nitrophenols and catechol

Catechol-O-methyltransferase (COMT) plays an important role in the deactivation of catecholamine neurotransmitters and hormones. Inhibitors of COMT, such as tolcapone and entacapone, are used clinically in the treatment of Parkinson's disease. Discovery of novel inhibitors has been hampered by a lack of suitable assays for high-throughput screening (HTS). Although assays using esculetin have been developed, these are affected by fluorescence, a common property of catechol-type compounds. We have therefore evaluated a new homogenous time-resolved fluorescence (HTRF)-based assay from CisBio (Codolet, France), which measures the production of S-adenosyl-L-homocysteine (SAH). The assay has been run in both HTS and medium-throughput screening (MTS) modes. The assay was established using membranes expressing human membrane-bound COMT and was optimized for protein and time to give an acceptable signal window, good potency for tolcapone, and a high degree of translation between data in fluorescence ratio and data in terms of [SAH] produced. pIC50 values for the hits from the HTS mode were determined in the MTS mode. The assay also proved suitable for kinetic studies such as Km,app determination.

Topics: Benzophenones; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Catechols; High-Throughput Screening Assays; Humans; Kinetics; Nitrophenols; Parkinson Disease; S-Adenosylhomocysteine; Small Molecule Libraries; Tolcapone

Despite knowing the fact that vanadium pentoxide is slightly soluble in aqueous medium, its photocatalytic activity was evaluated for the degradation of phenol and its derivatives (2-hydroxyphenol, 2-chlorophenol, 2-aminophenol and 2-nitrophenol) in natural sunlight exposure. The prime objective of the study was to differentiate between the homogeneous and heterogeneous photocatalysis incurred by dissolved and undissolved V2O5 in natural sunlight exposure. V2O5 was synthesized by chemical precipitation procedure using Triton X-100 as morphology mediator and characterized by DRS, PLS, Raman, FESEM and XRD. A lower solubility of ∼ 5% per 100ml of water at 23 °C was observed after calcination at 600 °C. The study revealed no contribution of the dissolved V2O5 in the photocatalytic process. In sunlight exposure, V2O5 powder exhibited substantial activity for the degradation, however, a low mineralization of phenolic substrates was observed. The initial low activity of V2O5 followed by a sharp increase both in degradation and mineralization in complete spectrum sunlight exposure, was further investigated that revealed the decrease in the bandgap and the reduction in the particle size with the interaction of UV photons (<420 nm) as this effect was not observable in the exposure of visible region of sunlight. The role of the chemically different substituents attached to an aromatic ring at 2-positions and the secondary interaction of released ions during the degradation process with the reactive oxygen species (ROS) was also explored.

Topics: Aminophenols; Catalysis; Catechols; Chlorophenols; Chromatography, High Pressure Liquid; Electrochemistry; Electrons; Hydrogen-Ion Concentration; Ions; Microscopy, Electron, Scanning; Nitrophenols; Particle Size; Phenol; Photochemistry; Photons; Reactive Oxygen Species; Semiconductors; Solubility; Spectrophotometry, Ultraviolet; Sunlight; Vanadium Compounds; X-Ray Diffraction

The gas-phase oxidation mechanism of phenol initiated by OH radical was investigated using DFT and ab initio calculations. The initiation of the reaction is dominated by OH addition to ortho-position, forming P2, which subsequently combines with O2 at the ipso-position to form P2-1-OO adduct. A concerted HO2 elimination process from P2-1-OO was found to be much faster than the common ring closure to bicyclic intermediates. The HO2 elimination process from P2-1-OO forms 2-hydroxy-3,5-cyclohexadienone (HCH) as the main product and is also responsible for the experimental fact that the rate constants for reaction between P2 and O2 are about 2 orders of magnitude higher than those between other aromatic-OH adducts and O2. It was speculated that HCH would isomerize to catechol, which is thermodynamically more stable than HCH and was the experimentally observed main product, possibly through heterogeneous processes. Reaction of P2 with NO2 proceeded by addition to form P2-n-NO2 (n = 1, 3, 5), followed by HONO elimination from P2-1/3-NO2 to form catechol. The barriers for HONO elimination and catechol formation are below the separate reactants P2 and NO2, being consistent with the experimental observation of catechol in the absence of O2, while H2O elimination from P2-1/3-NO2 to form 2-nitrophenol (2NP) is hindered by high barriers. The most likely pathway for 2NP is the reaction of phenoxy radical and NO2.

