerization domain 1/receptor-interacting protein 2) signaling pathway in myocardial remodeling in spontaneously hypertensive rats (SHRs). MATERIAL AND METHODS Blood pressure was measured using a tail cuff. The cardiac structure was observed using echocardiography. Slices of the myocardium were stained with hematoxylin and eosin. The expression of NOD1 and Rip2 was detected using real-time polymerase chain reaction, western blot, and immunohistochemistry. The content and distribution of collagen in the myocardium were observed using Van Gieson staining. Enzyme-linked immunosorbent assay was used to detect the interleukin-1 (IL-1) concentrations. SHRs were treated with the NOD1 agonist iE-DAP and NOD1 inhibitor ML130. RESULTS The NOD1 agonist increased blood pressure in SHRs, and the NOD1 inhibitor decreased blood pressure; the interventricular septum thickness (IVST) and left ventricular posterior wall thickness (LVPWT) of the agonist-treated group were thicker than those of the control group, and the antagonist exerted the opposite effects. The levels of the NOD1 and Rip2 mRNAs and proteins, serum IL-1 concentration, and myocardial collagen volume fraction (CVF%) increased in SHRs in the NOD1 agonist group, but the levels of NOD1 and Rip2, serum IL-1 concentration, and myocardial collagen volume fraction (CVF%) decreased in SHRs in the NOD1 inhibitor group. CONCLUSIONS NOD1/Rip2 expression increased during the progression of myocardial remodeling in SHRs. The NOD1 agonist increased NOD1 expression and promoted myocardial remodeling, while the NOD1 antagonist reduced NOD1/Rip2 expression and protected against myocardial remodeling.

[Hyperspectral Remote Sensing Estimation Models for Pasture Quality].

Crude protein (CP), crude fat (CFA) and crude fiber (CFI) are key indicators for evaluation of the quality and feeding value of pasture. Hence, identification of these biological contents is an essential practice for animal husbandry. As current approaches to pasture quality estimation are time-consuming and costly, and even generate hazardous waste, a real-time and non-destructive method is therefore developed in this study using pasture canopy hyperspectral data. A field campaign was carried out in August 2013 around Qinghai Lake in order to obtain field spectral properties of 19 types of natural pasture using the ASD Field Spec 3, a field spectrometer that works in the optical region (350-2 500 nm) of the electromagnetic spectrum. In additional to the spectral data, pasture samples were also collected from the field and examined in laboratory to measure the relative concentration of CP (%), CFA (%) and CFI (%). After spectral denoising and smoothing, the relationship of pasture quality parameters with the reflectance spectrum, the first derivatives of reflectance (FDR), band ratio and the wavelet coefficients (WCs) was analyzed respectively. The concentration of CP, CFA and CFI of pasture was found closely correlated with FDR with wavebands centered at 424, 1 668, and 918 nm as well as with the low-scale (scale = 2, 4) Morlet, Coiflets and Gassian WCs. Accordingly, the linear, exponential, and polynomial equations between each pasture variable and FDR or WCs were developed. Validation of the developed equations indicated that the polynomial model with an independent variable of Coiflets WCs (scale = 4, wavelength =1 209 nm), the polynomial model with an independent variable of FDR, and the exponential model with an independent variable of FDR were the optimal model for prediction of concentration of CP, CFA and CFI of pasture, respectively. The R2 of the pasture quality estimation models was between 0.646 and 0.762 at the 0.01 significance level. Results suggest that the first derivatives or the wavelet coefficients of hyperspectral reflectance in visible and near-infrared regions can be used for pasture quality estimation, and that it will provide a basis for real-time prediction of pasture quality using remote sensing techniques.

Crystal structure of tetraaquabis(8-chloro-9,10-dioxo-9,10-dihydroanthracene-1-carboxyl-ato-κO (1))cobalt(II) dihydrate.

