Quinone Products Research Articles

P-phenylenediamines (PPDs) and PPD-quinones (PPD-Qs) in human urine and breast milk samples: Urgent need for focus on PPD-Qs and the establishment of health threshold criteria

PPDs and their oxidation products, PPD-Qs, are emerging environmental contaminants arising from the addition and oxidation of rubber products. Although numerous studies have been conducted to elucidate their risks, the primary focus has been on 6PPD and 6PPD-Q, with limited attention given to other PPDs and especially other PPD-Qs. This study comprehensively examines the occurrences of frequently used PPDs and their degradation products, PPD-Qs, in human urine and breast milk samples. The average concentrations of ΣPPDs and ΣPPD-Qs in urine were 27 ± 78 ng/mL and 16 ± 12 ng/mL, respectively. IPPD and DNPD were the predominant PPDs, while DPPD-Q, CPPD-Q, and IPPD-Q were the predominant PPD-Qs. Notably, the concentrations of 6PPD, CPPD, and DPPD were significantly lower than their oxidized quinone products. Weak or no correlations were observed between most PPDs and their corresponding PPD-Qs, suggesting that PPD-Qs in the human body are primarily derived from direct environmental intake rather than in vivo conversion of PPDs. PPDs and PPD-Qs were widely detected in breast milk, exhibiting concentrations and patterns similar to those found in urine, with comparable major pollutants. Estimated daily intakes of PPDs + PPD-Qs for infants were several μg/(kg·day), with the 95th percentile intake approaching 10 μg/(kg·day).

Distinct Species-Specific and Toxigenic Metabolic Profiles for 6PPD and 6PPD Quinone by P450 Enzymes: Insights from In Vitro and In Silico Studies.

The tire rubber antioxidant N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its quinone product (6PPDQ) are prevalent emerging contaminants, yet their biotransformation profiles remain poorly understood, hampering the assessment of environmental and health risks. This study investigated the phase-I metabolism of 6PPD and 6PPDQ across aquatic and mammalian species through in vitro liver microsome (LM) incubations and in silico simulations. A total of 40 metabolites from seven pathways were identified using the highly sensitive nano-electrospray ionization mass spectrometry. Notably, 6PPDQ was consistently detected as a 6PPD metabolite with an approximate 2% yield, highlighting biotransformation as a neglected indirect exposure pathway for 6PPDQ in organisms. 6PPDQ was calculated to form through a facile two-step phenyl hydroxylation of 6PPD, catalyzed by cytochrome P450 enzymes. Distinct species-specific metabolic kinetics were observed, with fish LM demonstrating retarded biotransformation rates for 6PPD and 6PPDQ compared to mammalian LM, suggesting the vulnerability of aquatic vertebrates to these contaminants. Intriguingly, two novel coupled metabolites were identified for 6PPD, which were predicted to exhibit elevated toxicity compared to 6PPDQ and result from C-N oxidative coupling by P450s. These unveiled metabolic profiles offer valuable insights for the risk assessment of 6PPD and 6PPDQ, which may inform future studies and regulatory actions.

Identifying Radical Pathways for Cu(I)/Cu(II) Relay Catalyzed Oxygenation via Online Coupled EPR/UV-Vis/Near-IR Monitoring.

Copper-catalyzed C─H oxygenation has drawn considerable attention in mechanistic studies. However, a comprehensive investigation combining radical pathways with a metal-catalytic cycle is challenged by the intricate organic radicals and metallic intermediates. Herein, an online coupled EPR/UV-vis/near-IR detecting method is developed to simultaneously monitor both reactive radical species and copper complex intermediates during the reaction. Focusing on copper-catalyzed phenol oxygenation with cumene hydroperoxide, the short-lived alkylperoxyl radical (EPR signal at g=2.0143) as well as the unexpected square planar Cu(II)-alkoxyl radical complex (near-IR signal at 833nm) are unveiled during the reaction, in addition to the observable phenoxyl radical in EPR, quinone product in UV-vis, and Cu(II) center in EPR. With a comprehensive picture of diverse intermediates evolving over the same timeline, a novel Cu(I)/Cu(II) proposed relay-catalyzed sequential radical pathway. In this sequence, Cu(II) activates hydroperoxide through Cu(II)-OOR into the alkylperoxide radical, while the reaction between Cu(I) and hydroperoxide leads to Cu(II)(•OR)OH with high H-atom abstracting activity. These results provide a thorough understanding of the Cu(I)/Cu(II) relay catalysis for phenol oxygenation, setting the stage for mechanistic investigations into intricate radical reactions promoted by metallic complexes.

