Phenolic Ring Research Articles

Degradation of triclosan by chlorine dioxide: Reaction mechanism,2,4-dichlorophenol accumulation and toxicity evaluation

The mechanism and toxicity of TCS degradation by ClO2 was investigated. Intermediate products during the oxidation process were identified by GC/MS and LC/MS. A microtox bioassay and a SOS/umu assay were employed to evaluate the acute toxicity and genotoxicity of the resulting solutions during the chlorination process. The results showed that the reaction between TCS and ClO2 was of second-order overall. The pseudo first-order rate constants (kobs) exhibited significant dependence on solution pH and chlorine dioxide concentration, with the apparent second-order rate constant, kapp, being 7.07 × 104 M−1s−1 in the pH range of 6.80–7.02. TCS decomposition was accompanied by the accumulation of 2,4-dichlorophenol (2,4-DCP), and the maximum molar yield ratios of 2,4-DCP/TCS were in the range of 31.71%–35.43%. The major intermediates identified were 2,7/2,8-dichlorodibenzop-dioxin (2,7/2.8-Cl2DD), 2,4-DCP, 2,4,6-trichlorophenol (2,4,6-TCP), tetraclosan and pentaclosan. The proposed mechanism for TCS oxidation involved the cleavage of the ether link in TCS, chlorination of the phenolic ring and ring closure of a single TCS molecule. The transformation and degradation of TCS led to reduction of the acute toxicity and genotoxicity. However, irregular fluctuations in the toxicity changes indicated that the oxidation of TCS was not a simultaneous detoxification process.

Effect of Substituents on Luminescence of New Hydroxytetraphenylimidazole Derivatives

The effect of OMe and NO2 substituents in the phenol ring of hydroxytetraphenylimidazole (HTPI) derivatives on their luminescence in solutions and in the solid phase has been studied. The presence of the nitro group leads to multiple luminescence. In addition to the band of the photoproduct of intramolecular proton transfer, which is single for unsubstituted HTPI, nitrosubstituted imidazoles additionally have emission bands at shorter and longer wavelengths. The ratio between the bands depends on the solvent, concentration, and excitation wavelength. In solutions and polymer media, it is possible to switch luminescence by changing the excitation wavelength, and under certain conditions, white light emission is observed.

Crystal structure, Hirshfeld surface analysis and anti-oxidant capacity of 2,2'-{(1E,1'E)-[1,2-phenyl-enebis(aza-nylyl-idene)]bis-(methanylyl-idene)}bis-(5-benz-yloxy)phenol.

The whole mol-ecule of the title Schiff base compound, C34H28N2O4, is generated by mirror symmetry, with the mirror bis-ecting the central benzene ring. It was synthesized via the condensation reaction of 1,2-di-amine-benzene with 4-benz-yloxy-2-hy-droxy-benzaldehyde. The mol-ecule is V-shaped and there are two intra-molecular O-H⋯N hydrogen bonds present forming S(6) ring motifs. The configuration about the C=N imine bonds is E. The central benzene ring makes dihedral angles of 41.9 (2) and 43.6 (2)° with the phenol ring and the outer benz-yloxy ring, respectively. The latter two rings are inclined to each other by 84.4 (2)°. In the crystal, mol-ecules are linked by C-H⋯π inter-actions, forming layers lying parallel to the ab plane. The Hirshfeld surface analysis and the two-dimensional fingerprint plots confirm the predominance of these inter-actions in the crystal structure. The anti-oxidant capacity of the compound was determined by the cupric reducing anti-oxidant capacity (CUPRAC) process.