In the title complex, [Co(C15H6ClO4)2(H2O)4]·2H2O, the Co(II) ion is bound by two carboxylate O atoms of two 5-chloro-9,10-anthra-quinone-1-carboxyl-ate anions and four water O atoms in a trans conformation, forming an irregular octa-hedral coordination geometry. This arrangement is stabilized by intra-molecular O-H⋯O hydrogen bonds between water and carboxyl-ate. Further O-H⋯O hydrogen bonds between coordinating and non-coordinating water and carboxyl-ate produce layers of mol-ecules that extend parallel to (001). The organic ligands project above and below the plane. Those ligands of adjacent planes are inter-digitated and there are π-π inter-actions between them with centroid-centroid distances of 3.552 (2) and 3.767 (2) Šthat generate a three-dimensional supra-molecular structure.

Crystal structure of 4-acetamido-benzoic acid monohydrate.

In the title compound, C9H9NO3·H2O, the plane of the acetamide group is oriented at 20.52 (8)° with respect to the benzene ring, whereas the plane of the carb-oxy-lic acid group is essentially coplanar with the benzene ring [maximum deviation = 0.033 (1) Å]. In the crystal, classical O-H⋯O and N-H⋯O hydrogen bonds and weak C-H⋯O hydrogen bonds link the organic mol-ecules and water mol-ecules of crystallization into a three-dimensional supra-molecular architecture.

(2,2'-Bi-pyridine-κ(2) N,N')bis-(nitrato-κ(2) O,O')copper(II).

In the title complex, [Cu(NO3)2(C10H8N2)], the Cu(II) cation is chelated by two nitrate anions and by one 2,2'-bi-pyridine ligand in a distorted N2O4 octa-hedral geometry. The dihedral angle between the pyridine rings is 1.92 (11)°. In the crystal, π-π stacking between parallel pyridine rings of adjacent complex mol-ecules is observed, the centroid-centroid distance being 3.6788 (19) Å. Weak C-H⋯O hydrogen bonds further link the mol-ecules into a three-dimensional supra-molecular architecture.

Design, Synthesis, and Herbicidal Activity of Diphenyl Ether Derivatives Containing a Five-Membered Heterocycle.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) is an important target for discovering novel herbicides, and it causes bleaching symptoms by inhibiting the synthesis of chlorophyll and heme. In this study, the active fragments of several commercial herbicides were joined by substructure splicing and bioisosterism, and a series of novel diphenyl ether derivatives containing five-membered heterocycles were synthesized. The greenhouse herbicidal activity and the PPO inhibitory activity in vitro were discussed in detail. The results showed that most compounds had good PPO inhibitory activity, and target compounds containing trifluoromethyl groups tended to have higher activity. Among them, compound G4 showed the best inhibitory activity, with a half-maximal inhibitory concentration (IC50) of 0.0468 µmol/L, which was approximately 3 times better than that of oxyfluorfen (IC50 = 0.150 µmol/L). In addition, molecular docking indicated that compound G4 formed obvious π-π stacking interactions and hydrogen bond interactions with PHE-392 and ARG-98, respectively. Remarkably, compound G4 had good safety for corn, wheat, rice, and soybean, and the cumulative concentration in crops was lower than that of oxyfluorfen. Therefore, compound G4 can be used to develop potential lead compounds for novel PPO inhibitors.

trans-Bis(4,7-diphenyl-1,10-phenanthroline-κN,N')bis-(nitrato-κO,O')zinc(II).

The title compound, [Zn(NO(3))(2)(C(24)H(16)N(2))(2)], is a twofold axially symmetric coordination compound. Given that the Zn-O interactions [2.4926 (15) and 2.6673 (15) Å] can be considered as weakly bonding and the nitrate ions share the same C(2) axis of the Zn(dpp)(2) fragment (dpp is 4,7-diphenyl-1,10-phenanthroline), these anions belong to the coordination sphere of Zn(2+), leading to a complex with an overall coordination number of 8 for the metal ion.

An ab initio investigation of the mechanisms of photodissociation in bromobenzene and iodobenzene.