Topics: Atmosphere; Catechols; Gases; Hydroxyl Radical; Kinetics; Models, Chemical; Nitrogen Dioxide; Nitrophenols; Oxidation-Reduction; Phenol; Phenols; Quantum Theory; Thermodynamics

The electrochemical oxidation of pesticide, o-nitrophenol (ONP) as one kind of pesticide that is potentially dangerous and biorefractory, was studied by galvanostatic electrolysis using boron-doped diamond (BDD) as anode. The influence of several operating parameters, such as applied current density, supporting electrolyte, and initial pH value, was investigated. The best degradation occurred in the presence of Na2SO4 (0.05 M) as conductive electrolyte. After 8h, nearly complete degradation of o-nitrophenol was achieved (92%) using BDD electrodes at pH 3 and at current density equals 60 mA cm(-2). The decay kinetics of o-nitrophenol follows a pseudo-first-order reaction. Aromatic intermediates such as catechol, resorcinol, 1,2,4-trihydroxybenzene, hydroquinone and benzoquinone and carboxylic acids such as maleic glycolic, malonic, glyoxilic and oxalic, have been identified and followed during the ONP treatment by chromatographic techniques. From these anodic oxidation by-products, a plausible reaction sequence for ONP mineralization on BDD anodes is proposed.

Topics: Benzoquinones; Boron; Carboxylic Acids; Catechols; Diamond; Electrodes; Electrolysis; Hydrogen-Ion Concentration; Hydroquinones; Kinetics; Models, Chemical; Nitrophenols; Oxygen; Pesticides; Resorcinols; Water Pollutants, Chemical; Water Purification

A sequencing batch reactor (SBR) was inoculated with p-nitrophenol-degrading activated sludge to biodegrade a mixture of monosubstituted phenols: p-nitrophenol (PNP), PNP and o-cresol; and PNP, o-cresol and o-chlorophenol. Settling times were progressively decreased to promote biomass granulation. PNP was completely biodegraded. The PNP and o-cresol mixture was also biodegraded although some transitory accumulation of intermediates occurred (mainly hydroquinone and catechol). o-Chlorophenol was not biodegraded and resulted in inhibition of o-cresol and PNP biodegradation and complete failure of the SBR within a few days. The biomass had very good settling properties when a settling time of 1 min was applied: sludge volume index (SVI₅) below 50 mL g(-1), SVI₅/SVI₃₀ ratio of 1 and average particle size of 200 μm.

Topics: Acinetobacter; Aerobiosis; Arthrobacter; Batch Cell Culture Techniques; Biodegradation, Environmental; Biomass; Bioreactors; Catechols; Chlorophenols; Cresols; Hydroquinones; In Situ Hybridization, Fluorescence; Nitrophenols; Pseudomonas; Sewage; Temperature; Time Factors

A new class of phenol based unsymmetrical side-off tetra and hexa coordinate homobinuclear Cu(II) and heterobinuclear Cu(II)-Zn(II) complexes have been synthesized and characterized by elemental and spectral analysis. The electronic spectra of all the complexes show "Red shift" in LMCT band, for the ligand H(2)L(2) compared to that of the ligand H(2)L(1) due to the relatively higher electron donating nature of their substitutents. The homobinuclear Cu(II) complexes (1 and 2) illustrate an antiferromagnetic interaction (μ(eff): 1.58 and 1.60BM) at 298K with a broad EPR signal. Variable temperature magnetic moment study of the binuclear copper (II) complexes shows that the extent of antiferromagnetic coupling is greater in the case of H(2)L(2) complexes than H(2)L(1) complexes (-2J values: 192cm(-1) and 184cm(-1) respectively). The heterobinuclear Cu(II)-Zn(II) complexes (3 and 4) have a magnetic moment value close to the spin only value with four hyperfine EPR signals. Electrochemical studies of the complexes reveal that all the binuclear complexes show two irreversible one-electron transfer reduction waves in the cathodic region. There is an "anodic shift" in the first reduction potential of the complexes, of the ligand H(2)L(1) when compared to that of the ligand H(2)L(2) due to the presence of relatively higher electron donating N-substituents in the later case than in the former case. The catecholase activity of the complexes reveals that the homobinuclear Cu(II) complexes show higher catalytic activity than the corresponding heterobinuclear Cu(II)-Zn(II) complexes. In the hydrolysis of 4-nitrophenylphosphate, the heterobinuclear Cu(II)-Zn(II) complexes show better catalytic activity than the corresponding homobinuclear Cu(II) complexes.

