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Sample records for quinone

  1. Quinone

    Integrated Risk Information System (IRIS)

    Quinone ; CASRN 106 - 51 - 4 Human health assessment information on a chemical substance is included in the IRIS database only after a comprehensive review of toxicity data , as outlined in the IRIS assessment development process . Sections I ( Health Hazard Assessments for Noncarcinogenic Effects )

  2. Quinone Reductase 2 Is a Catechol Quinone Reductase

    SciTech Connect

    Fu, Yue; Buryanovskyy, Leonid; Zhang, Zhongtao

    2008-09-05

    The functions of quinone reductase 2 have eluded researchers for decades even though a genetic polymorphism is associated with various neurological disorders. Employing enzymatic studies using adrenochrome as a substrate, we show that quinone reductase 2 is specific for the reduction of adrenochrome, whereas quinone reductase 1 shows no activity. We also solved the crystal structure of quinone reductase 2 in complexes with dopamine and adrenochrome, two compounds that are structurally related to catecholamine quinones. Detailed structural analyses delineate the mechanism of quinone reductase 2 specificity toward catechol quinones in comparison with quinone reductase 1; a side-chain rotational difference between quinone reductase 1 and quinone reductase 2 of a single residue, phenylalanine 106, determines the specificity of enzymatic activities. These results infer functional differences between two homologous enzymes and indicate that quinone reductase 2 could play important roles in the regulation of catecholamine oxidation processes that may be involved in the etiology of Parkinson disease.

  3. Activity of quinone alkylating agents in quinone-resistant cells.

    PubMed

    Begleiter, A; Leith, M K

    1990-05-15

    The role of the quinone group in the antitumor activity of quinone alkylating agents, such as mitomycin C and 2,5-diaziridinyl-3,5-bis(carboethoxyamino)-1,4-benzoquinone, is still uncertain. The quinone group may contribute to antitumor activity by inducing DNA strand breaks through the formation of free radicals and/or by influencing the alkylating activity of the quinone alkylators. The cytotoxic activity and DNA damage produced by the model quinone alkylating agents, benzoquinone mustard and benzoquinone dimustard, were compared in L5178Y murine lymphoblasts sensitive and resistant to the model quinone antitumor agent, hydrolyzed benzoquinone mustard. The resistant cell lines, L5178Y/HBM2 and L5178Y/HBM10, have increased concentrations of glutathione and elevated catalase, superoxide dismutase, glutathione S-transferase, and DT-diaphorase activity. L5178Y/HBM2 and L5178Y/HBM10 cells were 7.4- and 8.5-fold less sensitive to benzoquinone mustard and 1.7- and 4.3-fold less sensitive to benzoquinone dimustard, respectively, compared with sensitive cells, but showed no resistance to the non-quinone alkylating agent, aniline mustard. The formation of DNA double strand breaks by benzoquinone mustard was reduced by 2- and 8-fold in L5178Y/HBM2 and L5178Y/HBM10 cells, respectively, while double strand break formation by benzoquinone dimustard was reduced only in the L5178Y/HBM10 cells. The number of DNA-DNA cross-links produced by benzoquinone mustard was 3- and 6-fold lower, and the number produced by benzoquinone dimustard was 35% and 2-fold lower in L5178Y/HBM2 and L5178Y/HBM10 cells, respectively, compared with L5178Y parental cells. In contrast, cross-linking by aniline mustard was unchanged in sensitive and resistant cells. Dicoumarol, an inhibitor of DT-diaphorase, increased the cytotoxic activity of both benzoquinone mustard and benzoquinone dimustard in L5178Y/HBM10 cells. This study provides evidence that elevated DT-diaphorase activity in the resistant cells

  4. Synthetic Strategies to Terpene Quinones/Hydroquinones

    PubMed Central

    Gordaliza, Marina

    2012-01-01

    The cytotoxic and antiproliferative properties of many natural sesquiterpene-quinones and -hydroquinones from sponges offer promising opportunities for the development of new drugs. A review dealing with different strategies for obtaining bioactive terpenyl quinones/hydroquinones is presented. The different synthetic approches for the preparation of the most relevant quinones/hydroquinones are described. PMID:22412807

  5. Benzofuran-, benzothiophene-, indazole- and benzisoxazole- quinones: excellent substrates for NAD(P)H:quinone oxidoreductase 1

    PubMed Central

    Newsome, Jeffery J.; Hassani, Mary; Swann, Elizabeth; Bibby, Jane M.; Beall, Howard D.; Moody, Christopher J.

    2013-01-01

    A series of heterocyclic quinones based on benzofuran, benzothiophene, indazole and benzisoxazole has been synthesized, and evaluated for their ability to function as substrates for recombinant human NAD(P)H:quinone oxidoreductase (NQO1), a two-electron reductase upregulated in tumor cells. Overall, the quinones are excellent substrates for NQO1, approaching the reduction rates observed for menadione PMID:23635904

  6. Quinone Photoreactivity: An Undergraduate Experiment in Photochemistry

    ERIC Educational Resources Information Center

    Vaughan, Pamela P.; Cochran, Michael; Haubrich, Nicole

    2010-01-01

    An experiment exploring the photochemical properties of quinones was developed. Their unique photochemistry and highly reactive nature make them an ideal class of compounds for examining structure-activity relationships. For several substituted quinones, photochemical reactivity was related to structure and ultimately to the Gibbs energy for…

  7. Quinone Photoreactivity: An Undergraduate Experiment in Photochemistry

    ERIC Educational Resources Information Center

    Vaughan, Pamela P.; Cochran, Michael; Haubrich, Nicole

    2010-01-01

    An experiment exploring the photochemical properties of quinones was developed. Their unique photochemistry and highly reactive nature make them an ideal class of compounds for examining structure-activity relationships. For several substituted quinones, photochemical reactivity was related to structure and ultimately to the Gibbs energy for…

  8. Quinone project. Progress report. [Poly(acene quinone)

    SciTech Connect

    Rickert, S.E.

    1986-01-10

    This report is divided into sections appropriate for the four publications which were or will soon be published from this research. Additional references and information can be obtained from these papers. The basic premise behind this work has been, and continues to be, the preparation of stable electronic polymeric conductors, which have reversible, high capacity, oxidation-reduction characteristics. The heavy synthetic component to the initial papers is unavoidable, as new ground needed to be broken in synthetic methods for all compounds studied. Unfortunately, previous investigators had not done a thorough job of studying the complexities of these 'simple' reactions. In the next year, high quality, high capacity films and fibers of both PBHQ and poly(acene quinones) should be produced. 4 refs.

  9. Effects of several quinones on insulin aggregation.

    PubMed

    Gong, Hao; He, Zihao; Peng, Anlin; Zhang, Xin; Cheng, Biao; Sun, Yue; Zheng, Ling; Huang, Kun

    2014-07-10

    Protein misfolding and aggregation are associated with more than twenty diseases, such as neurodegenerative diseases and metabolic diseases. The amyloid oligomers and fibrils may induce cell membrane disruption and lead to cell apoptosis. A great number of studies have focused on discovery of amyloid inhibitors which may prevent or treat amyloidosis diseases. Polyphenols have been extensively studied as a class of amyloid inhibitors, with several polyphenols under clinical trials as anti-neurodegenerative drugs. As oxidative intermediates of natural polyphenols, quinones widely exist in medicinal plants or food. In this study, we used insulin as an amyloid model to test the anti-amyloid effects of four simple quinones and four natural anthraquinone derivatives from rhubarb, a traditional herbal medicine used for treating Alzheimer's disease. Our results demonstrated that all eight quinones show inhibitory effects to different extent on insulin oligomerization, especially for 1,4-benzoquinone and 1,4-naphthoquinone. Significantly attenuated oligomerization, reduced amount of amyloid fibrils and reduced hemolysis levels were found after quinones treatments, indicating quinones may inhibit insulin from forming toxic oligomeric species. The results suggest a potential action of native anthraquinone derivatives in preventing protein misfolding diseases, the quinone skeleton may thus be further explored for designing effective anti-amyloidosis compounds.

  10. Quinone-Catalyzed Selective Oxidation of Organic Molecules

    PubMed Central

    Wendlandt, Alison E.

    2016-01-01

    Lead In Quinones are common stoichiometric reagents in organic chemistry. High potential para-quinones, such as DDQ and chloranil, are widely used and typically promote hydride abstraction. In recent years, many catalytic applications of these methods have been achieved by using transition metals, electrochemistry or O2 to regenerate the oxidized quinone in situ. Complementary studies have led to the development of a different class of quinones that resemble the ortho-quinone cofactors in Copper Amine Oxidases and mediate efficient and selective aerobic and/or electrochemical dehydrogenation of amines. The latter reactions typically proceed via electrophilic transamination and/or addition-elimination reaction mechanisms, rather than hydride abstraction pathways. The collective observations show that the quinone structure has a significant influence on the reaction mechanism and have important implications for the development of new quinone reagents and quinone-catalyzed transformations. PMID:26530485

  11. Bacterial growth response to photoactive quinones.

    PubMed

    Vaughan, Pamela P; Novotny, Paul; Haubrich, Nicole; McDonald, Luther; Cochran, Michael; Serdula, Julia; Amin, Raid W; Jeffrey, Wade H

    2010-01-01

    Quinones are known producers of reactive oxygen species (ROS) that may be toxic in natural aquatic environments. In this study, the effects of parent quinones and their photodegradation products on bacterial growth were determined, and photochemical ROS formation rates were measured. Using (3)H-leucine incorporation to measure growth of the bacterium Pseudomonas aeruginosa and natural seawater bacterioplankton, growth inhibition was observed when samples were exposed to dichlone, chloranil and sodium anthraquinone-2-sulfonate (AQ2S). For seawater, compared with other quinones tested, dichlone showed the greatest toxicity in the dark, and AQ2S toxicity was greatest during simultaneous exposure to sunlight. Photodegraded chloranil and dichlone showed decreased toxicity compared with nonirradiated samples. For P. aeruginosa, AQ2S and its photodegradation products showed the greatest toxicity during simultaneous exposure to sunlight. Chloranil photodegradation products showed reduced toxicity compared with the parent compound during simultaneous exposure to sunlight. Dichlone was the only compound to show any toxicity to P. aeruginosa in the dark, and its photodegradation products were more toxic than the parent compound. Based on the results of dark and light controlled experiments measuring bacterial growth and estimated ROS production rates, ROS alone does not account for relative differences in toxicity between these quinones. © 2010 The Authors. Journal Compilation. The American Society of Photobiology.

  12. Benzofuran-, benzothiophene-, indazole- and benzisoxazole-quinones: excellent substrates for NAD(P)H:quinone oxidoreductase 1.

    PubMed

    Newsome, Jeffery J; Hassani, Mary; Swann, Elizabeth; Bibby, Jane M; Beall, Howard D; Moody, Christopher J

    2013-06-01

    A series of heterocyclic quinones based on benzofuran, benzothiophene, indazole and benzisoxazole has been synthesized, and evaluated for their ability to function as substrates for recombinant human NAD(P)H:quinone oxidoreductase (NQO1), a two-electron reductase upregulated in tumor cells. Overall, the quinones are excellent substrates for NQO1, approaching the reduction rates observed for menadione.

  13. Isoprenoid quinones and fatty acids of Zoogloea.

    PubMed

    Hiraishi, A; Shin, Y K; Sugiyama, J; Komagata, K

    1992-04-01

    Nine Zoogloea strains including the type strain of Z. ramigera (IAM 12136 = ATCC 19544 = N.C. Dondero 106) and newly isolated strains were investigated for isoprenoid quinone composition and whole-cell fatty acid profiles. Seven of the tested strains, having phenotypic properties typical of Zoogloea, were characterized by their production of both ubiquinone-8 and rhodoquinone-8 as major quinones, whereas the remaining two strains, Z. ramigera IAM 12669 (= K. Crabtree I-16-M) and IAM 12670 (= P.R. Dugan 115), formed ubiquinone-10 and ubiquinone-8, respectively, as the sole quinone. All rhodoquinone-producing strains contained palmitoleic acid and 3-hydroxy-decanoic acid as the major components of nonpolar and hydroxylated fatty acids, respectively. Marked differences were noted in the fatty acid composition between the strains with and without rhodoquinones. The chemotaxonomic data suggested that the rhodoquinone-lacking strains should be excluded from the genus Zoogloea. Since there have been no reliable taxonomic tools for Zoogloea, rhodoquinone analysis may provide a new criterion of great promise for identifying Zoogloea strains.

  14. Quinone emissions from gasoline and diesel motor vehicles.

    PubMed

    Jakober, Chris A; Riddle, Sarah G; Robert, Michael A; Destaillats, Hugo; Charles, M Judith; Green, Peter G; Kleeman, Michael J

    2007-07-01

    Gas- and particle-phase emissions from gasoline and diesel vehicles operated on chassis dynamometers were collected using annular denuders, quartz filters, and PUF substrates. Quinone species were measured using O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine derivatization in conjunction with gas chromatography-mass spectrometry and high-performance liquid chromatography-mass spectrometry. Nine quinones were observed, ranging from C6 to C16. New species identified in motor vehicle exhaust include methyl-1,4-benzoquinone, 2-methyl-1,4-naphthoquinone (MNQN), and aceanthrenequinone. Gas-phase motor vehicle emissions of quinones are also reported for the first time. Six gas-phase quinones were quantified with emission rates of 2-28 000 microg L(-1) fuel consumed. The most abundant gas-phase quinones were 1,4-benzoquinone (BON) and MNQN. The gas-phase fraction was > or = 69% of quinone mass for light-duty gasoline emissions, and > or = 84% for heavy-duty diesel emissions. Eight particle-phase quinones were observed between 2 and 1600 microg L(-1), with BQN the most abundant species followed by 9,10-phenanthrenequinone and 1,2-naphthoquinone. Current particle-phase quinone measurements agree well with the few available previous results. Further research is needed concerning the gas-particle partitioning behavior of quinones in ambient and combustion source conditions.

  15. Hurdles to organic quinone flow cells. Electrode passivation by quinone reduction in acetonitrile Li electrolytes

    NASA Astrophysics Data System (ADS)

    Rueda-García, D.; Dubal, D. P.; Huguenin, F.; Gómez-Romero, P.

    2017-05-01

    The uses of quinones in Redox Flow Batteries (RFBs) has been mainly circumscribed to aqueous solutions (of derivatives with polar groups) despite a larger solubility and wider electrochemical window provided by organic media. The redox mechanism of quinones in protic media is simpler and better known than in aprotic media, where radical species are involved. This paper reports the behaviour of methyl-p-benzoquinone (MBQ) under electrochemical reduction conditions in a LiClO4sbnd CH3CN electrolyte and various working electrodes. We detected the reversible generation of a bright green coating on the working electrode and the subsequent formation of a polymer (the nature of which depends on the presence or absence of oxygen). These coatings prevent the regular redox process of methyl-p-benzoquinone from taking place on the surface of the electrode and is generated regardless of the electrode material used or the presence of O2 in solution. In addition to MBQ, the green passivating layer was also found for less sterically hindered quinones such as p-benzoquinone or 1,4-naphthoquinone, but not for anthraquinone. We have also shown the central role of Li+ in the formation of this green layer. This work provides important guidelines for the final use of quinones in RFBs with organic electrolytes.

  16. Reactivities of Quinone Methides versus o-Quinones in Catecholamine Metabolism and Eumelanin Biosynthesis

    PubMed Central

    Sugumaran, Manickam

    2016-01-01

    Melanin is an important biopolymeric pigment produced in a vast majority of organisms. Tyrosine and its hydroxylated product, dopa, form the starting material for melanin biosynthesis. Earlier studies by Raper and Mason resulted in the identification of dopachrome and dihydroxyindoles as important intermediates and paved way for the establishment of well-known Raper–Mason pathway for the biogenesis of brown to black eumelanins. Tyrosinase catalyzes the oxidation of tyrosine as well as dopa to dopaquinone. Dopaquinone thus formed, undergoes intramolecular cyclization to form leucochrome, which is further oxidized to dopachrome. Dopachrome is either converted into 5,6-dihydroxyindole by decarboxylative aromatization or isomerized into 5,6-dihydroxyindole-2-carboxylic acid. Oxidative polymerization of these two dihydroxyindoles eventually produces eumelanin pigments via melanochrome. While the role of quinones in the biosynthetic pathway is very well acknowledged, that of isomeric quinone methides, however, remained marginalized. This review article summarizes the key role of quinone methides during the oxidative transformation of a vast array of catecholamine derivatives and brings out the importance of these transient reactive species during the melanogenic process. In addition, possible reactions of quinone methides at various stages of melanogenesis are discussed. PMID:27657049

  17. Reactivities of Quinone Methides versus o-Quinones in Catecholamine Metabolism and Eumelanin Biosynthesis.

    PubMed

    Sugumaran, Manickam

    2016-09-20

    Melanin is an important biopolymeric pigment produced in a vast majority of organisms. Tyrosine and its hydroxylated product, dopa, form the starting material for melanin biosynthesis. Earlier studies by Raper and Mason resulted in the identification of dopachrome and dihydroxyindoles as important intermediates and paved way for the establishment of well-known Raper-Mason pathway for the biogenesis of brown to black eumelanins. Tyrosinase catalyzes the oxidation of tyrosine as well as dopa to dopaquinone. Dopaquinone thus formed, undergoes intramolecular cyclization to form leucochrome, which is further oxidized to dopachrome. Dopachrome is either converted into 5,6-dihydroxyindole by decarboxylative aromatization or isomerized into 5,6-dihydroxyindole-2-carboxylic acid. Oxidative polymerization of these two dihydroxyindoles eventually produces eumelanin pigments via melanochrome. While the role of quinones in the biosynthetic pathway is very well acknowledged, that of isomeric quinone methides, however, remained marginalized. This review article summarizes the key role of quinone methides during the oxidative transformation of a vast array of catecholamine derivatives and brings out the importance of these transient reactive species during the melanogenic process. In addition, possible reactions of quinone methides at various stages of melanogenesis are discussed.