In Vitro and In Vivo Biotransformation Profiling of 6PPD-Quinone toward Their Detection in Human Urine.

The antioxidant N-(1,3-Dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and its oxidized quinone product 6PPD-quinone (6PPD-Q) in rubber have attracted attention due to the ecological risk that they pose. Both 6PPD and 6PPD-Q have been detected in various environments that humans cohabit. However, to date, a clear understanding of the biotransformation of 6PPD-Q and a potential biomarker for exposure in humans are lacking. To address this issue, this study presents a comprehensive analysis of the extensive biotransformation of 6PPD-Q across species, encompassing both in vitro and in vivo models. We have tentatively identified 17 biotransformation metabolites in vitro, 15 in mice in vivo, and confirmed the presence of two metabolites in human urine samples. Interestingly, different biotransformation patterns were observed across species. Through semiquantitative analysis based on peak areas, we found that almost all 6PPD-Q underwent biotransformation within 24 h of exposure in mice, primarily via hydroxylation and subsequent glucuronidation. This suggests a rapid metabolic processing of 6PPD-Q in mammals, underscoring the importance of identifying effective biomarkers for exposure. Notably, monohydroxy 6PPD-Q and 6PPD-Q-O-glucuronide were consistently the most predominant metabolites across our studies, highlighting monohydroxy 6PPD-Q as a potential key biomarker for epidemiological research. These findings represent the first comprehensive data set on 6PPD-Q biotransformation in mammalian systems, offering insights into the metabolic pathways involved and possible exposure biomarkers.

Prohibitin StPHB3 affects the browning of fresh-cut potatoes via influencing antioxidant capacity and polyphenol oxidase activation

Enzymatic browning causes a decline in consumer’s acceptance of fresh-cut products. Previous study showed reactive oxygen species (ROS) is associated with enzymatic browning, and prohibitin (PHB) is involved in ROS formation. However, whether PHB influences the enzymatic browning is still unknown. In this paper, changes of StPHB3 transcript levels after cutting were investigated, then stphb3 mutants were constructed through CRISPR/Cas9 and the browning difference between stphb3 mutants and wild type was compared, finally the mechanism of PHB influencing the browning was explored. The results showed that the transcript levels of StPHB3 were enhanced in potato (cultivar Desiree) tubers after fresh cutting. Mutation of StPHB3 caused lower browning, less production of soluble quinones, decreased malondialdehyde (MDA) content, increased 1,1-Diphenyl-2-picrylhydrazyl (DPPH) inhibition, and increased total phenol contents. Additionally, polyphenol oxidase (PPO) activity and StPOT32 gene transcript level were also reduced after disturbing StPHB3 gene expression. StPHB3 was found to be located within the chloroplast same as the predominant location and activation site of PPO protein. Yeast two-hybrid (Y2H) and Co-Immunoprecipitation (Co-IP) assays showed StPHB3 interacted with PPO. And mature PPO contents were decreased in stphb3. These results suggest that suppression of StPHB3 can alleviate the browning of fresh-cut potatoes by enhancing the antioxidant activity and inhibiting PPO activation.