Hydrophobic zeolites for the upgrading of biomass-derived short oxygenated compounds in water/oil emulsions

Biomass-derived short oxygenates like furfural, cannot be directly incorporated into a fuel due to their low molecular weight. Therefore, conversion of these oxygenates into fuel range hydrocarbons via CC bond forming reactions is a desirable path. For example, in aqueous phase, furfural can be first converted to stable cyclopentanol via Piancatelli ring rearrangement coupled with hydrogenation under reducing conditions. This alcohol can be an effective alkylating agent to incorporate into phenolic rings. Therefore, we have investigated the alkylation of m-cresol with cyclopentanol, as two representative compounds of biomass-derived streams to generate products in the molecular weight range that is appropriate for transportation fuels. This reaction was studied in single and biphasic liquid systems over a hydrophobized H-USY zeolite (Si/Al = 30). In biomass conversion, the presence of liquid water is practically unavoidable, so it is important to investigate methods to deal with its presence. We show here that hydrophobization of the H-USY with octadecyltrichlorosilane (OTS) makes the zeolite able to stabilize water/oil emulsions and catalyze the alkylation of m-cresol and cyclopentanol with enhanced stability. By contrast, under the same conditions, the untreated H-USY zeolite is fully deactivated in about 3 h. From all of these results, it was concluded that the rate of alkylation is strongly dependent on temperature, solvent, and rate of mass transport, which is directly affected by the solubility of reactants and intermediates. This investigation provides strategies to convert different families of biomass-derived oxygenates into cyclic hydrocarbons with potential properties to be used as bio-fuel precursors.

Degradation of Triclosan by Heat Activated Persulfate Oxidation

Sulfate radical (SO4·-)-based advanced oxidation technologies (SR-AOPs) are widely used for remediation of contaminated groundwater and soils. This study investigated the reaction kinetics, products, and transformation pathways of triclosan, a widely used antimicrobial agent, during its degradation by heat activated persulfate oxidation. Experimental results revealed that increasing temperature or initial persulfate concentration significantly enhanced the degradation of triclosan. The reaction could be fitted in the pseudo-first-order kinetic model and the activation energy (Ea) was determined to be 142 kJ·mol-1. The presence of humic acid markedly inhibited triclosan degradation, whereas chloride (Cl-) showed a more complicated effect. Triclosan degradation was slightly accelerated in the presence of 5 μmol·L-1 Cl-, however, a higher concentration of Cl- (e.g., 10 μmol·L-1) showed an inhibitory effect. Using liquid chromatography-mass spectrometry, a total of six transformation products, including 4-chlorocatechol, 2,4-dichlorophenol, and 2-chloro-5-(2,4-dichloro-6-hydroxyphenoxy)-1,4-benzoquinone, were identified. Accordingly, the cleavage of the ether bond and hydroxylation of the phenol ring were proposed as the principal pathways of triclosan degradation upon reaction with SO4·-. The findings of this study can be used to evaluate the feasibility of decontamination of triclosan by SR-AOPs.

Ozonation of Para-Substituted Phenolic Compounds Yields p-Benzoquinones, Other Cyclic α,β-Unsaturated Ketones, and Substituted Catechols.

Phenolic moieties are common functional groups in organic micropollutants and in dissolved organic matter, and are exposed to ozone during drinking water and wastewater ozonation. Although unsubstituted phenol is known to yield potentially genotoxic p-benzoquinone during ozonation, little is known about the effects of substitution of the phenol ring on transformation product formation. With batch experiments employing differing ozone/target compound ratios, it is shown that para-substituted phenols ( p-alkyl, p-halo, p-cyano, p-methoxy, p-formyl, p-carboxy) yield p-benzoquinones, p-substituted catechols, and 4-hydroxy-4-alkyl-cyclohexadien-1-ones as common ozonation products. Only in a few cases did para-substitution prevent the formation of these potentially harmful products. Quantum chemical calculations showed that different reaction mechanisms lead to p-benzoquinone, and that cyclohexadienone can be expected to form if no such pathway is possible. These products can thus be expected from most phenolic moieties. Kinetic considerations showed that substitution of the phenolic ring results in rather small changes of the apparent second order rate constants for phenol-ozone reactions at pH 7. Thus, in mixtures, most phenolic structures can be expected to react with ozone. However, redox cross-reactions between different transformation products, as well as hydrolysis, can be expected to further alter product distributions under realistic treatment scenarios.