  18. Biochemistry: is pyrroloquinoline quinone a vitamin?

    PubMed

    Rucker, Robert; Storms, David; Sheets, Annemarie; Tchaparian, Eskouhie; Fascetti, Andrea

    2005-02-03

    The announcement by Kasahara and Kato of pyrroloquinoline quinone (PQQ) as a 'new' vitamin has received considerable attention. We have since attempted to reproduce the findings on which their conclusion is based, namely that defects in lysine metabolism occur in PQQ-deprived rodents. However, we find that the activity of alpha-aminoadipic acid-delta-semialdehyde (AAS) dehydrogenase in liver and plasma levels of alpha-aminoadipic acid (AAA), both of which act as indicators of lysine degradation in mammals, are not affected by changes in PQQ dietary status. Our results call into question the identification of PQQ as a new vitamin.

  19. Theoretical study of the adsorption of DOPA-quinone and DOPA-quinone chlorides on Cu (1 0 0) surface

    NASA Astrophysics Data System (ADS)

    Chen, Shuang-Kou; Wang, Bo-Chu; Zhou, Tai-Gang; Huang, Wen-Zhang

    2011-07-01

    The marine mussel secreted adhesive proteins and could bind strongly to all kinds of surfaces. Studies indicated that there was an unusual amino acid 3,4-dihydroxy-L-phenylanine (DOPA). DOPA could be oxidized to DOPA-quinone easily, which had a superior ability to on surface directly. The technology of electrolyzing seawater was employed to generate HOCl solution to react with DOPA-quinone and form DOPA-quinone chlorides (DOPA-quinone-Cl) to hinder the adhesion. However, the detailed hinder-mechanism remained unknown to be fully explained. Herein, using quantum chemical density functional theory methods, we have systematically studied three kinds of adsorption for DOPA-quinone and DOPA-quinone-Cl on Cu (1 0 0) surface: hydroxyl oxygen-side vertical, carbonyl oxygen-side vertical, amino N-terminal vertical adsorptions and carried out geometry optimization and energy calculation. The results showed that two molecules could absorb on the Cu (1 0 0) through hydroxyl oxygen-side vertical adsorption, while the other two kinds of adsorption could not form an effective adsorption. Calculations of adsorption energy for hydroxyl oxygen-side vertical adsorption indicated that: after HOCl modification, adsorption energy decreased from -247.2310 kJ/mol to -177.0579 kJ/mol for DOPA-quinone and DOPA-quinone-Cl; and the Mulliken Charges Populations showed that the electrons transferred from surface to DOPA-quinone-Cl was less than that to DOPA-quinone, namely, the fewer the number of electrons transferred, the weaker interaction between molecular and surface. After the theoretical calculation, we found that the anti-foul goal had been achieved by electrolysis of seawater to generate HOCl to modify DOPA-quinone, which led to the reduction of adsorption energy and transferred electrons.

  20. Formation and Biological Targets of Quinones: Cytotoxic versus Cytoprotective Effects

    PubMed Central

    2016-01-01

    Quinones represent a class of toxicological intermediates, which can create a variety of hazardous effects in vivo including, acute cytotoxicity, immunotoxicity, and carcinogenesis. In contrast, quinones can induce cytoprotection through the induction of detoxification enzymes, anti-inflammatory activities, and modification of redox status. The mechanisms by which quinones cause these effects can be quite complex. The various biological targets of quinones depend on their rate and site of formation and their reactivity. Quinones are formed through a variety of mechanisms from simple oxidation of catechols/hydroquinones catalyzed by a variety of oxidative enzymes and metal ions to more complex mechanisms involving initial P450-catalyzed hydroxylation reactions followed by two-electron oxidation. Quinones are Michael acceptors, and modification of cellular processes could occur through alkylation of crucial cellular proteins and/or DNA. Alternatively, quinones are highly redox active molecules which can redox cycle with their semiquinone radical anions leading to the formation of reactive oxygen species (ROS) including superoxide, hydrogen peroxide, and ultimately the hydroxyl radical. Production of ROS can alter redox balance within cells through the formation of oxidized cellular macromolecules including lipids, proteins, and DNA. This perspective explores the varied biological targets of quinones including GSH, NADPH, protein sulfhydryls [heat shock proteins, P450s, cyclooxygenase-2 (COX-2), glutathione S-transferase (GST), NAD(P)H:quinone oxidoreductase 1, (NQO1), kelch-like ECH-associated protein 1 (Keap1), IκB kinase (IKK), and arylhydrocarbon receptor (AhR)], and DNA. The evidence strongly suggests that the numerous mechanisms of quinone modulations (i.e., alkylation versus oxidative stress) can be correlated with the known pathology/cytoprotection of the parent compound(s) that is best described by an inverse U-shaped dose–response curve. PMID:27617882

  1. Molecular mechanism of quinone signaling mediated through S-quinonization of a YodB family repressor QsrR

    PubMed Central

    Ji, Quanjiang; Zhang, Liang; Jones, Marcus B.; Sun, Fei; Deng, Xin; Liang, Haihua; Cho, Hoonsik; Brugarolas, Pedro; Gao, Yihe N.; Peterson, Scott N.; Lan, Lefu; Bae, Taeok; He, Chuan

    2013-01-01

    Quinone molecules are intracellular electron-transport carriers, as well as critical intra- and extracellular signals. However, transcriptional regulation of quinone signaling and its molecular basis are poorly understood. Here, we identify a thiol-stress-sensing regulator YodB family transcriptional regulator as a central component of quinone stress response of Staphylococcus aureus, which we have termed the quinone-sensing and response repressor (QsrR). We also identify and confirm an unprecedented quinone-sensing mechanism based on the S-quinonization of the essential residue Cys-5. Structural characterizations of the QsrR–DNA and QsrR–menadione complexes further reveal that the covalent association of menadione directly leads to the release of QsrR from operator DNA following a 10° rigid-body rotation as well as a 9-Å elongation between the dimeric subunits. The molecular level characterization of this quinone-sensing transcriptional regulator provides critical insights into quinone-mediated gene regulation in human pathogens. PMID:23479646

  2. A copper-induced quinone degradation pathway provides protection against combined copper/quinone stress in Lactococcus lactis IL1403.

    PubMed

    Mancini, Stefano; Abicht, Helge K; Gonskikh, Yulia; Solioz, Marc

    2015-02-01

    Quinones are ubiquitous in the environment. They occur naturally but are also in widespread use in human and industrial activities. Quinones alone are relatively benign to bacteria, but in combination with copper, they become toxic by a mechanism that leads to intracellular thiol depletion. Here, it was shown that the yahCD-yaiAB operon of Lactococcus lactis IL1403 provides resistance to combined copper/quinone stress. The operon is under the control of CopR, which also regulates expression of the copRZA copper resistance operon as well as other L. lactis genes. Expression of the yahCD-yaiAB operon is induced by copper but not by quinones. Two of the proteins encoded by the operon appear to play key roles in alleviating quinone/copper stress: YaiB is a flavoprotein that converts p-benzoquinones to less toxic hydroquinones, using reduced nicotinamide adenine dinucleotide phosphate (NADPH) as reductant; YaiA is a hydroquinone dioxygenase that converts hydroquinone putatively to 4-hydroxymuconic semialdehyde in an oxygen-consuming reaction. Hydroquinone and methylhydroquinone are both substrates of YaiA. Deletion of yaiB causes increased sensitivity of L. lactis to quinones and complete growth arrest under combined quinone and copper stress. Copper induction of the yahCD-yaiAB operon offers protection to copper/quinone toxicity and could provide a growth advantage to L. lactis in some environments.

  3. The quinones of benzocyclobutadiene: a computational study.

    PubMed

    Golas, Ewa; Lewars, Errol; Liebman, Joel F

    2009-08-27

    The conventional (excluding non-Kekulé, singlet diradical structures) quinones of benzocyclobutadiene were studied computationally. Eight structures were examined, namely (based on the CA names for benzocyclobutenedione), benzocyclobutenedione or bicyclo[4.2.0]octa-1,3,5-triene-7,8-dione, bicyclo[4.2.0]octa-3,5,8-triene-2,7-dione, bicyclo[4.2.0]octa-1,4,6-triene-3,8-dione, bicyclo[4.2.0]octa-1(6),4,7-triene-2,3-dione, bicyclo[4.2.0]octa-1(8), 4,6-triene-2,3-dione, bicyclo[4.2.0]octa-1(6),3,7-triene-2,5-dione, bicyclo[4.2.0]octa-1(8),3,6-triene-2,5-dione, and bicyclo[4.2.0]octa-1,5,7-triene-3,4-dione (the question of resonance or tautomerism for the 2,3-dione pair and the 2,5-dione pair is considered). Using DFT (B3LYP/6-31G*) and ab initio (MP2/6-31G*) methods the geometries of the eight species were optimized, giving similar results for the two methods. The heats of formation of the quinones were calculated, placing them in low-energy (-17 kJ mol(-1), 7,8-dione), medium-energy (79-137 kJ mol(-1), 2,7-, 3,8-, and 3,4-diones), and high-energy (260-275 kJ mol(-1), 2,3- and 2,5-diones) groups. Diels-Alder reactivity as dienophiles with butadiene indicated the 2,7-, 3,8-, and particularly the 3,4-quinone may be relatively unreactive toward dimerization or polymerization and are attractive synthesis goals. Isodesmic ring-opening reactions and NICS calculations showed aromatic/nonaromatic properties to be essentially as expected from the presence of a benzene or cyclobutadiene ring. UV spectra, ionization energy electron affinity, and HOMO/LUMO energies were also calculated.

  4. Quenching of chlorophyll fluorescence by quinones.

    PubMed

    Samuilov, V D; Borisov AYu; Barsky, E L; Borisova, O F; Kitashov, A V

    1998-10-01

    Quinones caused quenching of Chl a fluorescence in native and model systems. Menadione quenched twofold the fluorescence of Chl a and BChl a in pea chloroplasts, chromatophores of purple bacteria, and liposomes at concentrations of 50-80 microM. To obtain twofold quenching in Triton X-100 micelles and in ethanol, the addition of 1.3 mM and 11 mM menadione was required, respectively. A proportional decrease in the lifetime and yield of Chl a fluorescence in chloroplasts, observed as the menadione concentration increased, is indicative of the efficient excitation energy transfer from bulk Chl to menadione. The decrease in the lifetime and yield of fluorescence was close to proportional in liposomes, but not in detergent micelles. The insensitivity of the menadione quenching effect to DCMU in chloroplasts, and similarity of its action in chloroplasts and liposomes indicate that menadione in chloroplasts interacts with antenna Chl, i.e., nonphotochemical quenching of fluorescence occurs.

  5. NMR Reveals Double Occupancy of Quinone-type Ligands in the Catalytic Quinone Binding Site of the Na+-translocating NADH:Quinone Oxidoreductase from Vibrio cholerae*

    PubMed Central

    Nedielkov, Ruslan; Steffen, Wojtek; Steuber, Julia; Möller, Heiko M.

    2013-01-01

    The sodium ion-translocating NADH:quinone oxidoreductase (Na+-NQR) from the pathogen Vibrio cholerae exploits the free energy liberated during oxidation of NADH with ubiquinone to pump sodium ions across the cytoplasmic membrane. The Na+-NQR consists of four membrane-bound subunits NqrBCDE and the peripheral NqrF and NqrA subunits. NqrA binds ubiquinone-8 as well as quinones with shorter prenyl chains (ubiquinone-1 and ubiquinone-2). Here we show that the quinone derivative 2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), a known inhibitor of the bc1 and b6f complexes found in mitochondria and chloroplasts, also inhibits quinone reduction by the Na+-NQR in a mixed inhibition mode. Tryptophan fluorescence quenching and saturation transfer difference NMR experiments in the presence of Na+-NQR inhibitor (DBMIB or 2-n-heptyl-4-hydroxyquinoline N-oxide) indicate that two quinone analog ligands are bound simultaneously by the NqrA subunit with very similar interaction constants as observed with the holoenzyme complex. We conclude that the catalytic site of quinone reduction is located on NqrA. The two ligands bind to an extended binding pocket in direct vicinity to each other as demonstrated by interligand Overhauser effects between ubiquinone-1 and DBMIB or 2-n-heptyl-4-hydroxyquinoline N-oxide, respectively. We propose that a similar spatially close arrangement of the native quinone substrates is also operational in vivo, enhancing the catalytic efficiency during the final electron transfer steps in the Na+-NQR. PMID:24003222

  6. [Quinones and their interactions with enzyme complexes of energy-transducing biomembranes].

    PubMed

    Oleskin, A V; Samuilov, V D

    1988-10-01

    The functionally essential properties of biomembrane quinones and the mechanism of their interaction with protein components are discussed. The hypotheses on the mobile quinone pool or the ability of protein-bound quinones to transfer redox equivalents in biomembranes are discussed. The idea of quinone domains is invoked, and evidence is provided for the presence of such domains in operative biomembranes.

  7. ortho-Quinone methides as key intermediates in cascade heterocyclizations

    NASA Astrophysics Data System (ADS)

    Osipov, D. V.; Osyanin, V. A.; Klimochkin, Yu N.

    2017-07-01

    Development of new methods of heterocyclic synthesis is still a topical issue. In this connection, the trend related to the use of highly reactive o-quinone methides for the synthesis and functionalization of heterocycles appears rather promising. Since most of o-quinone methides are unstable, the choice of precursors and generation conditions is highly important for subsequent transformations involving them. Various methods of generation of o-quinone methides and cascade heterocyclizations in which the formation of these compounds is a key step are surveyed in the review. The trends of using o-quinone methides in the synthesis of various heterocycles are analyzed and the heterocyclization reactions involving these compounds are classified. The bibliography includes 395 references.