Continuous monooxygenase-mediated biodegradation of phenol derivatives in wastewater: Optimization of flow conditions

Nitrophenols and halogenated phenols are major pollutants found in a pharmaceutical production, and have been included in US-EPA’s priority pollutant list. Biological treatment is increasingly attractive due to its low energy consumption and use of non-toxic reagents. In this work, we developed a system for degrading the phenol derivatives via HadA cells expressing a flavin-dependent monooxygenase HadA enzyme. The HadA cells were immobilized into alginate beads (so-called HadA@alginate), which could be set up into a fixed bed column for a continuous operation. Quinone products, generated from this enzymatic conversion, could be consumed by cells, highlighting the self-sustaining nature of this system. Flow compositions (e.g., carbon, nitrogen sources, calcium ions) and conditions (e.g., air feeding) were comprehensively optimized for a robust operation (e.g., no swelling of beads, prolonged cell activity). Upon optimal conditions, 0.05 mM solutions of 4-nitrophenols (4-NP), 2,4-dinitrophenols (2,4-DNP), and 4-chlorophenols (4-CP) could be completely degraded at recycle ratios (i.e., recycle-to-purge ratio) of 3.3, 0.5, and 7.6 respectively. We achieved the specific degradation rates of 3.24 × 10−4 mg4-NP/mgcell/h, 2.45 × 10−3 mg2,4-DNP/mgcell/h, and 3.43 × 10−3 mg4-CP/mgcell/h. We also demonstrated the use of technology to degrade 4-NP in a real wastewater collected from a pharmaceutical plant.

Multi-target genome editing reduces polyphenol oxidase activity in wheat (Triticum aestivum L.) grains.

Polyphenol oxidases (PPO) are dual activity metalloenzymes that catalyse the production of quinones. In plants, PPO activity may contribute to biotic stress resistance and secondary metabolism but is undesirable for food producers because it causes the discolouration and changes in flavour profiles of products during post-harvest processing. In wheat (Triticum aestivum L.), PPO released from the aleurone layer of the grain during milling results in the discolouration of flour, dough, and end-use products, reducing their value. Loss-of-function mutations in the PPO1 and PPO2 paralogous genes on homoeologous group 2 chromosomes confer reduced PPO activity in the wheat grain. However, limited natural variation and the proximity of these genes complicates the selection of extremely low-PPO wheat varieties by recombination. The goal of the current study was to edit all copies of PPO1 and PPO2 to drive extreme reductions in PPO grain activity in elite wheat varieties. A CRISPR/Cas9 construct with one single guide RNA (sgRNA) targeting a conserved copper binding domain was used to edit all seven PPO1 and PPO2 genes in the spring wheat cultivar 'Fielder'. Five of the seven edited T1 lines exhibited significant reductions in PPO activity, and T2 lines had PPO activity up to 86.7% lower than wild-type. The same construct was transformed into the elite winter wheat cultivars 'Guardian' and 'Steamboat', which have five PPO1 and PPO2 genes. In these varieties PPO activity was reduced by >90% in both T1 and T2 lines. In all three varieties, dough samples from edited lines exhibited reduced browning. This study demonstrates that multi-target editing at late stages of variety development could complement selection for beneficial alleles in crop breeding programs by inducing novel variation in loci inaccessible to recombination.

Biasing Divergent Polycyclic Aromatic Hydrocarbon Oxidation Pathway by Solvent-Free Mechanochemistry.

Precise control in reaction selectivity is the goal in modern organic synthesis, and it has been widely studied throughout the synthetic community. In comparison, control of divergent reactivity of a given reagent under different reaction conditions is relatively less explored aspect of chemical selectivity. We herein report an unusual reaction between polycyclic aromatic hydrocarbons and periodic acid H5IO6 (1), where the product outcome is dictated by the choice of reaction conditions. That is, reactions under solution-based condition give preferentially C-H iodination products, while reactions under solvent-free mechanochemical condition provide C-H oxidation quinone products. Control experiments further indicated that the iodination product is not a reaction intermediate toward the oxidation product and vice versa. Mechanistic studies unveiled an in situ crystalline-to-crystalline phase change in 2 during ball-milling treatment, where we assigned it as a polymeric hydrogen-bond network of 1. We believe that this polymeric crystalline phase shields the more embedded electrophilic I═O group of 1 from C-H iodination and bias a divergent C-H oxidation pathway (with I═O) in the solid state. Collectively, this work demonstrates that mechanochemistry can be employed to completely switch a reaction pathway and unmask hidden reactivity of chemical reagents.