Preparation, characterization, DFT calculations and ethylene oligomerization studies of iron(II) complexes bearing 2-(1H-benzimidazol-2-yl)-phenol derivatives

Five 2-(1H-benzimidazol-2-yl)-phenol derivatives including 1H (HL1), 5-chloro-(HL2), 5-methyl-(HL3), 5,6-dichloro-(HL4), and 5,6-dimethyl-(HL5) were synthesized by the reaction of their corresponding benzene-1,2-diamine precursors and 2-hydroxybenzaldehyde which subsequently was employed in complexation with Fe(II) to prepare complexes C1–C5, respectively. Indeed, in all complexes, the ligands were coordinated as bidentate, via the C=N nitrogen and hydroxy oxygen atom of benzimidazole moiety and phenol ring, respectively. The compounds were characterized by FTIR, UV–vis, 1H- and 13C-NMR spectropscopy, ICP, and elemental analysis (C, H, and N). The purity of these compounds was determined by melting point (m.p )and TLC. The synthesized ligands and complexes were geometrically optimized by Gaussian09 software at B3LYP/TZVP level of theory and satisfactory theoretical–experimental agreement was achieved for analysis of IR data of the compounds. Catalytic behavior of the iron(II) complexes was investigated for ethylene reactivity. On activation with diethylaluminum chloride (Et2AlCl), iron(II) complex (C4) showed the highest activity (1686 kg oligomers.mol−1(Fe).h−1) for ethylene oligomerization when it contains chlorine substituents and exhibits good selectivity for linear 1-butene. The steric and electronic effects of ligands were investigated in detail on the influence of their catalytic activities.

Curcumin and its demethoxy derivatives possess p300 HAT inhibitory activity and suppress hypertrophic responses in cardiomyocytes

The natural compound, curcumin (CUR), possesses several pharmacological properties, including p300-specific histone acetyltransferase (HAT) inhibitory activity. In our previous study, we demonstrated that CUR could prevent the development of cardiac hypertrophy by inhibiting p300-HAT activity. Other major curcuminoids isolated from Curcuma longa including demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) are structural analogs of CUR. In present study, we first confirmed the effect of these three curcuminoid analogs on p300-HAT activity and cardiomyocyte hypertrophy.Our results showed that DMC and BDMC inhibited p300-HAT activity and cardiomyocyte hypertrophy to almost the same extent as CUR. As the three compounds have structural differences in methoxy groups at the 3-position of their phenol rings, our results suggest that these methoxy groups are not involved in the inhibitory effects on p300-HAT activity and cardiac hypertrophy. These findings provide useful insights into the structure–activity relationship and biological activity of curcuminoids for p300-HAT activity and cardiomyocyte hypertrophy.

Corrosion protection for mild steel by extract from the waste of lychee fruit in HCl solution: Experimental and theoretical studies

Various experimental conditions were tested for the green extract process of corrosion inhibitor from lychee fruit waste, and the optimal extract parameters were selected using potentiodynamic polarization. The best inhibition effect of the ethanol extract of lychee’s peel and seed by ultrasound for 1.5 h (EELPS) for mild steel in 0.5 M HCl was obtained at 600 mg/L using electrochemical and weight loss measurements. Theoretical calculations illustrate the adsorption sites and adsorption behavior of effective compounds. Due to the existence of hydroxyl groups and phenol rings in the main components, EELPS is considered to be a good inhibitor.

Crystal structure and DFT study of (E)-4-[({4-[(pyri-din-2-yl-methyl-idene)amino]-phen-yl}amino)-meth-yl]phenol.