  8. Characterization of the quinones in purple sulfur bacterium Thermochromatium tepidum.

    PubMed

    Kimura, Yuuka; Kawakami, Tomoaki; Yu, Long-Jiang; Yoshimura, Miku; Kobayashi, Masayuki; Wang-Otomo, Zheng-Yu

    2015-07-08

    Quinone distributions in the thermophilic purple sulfur bacterium Thermochromatium tepidum have been investigated at different levels of the photosynthetic apparatus. Here we show that, on average, the intracytoplasmic membrane contains 18 ubiquinones (UQ) and 4 menaquinones (MQ) per reaction center (RC). About one-third of the quinones are retained in the light-harvesting-reaction center core complex (LH1-RC) with a similar ratio of UQ to MQ. The numbers of quinones essentially remains unchanged during crystallization of the LH1-RC. There are 1-2 UQ and 1 MQ associated with the RC-only complex in the purified solution sample. Our results suggest that a large proportion of the quinones are confined to the core complex and at least five UQs remain invisible in the current LH1-RC crystal structure. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  9. Production and Radioprotective Effects of Pyrroloquinoline Quinone

    PubMed Central

    Xiong, Xiang-Hua; Zhao, Yan; Ge, Xin; Yuan, Shou-Jun; Wang, Jian-Hua; Zhi, Jing-Juan; Yang, Yan-Xin; Du, Bao-Hua; Guo, Wan-Jun; Wang, Shan-Shan; Yang, De-Xuan; Zhang, Wei-Cai

    2011-01-01

    Pyrroloquinoline quinone (PQQ) was produced by fermentation of the Methylovorus sp. MP688 strain and purified by ion-exchange chromatography, crystallization and recrystallization. The yield of PQQ reached approximately 125 mg/L and highly pure PQQ was obtained. To determine the optimum dose of PQQ for radioprotection, three doses (2 mg/kg, 4 mg/kg, 8 mg/kg) of PQQ were orally administrated to the experimental animals subjected to a lethal dose of 8.0 Gy in survival test. Survival of mice in the irradiation + PQQ (4 mg/kg) group was found to be significantly higher in comparison with the irradiation and irradiation + nilestriol (10 mg/kg) groups. The numbers of hematocytes and bone marrow cells were measured for 21 days after sublethal 4 Gy gamma-ray irradiation with per os of 4 mg/kg of PQQ. The recovery of white blood cells, reticulocytes and bone marrow cells in the irradiation + PQQ group was faster than that in the irradiation group. Furthermore, the recovery of bone marrow cell in the irradiation + PQQ group was superior to that in irradiation + nilestriol group. Our results clearly indicate favourable effects on survival under higher lethal radiation doses and the ability of pyrroloquinoline quinine to enhance haemopoietic recovery after sublethal radiation exposure. PMID:22272111

  10. Quinone-induced protein handling changes: Implications for major protein handling systems in quinone-mediated toxicity

    SciTech Connect

    Xiong, Rui; Siegel, David; Ross, David

    2014-10-15

    Para-quinones such as 1,4-Benzoquinone (BQ) and menadione (MD) and ortho-quinones including the oxidation products of catecholamines, are derived from xenobiotics as well as endogenous molecules. The effects of quinones on major protein handling systems in cells; the 20/26S proteasome, the ER stress response, autophagy, chaperone proteins and aggresome formation, have not been investigated in a systematic manner. Both BQ and aminochrome (AC) inhibited proteasomal activity and activated the ER stress response and autophagy in rat dopaminergic N27 cells. AC also induced aggresome formation while MD had little effect on any protein handling systems in N27 cells. The effect of NQO1 on quinone induced protein handling changes and toxicity was examined using N27 cells stably transfected with NQO1 to generate an isogenic NQO1-overexpressing line. NQO1 protected against BQ–induced apoptosis but led to a potentiation of AC- and MD-induced apoptosis. Modulation of quinone-induced apoptosis in N27 and NQO1-overexpressing cells correlated only with changes in the ER stress response and not with changes in other protein handling systems. These data suggested that NQO1 modulated the ER stress response to potentiate toxicity of AC and MD, but protected against BQ toxicity. We further demonstrated that NQO1 mediated reduction to unstable hydroquinones and subsequent redox cycling was important for the activation of the ER stress response and toxicity for both AC and MD. In summary, our data demonstrate that quinone-specific changes in protein handling are evident in N27 cells and the induction of the ER stress response is associated with quinone-mediated toxicity. - Highlights: • Unstable hydroquinones contributed to quinone-induced ER stress and toxicity.

  11. Pyrroloquinoline quinone: Metabolism and analytical methods

    SciTech Connect

    Smidt, C.R.

    1990-01-01

    Pyrroloquinoline quinone (PQQ) functions as a cofactor for bacterial oxidoreductases. Whether or not PQQ serves as a cofactor in higher plants and animals remains controversial. Nevertheless, strong evidence exists that PQQ has nutritional importance. In highly purified, chemically defined diets PQQ stimulates animal growth. Further PQQ deprivation impairs connective tissue maturation, particularly when initiated in utero and throughout perinatal development. The study addresses two main objectives: (1) to elucidate basic aspects of the metabolism of PQQ in animals, and (2) to develop and improve existing analytical methods for PQQ. To study intestinal absorption of PQQ, ten mice were administered [[sup 14]C]-PQQ per os. PQQ was readily absorbed (62%) in the lower intestine and was excreted by the kidney within 24 hours. Significant amounts of labeled-PQQ were retained only by skin and kidney. Three approaches were taken to answer the question whether or not PQQ is synthesized by the intestinal microflora of mice. First, dietary antibiotics had no effect on fecal PQQ excretion. Then, no bacterial isolates could be identified that are known to synthesize PQQ. Last, cecal contents were incubated anaerobically with radiolabeled PQQ-precursors with no label appearing in isolated PQQ. Thus, intestinal PQQ synthesis is unlikely. Analysis of PQQ in biological samples is problematic since PQQ forms adducts with nucleophilic compounds and binds to the protein fraction. Existing analytical methods are reviewed and a new approach is introduced that allows for detection of PQQ in animal tissue and foods. PQQ is freed from proteins by ion exchange chromatography, purified on activated silica cartridges, detected by a colorimetric redox-cycling assay, and identified by mass spectrometry. That compounds with the properties of PQQ may be nutritionally important offers interesting areas for future investigation.

  12. Deep Learning to Predict the Formation of Quinone Species in Drug Metabolism.

    PubMed

    Hughes, Tyler B; Swamidass, S Joshua

    2017-02-20

    Many adverse drug reactions are thought to be caused by electrophilically reactive drug metabolites that conjugate to nucleophilic sites within DNA and proteins, causing cancer or toxic immune responses. Quinone species, including quinone-imines, quinone-methides, and imine-methides, are electrophilic Michael acceptors that are often highly reactive and comprise over 40% of all known reactive metabolites. Quinone metabolites are created by cytochromes P450 and peroxidases. For example, cytochromes P450 oxidize acetaminophen to N-acetyl-p-benzoquinone imine, which is electrophilically reactive and covalently binds to nucleophilic sites within proteins. This reactive quinone metabolite elicits a toxic immune response when acetaminophen exceeds a safe dose. Using a deep learning approach, this study reports the first published method for predicting quinone formation: the formation of a quinone species by metabolic oxidation. We model both one- and two-step quinone formation, enabling accurate quinone formation predictions in nonobvious cases. We predict atom pairs that form quinones with an AUC accuracy of 97.6%, and we identify molecules that form quinones with 88.2% AUC. By modeling the formation of quinones, one of the most common types of reactive metabolites, our method provides a rapid screening tool for a key drug toxicity risk. The XenoSite quinone formation model is available at http://swami.wustl.edu/xenosite/p/quinone .

  13. The Domestication of ortho-Quinone Methides

    PubMed Central

    2015-01-01

    Conspectus An ortho-quinone methide (o-QM) is a highly reactive chemical motif harnessed by nature for a variety of purposes. Given its extraordinary reactivity and biological importance, it is surprising how few applications within organic synthesis exist. We speculate that their widespread use has been slowed by the complications that surround the preparation of their precursors, the harsh generation methods, and the omission of this stratagem from computer databases due to its ephemeral nature. About a decade ago, we discovered a mild anionic triggering procedure to generate transitory o-QMs at low temperature from readily available salicylaldehydes, particularly OBoc derivatives. This novel reaction cascade included both the o-QM formation and the subsequent consumption reaction. The overall transformation was initiated by the addition of the organometallic reagent, usually a Grignard reagent, which resulted in the formation of a benzyloxy alkoxide. Boc migration from the neighboring phenol produced a magnesium phenoxide that we supposed underwent β-elimination of the transferred Boc residue to form an o-QM for immediate further reactions. Moreover, the cascade proved controllable through careful manipulation of metallic and temperature levers so that it could be paused, stopped, or restarted at various intermediates and stages. This new level of domestication enabled us to deploy o-QMs for the first time in a range of applications including diastereocontrolled reactions. This sequence ultimately could be performed in either multipot or single pot processes. The subsequent reaction of the fleeting o-QM intermediates included the 1,4-conjugate additions that led to unbranched or branched ortho-alkyl substituted phenols and Diels–Alder reactions that provided 4-unsubstituted or 4-substituted benzopyrans and chroman ketals. The latter cycloadducts were obtained for the first time with outstanding diastereocontrol. In addition, the steric effects of the newly

  14. Friedel Craft's synthesis and characterization of some acene quinone compounds

    SciTech Connect

    Galleguillos, R.; Litt, M.; Rickert, S.E.

    1987-01-01

    The synthesis and characterization of some linear acene quinones of up to nine fused rings prepared by the Friedel-Craft's reaction of hydroquinone (HQ) and 1,4,9,10 tetrahydroxy anthracene (THA) with pyromellitic dianhydride (PMDA), and fused AlCl/sub 3/, was carried out. The intermediate product of the reaction of THA and PMDA, 1,4 dihydroxy anthraquinone, 6,7 dicarboxylic acid (DADCA) was also isolated and its synthesis optimized. This material was reduced to 1,4,9,10-tetrahydroxy anthracene 6,7-dicarboxylic acid (TADCA) and further dehydrated to its anhydride (TADCAmh). These compounds contain the necessary chemical functionalities which may lead to the facile synthesis of higher molecular weight quinones. These acene quinones show electronic spectral absorptions extending far into the NIR region, an indication of their long conjunction length.

  15. Electronic transport properties of a quinone-based molecular switch

    NASA Astrophysics Data System (ADS)

    Zheng, Ya-Peng; Bian, Bao-An; Yuan, Pei-Pei

    2016-09-01

    In this paper, we carried out first-principles calculations based on density functional theory and non-equilibrium Green's function to investigate the electronic transport properties of a quinone-based molecule sandwiched between two Au electrodes. The molecular switch can be reversibly switched between the reduced hydroquinone (HQ) and oxidized quinone (Q) states via redox reactions. The switching behavior of two forms is analyzed through their I- V curves, transmission spectra and molecular projected self-consistent Hamiltonian at zero bias. Then we discuss the transmission spectra of the HQ and Q forms at different bias, and explain the oscillation of current according to the transmission eigenstates of LUMO energy level for Q form. The results suggest that this kind of a quinone-based molecule is usable as one of the good candidates for redox-controlled molecular switches.

  16. Quinones as Strecker degradation reagents in wine oxidation processes.

    PubMed

    Oliveira, Carla Maria; Santos, Sónia A O; Silvestre, Armando J D; Barros, António S; Ferreira, António César Silva; Silva, Artur M S

    2017-08-01

    The Strecker aldehydes formed during the reaction between α-amino acids (phenylalanine or methionine) and either gallic acid, caffeic acid or (+)-catechin ortho-quinones were evaluated in wine-model systems. It was demonstrated that phenylacetaldehyde was formed by quinone intermediates at wine pH. The highest amounts of phenylacetaldehyde during the 10days of experiment (69±5µg/L/day; 7x>Control) were obtained from (+) catechin, followed by gallic acid (61±4µg/L/day; 6x>Control) and caffeic acid (41±4µg/L/day; 4x>Control). The intermediate structures delivered from the reaction of ortho-quinones with α-amino acids were demonstrated by MS(n). Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Multicomponent Condensation Reactions via ortho-Quinone Methides.

    PubMed

    Allen, Emily E; Zhu, Calvin; Panek, James S; Schaus, Scott E

    2017-03-30

    Iron(III) salts promote the condensation of aldehydes or acetals with electron-rich phenols to generate ortho-quinone methides that undergo Diels-Alder condensations with alkenes. The reaction sequence occurs in a single vessel to afford benzopyrans in up to 95% yield. The reaction was discovered while investigating a two-component strategy using 2-(hydroxy(phenyl)methyl)phenols to access the desired ortho-quinone methide in a Diels-Alder condensation. The two-component condensation also afforded the corresponding benzopyran products in yields up to 97%. Taken together, the two- and three-component strategies using ortho-quinone methide intermediates provide efficient access to benzopyrans in good yields and selectivities.

  18. Xenobiotic induction of quinone oxidoreductase activity in lens epithelial cells.

    PubMed

    Tumminia, S J; Rao, P V; Zigler, J S; Russell, P

    1993-12-08

    Xenobiotic regulatory elements have been identified for enzymes which ameliorate oxidative damage in cells. Zeta (zeta)-crystallin, a taxon-specific enzyme/crystallin shown to be a novel NADPH-dependent quinone reductase, is found in a number of tissues and cell types. This study shows that zeta-crystallin is present in mouse lens epithelium, as well as in the alpha TN4 mouse lens epithelial cell line. To determine whether zeta-crystallin is an inducible quinone reductase, cell cultures were exposed to the xenobiotics, 1,2-naphthoquinone and beta-naphthoflavone. Assays of cellular homogenates showed that quinone reductase activity was stimulated greater than 70% and 90%, respectively, over the control cells. This observed activity was sensitive to dicumarol, a potent inhibitor of quinone reductase activity. 1,2-Naphthoquinone- and beta-naphthoflavone-exposed cells were found to exhibit 1.47- and 1.68-fold increases, respectively, in zeta-crystallin protein concentration. A comparable increase in zeta-crystallin mRNA was indicative of an induction in zeta-crystallin expression in response to naphthalene challenge. Lens epithelial cells were also checked for DT-diaphorase, a well-known cellular protective enzyme which can catalyze the two-electron reduction of quinones. Slot blot analyses indicated that alpha TN4 cells exposed to 1,2-naphthoquinone and beta-naphthoflavone exhibited 2.71- and 6.81-fold increases in DT-diaphorase concentration when compared to the control cells. The data suggest that while DT-diaphorase is most likely responsible for the majority of the observed increase in quinone reductase activity, the zeta-crystallin gene also undergoes activation which is apparently mediated by a xenobiotic-responsive element.

  19. Chlorophyll-quinone photochemical electron transfer in liposomes

    SciTech Connect

    Hurley, J.K.; Castelli, F.; Tollin, G.

    1981-09-01

    A study is described which involves the reduction of electron acceptors (quinones) by photoexcited chlorophyll (Chl). The experimental samples consisted of Chl a (from spinach) incorporated into phosphatidylcholine (either synthetic or from hen egg yolks) liposomes suspended in 10 mM phosphate buffer (pH 7.0). The quinones were either present during liposome formation or added later, depending on their water solubility. The measurement technique employed was laser flash photolysis. Results have provided considerable insight into the ways in which membranes may modify the photochemical properties of Chl by allowing molecular compartmentalization and by permitting cooperative interactions.

  20. Process for Preparing Microcapsules Having Gelatin Walls Crosslinked with Quinone.

    DTIC Science & Technology

    A process for conveniently producing microcapsules containing a gelatin wall crosslinked with quinone and a core of an active compound such as a...provides microcapsules of excellent strength, storage stability, and resistance to aqueous exposure, such that the rate of release of the fouling reducing agent can be controlled with precision. jg

  1. Quinone Reductase Induction as a Biomarker for Cancer Chemoprevention⊥

    PubMed Central

    Cuendet, Muriel; Oteham, Carol P.; Moon, Richard C.; Pezzuto, John M.

    2007-01-01

    Chemoprevention involves the use of natural or synthetic substances to reduce the risk of developing cancer. Strategies for protecting cells from initiation events include decreasing metabolic enzymes responsible for generating reactive species (phase I enzymes) while increasing phase II enzymes that can deactivate radicals and electrophiles known to intercede in normal cellular processes. Reduction of electrophilic quinones by quinone reductase is an important detoxification pathway. Following evaluation of approximately 3000 plant and marine organism extracts, the number characterized as “active” was established in the range of 12% of the total, and over 60 active compounds have been isolated as quinone reductase inducers. One of them, isoliquiritigenin (1), isolated from tonka bean, was shown to be a monofunctional inducer by having similar quinone reductase inducing ability in wild-type Hepa 1c1c7 cells and two mutant cell lines. To further investigate the mechanism of induction, HepG2 human hepatoma cells stably transfected with ARE-luciferase plasmid were used. Isoliquiritigenin (1) significantly induced the luciferase activity in a dose-dependent manner. On the basis of these results, a full-term cancer chemoprevention study was conducted with 7,12-dimethylbenz[a]anthracene (DMBA)-treated female Sprague-Dawley rats. Dietary administration of 1 increased tumor latency. Based on these promising preliminary results, additional mechanistic studies are underway, as well as full-term carcinogenesis studies with chronic administration schedules. PMID:16562858

  2. Synthesis of azobenzenes from quinone acetals and arylhydrazines.

    PubMed

    Carreño, M Carmen; Mudarra, Gerardo Fernández; Merino, Estíbaliz; Ribagorda, María

    2004-05-14

    Direct reaction between quinone bisacetals and arylhydrazines gives azobenzenes. The presence of catalytic amounts of cerium ammonium nitrate strongly accelerates the reaction. When the bisacetal has a substituent at the 2,5-cyclohexadiene framework, only one regioisomer is formed. The method represents a simple, mild, and novel synthetic access to differently substituted azocompounds in high to excellent yield.

  3. Removal of bisphenol derivatives through quinone oxidation by polyphenol oxidase and subsequent quinone adsorption on chitosan in the heterogeneous system.

    PubMed

    Kimura, Yuji; Takahashi, Ayumi; Kashiwada, Ayumi; Yamada, Kazunori

    2015-01-01

    In this study, the combined use of a biopolymer chitosan and an oxidoreductase polyphenol oxidase (PPO) was systematically investigated for the removal of bisphenol derivatives from aqueous medium. The process parameters, such as the pH value, temperature, and PPO concentration, were estimated to conduct the enzymatic quinone oxidation of bisphenol derivatives by as little enzyme as possible. Bisphenol derivatives effectively underwent PPO-catalysed quinone oxidation without H2O2 unlike other oxidoreductases, such as peroxidase and tyrosinase, and the optimum conditions were determined to be pH 7.0 and 40°C for bisphenol B, bisphenol E, bisphenol O, and bisphenol Z; pH 7.0 and 30°C for bisphenol C and bisphenol F; and pH 8.0 and 40°C for bisphenol T. They were completely removed through adsorption of enzymatically generated quinone derivatives on chitosan beads or chitosan powders. Quinone adsorption on chitosan beads or chitosan powders in the heterogeneous system was found to be a more effective procedure than generation of aggregates in the homogeneous system with chitosan solution. The removal time was shortened by increasing the amount of chitosan beads or decreasing the size of the chitosan powders.

