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Objective: Galactonolactone oxidase from Trypanosoma cruzi is a membrane enzyme catalyzing the final step of the biosynthesis of vitamin C, an antioxidant essential for T. cruzi causing Chagas disease. So, galactonolactone oxidase can be considered as a promising drug target. This work devoted to investigation of impact of the effectors, 1,4-benzoquinone, coenzymes Q, and their structural analogs, on the activity of galactonolactone oxidase from Trypanosoma cruzi and of the model homologous enzyme L-galactono-1,4-lactone dehydrogenase from Arabidopsis thaliana. Methods: Recombinant expression of galactonolactone oxidase and L-galactono-1,4-lactone dehydrogenase was carried out in Escherichia coli and refolding of galactonolactone oxidase was performed using reverse micelles system. Spectrophotometric determination of the activity of both enzymes was carried out in a surfactant reverse micelles system using a combination of one of the potential effectors and 2,6-dichlorophenolindophenol, a dye, which becomes colorless upon interaction with the product of reaction. Results and Discussion: Using two forms of L-galactono-1,4-lactone dehydrogenase, wild-type (dehydrogenase) and mutant (exhibiting oxidase activity), the role of 1,4-benzoquinone and its analogs as electron acceptors of galactono-1,4-lactone dehydrogenase and galactonolactone oxidase was revealed. It was established that compounds containing methoxy groups (coenzyme Q0, 2,6-dimethoxy-1,4-benzoquinone) are more effective electron acceptors for galactonolactone oxidase compared to those lacking OCH3 groups (2,5-dihydroxy-1,4benzoquinone). Conclusions: Basing on the use of 2,6-dimethoxy-1,4-benzoquinone as an electron acceptor, an approach was proposed to the spectrophotometric measurement of the galactonolactone oxidase activity by the changes in the absorption of the electron acceptor in the absence of additional components (a dye that becomes colorless when interacting with the reaction product, ascorbate). The results obtained enable more targeted search for inhibitors of galactonolactone oxidase, which may be regarded as a basis for the development of selective drugs against Chagas disease caused by T. cruzi. [ABSTRACT FROM AUTHOR]

The reaction mechanisms of C–S borylation of aryl sulfides catalyzed with 1,4-benzoquinone (BQ) were investigated by employing the M06-2X-D3/ma-def2-SVP method and basis set. In this study, the SMD model was taken to simulate the solvent effect of 1,4-dioxane. Also, TD-DFT calculations of BQ and methyl(p-tolyl)sulfane were performed in an SMD solvent model. The computational results indicated that BQ and methyl(p-tolyl)sulfane, serving as a photo-catalyst, would be excited under a blue LED of 450 nm, aligning well with experimental observations. Additionally, the role of 3O2 was investigated, revealing that it could be activated into 1O2 from the released energy of 1[BQ + methyl(p-tolyl)sulfane]* or 3[BQ + methyl(p-tolyl)sulfane]*→BQ + methyl(p-tolyl)sulfane process. Then, 1O2, bis(pinacolato)diboron, and methyl(p-tolyl)sulfane would, through a series of reactions, yield the final product, P. The Gibbs free energy surface shows that path a2-2 is optimal, and this path has fewer steps and a lower energy barrier. Electron spin density isosurface graphs were employed to analyze the structures and elucidate the single electron distribution. These computational results offer valuable insights into the studied interactions and related processes and shed light on the mechanisms governing C–S borylation from aryl sulfides and b2pin2 catalyzed with BQ and methyl(p-tolyl)sulfane. [ABSTRACT FROM AUTHOR]

A rapid and sensitive assessment of the toxicity of oxygenated polycyclic aromatic hydrocarbons (OPAHs), widely distributed persistent organic pollutants in the environment, is crucial for human health. In this study, using high-performance liquid chromatography, the separation and detection of four purines, xanthine (X), guanine (G), adenine (A), and hypoxanthine (HX) in cells were performed. The aim was to evaluate the cytotoxicity of three OPAHs, namely 1,4-benzoquinone (1,4-BQ), 1,2-naphthoquinone (1,2-NQ) and 9,10-phenanthrenequinone (9,10-PQ), with higher environmental concentrations, from the perspective of purine nucleotide metabolism in human skin fibroblast cells (HFF-1). The results revealed that the levels of G and A were low in HFF-1 cells, while the levels of HX and X showed a dose-response relationship with persistent organic pollutants concentration. With increased concentration of the three persistent organic pollutants, the purine metabolism in HFF-1 cells weakened, and the impact of the three persistent organic pollutants on purine metabolism in cells was in the order of 9,10-PQ > 1,4-BQ > 1,2-NQ. This study provided valuable insights into the toxic mechanisms of 1,4-BQ, 1,2-NQ and 9,10-PQ, contributing to the formulation of relevant protective measures and the safeguarding of human health. [ABSTRACT FROM AUTHOR]