Synergistic Lewis-Brønsted Acid Catalysis in Cascade Cyclization of ortho-Alkynylaryl Cyclopropylketones for the Synthesis of 2,3-Dihydronaphtho[1,2-b]furans.

In this work, a synthetic method for the synthesis of 2,3-dihydronaphtho[1,2-b]furans employing synergistic Lewis-Brønsted Acid catalyzed cyclization of ortho-alkynylarylcyclopropylketones has been developed. Benefits of our method included low catalyst loading, low cost of catalyst, short reaction time, and mild conditions which could be applied to a broad range of substrates, including a terminal alkyne (R = H), to provide generally high yields of the desired products. In addition, we found that 2,3-dihydronaphtho[1,2-b]furan derivatives could be isomerized to give 5,6-dihydrotetraphen-7-ol anaologs under acidic conditions via Friedel-Crafts-type alkylation in good to excellent yields. However, these products were not stable and gradually converted to the corresponding quinones. The competent transformation was successfully obtained by treating with m-CPBA in the presence of NaHCO3 to provide the desired quinone products in good to excellent yields.

Production of Fungal Quinones: Problems and Prospects

Fungal quinones can be used for a variety of applications, such as pharmaceuticals, food colorants, textile dyes, and battery electrolytes. However, when producing quinones by fungal cultivation, many considerations arise regarding the feasibility of a production system, such as the quinone yield, purity, ease of extraction, and the co-production of mycotoxins. In this work, we display the initial screening of filamentous fungi for quinone production and evaluate their potential for future optimization. We investigated toluquinone (TQ) potentially produced by Penicillium cf. griseofulvum, terreic acid (TA) produced by Aspergillus parvulus and A. christenseniae, and anthraquinone (AQ) monomers and dimers produced by Talaromyces islandicus. The strains grew on various agar and/or liquid media and were analyzed by ultra-high-performance liquid chromatography–diode array detection–quadrupole time-of-flight mass spectrometry (UHPLC-DAD-QTOF MS). In the case of AQs, feature-based molecular networking (FBMN) was used for the identification of AQ analogs. TQ was not observed in the production strains. TA constituted one of the major chromatogram peaks and was secreted into the growth medium by A. parvulus. The AQs constituted many major chromatogram peaks in the mycelium extracts and endocrocin and citreorosein were observed extracellularly in small amounts.

Phoenicin Switch: Discovering the Trigger for Radical Phoenicin Production in Multiple Wild-Type Penicillium Species.

Society faces the challenge of storing energy from sustainable sources in inexpensive, nontoxic ways that do not deplete the limited resources of Earth. In this regard, quinone redox flow batteries have been proposed as ideal; however, industrially used quinones have traditionally been synthesized from fossil fuels. Therefore, we investigated the production of phoenicin (compound 1), a deep violet dibenzoquinone produced by certain Penicillium species, for its industrial potential. Strains grew as surface cultures on customized growth media with varying production parameters, and phoenicin production was assessed by ultrahigh-performance liquid chromatography-diode array detection-quadrupole time of flight mass spectrometry (UHPLC-DAD-QTOF MS) analysis of the supernatant. Phoenicin production was reliant on the sucrose concentration, and by varying that, we produced 4.94 ± 0.56 g/L phoenicin on a Czapek yeast autolysate broth (CY)-based medium with Penicillium phoeniceum (CBS 249.32) as the production host, with 71.91% phoenicin purity in the resulting medium broth. Unexpectedly, metabolites corresponding to phoenicin polymers were tentatively identified in P. phoeniceum, of which the dimer (diphoenicin) was a major chromatographic peak. An MS-based metabolomics study was conducted on P. atrosanguineum using feature-based molecular networking and multivariate statistics, and it was found that few or no known secondary metabolites besides phoenicin were secreted into the growth medium. Finally, the effects of sucrose, sodium nitrate, and yeast extract (YE) in the growth medium were investigated in a 23 full factorial design. The results indicated an optimal sucrose concentration of 92.87 g/L on CY when NaNO3 and YE were fixed at 3 and 5 g/L, respectively. IMPORTANCE This work was undertaken to explore the production of fungal quinones in wild-type strains for use as electrolytes in redox flow batteries. As society converts energy production in a more sustainable direction, it becomes increasingly more important to store sustainable energy in smart ways. Conventional battery technologies imply the use of highly toxic, expensive, and rare metals; thus, quinone redox flow batteries have been proposed to be a desirable alternative. In this study, we explored the possibility of producing the fungal quinone phoenicin in Penicillium spp. by changing the growth parameters. The production of other secondary metabolites and known mycotoxins was also investigated in a metabolomics study. It was shown that phoenicin production was activated by optimizing the carbon concentration of the medium, resulting in high titers and purity of the single metabolite.