In the title Schiff base compound, C19H17N3O, the configuration about the C=N bond is E. The mol-ecule is non-planar, with the phenolic and pyridine rings being inclined to the central benzene ring by 56.59 (4) and 15.13 (14)°, respectively. In the crystal, mol-ecules are linked by pairs of O-H⋯N hydrogen bonds, forming inversion dimers. The dimers are connected to neighbouring dimers by N-H⋯O hydrogen bonds and C-H⋯π inter-actions, forming layers parallel to the bc plane. The layers are linked by offset π-π inter-actions [inter-centroid distance = 3.779 (2) Å], forming a three-dimensional supra-molecular structure. Quantum chemical calculations of the mol-ecule are in good agreement with the solid-state structure.

In silico binding of 4,4'-bisphenols predicts in vitro estrogenic and antiandrogenic activity.

Bisphenols, anthropogenic pollutants, leach from consumer products and have potential to be ingested and are excreted in waste. The endocrine disrupting effects of highly manufactured bisphenols (BPA, BPS, and BPF) are known, however the activities of others are not. Here, the estrogenic and androgenic activities of a series of 4,4'-bisphenols that vary at the inter-connecting bisphenol bridge were determined (BPA, BPB, BPBP, BPC2, BPE, BPF, BPS, and BPZ) and compared to in silico binding to estrogen receptor-alpha and the androgen receptor. Bioassay results showed the order of estrogenicity (BPC2 (strongest) > BPBP > BPB > BPZ > BPE > BPF > BPA > BPS, r2 = 0.995) and anti-androgenicity (BPC2 (strongest) > BPE, BPB, BPA, BPF, and BPS, r2 = 0.996) correlated to nuclear receptor binding affinities. Like testosterone and the anti-androgen hydroxyflutamide, bisphenol fit in the ligand-binding domain through hydrogen-bonding at residues Thr877 and Asn705, but also interacted at either Cys784/Ser778 or Gln711 through the other phenol ring. This suggests the 4,4'-bisphenols, like hydroxyflutamide, are androgen receptor antagonists. Hydrogen-bond trends between ERα and the 4,4'-bisphenols were limited to residue Glu353, which interacted with the -OH of one phenol and the -OH of the A ring of 17β-estradiol; hydrogen-bonding varied at the -OH of ring D of 17β-estradiol and the second phenol -OH group. While both estrogen and androgen bioassays correlated to in silico results, conservation of hydrogen-bonding residues in the androgen receptor provides a convincing picture of direct antagonist binding by 4,4'-bisphenols.

Contribution of the Hydroxyl Group and Phenol Ring of Tyrosine 780 of the Alpha-Subunit to NA+ Binding by the Na/K Pump

The Na/K pump is a heterodimeric(αβ) P-type ATPase that exports three Na+ and imports two K+ against their electrochemical gradients using the energy of ATP hydrolysis. Structural studies confirm three ion-binding sites in the catalytic α-subunit. Site-I and Site-II bind either Na+ or K+, while Site-III, the focus here, exclusively binds Na+. To determine the relative energetic contribution to Na+ binding of the hydroxyl group or the π-electrons of Tyr780 in site-III, we introduced the mutation Y780tag into the α-subunit cDNA for the purpose of using nonsense suppression. Y780tag-α- and β3-cRNA were co-injected in Xenopus oocytes with synthetic tRNA (ligated to Tyr, Phe or Phe derivatives) to compare the functional consequences of the chemical modifications at this position using two-electrode voltage clamp. Square voltage pulses in the absence of external K+ (K+o) and presence of external Na+ (Na+o) produce transient currents. The voltage dependence of steady-state charge moved by these transients is described by a Boltzmann distribution with a center (V1/2) related to the relative apparent affinity for Na+o (ΔV1/2= ­25 mV per 2-fold reduction in affinity). The centers of the distribution where V1/2= ­46.9 ±2.5 mV (n=10) for Tyr, V1/2= ­123 ± 9 mV for Phe, and V1/2= −54.6 ±2.1 mV (n=5) for mono-fluorinated at the 3’ position (mono-F)-Tyr. These results indicate ∼8-fold reduction in apparent affinity for Na+o by removal of the hydroxyl group and a smaller reduction (≪ 2-fold) by partial disruption of the cation-π interaction capability by monofluorination. Surprisingly, the apparent affinity for K+o estimated from the [K+]o dependence of pump current activation in the absence of Na+o was reduced by both Phe (∼4-fold) and mono-F-Tyr (∼1.5-fold). Measurements with other derivatives are underway. NSF-MCB 1515434.