Benzene exposure inhibits the hematopoietic system and leads to the occurrence of various types of leukemia. However, the mechanism underlying the hematotoxicity of benzene is still largely unclear. Emerging evidence has shown that exosomes are involved in toxic mechanisms of benzene. To understand the effect of 1,4‐benzoquinone (PBQ; an active metabolite of benzene in bone marrow) on the exosomal release characteristics and role of exosomal secretion in PBQ‐induced cytotoxicity. Exosomes were isolated from PBQ‐treated HL‐60 cells, purified by ultracentrifugation, and verified by transmission electron microscopy, nanoparticle tracking analysis and the presence of specific biomarkers. Our results showed that PBQ increased exosomal secretion in a dose‐dependent manner, reaching a peak in 3 h at 10 μM PBQ treatment and then slowly decreasing in HL‐60 cells. The exosomes contained miRNAs, which have been reported to be associated with benzene exposure or benzene poisoning. In particular, mir‐34a‐3p and mir‐34A‐5p were enriched in exosomes derived from PBQ‐treated cells. In addition, the inhibition of exosomal release by GW4869 (an inhibitor of exosomal release) exacerbated PBQ‐induced cytotoxicity, including increased intracellular reactive oxygen species levels, decreased mitochondrial membrane potential, and increased the apoptosis rate. Our findings illustrated that exosomes secretion plays an important role in antagonizing PBQ‐induced cytotoxicity and maintaining cell homeostasis. [ABSTRACT FROM AUTHOR]

The exploration on the redox properties of sodiated quinone molecules as organic cathode material in sodium-ion batteries has been comprehensively studied. As the electrochemical performance of the cathode material is known to depend on the intrinsic molecular properties such as conformations, the present work focuses on the redox properties of sodiated 1,4-benzoquinone (1,4-BQ) conformers employing the density functional theory. Such investigation on the sodiated structures might provide insight on the discharge state of the puckered conformers. The 38 conformers of 1,4-BQ (2 chairs, 6 boats, 6 skew-boats, 12 half-chairs, 12 envelopes) constructed from the torsion angles given by Berces et al. are optimized at B3LYP/6–311 + G(d,p) level of theory and their structural propensities during the reduction process are explored. The influence of puckering over the charge distribution of neutral, anionic and sodiated structures is analysed using the natural bond orbital method. The electrochemical performance of Na incorporated conformers is explored through the calculation of electron affinity, change in Gibbs free energies and redox potentials. The conductor-like polarizable continuum model (C-PCM) is used to include the solvation effects of the electrolyte such as ethylene carbonate. A good correlation between the conformers with more negative lowest unoccupied molecular orbital (LUMO) energies and their redox potentials and electron affinity is observed. Noticeable variation in the frontier energies and redox potentials of the sodiated quinone conformers emphasize the significance of intrinsic molecular level properties to play a major role in the overall electrochemical performance of quinone-like electrode materials in sodium-ion batteries. [ABSTRACT FROM AUTHOR]

Background: HSPCs are targets for benzene-induced hematotoxicity and leukemogenesis. However, benzene toxicity targeting microRNAs (miRNAs) and transcription factors (TF) that are involve in regulating self-renewing and differentiation of HSPCs comprising of different hematopoietic lineages remains poorly understood. In this study, the effect of a benzene metabolite, 1,4-benzoquinone (1,4-BQ) exposure, in HSPCs focusing on the self-renewing (miRNAs: miR-196b and miR-29a; TF: HoxB4, Bmi-1) and differentiation (miRNAs: miR-181a, TF: GATA3) pathways were investigated. Methods: Freshly isolated mouse BM cells were initially exposed to 1,4-BQ at 1.25 to 5 µM for 24 h, followed by miRNAs and TF studies in BM cells. Then, the miRNAs expression was further evaluated in HSPCs of different lineages comprised of myeloid, erythroid and pre-B lymphoid progenitors following 7-14 days of colony forming unit (CFU) assay. Results: Exposure to 1,4-BQ in BM cells significantly (p < 0.05) reduced the miR-196b (2.5 and 5 µM), miR-181a (1.25, 2.5 and 5 µM) and miR-29a (1.25 µM) along with upregulation of miR-29a at 2.5 µM. Meanwhile, 1,4-BQ exposure in HSPCs significantly increased the miR-196b expression level (p < 0.05) only in myeloid and pre-B lymphoid progenitors at 2.5 and 5 µM. Significant (p < 0.05) reduction in expression of miR-181a in myeloid (1.25 µM), erythroid (5 µM) progenitors along with miR-29a in myeloid (1.25 µM) and pre-B lymphoid (5 µM) progenitors were noted following exposure to 1,4-BQ. Meanwhile, increased expression of miR-181a was observed in pre-B lymphoid progenitor upon exposure to 1,4-BQ, but only at 5 µM. As for TF studies, expression of HoxB4 protein was significantly increased (p < 0.05) at all 1,4-BQ concentrations as compared to Bmi-1 and GATA3, which were significantly (p < 0.05) elevated starting at 2.5 µM of 1,4-BQ. Conclusion: 1,4-BQ induces aberration of miRNAs and transcription factors protein expression that are involved in regulating self-renewing and differentiation pathways of HSPCs. Moreover, epigenetic toxicity as evidenced from the miRNAs expression was found to be mediated by a lineage-driven mechanism. The role of cell lineage in governing the toxicity of 1,4-BQ in HSPCs lineages deserves further investigation. [ABSTRACT FROM AUTHOR]

Background HSPCs are targets for benzene-induced hematotoxicity and leukemogenesis. However, benzene toxicity targeting microRNAs (miRNAs) and transcription factors (TF) that are involve in regulating self-renewing and differentiation of HSPCs comprising of different hematopoietic lineages remains poorly understood. In this study, the effect of a benzene metabolite, 1,4-benzoquinone (1,4-BQ) exposure, in HSPCs focusing on the self-renewing (miRNAs: miR-196b and miR-29a; TF: HoxB4, Bmi-1) and differentiation (miRNAs: miR-181a, TF: GATA3) pathways were investigated. Methods Freshly isolated mouse BM cells were initially exposed to 1,4-BQ at 1.25 to 5 µM for 24 h, followed by miRNAs and TF studies in BM cells. Then, the miRNAs expression was further evaluated in HSPCs of different lineages comprised of myeloid, erythroid and pre-B lymphoid progenitors following 7–14 days of colony forming unit (CFU) assay. Results Exposure to 1,4-BQ in BM cells significantly (p