Aerobic Oxidation of Dihydroxyarenes Substrates Catalyzed by Polymer-Supported RuII-Pheox/Silica-Gel: A Beneficial Route for Purification of Industrial Water

Abstract: A broad class of dihydroxyarenes were easily oxidized by aerobic oxygen to quinone products in excellent yields under the catalytic effect of polymer-supported RuII-Pheox/silica-gel catalyst. By using this combined catalyst, hydroquinone and catechol derivatives with electron-donating groups were easily oxidized by molecular oxygen to quinone products in 90% to >99% yield, while in the case of electron-withdrawing group, only 70% was obtained. The biologically useful 1,4-Naphthoqinone products were obtained in 83% to 90%. The catalyst was easily obtained and reused many times without a significant decrease in reactivity. Interestingly, a sample of industrial water contaminated with phenolic compounds was subjected to aerobic oxidation by using this catalyst, and the resultant quinones were detected within one day and the catalyst was removed and reused several times with different contaminating samples with the same efficiency. Other catalytic oxidations by using this promising catalyst were investigated.

Profiling of Protein Adducts of Estrogen Quinones in 5-Year Survivors of Breast Cancer Without Recurrence.

AimsThe aim of this study was to simultaneously analyze estrogen quinone-derived adducts, including 17β-estradiol-2,3-quinone (E2-2,3-Q) and 17β-estradiol-3,4-quinone (E2-3,4-Q), in human albumin (Alb) and hemoglobin (Hb) derived from breast cancer patients with five-year postoperative treatment without recurrence in Taiwan and to evaluate the treatment-related effects on the production of these adducts.Settings and DesignCohortMethods and Material: Blood samples derived from breast cancer 5-year survivors without recurrence were collected. Albumin and hemoglobin adducts of E2-3,4-Q and E2-2,3-Q were analyzed to evaluate the degree of disposition of estrogen to quinones and to compare these adduct levels with those in patients before treatment.Statistical AnalysisAll data are expressed as mean ± standard deviation of three determinations. We used Student’s t-test to examine subgroups. Data were transformed to the natural logarithm and tested for normal distribution for parametric analyses. Linear correlations were investigated between individual adduct levels by simple regression. Statistical analysis was performed using the SPSS Statistics 20.0.ResultsResult confirmed that logged levels of E2-2,3-Q-derived adducts correlated significantly with those of E2-3,4-Q-derived adducts (correlation coefficient r=.336-.624). Mean levels of E2-2,3-Q-4-S-Alb and E2-3,4-Q-2-S-Alb in 5-year survivors were reduced by 60-70% when compared to those in the breast cancer patients with less than one year of diagnosis/preoperative treatment (P<.001).ConclusionsOur findings add support to the theme that hormonal therapy including aromatase inhibitors and Tamoxifen may dramatically reduce burden of estrogen quinones. We hypothesize that combination of treatment-related effects and environmental factors may modulate estrogen homeostasis and diminish the production of estrogen quinones in breast cancer patients.