Laccase-Catalyzed Synthesis of Low-Molecular-Weight Lignin-Like Oligomers and their Application as UV-Blocking Materials.

The laccase-catalyzed oxidative polymerization of monomeric and dimeric lignin model compounds was carried out with oxygen as the oxidant in aqueous medium. The oligomers were characterized by using gel permeation chromatography (GPC) and matrix-assisted laser desorption ionization time-of-flight mass spectroscopy (MALDI-TOF MS) analysis. Oxidative polymerization led to the formation of oligomeric species with a number-average molecular weight (Mn ) that ranged from 700 to 2300 Da with a low polydispersity index. Spectroscopic analysis provided insight into the possible modes of linkages present in the oligomers, and the oligomerization is likely to proceed through the formation of C-C linkages between phenolic aromatic rings. The oligomers were found to show good UV light absorption characteristics with high molar extinction coefficient (5000-38 000 m-1 cm-1 ) in the UV spectral region. The oligomers were blended independently with polyvinyl chloride (PVC) by using solution blending to evaluate the compatibility and UV protection ability of the oligomers. The UV/Vis transmittance spectra of the oligomer-embedded PVC films indicated that these lignin-like oligomers possessed a notable ability to block UV light. In particular, oligomers obtained from vanillyl alcohol and the dimeric lignin model were found to show good photostability in accelerated UV weathering experiments. The UV-blocking characteristics and photostability were finally compared with the commercial low-molecular-weight UV stabilizer 2,4-dihydroxybenzophenone.

Enhanced removal ability of phenol from aqueous solution using coal-based carbon membrane coupled with electrochemical oxidation process

A treatment system combining the coal-based carbon membrane with electrochemical oxidation process was designed for the enhanced phenol removal ability. The effects of various parameters including electric voltage, phenol concentration, solution pH, rotate speed, electrolyte type and concentration, and electrode distance on the permeate flux and removal efficiency of the treatment system were carried out. The degradation intermediates of phenol were detected by gas chromatography-mass spectrometry (GC–MS). The results showed the phenol removal ability of carbon membrane was significantly improved by coupling with electrochemical oxidation process. High phenol concentration usually increased the load of the treatment system, resulting in low permeate flux and removal efficiency because of limited decomposition ability. When the initial pH increased from 4.0 to 10.0, the enhanced permeate flux and removal efficiency were observed. The permeate flux displayed a decrease trend with the increase of electrode distance, while the removal efficiency showed an opposite trend. The optimum operation parameters of 2.0 V electric voltage, 7.5 r/min pump rotate speed, and 2.50 g/L Na2SO4 were recommended. During the degradation process, the reactive free radicals and H2O2 attacked the benzene ring of phenol to produce catechol, hydroquinone and resorcinol. And then, hydroquinone was degraded to benzoquinone, which was further decomposed to organic acids such as maleic, fumaric, and oxalic acids. Finally, these organic acids were oxidized into CO2 and H2O.