The synthesis of a series of some piperazine derivatives with quinone moiety was carried out in present study. Obtained 2-quinonyl piperazine derivatives were then reacted with some aliphatic or aromatic thiol nucleophiles and new N,S-substituted of 1,4-naphthoquinone synthesized. The structures of novel molecules were elucidated by microanalysis and spectroscopic methods such as FT-IR, 1H-NMR, 13C-NMR, UV-Vis. Mass and MS/MS fragmentation studies were also performed and fragmentation pathway of protonated novel piperazine derivatives were proposed. [ABSTRACT FROM AUTHOR]

The solubility of the compound is a crucial task for new drug design. Quinone is a promising candidate to develop as a new drug. In this research, the synthesis of 1,4-benzoquinone derivatives, that is, 2-(5-bromoamyl)-3,5-dimethyl-1,4-benzoquinone (2a) and 2-(5-bromoamyl)-5-methyl-1,4-benzoquinone (2b) were carried out by decarboxylation and insertion reaction of alkyl bromides. The product 2a and 2b are purified using SiO2 gel column chromatography and analyzed by UV-Visible, FT-IR, and NMR. The yield of 2a is 13.75%, and 2b is 4.04%. The solubility of 2a and 2b, expressed by log P, is measured in the n-octanol/water (3:7 (v/v)) system by the shake flask method. The log P of 2a and 2b are 2.99 and 1.36, respectively. It is showed that the log P of 2a is higher compared to 2b. The presence of two methyl substituents on the quinone ring of 2a supports the increase of hydrophobicity of the compound in the n-octanol/water system.

The biological activity and solubility of compounds are influenced by its chemical structure. These properties can be improved by substituting alkyl, alkoxy, and/or haloalkane in the parent skeleton. In this research, the synthesis of 3-(7-bromoheptyl)-2-methyl-5-methoxy-1,4-benzoquinone (3a) and 3-(10-bromodecyl)-2-methyl-5-methoxy-1,4-benzoquinone (3b) was achieved through the decarboxylation reaction. The solubility and biological activity of 3a and 3b were compared with that of thymoquinone (TQ), which acts as an anti-inflammatory agent. Compounds 3a and 3b were successfully synthesized and analyzed using Fourier Transform Infra-Red (FTIR) and Nuclear Magnetic Resonance (NMR). The FTIR spectrum showed the increasing intensity of C-H sp3 and the absorption of C-Br because of the presence of the bromoheptyl and bromodecyl substituents. 1H-NMR showed the prominent chemical shift of olefinic methylene at d 1.29-3.40 ppm. The solubility test showed the differences in the partition coefficient (log P) of 3a and 3b in the n-octanol/water system. The log P values of 3a and 3b are higher than those of TQ, indicating that methoxy, bromoheptyl, and bromodecyl support the increase in solubility. Biological activity test using the in silico approach showed that 3a and 3b have a higher tendency to bind with the translocator protein (TSPO) macromolecule than the phosphatase and tensin homolog (PTEN) macromolecule. The binding interactions of TSPO-3a and TSPO-3b, similar to that of TSPO-TQ, showed that both synthesized compounds have comparable activity. The binding energy of TSPO-3a is lower than that of TSPO-3b, indicating that 3a has a higher activity for anti-inflammatory drug candidates than 3b. [ABSTRACT FROM AUTHOR]

Oncocalyxone A, a 1,4-benzoquinone derived from Cordia oncocalyx, exhibits anti-inflammatory, antimicrobial and antidiabetic properties. The aim of this study was to (1) examine the cytotoxic actions of oncocalyxone A on human normal and tumor cell lines and (2) determine mechanistic actions underlying effects upon leukemia cells using cellular and molecular techniques. Antiproliferative studies on cancer cell lines, peripheral blood mononuclear cells, and human erythrocytes were performed using colorimetric assays. To understand cytotoxicity, assessments were performed with HL-60 leukemia cells (8, 16.5, or 33 µM) after 24 hr incubation using light and fluorescence microscopy, trypan blue, flow cytometry, Comet assay, western blot of caspases and poly-ADP-ribose polymerase (PARP), and effects on topoisomerase I and II. Oncocalyxone A exhibited cytotoxic action upon HL-60 cells and dividing leukocytes, but minimal hemolytic action on erythrocytes. Mechanistic investigations demonstrated reduction of cell viability, loss of membrane integrity, cell shrinking, chromatin condensation, blebbings, externalization of phosphatidylserine, caspase activation, PARP cleavage, mitochondrial depolarization, and DNA damage. Pre-treatment with N-acetylcysteine 4 mM significantly reduced DNA damage and prevented membrane integrity loss. Oncocalyxone A displayed free radical dependent antileukemic activity via apoptotic pathways and induced DNA damage in HL-60 cells. Oncocalyxone A possesses structural chemical simplicity enabling it to be a cost-effective alternative. These properties justify further improvements to enhance activity and selectivity and the development of pharmaceutical formulations. Abbreviations Acridine orange, AO; ANOVA, analysis of variance; BSA, bovine serum albumin; DI, Damage Index; DMSO, dimethylsulfoxide; EC50, effective concentration 50%; EDTA, ethylenediamine tetraacetic acid; EB, ethidium bromide; HCT-116, colon carcinoma line; HL-60, promyelocytic leukemia line; IC50, inhibitory concentration 50%; MTT, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide; OVCAR-8, ovarian carcinoma line; NAC, N-acetylcysteine, PBMC, peripheral blood mononuclear cells; PBS, phosphate-buffered saline; PI, propidium iodide; PARP, poly-ADP-ribose polymerase; RPMI-1640, Roswell Park Memorial Institute medium; SF-295, glioblastoma line; ROS, reactive oxygen species; 7-AAD, 7-amino-actinomycin D; H2-DCF-DA, 7′-dichlorodihydrofluorescein diacetate. [ABSTRACT FROM AUTHOR]