  4. Uranium Exerts Acute Toxicity by Binding to Pyrroloquinoline Quinone Cofactor

    SciTech Connect

    Michael R. VanEngelen; Robert I. Szilagyi; Robin Gerlach; Brady E. Lee; William A. Apel; Brent M. Peyton

    2011-02-01

    Uranium as an environmental contaminant has been shown to be toxic to eukaryotes and prokaryotes; however, no specific mechanisms of uranium toxicity have been proposed so far. Here a combination of in vivo, in vitro, and in silico studies are presented describing direct inhibition of pyrroloquinoline quinone (PQQ)-dependent growth and metabolism by uranyl cations. Electrospray-ionization mass spectroscopy, UV-vis optical spectroscopy, competitive Ca2+/uranyl binding studies, relevant crystal structures, and molecular modeling unequivocally indicate the preferred binding of uranyl simultaneously to the carboxyl oxygen, pyridine nitrogen, and quinone oxygen of the PQQ molecule. The observed toxicity patterns are consistent with the biotic ligand model of acute metal toxicity. In addition to the environmental implications, this work represents the first proposed molecular mechanism of uranium toxicity in bacteria, and has relevance for uranium toxicity in many living systems.

  5. Two new quinones from the roots of Juglans mandshurica.

    PubMed

    Jin, Mei; Sun, Jinfeng; Li, Ren; Diao, Shengbao; Zhang, Changhao; Cui, Jiongmo; Son, Jong-Keun; Zhou, Wei; Li, Gao

    2016-09-01

    Two new quinones, 1-hydroxy-5-pentyl-anthraquinone (1) and 4-(5-hydroxy-1,4-dioxo-1,4-dihydro-naphthalen-2-ylamino)-butyric acid methyl ester (2), together with two known quinones, 5-hydroxy-2-(2-hydroxy-ethylamino)-(1,4) naphthoquinone (3) and juglone (4) were isolated from the roots of Juglans mandshurica (Juglandaceae). Their structures were elucidated on the basis of spectral data. Compound 3 was isolated from the Juglans genus for the first time. Compounds 1-4 exhibited significant cytotoxicity towards cultured MDA-MB231, HepG2 and SNU638 cells with IC50 values ranging from 4.46 to 88.47 μM.

  6. Selective synthesis of the para-quinone region of geldanamycin.

    PubMed

    Andrus, Merritt B; Hicken, Erik J; Meredith, Erik L; Simmons, Bryon L; Cannon, John F

    2003-10-16

    [structure: see text] The quinone portion of the ansamycin geldanamycin was made with complete selectivity from the 1,4-dihydroquinone generated from a 1,4-bis-methoxymethyl (MOM) ether intermediate. Palladium catalysis with air gave the desired product in 98% isolated yield. The structure was established using NMR, UV, and X-ray analysis with comparisons to geldanamycin, ortho-quino-geldanamycin and a model compound.

  7. The Metabolic Fate of ortho-Quinones Derived from Catecholamine Metabolites.

    PubMed

    Ito, Shosuke; Yamanaka, Yuta; Ojika, Makoto; Wakamatsu, Kazumasa

    2016-01-27

    ortho-Quinones are produced in vivo through the oxidation of catecholic substrates by enzymes such as tyrosinase or by transition metal ions. Neuromelanin, a dark pigment present in the substantia nigra and locus coeruleus of the brain, is produced from dopamine (DA) and norepinephrine (NE) via an interaction with cysteine, but it also incorporates their alcoholic and acidic metabolites. In this study we examined the metabolic fate of ortho-quinones derived from the catecholamine metabolites, 3,4-dihydroxyphenylethanol (DOPE), 3,4-dihydroxyphenylethylene glycol (DOPEG), 3,4-dihydroxyphenylacetic acid (DOPAC) and 3,4-dihydroxyphenylmandelic acid (DOMA). The oxidation of catecholic substrates by mushroom tyrosinase was followed by UV-visible spectrophotometry. HPLC analysis after reduction with NaBH₄ or ascorbic acid enabled measurement of the half-lives of ortho-quinones and the identification of their reaction products. Spectrophotometric examination showed that the ortho-quinones initially formed underwent extensive degradation at pH 6.8. HPLC analysis showed that DOPE-quinone and DOPEG-quinone degraded with half-lives of 15 and 30 min at pH 6.8, respectively, and >100 min at pH 5.3. The major product from DOPE-quinone was DOPEG which was produced through the addition of a water molecule to the quinone methide intermediate. DOPEG-quinone yielded a ketone, 2-oxo-DOPE, through the quinone methide intermediate. DOPAC-quinone and DOMA-quinone degraded immediately with decarboxylation of the ortho-quinone intermediates to form 3,4-dihydroxybenzylalcohol (DHBAlc) and 3,4-dihydroxybenzaldehyde (DHBAld), respectively. DHBAlc-quinone was converted to DHBAld with a half-life of 9 min, while DHBAld-quinone degraded rapidly with a half-life of 3 min. This study confirmed the fact that ortho-quinones from DOPE, DOPEG, DOPAC and DOMA are converted to quinone methide tautomers as common intermediates, through proton rearrangement or decarboxylation. The unstable quinone

  8. Chlorophyll-quinone photochemical electron transfer in liposomes

    SciTech Connect

    Hurley, J.K.; Castelli, F.; Tollin, G.

    1981-09-01

    The study described involves the reduction of electron acceptors (quinones) by photoexcited Chloroplasts (Chl). Chl a (from spinach) is incorporated into phosphatidylcholine (either synthetic or from hen egg yolks) liposomes suspended in 10 mM phosphate buffer (pH 7.0). The quinones are either present during liposome formation or added later, depending upon their water solubility. The measurement technique employed is laser flash photolysis. A pulsed nitrogen laser pumps a dye laser, which delivers a short light flash (10 ns) to the sample at a wavelength (655-660 nm) within an absorption band of Chl. This raises Chl to an excited singlet level, which can rapidly cross to the lowest excited triple level (/sup 3/Chl). From this state Chl can transfer an electron to acceptors such as quinones, resulting in the formation of the Chl cation radical (Chl./sup +/) and the semiquinone anion radical (Q./sup +/). Transient absorbance changes ocurring within the sample cell are monitored and can be attributed to processes such as excited state quenching (of /sup 3/Chl by Q) and radical product formation and decay. (JMT)

  9. Quinone Methide Bioactivation Pathway: Contribution to Toxicity and/or Cytoprotection?

    PubMed Central

    Bolton, Judy L.

    2014-01-01

    The formation of quinone methides (QMs) from either direct 2-electron oxidation of 2- or 4-alkylphenols, isomerization of o-quinones, or elimination of a good leaving group could explain the cytotoxic/cytoprotective effects of several drugs, natural products, as well as endogenous compounds. For example, the antiretroviral drug nevirapine and the antidiabetic agent troglitazone both induce idiosyncratic hepatotoxicity through mechanisms involving quinone methide formation. The anesthetic phencyclidine induces psychological side effects potentially through quinone methide mediated covalent modification of crucial macromolecules in the brain. Selective estrogen receptor modulators (SERMs) such as tamoxifen, toremifene, and raloxifene are metabolized to quinone methides which could potentially contribute to endometrial carcinogenic properties and/or induce detoxification enzymes and enhance the chemopreventive effects of these SERMs. Endogenous estrogens and/or estrogens present in estrogen replacement formulations are also metabolized to catechols and further oxidized to o-quinones which can isomerize to quinone methides. Both estrogen quinoids could cause DNA damage which could enhance hormone dependent cancer risk. Natural products such as the food and flavor agent eugenol can be directly oxidized to a quinone methide which may explain the toxic effects of this natural compound. Oral toxicities associated with chewing areca quid could be the result of exposure to hydroxychavicol through initial oxidation to an o-quinone which isomerizes to a p-quinone methide. Similar o-quinone to p-quinone methide isomerization reactions have been reported for the ubiquitous flavonoid quercetin which needs to be taken into consideration when evaluating risk-benefit assessments of these natural products. The resulting reaction of these quinone methides with proteins, DNA, and/or resulting modulation of gene expression may explain the toxic and/or beneficial effects of the parent

  10. NADH-quinone oxidoreductase: PSST subunit couples electron transfer from iron–sulfur cluster N2 to quinone

    PubMed Central

    Schuler, Franz; Yano, Takahiro; Di Bernardo, Salvatore; Yagi, Takao; Yankovskaya, Victoria; Singer, Thomas P.; Casida, John E.

    1999-01-01

    The proton-translocating NADH-quinone oxidoreductase (EC 1.6.99.3) is the largest and least understood enzyme complex of the respiratory chain. The mammalian mitochondrial enzyme (also called complex I) contains more than 40 subunits, whereas its structurally simpler bacterial counterpart (NDH-1) in Paracoccus denitrificans and Thermus thermophilus HB-8 consists of 14 subunits. A major unsolved question is the location and mechanism of the terminal electron transfer step from iron–sulfur cluster N2 to quinone. Potent inhibitors acting at this key region are candidate photoaffinity probes to dissect NADH-quinone oxidoreductases. Complex I and NDH-1 are very sensitive to inhibition by a variety of structurally diverse toxicants, including rotenone, piericidin A, bullatacin, and pyridaben. We designed (trifluoromethyl)diazirinyl[3H]pyridaben ([3H]TDP) as our photoaffinity ligand because it combines outstanding inhibitor potency, a suitable photoreactive group, and tritium at high specific activity. Photoaffinity labeling of mitochondrial electron transport particles was specific and saturable. Isolation, protein sequencing, and immunoprecipitation identified the high-affinity specifically labeled 23-kDa subunit as PSST of complex I. Immunoprecipitation of labeled membranes of P. denitrificans and T. thermophilus established photoaffinity labeling of the equivalent bacterial NQO6. Competitive binding and enzyme inhibition studies showed that photoaffinity labeling of the specific high-affinity binding site of PSST is exceptionally sensitive to each of the high-potency inhibitors mentioned above. These findings establish that the homologous PSST of mitochondria and NQO6 of bacteria have a conserved inhibitor-binding site and that this subunit plays a key role in electron transfer by functionally coupling iron–sulfur cluster N2 to quinone. PMID:10097178

  11. Design and Synthesis of Novel Isoxazole Tethered Quinone-Amino Acid Hybrids

    PubMed Central

    Ravi Kumar, P.; Sambaiah, M.; Kandula, Venu; Payili, Nagaraju; Jaya Shree, A.; Yennam, Satyanarayana

    2014-01-01

    A new series of isoxazole tethered quinone-amino acid hybrids has been designed and synthesized involving 1,3-dipolar cycloaddition reaction followed by an oxidation reaction using cerium ammonium nitrate (CAN). Using this method, for the first time various isoxazole tethered quinone-phenyl alanine and quinone-alanine hybrids were synthesized from simple commercially available 4-bromobenzyl bromide, propargyl bromide, and 2,5-dimethoxybenzaldehyde in good yield. PMID:25709839

  12. Compositions comprising a polypeptide having cellulolytic enhancing activity and a quinone compound and uses thereof

    DOEpatents

    Quinlan, Jason; Xu, Feng; Sweeney, Matthew

    2016-03-01

    The present invention relates to compositions comprising: a polypeptide having cellulolytic enhancing activity and a quinone compound. The present invention also relates to methods of using the compositions.

  13. Catalytic asymmetric diels-alder reaction of quinone imine ketals: a site-divergent approach.

    PubMed

    Hashimoto, Takuya; Nakatsu, Hiroki; Maruoka, Keiji

    2015-04-07

    The catalytic asymmetric Diels-Alder reaction of quinone imine ketals with diene carbamates catalyzed by axially chiral dicarboxylic acids is reported herein. A variety of primary and secondary alkyl-substituted quinone derivatives which have not been applied in previous asymmetric quinone Diels-Alder reactions could be employed using this method. More importantly, we succeeded in developing a strategy to divert the reaction site in unsymmetrical 3-alkyl quinone imine ketals from the inherently favored unsubstituted C=C bond to the disfavored alkyl-substituted C=C bond. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Substituted quinoline quinones as surrogates for the PQQ cofactor: an electrochemical and computational study.

    PubMed

    Dorfner, Walter L; Carroll, Patrick J; Schelter, Eric J

    2015-04-17

    Pyrroloquinoline quinones (PQQ) are important cofactors that shuttle redox equivalents in diverse metalloproteins. Quinoline 7,8-quinones have been synthesized and characterized as surrogates for PQQ to elucidate redox energetics within metalloenzyme active sites. The quinoline 7,8-quinones were accessed using polymer-supported iodoxybenzoic acid and the compounds evaluated using solution electrochemistry. Together with a family of quinones, the products were evaluated computationally and used to generate a predictive correlation between a computed ΔG and the experimental reduction potentials.

  15. Type-II NADH:quinone oxidoreductase from Staphylococcus aureus has two distinct binding sites and is rate limited by quinone reduction.

    PubMed

    Sena, Filipa V; Batista, Ana P; Catarino, Teresa; Brito, José A; Archer, Margarida; Viertler, Martin; Madl, Tobias; Cabrita, Eurico J; Pereira, Manuela M

    2015-10-01

    A prerequisite for any rational drug design strategy is understanding the mode of protein-ligand interaction. This motivated us to explore protein-substrate interaction in Type-II NADH:quinone oxidoreductase (NDH-2) from Staphylococcus aureus, a worldwide problem in clinical medicine due to its multiple drug resistant forms. NDHs-2 are involved in respiratory chains and recognized as suitable targets for novel antimicrobial therapies, as these are the only enzymes with NADH:quinone oxidoreductase activity expressed in many pathogenic organisms. We obtained crystal and solution structures of NDH-2 from S. aureus, showing that it is a dimer in solution. We report fast kinetic analyses of the protein and detected a charge-transfer complex formed between NAD(+) and the reduced flavin, which is dissociated by the quinone. We observed that the quinone reduction is the rate limiting step and also the only half-reaction affected by the presence of HQNO, an inhibitor. We analyzed protein-substrate interactions by fluorescence and STD-NMR spectroscopies, which indicate that NADH and the quinone bind to different sites. In summary, our combined results show the presence of distinct binding sites for the two substrates, identified quinone reduction as the rate limiting step and indicate the establishment of a NAD(+)-protein complex, which is released by the quinone.

  16. In cellulo monitoring of quinone reductase activity and reactive oxygen species production during the redox cycling of 1,2 and 1,4 quinones.