In concert with the latest experiment of velocity imaging technique [X. P. Zhang et al., ChemPhysChem 9, 1130 (2008)], quantum chemical calculations with relativistic effect were performed on the photodissociation of bromobenzene (BrPh) and iodobenzene (IPh) at 266 nm. The method of multistate second order multiconfigurational perturbation theory in conjunction with spin-orbit interaction through complete active space state interaction was employed to calculate the potential energy curves for the ground and low-lying excited states of BrPh and IPh along their photodissociation reaction coordinates. The dissociation mechanisms with products of X((2)P(3/2)) and X(*)((2)P(1/2)) (X = Br,I) states were clarified.

Complexes of nickel(II) and copper(II) with 1,2,4-triazole-3-carboxylic acid and of cobalt(III) with 3-amino-1,2,4-triazole-5-carboxylic acid.

Because of their versatile coordination modes and strong coordination ability for metals, triazole ligands can provide a wide range of possibilities for the construction of metal-organic frameworks. Three transition-metal complexes, namely bis(µ-1,2,4-triazol-4-ide-3-carboxylato)-κ3N2,O:N1;κ3N1:N2,O-bis[triamminenickel(II)] tetrahydrate, [Ni2(C3HN3O2)2(NH3)6]·4H2O, (I), catena-poly[[[diamminediaquacopper(II)]-µ-1,2,4-triazol-4-ide-3-carboxylato-κ3N1:N4,O-[diamminecopper(II)]-µ-1,2,4-triazol-4-ide-3-carboxylato-κ3N4,O:N1] dihydrate], {[Cu2(C3HN3O2)2(NH3)4(H2O)2]·2H2O}n, (II), (µ-5-amino-1,2,4-triazol-1-ide-3-carboxylato-κ2N1:N2)di-µ-hydroxido-κ4O:O-bis[triamminecobalt(III)] nitrate hydroxide trihydrate, [Co2(C3H2N4O2)(OH)2(NH3)6](NO3)(OH)·3H2O, (III), with different structural forms have been prepared by the reaction of transition metal salts, i.e. NiCl2, CuCl2 and Co(NO3)2, with 1,2,4-triazole-3-carboxylic acid or 3-amino-1,2,4-triazole-5-carboxylic acid hemihydrate in aqueous ammonia at room temperature. Compound (I) is a dinuclear complex. Extensive O-H...O, O-H...N and N-H...O hydrogen bonds and π-π stacking interactions between the centroids of the triazole rings contribute to the formation of the three-dimensional supramolecular structure. Compound (II) exhibits a one-dimensional chain structure, with O-H...O hydrogen bonds and weak O-H...N, N-H...O and C-H...O hydrogen bonds linking anions and lattice water molecules into the three-dimensional supramolecular structure. Compared with compound (I), compound (III) is a structurally different dinuclear complex. Extensive N-H...O, N-H...N, O-H...N and O-H...O hydrogen bonding occurs in the structure, leading to the formation of the three-dimensional supramolecular structure.

Synthesis, crystal structures and luminescence properties of seven mononuclear zinc(II), cadmium(II), cobalt(II) and nickel(II) complexes with 5-(4-methylphenyl)-3-(pyridin-2-yl)-1H-1,2,4-triazole.