Widespread occupational and environmental exposure to benzene is unavoidable and poses a public health threat. Studies of potential interventions to prevent or relieve benzene toxicity are, thus, essential. Research has shown l‐carnitine (LC) has beneficial effects against various pathological processes and diseases. LC possesses antioxidant activities and participates in fatty acid oxidation (FAO). In this study, we investigated whether 1,4‐benzoquinone (1,4‐BQ) affects LC levels and the FAO pathway, as well as analyzed the influence of LC on the cytotoxic effects of 1,4‐BQ. We found that 1,4‐BQ significantly decreased LC levels and downregulated Cpt1a, Cpt2, Crat, Hadha, Acaa2, and Acadvl mRNA expression in K562 cells. Subsequent assays confirmed that 1,4‐BQ decreased cell viability and increased apoptosis and caspase‐3, ‐8, and ‐9 activities. It also induced obvious oxidative stress and DNA damage, including an increase in the levels of reactive oxygen species and malondialdehyde, tail DNA%, and olive tail moment. Additionally, the mitochondrial membrane potential was significantly reduced. Cotreatment with LC (500 μmol/L) relieved these alterations by reducing oxidative stress and increasing the protein expression levels of Cpt1a and Hadha, particularly in the 20 μmol/L 1,4‐BQ group. Thus, our results demonstrate that 1,4‐BQ causes cytotoxicity, reduces LC levels, and downregulates the FAO genes. In contrast, LC exhibits protective effects against 1,4‐BQ‐induced apoptosis and DNA damage by decreasing oxidative stress and promoting the FAO pathway. [ABSTRACT FROM AUTHOR]

There is a growing interest in photosynthetic microorganisms for converting solar energy to electricity aiming at practical application. Despite extensive research, existing methods are suffered from limited photocurrent. Here we report that appreciable photocurrent can be generated in a photo‐bioelectrochemical cell (PBEC) where reduced graphene oxide‐coated ITO electrode is used as an anode and wild type cyanobacterium Anabaena variabilis as photo‐biocatalyst that oxidizes water by solar light. With A. variabilis dispersed in buffer and 1,4‐benzoquinone as a redox mediator, our PBEC produced photocurrent of 223 μA cm−2 at an applied voltage of 0.4 V vs. Ag/AgCl. Incident photon to current efficiencies of 0.50 % and 5.2 % were obtained with white and monochromatic light at 660 nm, respectively. A complete PBEC with Pt/C cathode produced Pmax of 13 μW cm−2 at 115 μA cm−2. Methodology in this study can be extended to cover other cyanobacteria, electrode materials, and mediators to further enhance photocurrent and power density. Our results demonstrate the possibility of utilizing cyanobacteria that are ubiquitous in the environment as alternative energy sources. [ABSTRACT FROM AUTHOR]

D‐fructose amount in food and beverages should be carefully controlled in order to avoid its overconsumption by human, which can lead to various metabolic diseases. Thus, the development of a low‐cost and portable (bio)sensors, which realize the on‐site monitoring of D‐fructose, is still highly required. In this work, we proposed several reagentless bioelectrochemical systems (BioESs) based on fructose dehydrogenase EC1.1.99.11 from Gluconobacter japonicus (FDH) and on 2‐arylamine‐1,4‐benzoquinone (ABQ) derivatives as a platform for the development of D‐fructose electrochemical biosensor. To design a reliable and easily reproducible BioES, we used the simple physical sorption as the electrode modification strategy for ABQs and FDH immobilization that is suitable for low‐cost mass production of the biosensors by standard microfabrication techniques. To choose the most suitable ABQ compounds for BioESs design, we proposed a novel theoretical approach of potential ET mediator evaluation through its electrochemical properties. A set of newly synthesized and of previously applied ABQs was characterized both electrochemically and using the density functional theory (DFT). It was shown that results obtained by quantum chemical analysis were in a good agreement with the ABQ characteristics obtained in electrochemical measurements. We suggest that the calculated local ionization energy values and theoretical redox potential obtained by DFT are a powerful tool for prediction of ABQs electrochemical properties. The performance of the BioESs with FDH under study was determined by electrochemical and electronic properties of ABQ derivatives and FDH orientation and stabilization on the electrode surface. The most promising BioES was based on carbon paste electrodes and 2‐(3‐nitro(phenyl)amino)‐ cyclohexa‐2,5‐dien‐1,4‐dione as ET mediator, which accelerated FDH catalysis and improved its stability better, then other studied ABQs. The bioelectrocatalytic process was characterized by initial apparent maximum current density of 7.1 μA cm−2 at the optimal conditions (+400 mV vs. Ag/AgCl, McIlvaine's buffer, pH 5.0 and 20 °C). The findings of this research open new possibilities for development of cost‐effective biosensors with FDH and, potentially, with other redox enzymes. [ABSTRACT FROM AUTHOR]

