4-dimethylaminophenol Research Articles

Assessment of biodegradation kinetics and mass transfer aspects in attached growth bioreactor for effective treatment of brilliant green dye from wastewater

In this study, Bacillus licheniformis immobilized with low-density polyethylene (LDPE) was employed to degrade Brilliant Green (BG) dye from wastewater in a packed bed bioreactor (PBBR). Bacterial growth and extracellular polymeric substance (EPS) secretion were also assessed under different concentrations of BG dye. The impacts of external mass transfer resistance on BG biodegradation were also evaluated at different flow rates (0.3–1.2 L/h). A new mass transfer correlation JD=5.71NRe-0.3 was proposed to study the mass transfer aspects in attached-growth bioreactor. The intermediates, namely 3- dimethylamino phenol, benzoic acid, 1–4 benzenediol, and acetaldehyde were identified during the biodegradation of BG and, subsequently degradation pathway was proposed. Han - Levenspiel kinetics parameters μmax and Ks were found to be 0.185 per day and 115 mg/L, respectively. The new insight into mass transfer and kinetics support the design of efficiently attached growth bioreactor to treat a wide range of pollutants.

Gram-Scale Room-Temperature Synthesis of Solid-State Fluorescent Carbon Nanodots for Bright Electroluminescent Light Emitting Diodes.

The reaction conditions of high temperature and high pressure will introduce structural defects, high energy consumption, and security risks, severely hindering the industrial application of organic carbon nanodots (CDs). Moreover, the aggregation caused quenching effect also fundamentally limits the CDs based electroluminescent light emitting diodes (LEDs). Herein, for the first time, a rapid one-step room temperature synthetic strategy is introduced to prepare highly emissive solid-state-fluorescent CDs (RT-CDs). A strong oxidizing agent, potassium periodate (KIO4 ), is adopted as a catalyst to facilitate the cyclization of o-phenylenediamine and 4-dimethylamino phenol in aqueous solution at room temperature for only 5min. The resultant organic molecule, 2-(dimethylamino) phenazine, will self-assemble kinetically to generate supramolecular-structure CDs during crystallization. The elaborately arranged supramolecular structure (J aggregates) endows CDs with intense solid-state-fluorescence. Density functional theory (DFT) calculation shows that the excited state of RT-CDs exhibits charge transfer characteristic owing to the unique donor-Π-acceptor structure. A high-performance monochrome RT-CDs based electroluminescent LEDs (2967cd m-2 and 1.38cd A-1 ) werefabricated via systematic optimizations of device engineering. This work provides a concrete and feasible avenue for the rapid and massive preparation of CDs, advancing the commercialization of CDs based optoelectronic devices.

GENOTOXICITY OF N-HYDROXY AND AMINOPHENOL METABOLITES OF 2,6- AND 3,5-DIMETHYLANILINE AT THE HYPOXANTHINEGUANINE PHOSPHORIBOSYLTRANSFERASE LOCUS IN TK6 CELLS

Objective: The objective of this study as to characterize the genotoxicity of reactive metabolites of 2,6-dimethylaniline (2,6-DMA) and 3,5-DMA in the hypoxanthineguanine phosphoribosyltransferase (HPRT) gene of human lymphoblastoid TK6 cells.Methods: Cultures were exposed to N-hydroxylamine and aminophenol metabolites of 2,6- and 3,5-DMA for 1 h in serum-free medium. Cell survival 24 h after exposure was determined by trypan blue exclusion. Cells were then subcultured for 7–10 days to allow to phenotypic expression of HPRT mutants. After the expression period, cells were plated in the presence of 2 μg/ml 6-thioguanine for the selection of HPRT mutants. Plating efficiency was determined and mutant fraction calculated. Electron paramagnetic resonance (EPR) was also used to determine whether 3,5- dimethylaminophenol (DMAP) produced reactive oxygen species (ROS).Results: All of the metabolites tested were cytotoxic to these cells but exhibited a considerable variation in potency. The aminophenol metabolites of 2,6- and 3,5-DMA were considerably more toxic than the corresponding N-hydroxylamines. Furthermore, each metabolite of 3,5-DMA was more toxic than its 2,6-DMA counterpart; N-OH-3,5-DMA and 3,5-DMAP were clearly mutagenic at a level of 50 μM. EPR studies showed intracellular oxidative stress induced under 3,5-DMAP treatment.Conclusions: Our findings suggest that genotoxic responses of 2,6- and 3,5-DMA are mediated through the generation of ROS by hydroxylamine and/ or aminophenol metabolites.