    PubMed

    Cassagnes, Laure-Estelle; Perio, Pierre; Ferry, Gilles; Moulharat, Natacha; Antoine, Mathias; Gayon, Régis; Boutin, Jean A; Nepveu, Françoise; Reybier, Karine

    2015-12-01

    Quinones are highly reactive molecules that readily undergo either one- or two-electron reduction. One-electron reduction of quinones or their derivatives by enzymes such as cytochrome P450 reductase or other flavoproteins generates unstable semiquinones, which undergo redox cycling in the presence of molecular oxygen leading to the formation of highly reactive oxygen species. Quinone reductases 1 and 2 (QR1 and QR2) catalyze the two-electron reduction of quinones to form hydroquinones, which can be removed from the cell by conjugation of the hydroxyl with glucuronide or sulfate thus avoiding its autoxidation and the formation of free radicals and highly reactive oxygen species. This characteristic confers a detoxifying enzyme role to QR1 and QR2, even if this character is strongly linked to the excretion capacity of the cell. Using EPR spectroscopy and confocal microscopy we demonstrated that the amount of reactive oxygen species (ROS) produced by Chinese hamster ovary (CHO) cells overexpressing QR1 or QR2 compared to naive CHO cells was determined by the quinone structural type. Indeed, whereas the amount of ROS produced in the cell was strongly decreased with para-quinones such as menadione in the presence of quinone reductase 1 or 2, a strong increase in ROS was recorded with ortho-quinones such as adrenochrome, aminochrome, dopachrome, or 3,5-di-tert-butyl-o-benzoquinone in cells overexpressing QR, especially QR2. These differences could originate from the excretion process, which is different for para- and ortho-quinones. These results are of particular interest in the case of dopamine considering the association of QR2 with various neurological disorders such as Parkinson disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Menaquinone as pool quinone in a purple bacterium

    PubMed Central

    Schoepp-Cothenet, Barbara; Lieutaud, Clément; Baymann, Frauke; Verméglio, André; Friedrich, Thorsten; Kramer, David M.; Nitschke, Wolfgang

    2009-01-01

    Purple bacteria have thus far been considered to operate light-driven cyclic electron transfer chains containing ubiquinone (UQ) as liposoluble electron and proton carrier. We show that in the purple γ-proteobacterium Halorhodospira halophila, menaquinone-8 (MK-8) is the dominant quinone component and that it operates in the QB-site of the photosynthetic reaction center (RC). The redox potentials of the photooxidized pigment in the RC and of the Rieske center of the bc1 complex are significantly lower (Em = +270 mV and +110 mV, respectively) than those determined in other purple bacteria but resemble those determined for species containing MK as pool quinone. These results demonstrate that the photosynthetic cycle in H. halophila is based on MK and not on UQ. This finding together with the unusual organization of genes coding for the bc1 complex in H. halophila suggests a specific scenario for the evolutionary transition of bioenergetic chains from the low-potential menaquinones to higher-potential UQ in the proteobacterial phylum, most probably induced by rising levels of dioxygen 2.5 billion years ago. This transition appears to necessarily proceed through bioenergetic ambivalence of the respective organisms, that is, to work both on MK- and on UQ-pools. The establishment of the corresponding low- and high-potential chains was accompanied by duplication and redox optimization of the bc1 complex or at least of its crucial subunit oxidizing quinols from the pool, the Rieske protein. Evolutionary driving forces rationalizing the empirically observed redox tuning of the chain to the quinone pool are discussed. PMID:19429705

  18. Terpenoids from Diplophyllum taxifolium with quinone reductase-inducing activity.

    PubMed

    Wang, Xiao; Zhang, Jiao-Zhen; Zhou, Jin-Chuan; Shen, Tao; Lou, Hong-Xiang

    2016-03-01

    Two new ent-prenylaromadendrane-type diterpenoids, diplotaxifols A (1) and B (2), a new ent-eudesmol, ent-eudesma-4(15),11(13)-dien-6α,12-diol (3), eight new eudesmanolides enantiomers (4-11) of the corresponding compounds from higher plants along with four known ent-eudesmanolides (12-15) were isolated from the 95% EtOH extract of Chinese liverwort Diplophyllum taxifolium. Their structures were elucidated on the basis of MS, NMR and IR spectral data, and confirmed by single-crystal X-ray diffraction analysis. The quinone reductase-inducing activity of the compounds was evaluated.

  19. A new sesquiterpenoid quinone with cytotoxicity from Abelmoschus sagittifolius.

    PubMed

    Chen, De-Li; Zhang, Xiao-Po; Ma, Guo-Xu; Wu, Hai-Feng; Yang, Jun-Shan; Xu, Xu-Dong

    2016-01-01

    A new sesquiterpenoid quinone, Acyl hibiscone B (1), together with five known compounds, (R)-lasiodiplodin (2), (R)-de-O-methyllasiodiplodin, (3) dibutyl phthalate (4), (R)-9-phenylnonan-2-ol (5) and hibiscone B (6), was obtained from the stem tuber of Abelmoschus sagittifolius. The structure of compound 1 was elucidated by analysing its (1)H and (13)C NMR, (1)H-(1)H COSY, HSQC, HMBC, NOESY and HR-ESI-MS values. Compound 1 showed significant cytotoxicity against Hela and HepG-2 human cancer cell lines.

  20. Liquid Quinones for Solvent-Free Redox Flow Batteries.

    PubMed

    Shimizu, Akihiro; Takenaka, Keisuke; Handa, Naoyuki; Nokami, Toshiki; Itoh, Toshiyuki; Yoshida, Jun-Ichi

    2017-09-08

    Liquid benzoquinone and naphthoquinone having diethylene glycol monomethyl ether groups are designed and synthesized as redox active materials that dissolve supporting electrolytes. The Li-ion batteries based on the liquid quinones using LiBF4 /PC show good performance in terms of voltage, capacity, energy efficiency, and cyclability in both static and flow modes. A battery is constructed without using intentionally added organic solvent, and its high energy density (264 W h L(-1) ) demonstrates the potential of solvent-free organic redox flow batteries using liquid active materials. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Syntheses of covalently-linked porphyria-quinone complexes. I

    SciTech Connect

    Kong, J.L.Y.; Loach, P.A.

    1980-06-01

    A synthetic route for the preparation of covalently-linked prophyin-quinone and metalloporphyrinquinone complexes as models for the phototrap in bacterial photosynthesis is described. 5(5-Carboxyphenyl)-10,15,20-tritolylporphyrin, prepared by a mixed aldehyde approach, was attached to benzoquinone center with a propanediol bridge by means of ester linkages. The starting point for the benzoquinone moiety was 2,5-dihydroxyphenylacetic acid, whose hydroquinone function was first protected by preparing its dimethyl ether. The spacing between the two centers of the complex could be altered simply by varying the length of the bridging group (a diol) employed. Boron tribomide was used to unmask the quinol derivatives in the final coupled products. The zinc(II) derivative of porphyrin-quinone complex was prepared by addition of a saturated solution of zinc acetate in methanol to a solution of the corresponding prophyrin-hydroqyuinone complex in dichloromethane at room temperature. The structures of these complexes were confirmed by nmr spectroscopy, uv-visible absorption, and mass spectroscopy. Oxidation of the quinol moiety in the covalently-linked complex to its corresponding quinonoid derivative was accomplished by treating a solution of the complex in dichloromethane with a stoichiometric amount of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, a high potential benzoquinone.

  2. Loss of quinone reductase 2 function selectively facilitates learning behaviors.

    PubMed

    Benoit, Charles-Etienne; Bastianetto, Stephane; Brouillette, Jonathan; Tse, YiuChung; Boutin, Jean A; Delagrange, Philippe; Wong, TakPan; Sarret, Philippe; Quirion, Rémi

    2010-09-22

    High levels of reactive oxygen species (ROS) are associated with deficits in learning and memory with age as well as in Alzheimer's disease. Using DNA microarray, we demonstrated the overexpression of quinone reductase 2 (QR2) in the hippocampus in two models of learning deficits, namely the aged memory impaired rats and the scopolamine-induced amnesia model. QR2 is a cytosolic flavoprotein that catalyzes the reduction of its substrate and enhances the production of damaging activated quinone and ROS. QR2-like immunostaining is enriched in cerebral structures associated with learning behaviors, such as the hippocampal formation and the temporofrontal cortex of rat, mouse, and human brains. In cultured rat embryonic hippocampal neurons, selective inhibitors of QR2, namely S26695 and S29434, protected against menadione-induced cell death by reversing its proapoptotic action. S26695 (8 mg/kg) also significantly inhibited scopolamine-induced amnesia. Interestingly, adult QR2 knock-out mice demonstrated enhanced learning abilities in various tasks, including Morris water maze, object recognition, and rotarod performance test. Other behaviors related to anxiety (elevated plus maze), depression (forced swim), and schizophrenia (prepulse inhibition) were not affected in QR2-deficient mice. Together, these data suggest a role for QR2 in cognitive behaviors with QR2 inhibitors possibly representing a novel therapeutic strategy toward the treatment of learning deficits especially observed in the aged brain.

  3. Atypical features of Thermus thermophilus succinate:quinone reductase.

    PubMed

    Kolaj-Robin, Olga; Noor, Mohamed R; O'Kane, Sarah R; Baymann, Frauke; Soulimane, Tewfik

    2013-01-01

    The Thermus thermophilus succinate:quinone reductase (SQR), serving as the respiratory complex II, has been homologously produced under the control of a constitutive promoter and subsequently purified. The detailed biochemical characterization of the resulting wild type (wt-rcII) and His-tagged (rcII-His(8)-SdhB and rcII-SdhB-His(6)) complex II variants showed the same properties as the native enzyme with respect to the subunit composition, redox cofactor content and sensitivity to the inhibitors malonate, oxaloacetate, 3-nitropropionic acid and nonyl-4-hydroxyquinoline-N-oxide (NQNO). The position of the His-tag determined whether the enzyme retained its native trimeric conformation or whether it was present in a monomeric form. Only the trimer exhibited positive cooperativity at high temperatures. The EPR signal of the [2Fe-2S] cluster was sensitive to the presence of substrate and showed an increased rhombicity in the presence of succinate in the native and in all recombinant forms of the enzyme. The detailed analysis of the shape of this signal as a function of pH, substrate concentration and in the presence of various inhibitors and quinones is presented, leading to a model for the molecular mechanism that underlies the influence of succinate on the rhombicity of the EPR signal of the proximal iron-sulfur cluster.

  4. Study of quinones reactions with wine nucleophiles by cyclic voltammetry.

    PubMed

    Oliveira, Carla M; Barros, António S; Ferreira, António C S; Silva, Artur M S

    2016-11-15

    Quinones are electrophilic species which can react with various nucleophiles, like wine antioxidants, such as sulfur dioxide or ascorbic acid, thiols, amino acids, and numerous polyphenols. These reactions are very important in wine aging because they mediate oxygen reactions during both production and bottle aging phases. In this work, the major challenge was to determine the interaction between ortho-quinones and wine nucleophiles (amino acids, thiols, and the antioxidants SO2 and ascorbic acid), by cyclic voltammetry. Wine-model solutions with gallic acid, caffeic acid, or (+)-catechin and nucleophilic compounds were used. To understand the effect of nucleophilic addition in wine, a white wine with the same added nucleophiles was also analysed. Cyclic voltammograms were taken with glassy carbon electrode or screen-printed carbon electrodes, respectively, for wine-model and white wines solutions, in the absence and in the presence of nucleophiles. A nucleophilic order profile related to the cathodic current intensity decrease was observed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Crystal structure and characterization of pyrroloquinoline quinone disodium trihydrate

    PubMed Central

    2012-01-01

    Background Pyrroloquinoline quinone (PQQ), a tricarboxylic acid, has attracted attention as a growth factor, and its application to supplements and cosmetics is underway. The product used for these purposes is a water-soluble salt of PQQ disodium. Although in the past, PQQ disodiumpentahydrates with a high water concentration were used, currently, low hydration crystals of PQQ disodiumpentahydrates are preferred. Results We prepared a crystal of PQQ disodium trihydrate in a solution of ethanol and water, studied its structure, and analyzed its properties. In the prepared crystal, the sodium atom interacted with the oxygen atom of two carboxylic acids as well as two quinones of the PQQ disodium trihydrate. In addition, the hydration water of the prepared crystal was less than that of the conventional PQQ disodium crystal. From the results of this study, it was found that the color and the near-infrared (NIR) spectrum of the prepared crystal changed depending on the water content in the dried samples. Conclusions The water content in the dried samples was restored to that in the trihydrate crystal by placing the samples in a humid environment. In addition, the results of X-ray diffraction (XRD) and X-ray diffraction-differential calorimetry (XRD-DSC) analyses show that the phase of the trihydrate crystal changed when the crystallization water was eliminated. The dried crystal has two crystalline forms that are restored to the original trihydrate crystals in 20% relative humidity (RH). This crystalline (PQQ disodium trihydrate) is stable under normal environment. PMID:22713213

  6. Enhancing the Performance of Vanadium Redox Flow Batteries using Quinones

    NASA Astrophysics Data System (ADS)

    Mulcahy, James W., III

    The global dependence on fossil fuels continues to increase while the supply diminishes, causing the proliferation in demand for renewable energy sources. Intermittent renewable energy sources such as wind and solar, require electrochemical storage devices in order to transfer stored energy to the power grid at a constant output. Redox flow batteries (RFB) have been studied extensively due to improvements in scalability, cyclability and efficiency over conventional batteries. Vanadium redox flow batteries (VRFB) provide one of the most comprehensive solutions to energy storage in relation to other RFBs by alleviating the problem of cross-contamination. Quinones are a class of organic compounds that have been extensively used in chemistry, biochemistry and pharmacology due to their catalytic properties, fast proton-coupled electron transfer, good chemical stability and low cost. Anthraquinones are a subcategory of quinones and have been utilized in several battery systems. Anthraquinone-2, 6-disulfonic acid (AQDS) was added to a VRFB in order to study its effects on cyclical performance. This study utilized carbon paper electrodes and a Nafion 117 ion exchange membrane for the membrane-electrode assembly (MEA). The cycling performance was investigated over multiple charge and discharge cycles and the addition of AQDS was found to increase capacity efficiency by an average of 7.6% over the standard VRFB, while decreasing the overall cycle duration by approximately 18%. It is thus reported that the addition of AQDS to a VRFB electrolyte has the potential to increase the activity and capacity with minimal increases in costs.

  7. Universal quinone electrodes for long cycle life aqueous rechargeable batteries

    NASA Astrophysics Data System (ADS)

    Liang, Yanliang; Jing, Yan; Gheytani, Saman; Lee, Kuan-Yi; Liu, Ping; Facchetti, Antonio; Yao, Yan

    2017-08-01

    Aqueous rechargeable batteries provide the safety, robustness, affordability, and environmental friendliness necessary for grid storage and electric vehicle operations, but their adoption is plagued by poor cycle life due to the structural and chemical instability of the anode materials. Here we report quinones as stable anode materials by exploiting their structurally stable ion-coordination charge storage mechanism and chemical inertness towards aqueous electrolytes. Upon rational selection/design of quinone structures, we demonstrate three systems that coupled with industrially established cathodes and electrolytes exhibit long cycle life (up to 3,000 cycles/3,500 h), fast kinetics (>=20C), high anode specific capacity (up to 200-395 mAh g-1), and several examples of state-of-the-art specific energy/energy density (up to 76-92 Wh kg-1/ 161-208 Wh l-1) for several operational pH values (-1 to 15), charge carrier species (H+, Li+, Na+, K+, Mg2+), temperature (-35 to 25 °C), and atmosphere (with/without O2), making them a universal anode approach for any aqueous battery technology.

  8. Antiprotozoal isoflavan quinones from Abrus precatorius ssp. africanus.

    PubMed

    Hata, Yoshie; Raith, Melanie; Ebrahimi, Samad Nejad; Zimmermann, Stefanie; Mokoka, Tsholofelo; Naidoo, Dashnie; Fouche, Gerda; Maharaj, Vinesh; Kaiser, Marcel; Brun, Reto; Hamburger, Matthias

    2013-04-01

    A library of 206 extracts from selected South African plants was screened in vitro against a panel of protozoan parasites, Plasmodium falciparum, Trypanosoma brucei rhodesiense, and Leishmania donovani. A CH2Cl2/MeOH (1 : 1) extract of Abrus precatorius L. ssp. africanus strongly inhibited P. falciparum (98 %), T. b. rhodesiense (100 %), and L. donovani (76 %) when tested at a concentration of 10.0 µg/mL. The active constituents were tracked by HPLC-based activity profiling and isolated by preparative and semipreparative RP-HPLC chromatography. Structures were established by HR-ESIMS, and 1D and 2D NMR (1H, 13C, COSY, HMBC, HSQC, and NOE difference spectroscopy). Five compounds were obtained and identified as two isoflavan hydroquinones, abruquinone H (1) and abruquinone G (2), and three isoflavan quinones, abruquinone I (3), abruquinone B (4), and 7,8,3''5'-tetramethoxyisoflavan-1',4'-quinone (5). Compounds 1 and 3 were new natural products. The absolute configuration of compounds was determined by comparison of electronic circular dichroism spectra with calculated ECD data. Compounds 3 and 4 showed strong activity against T. b. rhodesiense (IC50 values of 0.30 and 0.16 µM, respectively) and good selectivity (selectivity indices of 73.7 and 50.5, respectively). Georg Thieme Verlag KG Stuttgart · New York.

  9. Respiratory quinones in Archaea: phylogenetic distribution and application as biomarkers in the marine environment.

    PubMed

    Elling, Felix J; Becker, Kevin W; Könneke, Martin; Schröder, Jan M; Kellermann, Matthias Y; Thomm, Michael; Hinrichs, Kai-Uwe

    2016-02-01

    The distribution of respiratory quinone electron carriers among cultivated organisms provides clues on both the taxonomy of their producers and the redox processes these are mediating. Our study of the quinone inventories of 25 archaeal species belonging to the phyla Eury-, Cren- and Thaumarchaeota facilitates their use as chemotaxonomic markers for ecologically important archaeal clades. Saturated and monounsaturated menaquinones with six isoprenoid units forming the alkyl chain may serve as chemotaxonomic markers for Thaumarchaeota. Other diagnostic biomarkers are thiophene-bearing quinones for Sulfolobales and methanophenazines as functional quinone analogues of the Methanosarcinales. The ubiquity of saturated menaquinones in the Archaea in comparison to Bacteria suggests that these compounds may represent an ancestral and diagnostic feature of the Archaea. Overlap between quinone compositions of distinct thermophilic and halophilic archaea and bacteria may indicate lateral gene transfer. The biomarker potential of thaumarchaeal quinones was exemplarily demonstrated on a water column profile of the Black Sea. Both, thaumarchaeal quinones and membrane lipids showed similar distributions with maxima at the chemocline. Quinone distributions indicate that Thaumarchaeota dominate respiratory activity at a narrow interval in the chemocline, while they contribute only 9% to the microbial biomass at this depth, as determined by membrane lipid analysis.