In order to efficiently deal with environmental pollution caused by industrial wastewater and drug molecules, a novel Fenton catalytic system of Fe2O3/C-(1,4-benzoquinone) has been successfully developed, which shows obviously enhanced Fenton catalytic activities for organic pollutants (Rhodamine B and ibuprofen) degradation than Fe2O3/C composite. The Fenton catalytic activity of the Fe2O3/C composite with 1,4-benzoquinone (BQ) as cocatalyst is 10.14 times higher than that of Fe2O3/C composite. Furthermore, with BQ as cocatalyst, the catalytic activity of the Fe2O3/C composite is 35.5 times and 15.8 times that of Fe2O3 and carbon, respectively. The concentration ratios of carbon in the Fe2O3/C composite and BQ in the system are also discussed, demonstrating that the 50 wt% carbon in Fe2O3/C composite and 3 wt% BQ in the system are the optimized conditions. The carbon in the Fe2O3/C composite acts as an adsorbent of organic pollutants and BQ. The contribution of BQ in the Fenton system is reflected in the scavenging of •O2– radical and photogenerated electrons, which promotes the production of FeII and photogenerated hole, resulting in a rapid degradation process. Furthermore, the BQ is also degraded with the degradation of organic pollutants, which does not cause secondary pollution to the water. This study sheds new light on the design and fabrication of novel Fenton catalytic system to solve the environmental crisis. [ABSTRACT FROM AUTHOR]

BACKGROUND: Hydroquinone (HQ) is an important fine chemical raw material and intermediate, which is widely used in chemistry industry. It is great significance to develop a new environmentally‐friendly synthesis method to produce HQ. RESULTS: Three [FeFe]‐hydrogenase model complexes (μ‐budt)[Fe(CO)3]2[1; budt = SCH(CH3)CH2CH2)S], (μ‐budt)[Fe(CO)3][Fe(CO)2PPh3](2), and (μ‐bust)[Fe(CO)3]2 [3; bust = SCH(CH3)CH2CH2)S(O)] were synthesized by direct CO/L substitution or sulfur based oxygenation. The synthesized new complexes were fully characterized by FT‐IR, 1H NMR, 13C NMR and X‐ray crystallography. The electrochemical properties of these model complexes were investigated by cyclic voltammetry in CH2CI2 to evaluate the redox properties of the iron atoms. It was indicated that these new complexes are not only electrochemical catalysts for proton reduction of hydrogen, but also efficient catalysts for catalytic the transfer hydrogenation of BQ (1, 4‐benzoquinone) to prepare HQ under mild conditions. Especially,complex 2 exhibited the highest catalytic activity for reduction of BQ with methanol as the proton source, which gave a BQ conversion of 91 % and 72 % selectivity for HQ. CONCLUSIONS: The complex 2 can be a new type catalyst for catalytic reduction of BQ to HQ under mild reaction conditions. In addition, the Kinetics and mechanism were also investigated for a proposed transfer hydrogenation process. © 2019 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

5-bromo-2,3-dimethoxy-6-methyl-1,4-benzoquinone 3, a key intermediate for preparing coenzyme Q compounds, was readily synthesized in two steps by a reaction sequence starting from the commercially available 3,4,5-trimethoxytoluene 1 via bromination and oxidation reactions. Persulfate salts were first employed as oxidants to synthesize 1,4-benzoquinone, the overall yield of title compound 3 was 65%.

Benzene exposure is associated with various hematological disorders, in particular leukemia. The reactive metabolite of benzene, 1,4-benzoquinone (BQ), generated in bone marrow, is suggested to be a key molecule in mediating benzene-induced hematotoxicity and carcinogenicity. However, its pathogenic role remains largely unknown due to a lack of suitable vertebrate whole-organism models. Here, we present an in vivo study to reveal the effect of BQ exposure on hematotoxicity in zebrafish. From embryonic stages to adulthood, BQ exposure suppressed erythroid and lymphoid hematopoiesis but led to abnormal accumulation of myeloid cells and precursors, which resembles benzene-induced cytopenia and myeloid dysplasia in humans. This myeloid expansion is caused by granulocyte, but not macrophage, lineage, emphasizing the significant role of lineage specificity in BQ-mediated hematopoietic toxicity. Analysis of the c-myb (also known as myb)-deficient mutant cmybhkz3 revealed that BQ induced neutrophilia in a c-myb-dependent manner, demonstrating that c-myb is a key intrinsic mediator of BQ hematotoxicity. Our study reveals that BQ causes lineage-specific hematotoxicity in zebrafish from embryonic stages to adulthood. Since c-myb is indispensable for BQ to induce neutrophilia, c-myb could serve as a potential drug target for reversing BQ hematotoxicity.