Synthesis, characterization, X-ray crystal structure and DFT calculations of 4-([2,2':6',2''-terpyridin]- 4'-yl)phenol

La síntesis de derivados terpiridinicos (Tpy) se ha investigado ampliamente debido a su potencial para la conversión de energía solar. En este artículo se sintetizó y caracterizó el 4-([2,2':6',2'' terpiridin]-4'-il)fenol (TpyOH), a través de varias metodologías como la cristalografía de rayos X y herramientas computacionales. El análisis de rayos X de monocristal mostró que el TpyOH es plano, con ángulos diedros de 5,03° entre el piridinilo central y el anillo fenólico, con presencia de ángulos de 6,05 y 12,2º en la porción terpiridínica. En el cristal, las moléculas están unidas por enlaces de hidrógeno intermoleculares y mediante interacciones de apilamiento π-π. Utilizando cálculos DFT dependientes del tiempo (TD-DFT) y teniendo en cuenta el efecto de los disolventes, se investigaron y compararon los espectros de absorción y fluorescencia de TpyOH. Las energías de transición TD-DFT de S0→Sn y S1→S0 concuerdan con los resultados experimentales. El análisis de orbitales moleculares de frontera mostró que la banda de absorción de baja energía corresponde a transferencia de carga intraligando (ICT); mientras que la banda de alta energía es común en las transiciones π-π* del resto Tpy. La emisión debido a la transición S1→S0 corresponde a ICT, con una contribución del 90% proveniente de transiciones HOMO→LUMO.

ЗМІНИ ПОКАЗНИКІВ КАРБОНІЛЬНО-ОКСИДАТИВНОГО СТРЕСУ В ЩУРІВ З ЕКСПЕРИМЕНТАЛЬНОЮ ІШЕМІЄЮ МІОКАРДА ПІД ВПЛИВОМ ДОКСИЦИКЛІНУ

Heart diseases, especially acute myocardial infarction (AMI), belong to the most severe illnesses that often lead to death. Despite a large number of studies, the biochemical mechanisms of AMI and post-infarction myocardial remodeling are poorly understood. Carbonyl-oxidative stress (COS) is one of the more important triggers of the post-infarction complications in these patients, so the neutralizing of the intermediates and final products of COS are a perspective direction in the treatment of AMI. Flavonoide antioxidants as well as inhibitors of carbonylation and glycation of proteins shown the cardioprotective effects but their use have some limitations. Recently, new studies have appeared concerning the cardioprotective action of the doxycycline (DC). This tetracycline antibiotic can inhibit matrix metalloproteinases and proteolysis in extracellular matrix. At the same time, the presence of a multiple-substituted phenol ring can provide the ability of DC to neutralize free radicals, so we hypothesized that it can inhibit the COS. This article compares the effects of small (4,2 mg/kg) and of large (16.8 mg/kg) doses of DC with the effects of classical antioxidants, corvitin and aminoguanidine. The COS-markers and activity of antioxidant enzymes were determined in the blood and subcellular heart fractions of the rats with pituitrin-isoproterenol-induced myocardial damage. It has been established that DC exhibits cardioprotective properties, reducing the formation of products of carbonyl and oxidative modification of biomolecules TBA-active substances, fluorescent end products of glycation (fAGE), aldehyde phenylhydrazones (AFH) and ketone phenylhydrazones (CPH), and a more pronounced effect was shown for the low doses of this drug. Simultaneously, the DC activates enzymes of antioxidant protection, first of all, glutathione peroxidase. Effects of small doses of DC are comparable or exceed the action of aminoguanidine and corvitin, so DC can be useful in the treatment of postinfarction heart failure.

An extended excited-state intramolecular proton transfer (ESIPT) emitter for random lasing applications.

An original molecular fluorophore displaying single keto (K*) excited-state intramolecular proton transfer (ESIPT) emission is presented in this article. Substitution at the 3 and 5 positions of the phenol ring of a 2-(2'-hydroxyphenylbenzoxazole) (HBO) dye by triethylsilyl-ethynyl fragments leads to a drastic enhancement of fluorescence in the solution-state as compared to unsubstituted analogues. This intense fluorescence emission is also retained in a protic solvent like ethanol and in the solid-state as embedded in a potassium bromide pellet or as 1% doped in a poly(methyl methacrylate) (PMMA) film. The experimental optical properties were confirmed by ab initio calculations. Random lasing (RL) studies performed on this ESIPT emitter show the presence of stimulated emission occurring above the threshold level of pumping energy density (ρth ≈ 300 μJ cm-2) in the PMMA matrix. To the best of our knowledge, this study constitutes the first observation of RL based on ESIPT fluorescence.