Topics: Catechol Oxidase; Catechols; Coordination Complexes; Copper; Electrochemical Techniques; Electron Spin Resonance Spectroscopy; Electrons; Hydrolysis; Kinetics; Magnetics; Nitrophenols; Organophosphorus Compounds; Oxidation-Reduction; Spectroscopy, Fourier Transform Infrared; Temperature; Zinc

A number of approaches have been proposed for screening level ecological risk assessment. In this paper, we first established a mass spectrum library including 50 phenols using retention time locking (RTL) technology and deconvolution reporting software (DRS). Distribution of phenols in surface water of the Taihu Lake was screened. Among the 22 identified phenols, 14 phenols were quantified. The concentrations of total phenols ranged 675.2-3346.1 ng L(-1). The distributions of ecological effect quotients (EEQs) of 14 phenols were characterized in terms of the exposure concentration distributions (ECDs) and species sensitivity distributions (SSDs). Those phenols with EEQs exceeding the threshold proposed by Water Environment Research Foundation of Alexandria were selected as priorities. As a result, 2-nitrophenol (2-NP), p-chloro-m-xylenol (PCMX) and pyrocatechol were determined as potential ecological risk stressors in surface water of the Taihu Lake. Results of the present study suggested that the proposed approach is feasible for the screening level ecological risk assessment.

Topics: Catechols; Fresh Water; Nitrophenols; Phenols; Risk Assessment; Water Pollutants, Chemical; Xylenes

The aim of this study was to (i) isolate and characterize bacteria capable of degrading p-nitrophenol (PNP); (ii) determine the kinetics of biodegradation, (iii) clone and express the PNP-degrading related genes.. Enrichment method and serial dilution spread-plate method were employed to isolate PNP-degrading strain. Morphological, physiological & biochemical tests and 16S rDNA sequence analysis were used to identify the isolate. Degradation kinetics was studied by flask test. PNP-degrading related genes were cloned by SEFA-PCR method. Hydroxyquinol 1,2-dioxygenase encoding gene pnpC was cloned into pET29a to construct the recombinant plasmid pETpnpC and expressed in E. coli BL21 (DE3). The activity of the expressed product was determined by spectrophotometric method.. Strain PDS-7 capable of utilizing PNP as the sole carbon, nitrogen and energy source was isolated and identified as Pseudomonas sp. It could tolerate the PNP concentration up to 80 mg/L, the optimal temperature for degradation was about 30 degrees C and alkaline pH benefited PNP degradation. Hydroxyquinol 1,2-dioxygenase and maleylacetate reductase encoding gene pnpC and pnpD were cloned and sequenced respectively, the sequence was deposited in GenBank with the accession number EU233791. pnpC was expressed in E. coli BL21 (DE3), the expressed product in cell-free crude extracts showed ortho ring cleavage activity to hydroxyquinol and catechol, with the special activity 0.45 U/mg protein and 0.37 U/mg protein, respectively, indicating pnpC gene encoding hydroxyquinol 1,2-dioxygenase was actively expressed.. One PNP-degrading strain Pseudomonas sp. PDS-7 was isolated and identified. Its degradation kinetics was studied. Its degradation relevant genes were cloned and expressed.

Topics: Biodegradation, Environmental; Catechols; Cloning, Molecular; Dioxygenases; DNA, Bacterial; Molecular Sequence Data; Nitrophenols; Pharmacokinetics; Pseudomonas

In this work, we present a comparative case study of "ortho-" and "meta-nitrated" catecholic inhibitors of catechol-O-methyltransferase (COMT), with regard to their interaction with the catalytic site of the enzyme and the in vitro regioselective formation of their mono-O-methyl ether metabolites. In particular, the effects of altering the attachment position of the inhibitors' side-chain substituent, within the classic nitrocatechol pharmacophore, were investigated. For this purpose, we compared two simple regioisomeric nitrocatechol-type inhibitors of COMT, BIA 3-228 and BIA 8-176, which contain the benzoyl substituent attached at the meta and ortho positions, respectively, relative to the nitro group. The two compounds were slowly O-methylated by COMT in vitro, but the particular substitution pattern of each compound was shown to have a profound impact on the regioselectivity of their O-methylation. To provide a plausible interpretation of these results, a comprehensive analysis of the protein-inhibitor interactions and of the relative chemical susceptibility to O-methylation of the catechol hydroxyl groups was performed by means of docking simulations and ab initio molecular orbital calculations. The major structural and chemical factors that determine the enzyme regioselectivity of O-methylation were identified, and the X-ray structure of the complex of COMT with S-adenosyl-l-methionine and BIA 8-176 is herein disclosed. This is the first reported structure of the soluble form of COMT complexed with a nitrocatecholic inhibitor having a bulky substituent group in adjacent position (ortho) to the nitro group. Structural and dynamic aspects of this complex are analyzed and discussed, in the context of the present study.