Previous reports on hematotoxicity and leukemogenicity related to benzene exposure highlighted its adverse effects on hematopoiesis. Despite the reported findings, studies concerning the mechanism of benzene affecting chromosomal integrity in lineage-committed hematopoietic stem/progenitor cells (HSPCs) remain unclear. Here, we studied the clastogenicity and aneugenicity of benzene in lineage-committed HSPCs via karyotyping. Isolated mouse bone marrow cells (MBMCs) were exposed to the benzene metabolite 1,4-benzoquinone (1,4-BQ) at 1.25, 2.5, 5, 7, and 12 μM for 24 h, followed by karyotyping. Then, the chromosomal aberration (CA) in 1,4-BQ-exposed hematopoietic progenitor cells (HPCs) comprising myeloid, Pre-B lymphoid, and erythroid lineages were evaluated following colony-forming cell (CFC) assay. Percentage of CA, predominantly via Robertsonian translocation (Rb), was increased significantly (p < 0.05) in MBMCs and all progenitors at all concentrations. As a comparison, Pre-B lymphoid progenitor demonstrated a significantly higher percentage of CA (p < 0.05) than erythroid progenitor at 1.25, 2.5, and 7 μM as well as a significantly higher percentage (p < 0.05) than myeloid progenitor at 7 μM of 1,4-BQ. In conclusion, 1,4-BQ induced CA, particularly via Rb in both MBMCs and HPCs, notably via a lineage-dependent response. The role of lineage specificity in governing the clastogenicity and aneugenicity of 1,4-BQ deserves further investigation.

Previous investigations have evaluated the efficacy of anions such as NO3−, Cl−, Br−, CH3COO−, and CF3COO− as additives to generate or enhance mass spectrometric signals from explosives under plasma ionization conditions. The results of this study demonstrate that for detecting nitramine-class explosives, such as 1,3,5-trinitroperhydro-1,3,5-triazine (RDX) and 1,3,5,7-tetranitro-1,3,5,7-tetrazacyclooctane (HMX), 1,4-benzoquinone (BQ) is a highly effective and efficient dopant. When used in conjunction with ambient-pressure negative-ion helium-plasma ionization (HePI), 1,4-benzoquinone readily captures an electron, forming an abundant molecular anion (m/z 108), which upon exposure to vapors of RDX and HMX generates adduct ions of m/z 330 and 404, respectively. The signal level recorded for RDX upon adduction to the radical anion of 1,4-benzoquinone under our experimental conditions was significantly higher than that realized by chloride adduction using dichloromethane (DCM) as the dopant. [ABSTRACT FROM AUTHOR]

The title compound, a key intermediate for preparing Coenzyme Qn family, was prepared in an excellent yield by a reaction sequence starting from the commercially available 3,4,5-trimethoxytoluene 1 via bromination, methoxylation and oxidation reactions. An 80% overall yield was demonstrated on a multi-gram scale. [ABSTRACT FROM AUTHOR]

A series of new potential electron transfer mediators, 2-substituted 1,4-benzoquinone derivatives bearing an arylamino group with various substituents in o-, m- and p-positions of an aromatic ring were synthesised by adding a solution of aniline derivatives in aqueous acetic acid to an aqueous solution of 1,4-benzoquinone. The structure and properties of synthesised compounds were investigated by NMR spectroscopy methods in detail. The redox ability of 2-arylamino-1,4-benzoquinone derivatives has been estimated by calculations of quantum chemical structure-activity relationship (QSAR) descriptors within the framework of density functional theory. [ABSTRACT FROM AUTHOR]

Chemically induced dynamic nuclear polarization during photolysis of unsubstituted benzoquinone in an acidic medium was observed upon reduction with tertiary butyl alcohol. It was found that protonated triplet quinone molecules accept an electron from alcohol. Elementary acts of the formation of nuclear polarization by the triplet mechanism were revealed. [ABSTRACT FROM AUTHOR]

Reactions of 1,4-benzoquinone with 2-(2-oxo-2-arylethylidene)-2,3-dihydro-1H-pyrimidine-4-ones in glacial acetic acid proceed selectively to give 2-[1-(2,5-dihydrophenyl)-2-oxo-2-arylethylidene]-2,3-dihydropyrimidine-4(1H)-ones. [ABSTRACT FROM AUTHOR]

Hematotoxicity of benzene is derived mainly from its active metabolite, 1,4-Benzoquinone (1,4-BQ), which induces cell apoptosis and mitochondrial damage. Damaged mitochondria are degraded through a specialized autophagy pathway, called mitophagy, which is driven by PINK1/Parkin signaling. However, whether mitophagy is involved in 1,4-BQ-induced toxicity remains unclear. This study was designed to investigate whether PINK1/Parkin-mediated mitophagy is activated in 1,4-BQ-treated HL-60 cells, and the roles mitophagy plays in 1,4-BQ-induced apoptosis. Our results demonstrated that 1,4-BQ induced autophagy in HL-60 cells, characterized by increased LC3-II/LC3-I ratio and Beclin1 expression, as well as decreased expression of p62. We confirmed the presence of mitophagosomes using electron microscopy, and found that 1,4-BQ-induced autophagy was blocked by pretreatment with the mitophagy inhibitor Cyclosporine A (CsA). In addition, we found that 1,4-BQ induced mitochondrial stress through decreased mitochondrial membrane potential (MMP) and increasedproduction of reactive oxygen species (ROS). We also confirmed that 1,4-BQ-induced mitophagy was mediated by the PINK1/Parkin pathway, illustrated by increased expression of PINK1 and Parkin mRNA and protein. Finally, we examined 1,4-BQ-induced apoptosis with or without CsA, which demonstrated that apoptosis increased after mitophagy inhibition, suggesting that mitophagy has a protective effect in this context. In conclusion, this study demonstrates that the activated PINK1/Parkin-mediated mitophagy exerts a significantly protective effect against 1,4-BQ-induced apoptosis in HL-60 cells. [ABSTRACT FROM AUTHOR]