  10. On the importance of hydroquinone/p-quinone redox system in the photoyellowing of mechanical pulps

    Treesearch

    Umesh P. Agarwal

    1999-01-01

    In the area of photoyellowing of mechanical pulps, recently obtained experimental evidence has shown that hydroquinone/p-quinone redox couple is present in lignin-rich mechanical pulps. It was also noted that compared to a control pulp the concentration of p-quinones was significantly higher in a photoyellowed pulp. Under ambient conditions, upon exposure to light, the...

  11. Electron affinity of p-quinones. Improved method of electrochemical estimation

    NASA Astrophysics Data System (ADS)

    Jaworski, Jan S.

    1986-06-01

    Electron affinities of four p-quinones are estimated from enthalpy changes obtained on the basis of measured formal potentials and reaction entropies in the electroreduction process. A linear correlation between electron affinities of p-quinones and parent hydrocarbons is found.

  12. Quinone-based stable isotope probing for assessment of 13C substrate-utilizing bacteria

    NASA Astrophysics Data System (ADS)

    Kunihiro, Tadao; Katayama, Arata; Demachi, Toyoko; Veuger, Bart; Boschker, Henricus T. S.; van Oevelen, Dick

    2015-04-01

    In this study, we attempted to establish quinone-stable-isotope probing (SIP) technique to link substrate-utilizing bacterial group to chemotaxonomic group in bacterial community. To identify metabolically active bacterial group in various environments, SIP techniques combined with biomarkers have been widely utilized as an attractive method for environmental study. Quantitative approaches of the SIP technique have unique advantage to assess substrate-incorporation into bacteria. As a most major quantitative approach, SIP technique based on phospholipid-derived fatty acids (PLFA) have been applied to simultaneously assess substrate-incorporation rate into bacteria and microbial community structure. This approach is powerful to estimate the incorporation rate because of the high sensitivity due to the detection by a gas chromatograph-combustion interface-isotope ratio mass spectrometer (GC-c-IRMS). However, its phylogenetic resolution is limited by specificity of a compound-specific marker. We focused on respiratory quinone as a biomarker. Our previous study found a good correlation between concentrations of bacteria-specific PLFAs and quinones over several orders of magnitude in various marine sediments, and the quinone method has a higher resolution (bacterial phylum level) for resolving differences in bacterial community composition more than that of bacterial PLFA. Therefore, respiratory quinones are potentially good biomarkers for quantitative approaches of the SIP technique. The LC-APCI-MS method as molecular-mass based detection method for quinone was developed and provides useful structural information for identifying quinone molecular species in environmental samples. LC-MS/MS on hybrid triple quadrupole/linear ion trap, which enables to simultaneously identify and quantify compounds in a single analysis, can detect high molecular compounds with their isotope ions. Use of LC-MS/MS allows us to develop quinone-SIP based on molecular mass differences due to

  13. Application of modified supercritical carbon dioxide extraction to microbial quinone analysis.

    PubMed

    Irvan; Hasanudin, Udin; Faisal, Muhammad; Daimon, Hiroyuki; Fujie, Koichi

    2006-01-01

    Supercritical carbon dioxide (scCO2) was applied to extract microbial quinones from activated sludge. Identification and analysis was then performed using high-performance liquid chromatography (HPLC) equipped with ultraviolet-visible (UV-Vis) detector and photodiode array detector (PDA). Extracted microbial quinones were trapped and separated as menaquinones (MK) and ubiquinones (Q) species using two Sep-Pak Plus Silica cartridges joined in series. Four ubiquinones and 12 menaquinones species were identified in 0.1 g dried activated sludge based on retention time and spectrum analysis. Among the tested various polar solvents, methanol showed to be the best modifier, based on the highest total quinone content extracted and the lowest dissimilarity index. The diversity index of quinone and the number of quinone species using methanol-modified scCO2 were similar to that of the conventional method (organic solvent extraction).

  14. Activation of Electron-Deficient Quinones through Hydrogen-Bond-Donor-Coupled Electron Transfer.

    PubMed

    Turek, Amanda K; Hardee, David J; Ullman, Andrew M; Nocera, Daniel G; Jacobsen, Eric N

    2016-01-11

    Quinones are important organic oxidants in a variety of synthetic and biological contexts, and they are susceptible to activation towards electron transfer through hydrogen bonding. Whereas this effect of hydrogen bond donors (HBDs) has been observed for Lewis basic, weakly oxidizing quinones, comparable activation is not readily achieved when more reactive and synthetically useful electron-deficient quinones are used. We have successfully employed HBD-coupled electron transfer as a strategy to activate electron-deficient quinones. A systematic investigation of HBDs has led to the discovery that certain dicationic HBDs have an exceptionally large effect on the rate and thermodynamics of electron transfer. We further demonstrate that these HBDs can be used as catalysts in a quinone-mediated model synthetic transformation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Quinone formation as a chemoprevention strategy for hybrid drugs: balancing cytotoxicity and cytoprotection.

    PubMed

    Dunlap, Tareisha; Chandrasena, R Esala P; Wang, Zhiqiang; Sinha, Vaishali; Wang, Zhican; Thatcher, Gregory R J

    2007-12-01

    Cellular defense mechanisms that respond to damage from oxidative and electrophilic stress, such as from quinones, represent a target for chemopreventive agents. Drugs bioactivated to quinones have the potential to activate antioxidant/electrophile responsive element (ARE) transcription of genes for cytoprotective phase 2 enzymes such as NAD(P)H-dependent quinone oxidoreductase (NQO1) but can also cause cellular damage. Two isomeric families of compounds were prepared, including the NO-NSAIDs (NO-donating nonsteroidal anti-inflammatory drugs) NCX 4040 and NCX 4016; one family was postulated to release a quinone methide on esterase bioactivation. The study of reactivity and GSH conjugation in model and cell systems confirmed the postulate. The quinone-forming family, including NCX 4040 and conisogenic bromides and mesylate, was rapidly bioactivated to a quinone, which gave activation of ARE and consequent induction of NQO1 in liver cells. Although the control family, including NCX 4016 and conisogenic bromides and mesylates, cannot form a quinone, ARE activation and NQO1 induction were observed, compatible with slower SN2 reactions with thiol sensor proteins, and consequent ARE-luciferase and NQO1 induction. Using a Chemoprevention Index estimate, the quinone-forming compounds suffered because of high cytoxicity and were more compatible with cancer therapy than chemoprevention. In the Comet assay, NCX 4040 was highly genotoxic relative to NCX 4016. There was no evidence that NO contributes to the observed biological activity and no evidence that NCX 4040 is an NO donor, instead, rapidly releasing NO3- and quinone. These results indicate a strategy for studying the quinone biological activity and reinforce the therapeutic attributes of NO-ASA through structural elements other than NO and ASA.

  16. Profiling quinones in ambient air samples collected from the Athabasca region (Canada).

    PubMed

    Wnorowski, Andrzej; Charland, Jean-Pierre

    2017-09-05

    This paper presents new findings on polycyclic aromatic hydrocarbon oxidation products-quinones that were collected in ambient air samples in the proximity of oil sands exploration. Quinones were characterized for their diurnal concentration variability, phase partitioning, and molecular size distribution. Gas-phase (GP) and particle-phase (PM) ambient air samples were collected separately in the summer; a lower quinone content was observed in the PM samples from continuous 24-h sampling than from combined 12-h sampling (day and night). The daytime/nocturnal samples demonstrated that nighttime conditions led to lower concentrations and some quinones not being detected. The highest quinone levels were associated with wind directions originating from oil sands exploration sites. The statistical correlation with primary pollutants directly emitted from oil sands industrial activities indicated that the bulk of the detected quinones did not originate directly from primary emission sources and that quinone formation paralleled a reduction in primary source NOx levels. This suggests a secondary chemical transformation of primary pollutants as the origin of the determined quinones. Measurements of 19 quinones included five that have not previously been reported in ambient air or in Standard Reference Material 1649a/1649b and seven that have not been previously measured in ambient air in the underivatized form. This is the first paper to report on quinone characterization in secondary organic aerosols originating from oil sands activities, to distinguish chrysenequinone and anthraquinone positional isomers in ambient air, and to report the requirement of daylight conditions for benzo[a]pyrenequinone and naphthacenequinone to be present in ambient air. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

  17. Molecular structures of porphyrin-quinone models for electron transfer

    SciTech Connect

    Fajer, J.; Barkigia, K.M.; Melamed, D.; Sweet, R.M.; Kurreck, H.; Gersdorff, J. von; Plato, M.; Rohland, H.C.; Elger, G.; Moebius, K.

    1996-08-15

    Synthetic porphyrin-quinone complexes are commonly used to mimic electron transport in photosynthetic reaction centers and to probe the effects of energetics, distances, and relative orientations on rates of electron transfer between donor-acceptor couples. The structures of two such models have been determined by X-ray diffraction. The redox pairs consist of a zinc porphyrin covalently linked to benzoquinone in cis and trans configurations via a cyclohexanediyl bridge. The crystallographic studies were undertaken to provide a structural foundation for the extensive body of experimental and theoretical results that exists for these compounds in both the ground and photoinduced charge-separated states. The results validate conclusions reached from theoretical calculations, EPR and two-dimensional NMR results for these states. 15 refs., 6 figs., 2 tabs.

  18. Hysteresis Behaviors of Poly (Naphthalene Quinone) Radical Electrorheological Fluid

    NASA Astrophysics Data System (ADS)

    Choi, Hyoung J.; Cho, Min S.; Jhon, Myung S.

    As a potential electrorheological(ER) material, poly(naphthalene quinone) radical (PNQR) ER fluid was prepared, and its rheological behavior and hysteresis phenomenon were investigated. PNQR was synthesized by Friedel-Crafts acylation between naphthalene and phthalic anhydride, using zinc chloride as a catalyst at 256°C. A Physica rheometer equipped with a high voltage generator was used to measure the rheological properties of the ER fluids, which were prepared by dispersing PNQR in silicone oil at several particle concentrations. Shear stresses were observed to decrease as shear rate increased in the region of slow deformation rate. It was further found that ER fluid showed different hysteresis behaviors according to the shear rate ranges; thixotropy was observed in the low shear rate region (0.007-0.51/s) and anti-thixotropy in the high shear rate region (0.5-10001/s). Controlled shear stress mode was also applied to observe similar behaviors.

  19. Evaluation of Sulfatase-Directed Quinone Methide Traps for Proteomics

    PubMed Central

    Lenger, Janina; Schröder, Marius; Ennemann, Eva; Müller, Benjamin; Wong, Chi-Huey; Noll, Thomas; Dierks, Thomas; Hanson, Sarah R.; Sewald, Norbert

    2012-01-01

    Sulfatases hydrolytically cleave sulfate esters through a unique catalytic aldehyde, which is introduced by a posttranslational oxidation. To profile active sulfatases in health and disease, activity-based proteomic tools are needed. Herein, quinone methide (QM) traps directed against sulfatases are evaluated as activity-based proteomic probes (ABPPs). Starting from a p-fluoromethylphenyl sulfate scaffold, enzymatically generated QM traps can inactivate bacterial aryl sulfatases from Pseudomonas aeruginosa and Klebsiella pneumonia and human steroid sulfatase. However, multiple enzyme-generated QMs form, diffuse, and non-specifically label purified enzyme. In complex proteomes, QM labelling is sulfatase-dependent but also non-specific. Thus, fluoromethylphenyl sulfates are poor ABPPs for sulfatases. PMID:21570853

  20. Quinones as Reversible Electron Relays in Artificial Photosynthesis.

    PubMed

    Rodenberg, Alexander; Orazietti, Margherita; Mosberger, Mathias; Bachmann, Cyril; Probst, Benjamin; Alberto, Roger; Hamm, Peter

    2016-05-04

    We explore the potential of various hydroquinone/quinone redox couples as electron relays in a homogenous water reduction system between a Re-based photosensitizer and a sacrificial electron donor [tris-(2-carboxyethyl)-phosphine, TCEP]. By using transient IR spectroscopy, flash photolysis as well as stopped-flow techniques covering timescales from picoseconds to 100 ms, we determine quenching rates and cage escape yields, the kinetics of the follow-up chemistry of the semiquinone, the recombination rates, as well as the re-reduction rates by TCEP. The overall quantum yield of hydrogen production is low, and we show that the limiting factors are the small cage escape yields and, more importantly, the slow regeneration rate by TCEP in comparison to the undesired charge recombination with the reduced water reduction catalyst. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  1. Pyrroloquinoline quinone inhibits the fibrillation of amyloid proteins

    PubMed Central

    Kim, Jihoon; Kobayashi, Masaki; Fukuda, Makoto; Ogasawara, Daisuke; Kobayashi, Natsuki; Han, Sungwoong; Nakamura, Chikashi; Inada, Masaki; Miyaura, Chisato; Ikebukuro, Kazunori

    2010-01-01

    Several neurodegenerative diseases involve the selective damage of neuron cells resulting from the accumulation of amyloid fibril formation. Considering that the formation of amyloid fibrils as well as their precursor oligomers is cytotoxic, the agents that prevent the formation of oligomers and/or fibrils might allow the development of a novel therapeutic approach to neurodegenerative diseases. Here, we show pyrroloquinoline quinone (PQQ) inhibits the amyloid fibril formation of the amyloid proteins, amyloid β (1–42) and mouse prion protein. The fibril formation of mouse prion protein in the presence of PQQ was dramatically prevented. Similarly, the fibril formation of amyloid β (1–42) also decreased. With further advanced pharmacological approaches, PQQ may become a leading anti-neurodegenerative compound in the treatment of neurodegenerative diseases. PMID:20083898

  2. Genotoxicity of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™).

    PubMed

    Nakano, Masahiko; Suzuki, Hiroshi; Imamura, Tadashi; Lau, Annette; Lynch, Barry

    2013-11-01

    The genotoxic potential of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) was evaluated in a battery of genotoxicity tests. The results of the bacterial mutation assay (Ames test) were negative. Weak positive results were obtained in 2 separate in vitro chromosomal aberration test in Chinese hamster lung (CHL) fibroblasts. Upon testing in an in vitro chromosomal aberration test in human peripheral blood lymphocytes, no genotoxic activity of PQQ was noted. In the in vivo micronucleus assay in mice, PQQ at doses up to 2,000 mg/kg body weight demonstrated that no genotoxic effects are expressed in vivo in bone marrow erythrocytes. The weak responses in the in vitro test CHL cells were considered of little relevance under conditions of likely human exposure. PQQ disodium was concluded to have no genotoxic activity in vivo. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Theoretical estimation of redox potential of biological quinone cofactors.

    PubMed

    Gillet, Natacha; Lévy, Bernard; Moliner, Vicent; Demachy, Isabelle; de la Lande, Aurélien

    2017-07-05

    Redox potentials are essential to understand biological cofactor reactivity and to predict their behavior in biological media. Experimental determination of redox potential in biological system is often difficult due to complexity of biological media but computational approaches can be used to estimate them. Nevertheless, the quality of the computational methodology remains a key issue to validate the results. Instead of looking to the best absolute results, we present here the calibration of theoretical redox potential for quinone derivatives in water coupling QM + MM or QM/MM scheme. Our approach allows using low computational cost theoretical level, ideal for long simulations in biological systems, and determination of the uncertainties linked to the calculations. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  4. Interactive enhancements of ascorbic acid and iron in hydroxyl radical generation in quinone redox cycling.

    PubMed

    Li, Yi; Zhu, Tong; Zhao, Jincai; Xu, Bingye

    2012-09-18

    Quinones are toxicological substances in inhalable particulate matter (PM). The mechanisms by which quinones cause hazardous effects can be complex. Quinones are highly active redox molecules that can go through a redox cycle with their semiquinone radicals, leading to formation of reactive oxygen species. Electron spin resonance spectra have been reported for semiquinone radicals in PM, indicating the importance of ascorbic acid and iron in quinone redox cycling. However, these findings are insufficient for understanding the toxicity associated with quinone exposure. Herein, we investigated the interactions among anthraquinone (AQ), ascorbic acid, and iron in hydroxyl radical (·OH) generation through the AQ redox cycling process in a physiological buffer. We measured ·OH concentration and analyzed the free radical process. Our results showed that AQ, ascorbic acid, and iron have synergistic effects on ·OH generation in quinone redox cycling; i.e., ascorbyl radical oxidized AQ to semiquinone radical and started the redox cycling, iron accelerated this oxidation and enhanced ·OH generation through Fenton reactions, while ascorbic acid and AQ could help iron to release from quartz surface and enhance its bioavailability. Our findings provide direct evidence for the redox cycling hypothesis about airborne particle surface quinone in lung fluid.