Burkholderia cepacia immobilized on eucalyptus leaves used to simultaneously remove malachite green (MG) and Cr(VI).

A multifunctional biomaterial capable of simultaneously removing malachite green (MG) and Cr(VI) was prepared by immobilizing Burkholderia cepacia (B. cepacia) on eucalyptus leaves (EL). The maximum uptake of MG (60 mg/L) and Cr(VI) (20 mg/L) were 94.8% and 71.9% respectively, which was more efficient than when using EL or free cells alone. SEM-EDS demonstrated that B. cepacia was attached to EL and that Cr(VI) was biosorbed into the immobilized cells. FTIR showed that the degradation by functional groups of immobilized cells was in keeping with the products, detected by GC-MS, which suggested that MG could be degraded to 4-dimethylamino benzophenone and 4-dimethylamino phenol. The removal of both MG and Cr(VI) by EL immobilized cells fit the pseudo-second order adsorption kinetic model well (with both R2>0.983). The equilibrium adsorption capacity of MG was 9.59, 18.67 and 28.64 mg/g for initial MG concentrations of from 30, 60, 90 mg/L, respectively when the concentration of Cr(VI) was held constant at 20 mg/L. The adsorption capacity of Cr(VI) increased from 3.49, 7.68 to 9.79 mg/g as the initial Cr(VI) concentrations increased (10, 20, 30 mg/L) while the MG concentration was kept constant at 60 mg/L. The results showed that eucalyptus leaves as a low cost and eco-friendly material have some potential to be an effective immobilization for environmental applications.

O-Toluidine in Breath-Non-Invasive Prilocaine Monitoring

The generation of methaemoglobin is a rare but potential life-threatening side effect in the use of the local anaesthetic prilocaine. It is currently only possible to ensure the diagnosis by means of blood tests. Rapid noninvasive diagnosis is desirable, especially for risk patients. Using a pig model, we induced methaemoglobinemia via application of dimethyl aminophenol and prilocaine (setup I) or natrium nitrite and prilocaine (setup II). Continuous real time breath gas monitoring was performed by proton transfer reaction-time-of-flight-mass spectrometry (PTR-TOF-MS) for non-invasive determination of volatile organic compounds (VOCs). O-Toluidine, the main metabolite of prilocaine, could be detected in alveolar breath gas by means of PTR-TOFMS and was confirmed by NTME-GC-MS (needle trap micro-extraction gas chromatography-mass spectrometry). The administration of prilocaine intravenously was clearly reflected with a time lag of a few min by the detection of O-Toluidine in the respiratory gas. If reliable correlations between prilocaine and methaemoglobin concentrations in blood and O-Toluidine levels in breath can be established, detection of prilocaine induced methaemoglobinemia and prevention of prilocaine poisoning with potentially life threatening hypoxia might be possible by means of non-invasive O-Toluidine analysis in breath.