Flow-Through Electrochemical Biosensor with a Replaceable Enzyme Reactor and Screen-Printed Electrode for the Determination of Uric Acid and Tyrosine

A flow-through biosensor has been developed and manufactured by 3D printing from poly(lactic acid). Uricase or tyrosinase were immobilized on the inner walls of the reactor cell and the concentrations of the reaction products, i.e., hydrogen peroxide in the case of uricase and quinone product of the tyrosine oxidation in the case of tyrosinase, were monitored in the amperometric mode. The screen-printed electrode modified with carbon black, pillar[5]arene and electropolymerized thionine and methylene blue was separated from the enzyme layer by 0.1 mm gap and used as a biosensor transducer. The components of the modifier layer exerted a synergetic effect and increased the cathodic current up to seven times compared to electrodes modified with individual components, increasing the sensitivity of the analysis. In the optimal conditions, biosensor allowed the determination of 1 × 10−7 to 1 × 10−5 M uric acid and 2 × 10−7 to 1 × 10−5 M tyrosine. The biosensors analyzed spiked samples of blood serum and urine and provided recoveries from 95 to 110%. Easy mounting of the flow-through cell and low cost of the replaceable parts make promising future application of the biosensor for routine clinical assays.

Metabolites profiling reveals gut microbiome-mediated biotransformation of green tea polyphenols in the presence of N-nitrosamine as pro-oxidant

The gut microbiome contributes to host physiology and nutrition metabolism. The interaction between nutrition components and the gut microbiota results in thousands of metabolites that can contribute to various health and disease outcomes. In parallel, the interactions between foods and their toxicants have captured increasing interest due to their impact on human health. Taken together, investigating dietary interactions with endogenous and exogenous factors and detecting interaction biomarkers in a specific and sensitive manner is an important task. The present study sought to identify for the first time the metabolites produced during the interaction of diet-derived toxicants e.g., N-nitrosamines with green tea polyphenols, using liquid chromatography electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS). In addition, the metabolic products resulting from the incubation of green tea with a complex gut microbiome in the presence of N-nitrosamine were assessed in the same manner. The quinone products of (epi)catechin, quercetin, and kaempferol were identified when green tea was incubated with N-nitrosamine only; whereas, incubation of green tea with N-nitrosamine and a complex gut microbiome prevented the formation of these metabolites. This study provides a new perspective on the role of gut microbiome in protecting against potential negative interactions between food-derived toxicants and dietary polyphenols.

Establishment of hairy root culture of Rubia yunnanensis Diels: Production of Rubiaceae-type cyclopeptides and quinones

Rubia yunnanensis is an important medicinal plant with various bioactive secondary metabolites. In order to reduce the dependence on wild populations of the species, we aim to establish in vitro culture system that can produce Rubiaceae-type cyclopeptides (RAs) and quinones. Agrobacterium rhizogenes-mediated transformation of stem segments of in vitro grown R. yunnanensis plants using four A. rhizogenes strains was studied and transformation conditions were optimized. Hairy roots appeared with the highest frequency (68.89%) when stem segments (with leaves) without pre-culture were immersed in A. rhizogenes A4 strain bacterial suspension for 30 min, co-cultured on Murashige and Skoog (MS) solid medium in the dark for three days, and afterwards incubated in darkness. PCR analysis of rolB and rolC genes confirmed transformed nature of six hairy root clones. The hairy roots grew rapidly, especially showing the highest accumulation of biomass in MS liquid medium compared to in vitro grown plants and calli. Histological observation of hairy root revealed anatomical difference in vascular cylinder, where the cells exhibited high mitotic activity characterized by vigorous growth. The UPLC-MS/MS analysis revealed that the amount of RAs in the hairy roots grown in ½MS liquid medium (4.611 μg g−1 DW) was higher than that in in vitro grown plants (0.331 and 4.096 μg g−1 DW for shoots and roots respectively) and calli (1.082 μg g−1 DW), but still far lower than that in the roots of seed-borne plants (80.296 μg g−1 DW). However, the hairy roots accumulated high level of quinones (2320.923 and 5067.801 μg g−1 DW for MS and ½MS liquid media respectively), of the same order of magnitude as the roots of seed-borne plants (7409.973 μg g−1 DW). Hairy root culture of R. yunnanensis, with high accumulation of biomass and production of quinones, may offer an attractive perspective for the production of the RAs and quinones that could be further optimized for pharmaceutical use.