Polyphenol Family in Cardiovascular disease (CVD): Versatile Therapeutic Outcome

Epidemiological evidence support that diet rich in polyphenolic compound reduce the risk of cardio vascular disease (CVD). Polyphenols (500-4000 Da) are the main organic constituent presenting with 5-7 phenolic ring with >12 phenolic hydroxyl groups, water soluble plant derived compound. These compounds are also able to generate NO from vascular endothelium. The aim of the mini review was to investigate the role of the most commonly consumed polyphenols in the pathophisiology of the risk of ischemic stroke and CVD. Polyphenol can reduce endothelial dysfunction, in the development of atherosclerosis with the inhibition of the aggregation of platelet and lowering blood pressure. This paper reviews the current advances in polyphenols in food, with emphasising on health aspects on the basis of the published literature, which may provide some guidance for researchers in further investigations and for industries in developing practical health agents.

Saccharide Recognition and Helix Formation in Water with an Amphiphilic Pyridine–Phenol Alternating Oligomer

An amphiphilic pyridine–phenol alternating oligomer, in which oligo(ethylene glycol) chains are attached at the 4‐positions of the pyridine and the phenol rings, was synthesized as a helical host to realize saccharide recognition in water. This oligomer was soluble not only in less‐polar solvents but also in water at room temperature. Circular dichroism investigations revealed that the oligomer could recognize several kinds of saccharides and their derivatives, including glycodrugs to form chiral higher‐order structures in water. Especially, the oligomer showed high affinity for d‐glucosamine, and their association constants were over 103 m–1.

Conjugation of nitrated acetaminophen to Der p1 amplifies peripheral blood monocyte response to Der p1.

BackgroundAn association of acetaminophen use and asthma was observed in the International Study of Asthma and Allergies in Childhood study. However there are no clear mechanisms to explain an association between acetaminophen use and immunologic pathology. In acidic conditions like those in the stomach and inflamed airway, tyrosine residues are nitrated by nitrous and peroxynitrous acids. The resulting nitrotyrosine is structurally similar to 2,4-dinitrophenol and 2,4-dinitrochlorobenzene, known haptens that enhance immune responses by covalently binding proteins. Nitrated acetaminophen shares similar molecular structure.ObjectiveWe hypothesized the acetaminophen phenol ring undergoes nitration under acidic conditions, producing 3-nitro-acetaminophen which augments allergic responses by acting as a hapten for environmental allergens.Methods3-nitro-acetaminophen was formed from acetaminophen in the presence of acidified nitrite, purified by high performance liquid chromatography, and assayed by gas-chromatography mass spectrometry. Purified 3-nitro-acetaminophen was reacted with Dermatophagoides pteronyssinus (Der p1) and analyzed by mass spectrometry to identify the modification site. Human peripheral blood mononuclear cells proliferation response was measured in response to 3-nitro-acetaminophen and to 3-nitro-acetaminophen-modified Der p1.ResultsAcetaminophen was modified by nitrous acid forming 3-nitro-acetaminophen over a range of different acidic conditions consistent with airway inflammation and stomach acidity. The Der p1 protein-hapten adduct creation was confirmed by liquid chromatography-mass spectrometry proteomics modifying cysteine 132. Peripheral blood mononuclear cells exposed to 3-nitro-acetaminophen-modified Der p1 had increased proliferation and cytokine production compared to acetaminophen and Der p1 alone (n = 7; p < 0.05).ConclusionThese data suggests 3-nitro-acetaminophen formation and reaction with Der p1 provides a mechanism by which stomach acid or infection-induced low airway pH in patients could enhance the allergic response to proteins such as Der p1.