Benzene exposure affects the hematopoietic system and leads to the occurrence of various types of leukemia and hematotoxicity. It has been confirmed that active metabolites of benzene, including 1,4-benzoquinone (1,4- BQ), can induce reactive oxygen species (ROS) and apoptosis in the bone marrow, and recent studies have also suggested that benzene exposure can affect mitochondrial function in both experimental animals and cell lines. However, the potential relationship among ROS production, mitochondrial damages, and subsequent apoptosis following benzene exposure has not been well studied in detail. In the present study, we utilized HL-60 cells, a well-characterized human myeloid cell line, as an in vitro model and examined the effects of 1,4-BQ on intracellular ROS formation, mitochondria damage, and the occurrence of apoptotic events with or without using the ROS scavenger N-acetyl-L-cysteine (NAC). The results demonstrated that 1,4-BQ could dosedependently induce production of ROS and mitochondrial damage as characterized by mitochondrial membrane potential disruption, mitochondrial ultrastructure alteration, and induced apoptosis and activated caspase-3 and caspase-9. Preincubation of HL-60 cells with NAC prior to 1,4-BQ treatment could block 1,4- BQ-induced production of ROS and the occurrence of apoptosis. These results demonstrated that 1,4-BQ induced apoptosis in HL-60 cells through a ROS-dependent mitochondrial-mediated pathway. [ABSTRACT FROM AUTHOR]

Despite of reports on hematotoxic and leukemogenic evidences related to benzene exposure, the mechanism of benzene toxicity affecting the hematopoietic stem and progenitor cells (HSPCs) fate remains unclear. This study aims to elucidate the benzene's effect on the lineages-committed progenitors and genes-regulating self-renewal and differentiation of HSPCs. Isolated mouse bone marrow (BM) cells were exposed to the benzene metabolite, 1,4-benzoquinone (1,4-BQ) at 1.25, 2.5, and 5 μM for 24 h. The clonogenic potency of erythroid, myeloid, and Pre-B lymphoid progenitors was evaluated through colony-forming-cell assay. Quantitative real time-PCR was used to analyze the self-renewal ( Bmi-1 , HoxB4 , and Wnt3 ) and differentiation ( GATA1 , GATA2 , and GATA3 )-related genes' expression levels. 1,4-BQ exposure significantly lowered the clonogenicity of the myeloid progenitor at 1.25 and 2.5 μM ( p < 0.05), but affected neither the erythroid nor Pre-B lymphoid progenitors. Furthermore, significant upregulation of HoxB4 expression level was observed at all concentrations. GATA3 and Bmi-1 expressions were also significant upregulated at 2.5 and 5 μM 1,4-BQ, respectively. In conclusion, 1,4-BQ could modulate the fate of HSPCs by altering the self-renewal and differentiation related genes. The definite role of lineages specificity and responsive genes in governing the hematotoxicity and leukemogenicity of 1,4-BQ should be further investigated. [ABSTRACT FROM AUTHOR]

Benzene, a known occupational and environmental contaminant, is associated with increased risk of leukemia. The objectives of this study were to elucidate the regulatory mechanism of the hypomethylated STAT3 involved in benzene toxicity in vitro. As 1,4-benzoquinone (1,4-BQ) is one of benzene’s major toxic metabolites, AHH-1 cells were treated by 1,4-BQ for 24 h with or without pretreatment of the antioxidant a-LA or the methyltransferase inhibitor, 5-aza-2′ deoxycytidine (5-aza). The cell viability was investigated using the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. ROS was determined via 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) flow cytometric assays. The level of oxidative stress marker 8-OHdG was measured by enzyme-linked immunosorbent assay. Methylation-specific PCR was used to detect the methylation status of STAT3. Results indicated the significantly increasing expression of ROS and 8-OHdG which accompanied with STAT3 hypomethylation in 1,4-BQ-treated AHH-1 cells. α-LA suppressed the expression of both ROS and 8-OHdG, simultaneously reversed 1,4-BQ-induced STAT3 hypomethylation. However, although the methylation inhibitor, 5-aza reduced the expression level of ROS and 8-OHdG, but had no obvious inhibiting effect on STAT3 methylation level. Taken together, oxidative stress are involved 1,4-BQ-induced STAT3 methylation expression.

A novel approach has been proposed to the synthesis of phosphonium salts containing a 1,4-dihydroxybenzo fragment via reaction of 2-methyl-1,4-benzoquinone or 2-isopropyl-5-methyl-1,4-benzoquinone with PH-phosphonium salts generated in situ from triphenylphosphine and trifluoromethanesulfonic or trifluoroacetic acid. The structure of the synthesized phosphonium salts was determined by NMR spectroscopy and X-ray analysis. [ABSTRACT FROM AUTHOR]

A differential pulse voltammetry (DPV) method for the determination of lactic acid (LA) was developed with a glassy carbon electrode. LA causes the appearance of new paired peaks at a more positive potential during the reduction of 1,4-benzoquinone (BQ).The new peaks are attributed to the drastic change in pH at the electrode surface. As proton donors, LA provides protons and inhibits the pH increase at the electrode surface. The height of the new cathodic peak is dependent on the concentration of LA but is independent of BQ, phosphate, and insoluble solid matter in yogurt. The cathodic peak potential is dependent on the acid p Ka, which can be used to identify the other adulterated acids in yogurt. The proposed method was performed to measure the LA content of untreated yogurt samples. Results were consistent with those obtained by the potentiometric titration method. [ABSTRACT FROM AUTHOR]