Synthesis and Characterization of New Xanthene Derivatives, and Their Electrochemical Study

AbstractThis work investigated the synthesis of biphenyl‐3,3′,4,4′‐tetracarboxylic dianhydride and benzophenone‐3,3′,4,4′‐tetracarboxylic dianhydride derivatives (3a–e and 6a–e) with different substituted phenols via Friedel‐Crafts acylation reaction in the presence of dilute sulfuric acid. Dianhydride derivatives with 3‐N,N′‐dimethylamino phenol (3d and 6d) and resorcinol (3e and 6e) have been found to be highly fluorescent. The structures of all newly synthesized compounds were confirmed by the chromatographic, spectral and elemental data. Electrochemical study was done to determine to band gap energy, LUMO and HOMO levels energy. Band gap and LUMO energy levels were found to be lowest in xanthene derivatives substituted with 3‐N,N′‐dimethylamino group having value 2.24 and 4.85 eV respectively.

Past, present and future of cyanide antagonism research: From the early remedies to the current therapies.

This paper reviews milestones in antidotal therapies for cyanide (CN) spanning early remedies, current antidotal systems and research towards next generation therapies. CN has been a part of plant defense mechanisms for millions of years. It became industrially important in the nineteenth century with the advent of CN assisted gold mining and the use of CN as a pest control agent. The biochemical basis of CN poisoning was actively studied and key mechanisms were understood as early as 1929. These fundamental studies led to a variety of antidotes, including indirect CN binders that generate methemoglobin, direct CN binders such as hydroxocobalamin, and sulfur donors that convert CN to the less toxic thiocyanate. Research on blood gases at the end of the twentieth century shed new light on the role of nitric oxide (NO) in the body. The discovery of NO's ability to compete with CN for enzymatic binding sites provided a previously missed explanation for the rapid efficacy of NO generating antidotes such as the nitrites. Presently used CN therapies include: methemoglobin/NO generators (e.g., sodium nitrite, amyl nitrite, and dimethyl aminophenol), sulfur donors (e.g., sodium thiosulfate and glutathione), and direct binding agents [(e.g., hydroxocobalamin and dicobalt salt of ethylenediaminetetraacetic acid (dicobalt edetate)]. A strong effort is being made to explore novel antidotal systems and to formulate them for rapid administration at the point of intoxication in mass casualty scenarios. New antidotes, formulations, and delivery systems are enhancing bioavailability and efficacy and hold promise for a new generation of improved CN countermeasures.

Rational Design of a Structural Framework with Potential Use to Develop Chemical Reagents That Target and Modulate Multiple Facets of Alzheimer’s Disease

Alzheimer's disease (AD) is characterized by multiple, intertwined pathological features, including amyloid-β (Aβ) aggregation, metal ion dyshomeostasis, and oxidative stress. We report a novel compound (ML) prototype of a rationally designed molecule obtained by integrating structural elements for Aβ aggregation control, metal chelation, reactive oxygen species (ROS) regulation, and antioxidant activity within a single molecule. Chemical, biochemical, ion mobility mass spectrometric, and NMR studies indicate that the compound ML targets metal-free and metal-bound Aβ (metal-Aβ) species, suppresses Aβ aggregation in vitro, and diminishes toxicity induced by Aβ and metal-treated Aβ in living cells. Comparison of ML to its structural moieties (i.e., 4-(dimethylamino)phenol (DAP) and (8-aminoquinolin-2-yl)methanol (1)) for reactivity with Aβ and metal-Aβ suggests the synergy of incorporating structural components for both metal chelation and Aβ interaction. Moreover, ML is water-soluble and potentially brain permeable, as well as regulates the formation and presence of free radicals. Overall, we demonstrate that a rational structure-based design strategy can generate a small molecule that can target and modulate multiple factors, providing a new tool to uncover and address AD complexity.