Due to their versatile coordination modes and metal-binding conformations, triazolyl ligands can provide a wide range of possibilities for the construction of supramolecular structures. Seven mononuclear transition metal complexes with different structural forms, namely aquabis[3-(4-methylphenyl)-5-(pyridin-2-yl)-1H-1,2,4-triazolato-κ2N1,N5]zinc(II), [Zn(C14H11N4)2(H2O)], (I), bis[5-(4-methylphenyl)-3-(pyridin-2-yl)-1H-1,2,4-triazole-κ2N3,N4]bis(nitrato-κO)zinc(II), [Zn(NO3)2(C14H12N4)2], (II), bis(methanol-κO)bis[3-(4-methylphenyl)-5-(pyridin-2-yl)-1H-1,2,4-triazolato-κ2N1,N5]zinc(II), [Zn(C14H11N4)2(CH4O)2], (III), diiodidobis[5-(4-methylphenyl)-3-(pyridin-2-yl)-1H-1,2,4-triazole-κ2N3,N4]cadmium(II), [CdI2(C14H12N4)2], (IV), bis[5-(4-methylphenyl)-3-(pyridin-2-yl)-1H-1,2,4-triazole-κ2N3,N4]bis(nitrato-κO)cadmium(II), [Cd(NO3)2(C14H12N4)2], (V), aquabis[3-(4-methylphenyl)-5-(pyridin-2-yl)-1H-1,2,4-triazolato-κ2N1,N5]cobalt(II), [Co(C14H11N4)2(H2O)], (VI), and diaquabis[3-(4-methylphenyl)-5-(pyridin-2-yl)-1H-1,2,4-triazolato-κ2N1,N5]nickel(II), [Ni(C14H11N4)2(H2O)2], (VII), have been prepared by the reaction of transition metal salts (ZnII, CdII, CoII and NiII) with 3-(4-methylphenyl)-5-(pyridin-2-yl)-1H-1,2,4-triazole (pymphtzH) under either ambient or hydrothermal conditions. These compounds have been characterized by elemental analysis, IR spectroscopy and single-crystal X-ray diffraction. All the complexes form three-dimensional supramolecular structures through hydrogen bonds or through π-π stacking interactions between the centroids of the pyridyl or arene rings. The pymphtzH and pymphtz- entities act as bidentate coordinating ligands in each structure. Moreover, all the pyridyl N atoms are coordinated to metal atoms (Zn, Cd, Co or Ni). The N atom in the 4-position of the triazole group is coordinated to the Zn and Cd atoms in the crystal structures of (II), (IV) and (V), while the N atom in the 1-position of the triazolate group is coordinated to the Zn, Co and Ni atoms in (I), (III), (VI) and (VII).

Covalent linking of near-infrared luminescent ternary lanthanide (Er(3+), Nd(3+), Yb(3+)) complexes on functionalized mesoporous MCM-41 and SBA-15.

The near-infrared (NIR) luminescent lanthanide ions, such as Er(III), Nd(III), and Yb(III), have been paid much attention for the potential use in the optical communications or laser systems. For the first time, the NIR-luminescent Ln(dbm)(3)phen complexes have been covalently bonded to the ordered mesoporous materials MCM-41 and SBA-15 via a functionalized phen group phen-Si (phen-Si = 5-(N,N-bis-3-(triethoxysilyl)propyl)ureyl-1,10-phenanthroline; dbm = dibenzoylmethanate; Ln = Er, Nd, Yb). The synthesis parameters X = 12 and Y = 6 h (X denotes Ln(dbm)(3)(H(2)O)(2)/phen-MCM-41 molar ratio or Ln(dbm)(3)(H(2)O)(2)/phen-SBA-15 molar ratio and Y is the reaction time for the ligand exchange reaction; phen-MCM-41 and phen-SBA-15 are phen-functionalized MCM-41 and SBA-15 mesoporous materials, respectively) were selected through a systematic and comparative study. The derivative materials, denoted as Ln(dbm)(3)phen-MCM-41 and Ln(dbm)(3)phen-SBA-15 (Ln = Er, Nd, Yb), were characterized by powder X-ray diffraction, nitrogen adsorption/desorption, Fourier transform infrared (FT-IR), elemental analysis, and fluorescence spectra. Upon excitation of the ligands absorption bands, all these materials show the characteristic NIR luminescence of the corresponding lanthanide ions through the intramolecular energy transfer from the ligands to the lanthanide ions. The excellent NIR-luminescent properties enable these mesoporous materials to have potential uses in optical amplifiers (operating at 1.3 or 1.5 mum), laser systems, or medical diagnostics. In addition, the Ln(dbm)(3)phen-SBA-15 materials show an overall increase in relative luminescent intensity and lifetime compared to the Ln(dbm)(3)phen-MCM-41 materials, which was explained by the comparison of the lanthanide ion content and the pore structures of the two kinds of mesoporous materials in detail.