The monoamine oxidase (MAO) enzymes are of considerable pharmacological interest and inhibitors are used in the clinic for the treatment of major depressive disorder and Parkinson's disease. A limited number of studies have shown that the quinone class of compounds possesses MAO inhibition properties. Most notable among these is a report that 2,3,6-trimethyl-1,4-naphthoquinone (TMN), present in extracts of cured tobacco leafs, is a non-selective inhibitor of both MAO isoforms. An older study reports that 1,4-benzoquinone inhibits MAO-A and MAO-B from human synaptosomes. Both 1,4-naphthoquinones and 1,4-benzoquinone are reported to inhibit the MAOs with a reversible mode of action. Since the MAO inhibition properties of additional members of the 1,4-benzoquinone class of compounds have not yet been explored, the present study investigates a small series of four 1,4-benzoquinones which incorporate phenyl, benzyl, benzyloxy and cyclopentyl monosubstitution on C2. The 1,4-benzoquinones were found to be moderately potent MAO inhibitors with IC 50 values of 5.03–13.2 μM (MAO-A) and 3.69–23.2 μM (MAO-B). These values are comparable to those recorded for 1,4-benzoquinone of 4.82 μM (MAO-A) and 10.2 μM (MAO-B). Of interest however, is the finding that the 1,4-benzoquinones are irreversible inhibitors of MAO-A since prolonged incubation results in near complete inhibition, and enzyme activity is not recovered by dialysis. MAO-B is much less sensitive to inactivation by the 1,4-benzoquinones. These findings are discussed with reference to a possible mechanism by which irreversible inhibition occurs. It may be concluded that irreversible 1,4-benzoquinone-derived inhibitors may act as probes for investigating quinone reactive sites in the MAOs. [ABSTRACT FROM AUTHOR]

The natural antioxidants of olive oil have phenolic structure and their activities are related to the formation of stable derivatives. In this study, the single components of the phenolic fraction of olive oil (1,4-hydroquinone, Semiquinone and 1,4-benzoquinone) have been studied as theoretical by using DFT (Density functional Theory). The behaviors of phenolic compounds of olive against to the alkyl peroxy radicals were investigated. Our data show that 1,4-benzoquinone is the best electron transfer agent in primary metabolic processes to human life. The frontier orbital gap, namely HOMO (highest occupied molecular orbital) eLUMO (lowest unoccupied molecular orbital) gap is the smallest for 1,4-benzoquinone. Hence, it is more stable than the others in blood. The natural phenolic compound's mechanism of many plants can be explained by using DFT method without consuming time and money. In this study, we have indicated the behaviors of natural antioxidants of olive oil's single components phenolic structure in blood phase. [ABSTRACT FROM AUTHOR]

The two-stage method for poly(methyl acrylate) grafting starch using triethylborane and 1,4-benzoquinone has been developed. The first stage was borylation of alcohol groups of starch. The second stage was polymerization of methyl acrylate in the inhibitor - 1,4-benzoquinone - presence accompanied by the S2-substitution at the boron atom. The advantages of developed method were the homogeneity of the process, the high yield of graft-copolymer, the possibility to control of chain length of synthetic polymer, and the absence of homopolymer in the final product. The molecular weight characteristics of starch-graft-poly(methyl acrylate) copolymer was determined by gel-permeation chromatography. The evidence of the graft-copolymer formation was B nuclear magnetic resonance data and its glass-transition temperature. The resulting graft-copolymer has an amphiphilic nature and a high thermal stability compared to the corresponding homopolymers (starch and poly(methyl acrylate)). According to the calculated values of the surface Gibbs energy the surface of starch-graft-poly(methyl acrylate) films is characterized as a high-energy surface. [ABSTRACT FROM AUTHOR]

Copolymerization of N-vinylpyrrolidone with vinyl acetate in the presence of tributylborane and 1,4-benzoquinone has been investigated. The curves of copolymer composition and relative reactivity of monomers were obtained. An introduction of tributylborane in the monomer mixture leads to the formation of complex with N-vinylpyrrolidone. Molecular weight of the copolymers and the rate of the copolymerization decreases with the addition of tributylborane and 1,4-benzoquinone compare to conventional copolymerization initiated by dicyclohexyl peroxydicarbonate. The curve of the copolymer composition acquires an S-shape. Triad composition of the copolymers differs from the theoretical values. The reason for the observed pheno mena is realization of the effect of preferential solvation (bootstrap-effect). [ABSTRACT FROM AUTHOR]

The bromination reaction of p -benzoquinone-fused norbornadiene was studied at various temperatures (−78, −50, 0, 25, and 77 °C). At room temperature, the double bonds of the p- benzoquinone units were mainly brominated. The double bond of the norbornene unit also underwent a bromination reaction in a yield of only 2%. However, the reaction at −78 °C resulted in the formation of products derived from the attack of bromine on the norbornene double bond with higher charge density. In contrast to the bromination reaction, the epoxidation reaction of the same compound with m -chloroperbenzoic acid and dimethyldioxirane exclusively resulted in the formation of products derived from the addition to the double bond of norbornadiene. The regioselectivity observed was investigated and the results were supported by theoretical calculations. [ABSTRACT FROM AUTHOR]

A series of 1,4-benzoquinones was prepared in a high yield by a two-step reaction starting from 2,3,4,5-tetramethoxytoluene by a Blanc reaction and subsequent oxidation. [ABSTRACT FROM AUTHOR]