Topics: Animals; Benzophenones; Binding Sites; Catalytic Domain; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Catechols; Crystallization; Dimerization; Enzyme Inhibitors; Methylation; Models, Molecular; Molecular Structure; Nitrates; Nitrophenols; Protein Binding; Rats; Stereoisomerism

Twenty-one microorganisms were screened for their ability to convert nitroaromatics into 3-nitrocatechol as a result of the action of an oxygenase. Cultures containing toluene dioxygenases and phenol monooxygenases accumulated 3-nitrocatechol during incubation with nitrobenzene and nitrophenol, respectively. Nocardia S3 was selected and studied in more detail. Toluene-pregrown cultures were able to degrade nitrobenzene with a concomitant formation of 3-nitrocatechol. The rates of nitrobenzene utilization decreased throughout the biotransformation period and finally the accumulation ceased. The gradual deterioration of the biotransformation rates was not a consequence of depletion of the NADH pool, but was due to the accumulation of 3-nitrocatechol. The inhibition of nitrobenzene biotransformation by 3-nitrocatechol greatly impacts 3-nitrocatechol production processes.

Topics: Biotransformation; Catechols; Culture Media; Nitrobenzenes; Nitrophenols; Nocardia; Oxidoreductases; Oxygen Consumption; Oxygenases; Toluene

The interaction between beta-cyclodextrin and five mono- and disubstituted benzenes in water was investigated by means of molecular dynamics. The trajectories were calculated for each system, imposing a 1:1 host-guest stoichiometry with 512 water molecules. Periodic boundary conditions were adopted. The results account for the formation of stable adducts and the predicted geometry agrees with experimental circular dichroism data.

Topics: Aniline Compounds; Benzene; beta-Cyclodextrins; Catechols; Computer Simulation; Cyclodextrins; Models, Molecular; Nitrophenols; Phenol

Salicylate hydroxylase [EC 1.14.13.1] from Pseudomonas putida catalyzed the formation of catechol from substrate analogues such as o-nitro-, o-amino-, o-iodo-, o-bromo-, and o-chloro-phenol by removing the ortho-substituted groups. They are converted into nitrite, ammonia, and halide ions, respectively. Kinetic parameters of these reactions were determined by spectrophotometric and polarographic methods. Hydroxylation of o-nitro- or o-iodophenol proceeds with the unusual stoichiometry of 2:1:1 for consumed NADH, O2-uptake, and catechol formed. Other ortho-substituted phenols examined also gave the same results. Like salicylate, these substrates perturb the absorption spectrum of salicylate hydroxylase in the visible region, indicating the formation of enzyme.substrate complexes. Titration experiments with ortho-substituted phenols gave the dissociation constants of the complexes. The complexes were quantitatively reduced with NADH or dithionite without detectable formation of the intermediates. The fact that one atom of 18O2 was incorporated into the produced catechol in hydroxylation of o-nitrophenol indicates that the reaction is of monooxygenase nature. It is concluded that salicylate hydroxylase cleaves the C-N and C-X bonds of ortho-substituted phenols.

Topics: Catechols; Chlorophenols; Halogens; Hydrogen-Ion Concentration; Hydroxylation; Kinetics; Mixed Function Oxygenases; NAD; Nitrophenols; Phenols; Pseudomonas; Spectrophotometry; Substrate Specificity

Topics: Aldehydes; Benzaldehydes; Benzoates; Catechols; Chromatography; Cinnamates; Hippurates; Indoles; Mandelic Acids; Naphthalenes; Nitrophenols; Phenol; Phenols; Quinolines; Research; Resorcinols; Tryptamines

Topics: Catechols; Mycobacterium; Nitrophenols; Oxidation-Reduction

Topics: 17-Ketosteroids; Borates; Catechols; Chlorides; Cortisone; Dehydroepiandrosterone; Enzyme Inhibitors; Esters; Estrone; Hydrolysis; Kinetics; Nitrophenols; Phenolphthaleins; Phosphates; Pregnenolone; Research; Snails; Steroids; Sulfatases; Sulfates; Testosterone