  5. Identification of quinone imine containing glutathione conjugates of diclofenac in rat bile.

    PubMed

    Waldon, Daniel J; Teffera, Yohannes; Colletti, Adria E; Liu, Jingzhou; Zurcher, Danielle; Copeland, Katrina W; Zhao, Zhiyang

    2010-12-20

    High-resolution accurate MS with an LTQ-Orbitrap was used to identify quinone imine metabolites derived from the 5-hydroxy (5-OH) and 4 prime-hydroxy (4'-OH) glutathione conjugates of diclofenac in rat bile. The initial quinone imine metabolites formed by oxidation of diclofenac have been postulated to be reactive intermediates potentially involved in diclofenac-mediated hepatotoxicity; while these metabolites could be formed using in vitro systems, they have never been detected in vivo. This report describes the identification of secondary quinone imine metabolites derived from 5-OH and 4'-OH diclofenac glutathione conjugates in rat bile. To verify the proposed structures, the diclofenac quinone imine GSH conjugate standards were prepared synthetically and enzymatically. The novel metabolite peaks displayed the identical retention times, accurate mass MS/MS spectra, and the fragmentation patterns as the corresponding authentic standards. The formation of these secondary quinone metabolites occurs only under conditions where bile salt homeostasis was experimentally altered. Standard practice in biliary excretion experiments using bile duct-cannulated rats includes infusion of taurocholic acid and/or other bile acids to replace those lost due to continuous collection of bile; for this experiment, the rats received no replacement bile acid infusion. High-resolution accurate mass spectrometry data and comparison with chemically and enzymatically prepared quinone imines of diclofenac glutathione conjugates support the identification of these metabolites. A mechanism for the formation of these reactive quinone imine containing glutathione conjugates of diclofenac is proposed.

  6. A Structural Determinant of Chemical Reactivity and Potential Health Effects of Quinones from Natural Products

    PubMed Central

    Tu, Tingting; Giblin, Daryl; Gross, Michael L.

    2011-01-01

    Although many phenols and catechols found as polyphenol natural products are antioxidants and have putative disease-preventive properties, others have deleterious health effects. One possible route to toxicity is the bioactivation of the phenolic function to quinones that are electrophilic, redox-agents capable of modifying DNA and proteins. The structure-property relationships of biologically important quinones and their precursors may help understand the balance between their health benefits and risks. We describe a mass-spectrometry-based study of four quinones produced by oxidizing flavanones and flavones. Those with a C2-C3 double bond on ring C of the flavonoid stabilize by delocalization an incipient positive charge from protonation and render the protonated quinone particularly susceptible to nucleophilic attack. We hypothesize that the absence of this double bond is one specific structural determinant that is responsible for the ability of quinones to modify biological macromolecules. Those quinones containing a C2-C3 single bond have relative higher aqueous stability and longer half-lives than those with a double bond at the same position; the latter have short half-lives at or below ~ 1 s. Quinones with a C2-C3 double bond show little ability to depurinate DNA because they are rapidly hydrated to unreactive species. Molecular-orbital calculations support that quinone hydration by a highly structure-dependent mechanism accounts for their chemical properties. The evidence taken together support a hypothesis that those flavonoids and related natural products that undergo oxidation to quinones and are then rapidly hydrated are unlikely to damage important biological macromolecules. PMID:21721570

  7. Quinones as photosensitizer for photodynamic therapy: ROS generation, mechanism and detection methods.

    PubMed

    Rajendran, M

    2016-03-01

    Photodynamic therapy (PDT) is based on the dye-sensitized photooxidation of biological matter in the target tissue, and utilizes light activated drugs for the treatment of a wide variety of malignancies. Quinones and porphyrins moiety are available naturally and involved in the biological process. Quinone metabolites perform a variety of key functions in plants which includes pathogen protection, oxidative phosphorylation, and redox signaling. Quinones and porphyrin are biologically accessible and will not create any allergic effects. In the field of photodynamic therapy, porphyrin derivatives are widely used, because it absorb in the photodynamic therapy window region (600-900 nm). Hence, researchers synthesize drugs based on porphyrin structure. Benzoquinone and its simple polycyclic derivatives such as naphthaquinone and anthraquinones absorb at lower wavelength region (300-400 nm), which is lower than porphyrin. Hence they are not involved in PDT studies. However, higher polycyclic quinones absorb in the photodynamic therapy window region (600-900 nm), because of its conjugation and can be used as PDT agents. Redox cycling has been proposed as a possible mechanism of action for many quinone species. Quinones are involved in the photodynamic as well as enzymatic generation of reactive oxygen species (ROS). Generations of ROS may be measured by optical, phosphorescence and EPR methods. The photodynamically generated ROS are also involved in many biological events. The photo-induced DNA cleavage by quinones correlates with the ROS generating efficiencies of the quinones. In this review basic reactions involving photodynamic generation of ROS by quinones and their biological applications were discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Steroidal pyrazolines evaluated as aromatase and quinone reductase-2 inhibitors for chemoprevention of cancer.

    PubMed

    Abdalla, Mohamed M; Al-Omar, Mohamed A; Bhat, Mashooq A; Amr, Abdel-Galil E; Al-Mohizea, Abdullah M

    2012-05-01

    The aromatase and quinone reductase-2 inhibition of synthesized heterocyclic pyrazole derivatives fused with steroidal structure for chemoprevention of cancer is reported herein. All compounds were interestingly less toxic than the reference drug (Cyproterone(®)). The aromatase inhibitory activities of these compounds were much more potent than the lead compound resveratrol, which has an IC(50) of 80 μM. In addition, all the compounds displayed potent quinone reductase-2 inhibition. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). The aromatase and quinone reductase-2 inhibitors resulting from this study have potential value in the treatment and prevention of cancer.

  9. Monitoring Dopamine Quinone-Induced Dopaminergic Neurotoxicity Using Dopamine Functionalized Quantum Dots.

    PubMed

    Ma, Wei; Liu, Hui-Ting; Long, Yi-Tao

    2015-07-08

    Dopamine (DA) quinone-induced dopaminergic neurotoxicity is known to occur due to the interaction between DA quinone and cysteine (Cys) residue, and it may play an important a role in pathological processes associated with neurodegeneration. In this study, we monitored the interaction process of DA to form DA quinone and the subsequent Cys residue using dopamine functionalized quantum dots (QDs). The fluorescence (FL) of the QD bioconjugates changes as a function of the structure transformation during the interaction process, providing a potential FL tool for monitoring dopaminergic neurotoxicity.

  10. Quinone reduction by Rhodothermus marinus succinate:menaquinone oxidoreductase is not stimulated by the membrane potential

    SciTech Connect

    Fernandes, Andreia S.; Konstantinov, Alexander A.; Teixeira, Miguel; Pereira, Manuela M. . E-mail: mpereira@itqb.unl.pt

    2005-05-06

    Succinate:quinone oxidoreductase (SQR), a di-haem enzyme purified from Rhodothermus marinus, reveals an HQNO-sensitive succinate:quinone oxidoreductase activity with several menaquinone analogues as electron acceptors that decreases with lowering the redox midpoint potential of the quinones. A turnover with the low-potential 2,3-dimethyl-1,4-naphthoquinone that is the closest analogue of menaquinone, although low, can be detected in liposome-reconstituted SQR. Reduction of the quinone is not stimulated by an imposed K{sup +}-diffusion membrane potential of a physiological sign (positive inside the vesicles). Nor does the imposed membrane potential increase the reduction level of the haems in R. marinus SQR poised with the succinate/fumarate redox couple. The data do not support a widely discussed hypothesis on the electrogenic transmembrane electron transfer from succinate to menaquinone catalysed by di-haem SQRs. The role of the membrane potential in regulation of the SQR activity is discussed.

  11. Transimination of quinone imines: a mechanism for embedding exogenous redox activity into the nucleosome.

    PubMed

    Ye, Wenjie; Seneviratne, Uthpala I; Chao, Ming-Wei; Ravindra, Kodihalli C; Wogan, Gerald N; Tannenbaum, Steven R; Skipper, Paul L

    2012-12-17

    Aminophenols can redox cycle through the corresponding quinone imines to generate ROS. The electrophilic quinone imine intermediate can react with protein thiols as a mechanism of immobilization in vivo. Here, we describe the previously unkown transimination of a quinone imine by lysine as an alternative anchoring mechanism. The redox properties of the condensation product remain largely unchanged because the only structural change to the redox nucleus is the addition of an alkyl substituent to the imine nitrogen. Transimination enables targeting of histone proteins since histones are lysine-rich but nearly devoid of cysteines. Consequently, quinone imines can be embedded in the nucleosome and may be expected to produce ROS in maximal proximity to the genome.

  12. Quinone and Hydroquinone Metabolites from the Ascidians of the Genus Aplidium

    PubMed Central

    Bertanha, Camila Spereta; Januário, Ana Helena; Alvarenga, Tavane Aparecida; Pimenta, Letícia Pereira; e Silva, Márcio Luis Andrade; Cunha, Wilson Roberto; Pauletti, Patrícia Mendonça

    2014-01-01

    Ascidians of the genus Aplidium are recognized as an important source of chemical diversity and bioactive natural products. Among the compounds produced by this genus are non-nitrogenous metabolites, mainly prenylated quinones and hydroquinones. This review discusses the isolation, structural elucidation, and biological activities of quinones, hydroquinones, rossinones, longithorones, longithorols, floresolides, scabellones, conicaquinones, aplidinones, thiaplidiaquinones, and conithiaquinones. A compilation of the 13C-NMR spectral data of these compounds is also presented. PMID:24927227

  13. Crystal Structure and Density Functional Theory Studies of Toxic Quinone Metabolites of Polychlorinated Biphenyls

    PubMed Central

    Song, Yang; Ambati, Jyothirmai; Parkin, Sean; Rankin, Stephen E.; Robertson, Larry W.; Lehmler, Hans-Joachim

    2011-01-01

    Lower chlorinated polychlorinated biphenyls (PCBs) are readily metabolized via hydroxylated metabolites to reactive PCB quinones. Although these PCB metabolites elicit biochemical changes by mechanisms involving cellular target molecules, such as the Aryl hydrocarbon receptor, and toxicity by interacting with enzymes like topoisomerases, only few PCB quinones have been synthesized and their conformational properties investigated. Similar to the parent compounds, knowledge of the three-dimensional structure of PCB quinones may therefore be important to assess their fate and risk. To address this gap in our knowledge, the gas phase molecular structure of a series of PCB quinones was predicted using HF/3-21G, B3LYP/6-31G** and UB3LYP/6-311G** calculations and compared to the respective solid state structure. All three methods overestimated the Cl-C bond length, but otherwise provided a reasonable approximation of the solid state bond angles and bond lengths. Overall, the UB3LYP/6-311G** level of theory yielded the best approximation of the molecular structure of PCB quinones in the solid state. Chlorine addition at the ortho position of both rings was found to increase the dihedral angle of the resulting quinone compound, which may have important implications for their interaction with cellular targets and, thus, their toxicity. PMID:21824639

  14. Quinone- and nitroreductase reactions of Thermotoga maritima peroxiredoxin-nitroreductase hybrid enzyme.

    PubMed

    Anusevičius, Žilvinas; Misevičienė, Lina; Šarlauskas, Jonas; Rouhier, Nicolas; Jacquot, Jean-Pierre; Čėnas, Narimantas

    2012-12-01

    Thermotoga maritima peroxiredoxin-nitroreductase hybrid enzyme (Prx-NR) consists of a FMN-containing nitroreductase (NR) domain fused to a peroxiredoxin (Prx) domain. These domains seem to function independently as no electron transfer occurs between them. The reduction of quinones and nitroaromatics by NR proceeded in a two-electron manner, and follows a 'ping-pong' scheme with sometimes pronounced inhibition by quinone substrate. The comparison of steady- and presteady-state kinetic data shows that in most cases, the oxidative half-reaction may be rate-limiting in the catalytic cycle of NR. The enzyme was inhibited by dicumarol, a classical inhibitor of oxygen-insensitive nitroreductases. The reduction of quinones and nitroaromatic compounds by Prx-NR was characterized by the linear dependence of their reactivity (logk(cat)/K(m)) on their single-electron reduction potentials E(7)(1), while the reactivity of quinones markedly exceeded the one with nitroaromatics. It shows that NR lacks the specificity for the particular structure of these oxidants, except their single-electron accepting potency and the rate of electron self-exchange. It points to the possibility of a single-electron transfer step in a net two-electron reduction of quinones and nitroaromatics by T. maritima Prx-NR, and to a significant diversity of the structures of flavoenzymes which may perform the two-electron reduction of quinones and nitroaromatics.

  15. Cyclooxygenase-independent neuroprotective effects of aspirin against dopamine quinone-induced neurotoxicity.

    PubMed

    Asanuma, Masato; Miyazaki, Ikuko; Kikkawa, Yuri; Kimoto, Naotaka; Takeshima, Mika; Murakami, Shinki; Miyoshi, Ko

    2012-09-01

    Prostaglandin H synthase exerts not only cyclooxygenase activity but also peroxidase activity. The latter activity of the enzyme is thought to couple with oxidation of dopamine to dopamine quinone. Therefore, it has been proposed that cyclooxygenase inhibitors could suppress dopamine quinone formation. In the present study, we examined effects of various cyclooxygenase inhibitors against excess methyl L-3,4-dihydroxyphenylalanine (L-DOPA)-induced quinoprotein (protein-bound quinone) formation and neurotoxicity using dopaminergic CATH.a cells. The treatment with aspirin inhibited excess methyl L-DOPA-induced quinoprotein formation and cell death. However, acetaminophen did not show protective effects, and indomethacin and meloxicam rather aggravated these methyl L-DOPA-induced changes. Aspirin and indomethacin did not affect the level of glutathione that exerts quenching dopamine quinone in dopaminergic cells. In contrast with inhibiting effects of higher dose in the previous reports, relatively lower dose of aspirin that affected methyl L-DOPA-induced quinoprotein formation and cell death failed to prevent cyclooxygenase-induced dopamine chrome generation in cell-free system. Furthermore, aspirin but not acetaminophen or meloxicam showed direct dopamine quinone-scavenging effects in dopamine-semiquinone generating systems. The present results suggest that cyclooxygenase shows little contribution to dopamine oxidation in dopaminergic cells and that protective effects of aspirin against methyl L-DOPA-induced dopamine quinone neurotoxicity are based on its cyclooxygenase-independent property.

  16. Preventing effects of a novel anti-parkinsonian agent zonisamide on dopamine quinone formation.

    PubMed

    Asanuma, Masato; Miyazaki, Ikuko; Diaz-Corrales, Francisco J; Miyoshi, Ko; Ogawa, Norio; Murata, Miho

    2008-01-01

    The neurotoxicity of dopamine (DA) quinones as dopaminergic neuron-specific oxidative stress is considered to play a role in the pathogenesis and/or progression of Parkinson's disease (PD), since DA quinones conjugate with several key PD pathogenic molecules (e.g., tyrosine hydroxylase, alpha-synuclein and parkin) to form protein-bound quinone (quinoprotein) and consequently inhibit their functions. Zonisamide (ZNS) is used as an anti-epileptic agent but also improved the cardinal symptoms of PD in recent clinical trials in Japan. To evaluate the effects of ZNS on excess cytosolic free DA-induced quinone toxicity, we examined changes in DA quinone-related indices after ZNS treatment both in in vitro cell-free system and in cultured cells. Co-incubation of DA and ZNS in a cell-free system caused conversion of DA to stable melanin via formation of DA-semiquinone radicals and DA chrome. Long-term (5 days) treatment with ZNS decreased quinoprotein and increased DA/DOPA chromes in dopaminergic CATH.a cells. ZNS significantly inhibited quinoprotein formation induced by treatment with tetrahydrobiopterin and ketanserin that elevate cytosolic free DA in the cells. Our results suggest that the novel anti-parkinsonian agent ZNS possesses preventing effects against DA quinone formation induced by excess amount of cytosolic DA outside the synaptic vesicles.

  17. Toxocara canis: anthelmintic activity of quinone derivatives in murine toxocarosis.

    PubMed

    Mata-Santos, T; Mata-Santos, H A; Carneiro, P F; De Moura, K C G; Fenalti, J M; Klafke, G B; Cruz, L A X; Martins, L H R; Pinto, N F; Pinto, M C F R; Berne, M E A; Da Silva, P E A; Scaini, C J

    2016-04-01

    Human toxocarosis is a chronic tissue parasitosis most often caused by Toxocara canis. The seroprevalence can reach up to 50%, especially among children and adolescents. The anthelmintics used in the treatment have moderate efficacy. The aim of this study was to evaluate the in vitro and in vivo anthelmintic activity of quinones and their derivatives against T. canis larvae and the cytotoxicity of the larvicidal compounds. The compounds were evaluated at 1 mg mL(-1) concentration in microculture plates containing third stage larvae in an Roswell Park Memorial Institute (RPMI) 1640 environment, incubated at 37 °C in 5% CO2 tension for 48 h. Five naphthoxiranes were selected for the cytotoxicity analysis. The cell viability evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays using murine peritoneal macrophages isolated from C57BL/6 mice revealed that the naphthoxiranes (1 and 3) were less cytotoxic at a concentration of 0.05 mg mL(-1). The efficacy of naphthoxiranes (1 and 3) was examined in murine toxocarosis also. The anthelmintic activity was examined by evaluating the number of larvae in the brain, carcass, liver, lungs, heart, kidneys and eyes. Compound (3) demonstrated anthelmintic activity similar to that of albendazole by decreasing the number of larvae in the organs of mice and thus could form the basis of the development of a new anthelmintic drug.