Investigation of the intermediates formed during the degradation of Malachite Green in the presence of Fe3+ and H2O2 under visible irradiation

The photodegradation of Malachite Green (MG) was investigated in the presence of Fe3+ and H2O2 under visible irradiation (λ > 470 nm) and the intermediates produced during the degradation were determined by FTIR, GC-MS and 1H NMR. The mineralized products of nitrogen atoms in the dye molecule were analyzed by ammonia ion-selective electrode and ion chromatography. N,N-dimethylaniline, 4-dimethylamino phenol, 4-methylamino benzophenone, 4-dimethylamino benzophenone, benzeneacetic acids and 4-hydroxybenzoic acid were found during the photodegradation of MG. It can be concluded that the dye underwent two different principal degradation pathways in the initial period of the photodecomposition, one is that the dye molecule is splittingly decomposed into small species by attack of HO• radicals on the central carbon, another is that the N-methyl groups are oxidized by HO• radicals, leading to demethylation. Nitrogen atoms in the dye molecules are finally transformed into ammonium ions. A possible degradation mechanism is proposed.

Effectiveness of intramuscularly administered cyanide antidotes on methemoglobin formation and survival.

Successful first aid therapy for cyanide intoxication is dependent upon immediate administration of antidotes which directly or indirectly interact with the cyanide ion to remove it from circulation. Owing to the severe respiratory, cardiovascular and convulsive episodes following acute cyanide intoxication, the most practical approach is to administer antidotes by intramuscular injection. Exceptionally rapid methemoglobin formers-hydroxylamine hydrochloride (HH) and dimethylaminophenol (DMAP)-are usually able to prevent the lethal effect of cyanide following intramuscular injections in doses sufficient to induce 20% methemoglobin (HH = 20 mg kg-1 and DMAP = 2 mg kg-1). Sodium nitrite, the methemoglobin inducer approved for military use, must be administered by intravenous infusion because it is not an effective cyanide antidote by the intramuscular route. In the normal unintoxicated animal an intramuscular injection of 20 mg kg-1 sodium nitrite will form 20% methemoglobin; however, in acute cyanide intoxication the associated severe bradycardia appears to limit the rate of absorption and thus the rapid formation of methemoglobin. If the bradycardia is prevented or reversed by atropine, the rate of absorption of sodium nitrite and the formation of methemoglobin is able to reverse the otherwise lethal effects of cyanide. Thus, an intramuscularly administered combination of 20 mg kg-1 sodium nitrite and 1 mg kg-1 atropine sulfate, rapidly absorbed from the intramuscular site, appears to achieve the same degree of effectiveness against acute cyanide intoxication as intramuscularly administered HH or DMAP. It would appear from these studies that HH, DMAP and sodium nitrite with atropine are all potentially effective intramuscular antidotes for acute cyanide poisoning.

Reactivity of glutathione adducts of 4-(dimethylamino)phenol. Involvement of reactive oxygen species during the interaction with oxyhemoglobin.

Ferrihemoglobin formation by 4-(dimethylamino)phenol (DMAP), a potent cyanide antidote, is influenced by GSH under formation of various glutathione S-conjugates. Two of these were shown to be still reactive and able to produce ferrihemoglobin. The mechanism of ferrihemoglobin formation is fundamentally different from that found with the parent compound. First of all, induction periods of ferrihemoglobin formation were observed when 4-(dimethylamino)-2-(glutathion-S-yl)-phenol (2-GS-DMAP) and 4-(dimethylamino)-2,6-bis(glutathion-S-yl)phenol (2,6-bis-GS-DMAP) reacted with oxyhemoglobin at 100% and 20% oxygen, but not at 2% oxygen. This behavior points to thioether activation by autoxidation. Autoxidation proceeded in an autocatalytic manner, and the process was markedly modified by reducing agents, e.g., ferrihemoglobin and GSH, and by nucleophiles like GSH. Superoxide dismutase extended the lag phase of autoxidation and ferrihemoglobin formation. Catalase diminished markedly ferrihemoglobin formation, particularly at low oxygen pressure. The extent of this effect was much higher than expected if H2O2 had formed ferrihemoglobin directly. Conceivably, H2O2 might react with the thioethers or their oxidation products to give hitherto unidentified compounds of high catalytic activity in ferrihemoglobin formation. The results indicate that ferrihemoglobin formation by reactive glutathione conjugates of DMAP is essentially not a co-oxidation process as found with the parent DMAP and other aminophenols, but is mainly caused by an autocatalytic autoxidation process with formation of various reactive intermediates including superoxide radical anions and hydrogen peroxide. It appears that glutathione conjugation of autoxidizable aromatics does not necessarily lead to inactive phase II metabolites but opens new avenues of toxication reactions that may be a broader toxicological significance.