Near-infrared luminescent hybrid materials doped with lanthanide (Ln) complexes (Ln = Nd, Yb) and their possible laser application.

The crystal structures of ternary Ln(DBM)(3)phen complexes (DBM = dibenzoylmethane, phen = 1,10-phenanthroline, and Ln = Nd, Yb) and their in situ syntheses via the sol-gel process are reported. The properties of the Ln(DBM)(3)phen complexes and their corresponding Ln(3+)/DBM/phen-co-doped luminescent hybrid gels obtained via an in situ method (Ln-D-P gel) have been studied. The results reveal that the lanthanide complexes are successfully in situ synthesized in the corresponding Ln-D-P gels. Both Ln(DBM)(3)phen complexes and Ln-D-P gels display sensitized near-infrared (NIR) luminescence upon excitation at the maximum absorption of the ligands, which contributes to the efficient energy transfer from the ligands to the Ln(3+) ions (Ln = Nd, Yb), an antenna effect. The radiative properties of the Nd(3+) ion in a Nd-D-P gel are discussed using Judd-Ofelt analysis, which indicates that the (4)F(3/2) --> (4)I(11/2) transition of the Nd(3+) ion in the Nd-D-P gel can be considered as a possible laser transition.

Synthesis and crystal structures of two coordination polymers and a binuclear cadmium(II) complex containing 3- and 4-aminobenzoate ligands.

Due to their wide range of coordination modes and versatile conformations when binding to metal atoms, multicarboxylate ligands are of interest in the design of metal-organic frameworks (MOFs). Three Cd(II) complexes, namely catena-poly[diammonium [[chloridocadmium(II)]-di-µ-chlorido-[chloridocadmium(II)]-bis(µ-3-aminobenzoato)-κ(3)N:O,O';κ(3)O,O':N]], {(NH4)[CdCl2(C7H6NO2)]}n, (I), catena-poly[[[aquacadmium(II)]-bis(µ-4-aminobenzoato)-κ(3)N:O,O';κ(3)O,O':N] monohydrate], {[Cd(C7H6NO2)2(H2O)]·H2O}n, (II), and di-µ-acetato-κ(4)O:O'-bis[(4-aminobenzoato-κ(2)O,O')(2,2'-bipyridine-κ(2)N,N')cadmium(II)], [Cd2(CH3COO)2(C7H6NO2)2(C10H8N2)2], (III), with different stuctural forms are reported. Complex (I) has a one-dimensional ladder structure, with strong N-H···O and weak N-H···Cl hydrogen bonds linking the cations and anions in the three-dimensional supramolecular structure. Complex (II) has a one-dimensional chain structure. Extensive O-H···O and N-H···O hydrogen bonds between the anionic ligands and the solvent water molecules and π-π stacking interactions between the centroids of the benzene rings lead to the three-dimensional supramolecular structure. Complex (III) is a binuclear molecule which is extended into a three-dimensional supramolecular structure via strong N-H···O and weak C-H···O hydrogen bonds.

Novel 4H-1,3,4-oxadiazin-5(6H)-ones with hydrophobic and long alkyl chains: design, synthesis, and bioactive diversity on inhibition of monoamine oxidase, chitin biosynthesis and tumor cell.

A new series of nitrogen-containing heterocycles 4H-1,3,4-oxadiazin-5(6H)-ones derivatives with hydrophobic and long chains were designed and synthesized by direct cyclization reaction of N'-alkylation substituted aroylhydrazines with chloroacetyl chloride. The preliminary assays showed that some of the compounds displayed moderate to good inhibitory activities toward monoamine oxidase (MAO) at the concentration of 10(-5)-10(-3)M, and antitumor activities against human lung cancer A-549 and human prostate cancer PC-3 cell lines at muM level, which might provide new scaffold for anticancer agents. Furthermore, compounds 5i and 5m exhibited significant inhibitory activity on chitin biosynthesis, which might represent a novel class of highly potential inhibitors of chitin synthesis.