2,6-Di-tert-butylphenol and its quinone metabolite trigger aberrant transcriptional responses in C57BL/6 mice liver

2,6-Di-tert-butylphenol (2,6-DTBP) is used as an antioxidant with wide commercial applications and its residues have been detected in various environmental matrices. 2,6-DTBP may enter human body via ingestion, inhalation or other exposure pathways. However, its susceptibility to biotransformation and potential of the metabolic products to trigger aberrant transcriptional responses remain unclear. Here, we investigated in vitro and in vivo biotransformation of 2,6-DTBP and characterized the RNA-Seq based transcriptional profiling of C57BL/6 mice liver after the exposure to 2,6-DTBP and its metabolites. 2,6-DTBP was metabolized into hydroxylated (2,6-DTBH) and para-quinone (2,6-DTBQ) products with residues detected in serum and liver of C57BL/6 mice. 2,6-DTBP and 2,6-DTBQ induced the aberrant transcription in C57BL/6 mice liver featured with 373-2861 differentially expressed genes (DEGs). They also up-regulated 1.09-2.92 fold mRNA expression of carcinogenesis-related genes such as Ccnd1, TGFβ1 and FOS in C57BL/6 mice liver. Our study indicated potential carcinogenic risk of 2,6-DTBP and its metabolites, beneficial to further evaluation of health risk of TBPs-related contaminants.

Development of Sinningia magnifica (Otto & A. Dietr.) Wiehler (Gesneriaceae) tissue culture for in vitro production of quinones and bioactive molecules

Quinones and phenolic glycosides display several biological activities and has been reported in Sinningia species (Gesneriaceae family). The plant tissue culture technique is an excellent tool for metabolism process studies and metabolites extraction. The aim of this work was the callogenesis induction and the secondary callus culture optimization in Sinningia magnifica (Otto & A. Dietr.) Wiehler, varying different types and concentrations of growth regulators, light, antioxidant, and culture medium. These conditions may influence the potential and the morphology of the induced callus, and thus the production and variation of secondary metabolites. Our studies found that for S. magnifica, the best method was fixed using Murashige and Skoog medium culture, in the absence of light, at a concentration of 8.0 mgL−1 of 6-Benzylaminopurine and of 2,4-dichlorophenoxyacetic acid, with a callus development reaching a plateau in about 45 days. The potent antioxidant activity of calli was compared with the in natura plant and demonstrated the greater variety of secondary metabolites. 7-hydroxy-6-methoxy-tectoquinone and 7-hydroxy-6-methoxy-α-dunnione were found in higher quantities in in vitro plants culture compared with the in natura plant, demonstrating the importance of using other methods in order to improve the secondary metabolites production and the advantages of this source for bioactive compounds development and exploitation.

Regioselective Oxidative Arylation of Fluorophenols.

A metal free and highly regioselective oxidative arylation reaction of fluorophenols is described. The relative position of the fluoride leaving group (i.e., ortho or para) controls the 1,2 or 1,4 nature of the arylated quinone product, lending versatility and generality to this oxidative, defluorinative, arylation concept.

From phenols to quinones: Thermodynamics of radical scavenging activity of para-substituted phenols

Radical scavenging activity and subsequent oxidation resulting in quinone products represent one of the important features of phenols occurring in plants and other biological systems. However, corresponding thermochemistry data can be still considered scarce. For phenol and 25 para-substituted phenols, we investigate the thermodynamics of the individual reaction steps, including three subsequent hydrogen atom transfers, as well as hydroxyl HO radical addition, leading to final ortho-quinone formation. The substituent and solvent effect of water on corresponding reactions enthalpies is elucidated. Solvent enhances substituent induced changes in the investigated reaction enthalpies. The reliability of employed computational methods for the thermodynamics of hydrogen atom donating ability of studied phenols and catechols is assessed, too. Obtained linear equations enable estimation of studied reaction enthalpies from Hammett constants of substituents.