Oxidation versus Addition Reactions of Glutathione during the Interactions with Quinoid Thioethers of 4-(Dimethylamino)phenol

4-(Dimethylamino)phenol (DMAP) is a potent cyanide antidote which forms many equivalents of ferrihemoglobin in vivo and in vitro. During this process formation of phenoxyl radicals was observed which are reduced by ferrohemoglobin, thereby sustaining a catalytic cycle of ferrihemoglobin formation, or which disproportionate to give the quinone imine of DMAP. In the presence of thiols, e.g., glutathione (GSH), formation of 4-(dimethylamino)-2-(glutathion-S-yl)phenol (2-GS-DMAP), 4-(dimethylamino)-2,6-bis(glutathion-S-yl)phenol (2,6-bis-GS-DMAP), and 4-(dimethylamino)-2,3,6-tris(glutathion-S-yl)phenol (2,3,6-tris-GS-DMAP) was observed. While the trisubstituted glutathione conjugate is a stable end product, 2-GS-DMAP and 2,6-bis-GS-DMAP were still reactive and produced ferrihemoglobin. It is concluded that formation of polysubstituted DMAP thioethers is a result of sequential oxidation/addition reactions with quinoid intermediates. Formation of glutathione disulfide (GSSG) was minimal during the interaction of oxidized DMAP or 2-GS-DMAP with glutathione but became significant when oxidized 2,6-bis-GS-DMAP reacted with GSH. Thus it is conceivable that the bulky glutathione substituents in 2,6-bis-GS-DMAP render the addition of a third GSH molecule to the quinone imine derivative more difficult, and other reactions may get a chance. The reaction mechanism of GSSG formation has not been fully resolved, but a radical pathway mechanism involving thiyl radicals is proposed. Oxidation and addition reactions were also observed in the absence of oxygen when ferrihemoglobin served as oxidant. In the presence of oxygen, however, GSSG formation was increased, Partly due to hydrogen peroxide formation, partly due to an additional trapping reaction of the glutathione disulfide radical anion.(ABSTRACT TRUNCATED AT 250 WORDS)

Reactivity of glutathione adducts of 4-(dimethylamino)phenol. Formation of a highly reactive cyclization product.

During ferrihemoglobin formation, 4-(dimethylamino)phenol (DMAP), a potent cyanide antidote, forms a quinoid compound that is prone to sequential oxidation/addition reactions. In human red cells and hemoglobin solutions fortified with glutathione, a transient adduct has been isolated and identified as 4-(dimethylamino)-2-(glutathion-S-yl)phenol (2-GS-DMAP). This compound still formed ferrihemoglobin but differed from parent DMAP in that the reaction rate was roughly proportional to the oxygen concentration and exhibited a lag phase, pointing to a reactive autoxidation product. The compound was isolated and tentatively identified as an intramolecular cyclization product of 2-GS-DMAP. Formation of this product includes three reaction steps: (1) formation of a quinoid intermediate, (2) addition of the alpha-amino nitrogen atom of the glutamate residue to the aromatic ring, and (3) autoxidation of the cyclization product to give a highly reactive o-quinone imine. The isolated compound existed in two isomeric states (1H-NMR) which upon reduction could be separated by HPLC. The isolated reduced isomers mutually converted into each other. A model compound which was synthesized to mimic the most important structural features, 4-(dimethylamino)-6-[S-(2'-hydroxyethyl)-thio]-N-(2"-phenylethyl)-1,2- quinone imine, had a very similar visible spectum and exhibited an even higher ferrihemoglobin activity than the cyclization product. A similar phenomenon of intramolecular cyclization of a thioether of DMAP had been observed earlier: DMAP covalently bound to the SH groups of the beta-chains in hemoglobin formed a cross-link with the C-terminal histidine residue in the presence of oxygen but not in its absence.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of Cyanide Poisoning

The object of this study was to evaluate the effectiveness of five regimens in treating cyanide poisoning. A series of anesthetized adult beagle dogs were instrumented to record hemodynamic and respiratory function and given 2.5 mg/kg sodium cyanide intravenously. The 10 control animals given only cyanide died at from 5 to 7 minutes. Therapy, as described below, was given to other groups at from 2 to 3 minutes following the cyanide administration. Artificial respiration did not alter the lethal effects of cyanide nor prolong survival time in any of the 10 animals. Amyl nitrite given by inhalation or by the intravenous route allowed survival of all 15 animals. Sodium nitrite (20 mg/kg), dimethylaminophenol (DMAP) (5 mg/kg), and hydroxylamine hydrochloride (5 mg/kg) given intravenously with no artificial ventilation also allowed for 100% survival (15 animals). Amyl nitrite, sodium nitrite, and sodium thiosulfate were ineffective when given intramuscularly (I.M.) (0 of 12 dogs); however, I.M. DMAP (5 mg/kg) and I.M. hydroxylamine hydrochloride (50 mg/kg) increased heart rate and blood pressure and restored spontaneous breathing. All 15 animals treated with I.M. doses of either of these drugs survived the lethal dose of cyanide. Results of these studies indicate that intravenous sodium nitrite, DMAP, and hydroxylamine hydrochloride, and amyl nitrite by inhalation, are all effective in reversing the lethal effects of cyanide poisoning. Only DMAP and hydroxylamine hydrochloride are effective when given by the intramuscular route. These results provide data to support an approach to therapy that is more practical and applicable where expert medical care may not be available following cyanide exposure.

Structure-activity relationships of putative primaquine metabolites causing methemoglobin formation in canine hemolysates

A rapid and reproducible in vitro test system was developed to measure the methemoglobin (MHb)-forming properties of various 8-aminoquinoline derivatives. Initial rates and extents of reaction were measured spectrophotometrically with either canine hemolysates from which ferrihemoglobin reductase was removed, or with purified human oxyhemoglobin (Hb). The results demonstrate that primaquine derivatives that can be oxidized to quinones or iminoquinones (5-hydroxy,6-desmethyl primaquine; 5-hydroxyprimaquine; 5,6-dihydroxy-8-aminoquinoline; and 5-hydroxy, 6-methoxy-8-aminoquinoline) are potent MHb-forming compounds. Studies on the extent of reaction in hemolysates and purified oxyhemoglobin suggest that the extent of MHb formation may be limited by the rate at which the corresponding iminoquinones or quinones arylate nucleophiles. The effects of glutathione, mannitol, ascorbate, and superoxide dismutase on the rate and extent of hemoglobin oxidation by 5,6-dihydroxy-8-aminoquinoline suggest that these compounds oxidize Hb similar to the mechanism known for dimethylaminophenol (DMAP), in which Hb oxidizes the quinoline to semiquinone radical and quinone species which are the oxidizing and arylating agents.

The mutagenicity of a cyanide antidote, dimethylaminophenol, in Chinese hamster cells

The mutagenic activity of a cyanide antidote, dimethylaminophenol (DMAP), has been studied at the hypoxanthine-guanine-phosphoribosyltransferase (HPRT) locus in a line of Chinese hamster cells (V79), using induced resistance to 8-azaguanine as a marker for forward, point mutation. In a replating type of assay DMAP produced a dose-dependent increase in mutation frequency in suspension-treated cells, in the absence of any extrinsic metabolic activation system. The incorporation of a liver microsome preparation raised the concentration of DMAP required to induce mutation, but similar levels of induced mutation frequency (IMF) were produced.