  18. Terreic Acid, a Quinone Epoxide Inhibitor of Bruton's Tyrosine Kinase

    NASA Astrophysics Data System (ADS)

    Kawakami, Yuko; Hartman, Stephen E.; Kinoshita, Eiji; Suzuki, Hidefumi; Kitaura, Jiro; Yao, Libo; Inagaki, Naoki; Franco, Alessandra; Hata, Daisuke; Maeda-Yamamoto, Mari; Fukamachi, Hiromi; Nagai, Hiroichi; Kawakami, Toshiaki

    1999-03-01

    Bruton's tyrosine kinase (Btk) plays pivotal roles in mast cell activation as well as in B cell development. Btk mutations lead to severe impairments in proinflammatory cytokine production induced by cross-linking of high-affinity IgE receptor on mast cells. By using an in vitro assay to measure the activity that blocks the interaction between protein kinase C and the pleckstrin homology domain of Btk, terreic acid (TA) was identified and characterized in this study. This quinone epoxide specifically inhibited the enzymatic activity of Btk in mast cells and cell-free assays. TA faithfully recapitulated the phenotypic defects of btk mutant mast cells in high-affinity IgE receptor-stimulated wild-type mast cells without affecting the enzymatic activities and expressions of many other signaling molecules, including those of protein kinase C. Therefore, this study confirmed the important roles of Btk in mast cell functions and showed the usefulness of TA in probing into the functions of Btk in mast cells and other immune cell systems. Another insight obtained from this study is that the screening method used to identify TA is a useful approach to finding more efficacious Btk inhibitors.

  19. Pyrroloquinoline quinone (PQQ) prevents fibril formation of alpha-synuclein.

    PubMed

    Kobayashi, Masaki; Kim, Jihoon; Kobayashi, Natsuki; Han, Sungwoong; Nakamura, Chikashi; Ikebukuro, Kazunori; Sode, Koji

    2006-10-27

    Pyrroloquinoline quinone (PQQ) is a noncovalently bound cofactor in the bacterial oxidative metabolism of alcohols. PQQ also exists in plants and animals. Due to its inherent chemical feature, namely its free-radical scavenging properties, PQQ has been drawing attention from both the nutritional and the pharmacological viewpoint. alpha-Synuclein, a causative factor of Parkinson's disease (PD), has the propensity to oligomerize and form fibrils, and this tendency may play a crucial role in its toxicity. We show that PQQ prevents the amyloid fibril formation and aggregation of alpha-synuclein in vitro in a PQQ-concentration-dependent manner. Moreover, PQQ forms a conjugate with alpha-synuclein, and this PQQ-conjugated alpha-synuclein is also able to prevent alpha-synuclein amyloid fibril formation. This is the first study to demonstrate the characteristics of PQQ as an anti-amyloid fibril-forming reagent. Agents that prevent the formation of amyloid fibrils might allow a novel therapeutic approach to PD. Therefore, together with further pharmacological approaches, PQQ is a candidate for future anti-PD reagent compounds.

  20. The Neuroprotective Effect of Pyrroloquinoline Quinone on Traumatic Brain Injury

    PubMed Central

    Zhang, Lili; Liu, Jie; Cheng, Chun; Yuan, Ying; Yu, Biyun; Shen, Aiguo

    2012-01-01

    Abstract Pyrroloquinoline quinone (PQQ) is a water-soluble, anionic, quinonoid substance that has been established as an essential nutrient in animals. Owing to the inherent properties of PQQ as an antioxidant and redox modulator in various systems, PQQ is expected to be used in pharmacological applications in the near future. Although many recent studies have investigated its neuroprotective effects, the effect of PQQ on traumatic brain injury (TBI) has not been examined. In this study we employed Morris water maze (MWM) training, the results of which showed that PQQ led to improved behavioral performance in post-TBI animals. Considering that many experiments have suggested that β-1,4-galactosyltransferase I (β-1,4-GalT-I) and -V play significant roles in inflammation and the nervous system, in the present study we used Western blot analysis to study the effect of PQQ on the expression of β-1,4-GalT-I and -V. We found apparent expression upregulation of β-1,4-GalT-I and -V after PQQ was systemically administered. Lectin-fluorescent staining with RCA-I also revealed that PQQ contributed to expression upregulation of the galactosidase β-1 (Gal β-1), 4-galactosyltransferase N-acylsphingosine (4-GlcNAc) group in microglia and neurons of the cortex and hippocampal CA2 region. In summary, our experiment established that PQQ may play an important role in recovery post-TBI. PMID:22040225

  1. Ultrasensitive determination of pyrroloquinoline quinone in human plasma by HPLC with chemiluminescence detection using the redox cycle of quinone.

    PubMed

    Fukuda, Mizuho; El-Maghrabey, Mahmoud H; Kishikawa, Naoya; Ikemoto, Kazuto; Kuroda, Naotaka

    2017-10-25

    A fast, accurate, and ultrasensitive high-performance liquid chromatography method with chemiluminescence detection (HPLC-CL) was optimized and validated for the determination of pyrroloquinoline quinone (PQQ) concentration in human plasma following solid-phase extraction (SPE). This method is based on the redox cycle of the reaction between PQQ and dithiothreitol, which generates reactive oxygen species that can be detected using luminol as a CL probe. The isocratic HPLC system comprised an ODS column and 4.0mM tetra-n-butylammonium bromide in Tris-HNO3 buffer (pH 8.8; 50mM)-acetonitrile (7:3, v/v) as mobile phase. A novel, rapid, and simple SPE method was also developed providing excellent %recovery (≥95.2%) for PQQ from human plasma samples. The proposed method was linear over the range of 4.0-400nmol/L plasma of PQQ with a lower detection limit (S/N=3) of 1.08 nmol/L plasma (0.27nM). The method was successfully implemented to determine PQQ concentration in the plasma of healthy individuals after administration of PQQ supplements. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Syntrophic growth via quinone-mediated interspecies electron transfer

    PubMed Central

    Smith, Jessica A.; Nevin, Kelly P.; Lovley, Derek R.

    2015-01-01

    The mechanisms by which microbial species exchange electrons are of interest because interspecies electron transfer can expand the metabolic capabilities of microbial communities. Previous studies with the humic substance analog anthraquinone-2,6-disulfonate (AQDS) suggested that quinone-mediated interspecies electron transfer (QUIET) is feasible, but it was not determined if sufficient energy is available from QUIET to support the growth of both species. Furthermore, there have been no previous studies on the mechanisms for the oxidation of anthrahydroquinone-2,6-disulfonate (AHQDS). A co-culture of Geobacter metallireducens and G. sulfurreducens metabolized ethanol with the reduction of fumarate much faster in the presence of AQDS, and there was an increase in cell protein. G. sulfurreducens was more abundant, consistent with G. sulfurreducens obtaining electrons from acetate that G. metallireducens produced from ethanol, as well as from AHQDS. Co-cultures initiated with a citrate synthase-deficient strain of G. sulfurreducens that was unable to use acetate as an electron donor also metabolized ethanol with the reduction of fumarate and cell growth, but acetate accumulated over time. G. sulfurreducens and G. metallireducens were equally abundant in these co-cultures reflecting the inability of the citrate synthase-deficient strain of G. sulfurreducens to metabolize acetate. Evaluation of the mechanisms by which G. sulfurreducens accepts electrons from AHQDS demonstrated that a strain deficient in outer-surface c-type cytochromes that are required for AQDS reduction was as effective at QUIET as the wild-type strain. Deletion of additional genes previously implicated in extracellular electron transfer also had no impact on QUIET. These results demonstrate that QUIET can yield sufficient energy to support the growth of both syntrophic partners, but that the mechanisms by which electrons are derived from extracellular hydroquinones require further investigation. PMID

  3. Biotransformation of lepidocrocite in the presence of quinones and flavins

    NASA Astrophysics Data System (ADS)

    Bae, Sungjun; Lee, Woojin

    2013-08-01

    This study investigated the bioreduction of lepidocrocite (γ-FeIIIOOH) and its mineral transformation in the presence of exogenous (quinones) and endogenous (flavins) electron transfer mediators (ETMs) at low concentrations of the ETMs and bacterial cells (Shewanella putrefaciens CN32). It is very important to investigate the bioreduction of lepidocrocite in the presence of different ETMs because biotransformation of Fe(III)-containing minerals can be stimulated by ETMs and affect fate and transport of contaminants in contaminated environments. In the absence of phosphate, green rust formation was observed with fast Fe(II) production rate (0.44-0.56 mM d-1) during the bioreduction of lepidocrocite with exogenous ETMs, while goethite formed at slow Fe(II) production rate (0.24-0.29 mM d-1) with endogenous ETMs. In the presence of phosphate, formation of green rust and vivianite was observed with fast Fe(II) production rate (0.54-0.74 mM d-1) during the bioreduction of lepidocrocite with exogenous ETMs, while vivianite formed at moderate Fe(II) production rate (0.36-0.40 mM d-1) with endogenous ETMs. Vivianite formed in all experimental cases with phosphate in a broad range of Fe(II) production rates (0.23-0.74 mM d-1). Our results (1) suggest that exogenous and endogenous ETMs can significantly but differently affect the biotransformation of lepidocrocite, especially at low concentrations of the ETMs and bacterial cells, (2) highlight the importance of Fe(II) production rate to determine the formation of specific biogenic minerals, (3) provide additional evidence that phosphate can significantly affect the bioreduction rate and the mineral transformation, and (4) help to understand the basic knowledge about complex interactions among microbial cell, soil mineral, and ETM in natural environments and engineered systems.

  4. Changes in Quinone Profiles of Hot Spring Microbial Mats with a Thermal Gradient

    PubMed Central

    Hiraishi, Akira; Umezawa, Taichi; Yamamoto, Hiroyuki; Kato, Kenji; Maki, Yonosuke

    1999-01-01

    The respiratory and photosynthetic quinones of microbial mats which occurred in Japanese sulfide-containing neutral-pH hot springs at different temperatures were analyzed by spectrochromatography and mass spectrometry. All of the microbial mats that developed at high temperatures (temperatures above 68°C) were so-called sulfur-turf bacterial mats and produced methionaquinones (MTKs) as the major quinones. A 78°C hot spring sediment had a similar quinone profile. Chloroflexus-mixed mats occurred at temperatures of 61 to 65°C and contained menaquinone 10 (MK-10) as the major component together with significant amounts of either MTKs or plastoquinone 9 (PQ-9). The sunlight-exposed biomats growing at temperatures of 45 to 56°C were all cyanobacterial mats, in which the photosynthetic quinones (PQ-9 and phylloquinone) predominated and MK-10 was the next most abundant component in most cases. Ubiquinones (UQs) were not found or were detected in only small amounts in the biomats growing at temperatures of 50°C and above, whereas the majority of the quinones of a purple photosynthetic mat growing at 34°C were UQs. A numerical analysis of the quinone profiles was performed by using the following three parameters: dissimilarity index (D), microbial divergence index (MDq), and bioenergetic divergence index (BDq). A D matrix tree analysis showed that the hot spring mats consisting of the sulfur-turf bacteria, Chloroflexus spp., cyanobacteria, and purple phototrophic bacteria formed distinct clusters. Analyses of MDq and BDq values indicated that the microbial diversity of hot spring mats decreased as the temperature of the environment increased. The changes in quinone profiles and physiological types of microbial mats in hot springs with thermal gradients are discussed from evolutionary viewpoints. PMID:9872780

  5. Roles of bound quinone in the single subunit NADH-quinone oxidoreductase (Ndi1) from Saccharomyces cerevisiae.

    PubMed

    Yamashita, Tetsuo; Nakamaru-Ogiso, Eiko; Miyoshi, Hideto; Matsuno-Yagi, Akemi; Yagi, Takao

    2007-03-02

    To understand the biochemical basis for the function of the rotenone-insensitive internal NADH-quinone (Q) oxidoreductase (Ndi1), we have overexpressed mature Ndi1 in Escherichia coli membranes. The Ndi1 purified from the membranes contained one FAD and showed enzymatic activities comparable with the original Ndi1 isolated from Saccharomyces cerevisiae. When extracted with Triton X-100, the isolated Ndi1 did not contain Q. The Q-bound form was easily reconstituted by incubation of the Q-free Ndi1 enzyme with ubiquinone-6. We compared the properties of Q-bound Ndi1 enzyme with those of Q-free Ndi1 enzyme, with higher activity found in the Q-bound enzyme. Although both are inhibited by low concentrations of AC0-11 (IC(50) = 0.2 microm), the inhibitory mode of AC0-11 on Q-bound Ndi1 was distinct from that of Q-free Ndi1. The bound Q was slowly released from Ndi1 by treatment with NADH or dithionite under anaerobic conditions. This release of Q was prevented when Ndi1 was kept in the reduced state by NADH. When Ndi1 was incorporated into bovine heart submitochondrial particles, the Q-bound form, but not the Q-free form, established the NADH-linked respiratory activity, which was insensitive to piericidin A but inhibited by KCN. Furthermore, Ndi1 produces H(2)O(2) as isolated regardless of the presence of bound Q, and this H(2)O(2) was eliminated when the Q-bound Ndi1, but not the Q-free Ndi1, was incorporated into submitochondrial particles. The data suggest that Ndi1 bears at least two distinct Q sites: one for bound Q and the other for catalytic Q.

  6. Quinone profiles in lake sediments: Implications for microbial diversity and community structures.

    PubMed

    Hiraishi, Akira; Kato, Kenji

    1999-10-01

    Microbial quinone compositions of sediment mud samples from five different lakes in Japan were studied by spectrochromatography and mass spectrometry. The total quinone content of these samples ranged from 1.97 to 18.0 nmol/g dry weight of sediment, of which a combined fraction of ubiquinones and menaquinones accounted for 42 to 74%. The remaining fraction (26 to 58%) consisted of the photosynthetic quinones, plastoquinones and phylloquinone. The sediment samples produced PQ-9 or Q-8 as the most abundant quinone type regardless of their geographic locations and depths. These results indicate that oxygenic phototrophic microorganisms and Q-8-containing proteobacteria constituted major parts of microbial populations in the lake sediment. In the surface water of the same sampling sites, plastoquinones and phylloquinone occurred in much higher proportions. These findings suggested that the high abundance of oxygenic phototrophs in the sediment muds resulted from their constant movement or sedimentation from the surface water. Numerical analyses of the quinone profiles showed that the microbial communities of the sediment were diverse and different in different lakes but similar to each other in the diversity of bioenergetic modes. Three physiological groups of microbes showing ubiquinone-mediated aerobic respiration, oxygenic photosynthesis, and menaquinone-associated respiration were suggested to inhabit the lake sediments in balance.

  7. Chlorophyll-quinone photochemistry in liposomes: mechanisms of radical formation and decay

    SciTech Connect

    Hurley, J.K.; Tollin, G.

    1980-01-01

    Laser flash photolysis has been used to investigate the mechanism of formation and decay of the radical species generated by light induced electron transfer from chlorophyll a triplet to quinone in egg phosphatidyl choline bilayer vesicles. Chlorophyll triplet quenching by quinone is controlled by diffusion occurring within the bilayer membrane and reflects bilayer viscosity. Radical formation via separation of the intermediate ion pair is also inhibited by increased bilayer viscosity. Cooperativity is observed in this process due to an enhancement of radical separation by electron transfer from semiquinone anion radical to a neighboring quinone molecule. Two modes of radical decay are observed, a rapid recombination occurring within the bilayer and a much slower recombination occurring across the bilayer. The slow decay is only observed with quinones which are not tightly anchored into the bilayer, and is probably the result of electron transfer from semiquinone anion radical formed within the bilayer to a quinone molecule residing at the bilayer-water interface. With benzoquinone, approximately 60% of the radical decay occurs via the slow mode. Triplet to radical conversion efficiencies in the bilayer systems are comparable to those obtained in fluid solution (approx. 60%). However, radical recombination, at least for the slow decay mechanism, is considerably retarded.

  8. Redox potential tuning through differential quinone binding in the photosynthetic reaction center of Rhodobacter sphaeroides

    DOE PAGES

    Vermaas, Josh V.; Taguchi, Alexander T.; Dikanov, Sergei A.; ...

    2015-03-03

    Ubiquinone forms an integral part of the electron transport chain in cellular respiration and photosynthesis across a vast number of organisms. Prior experimental results have shown that the photosynthetic reaction center (RC) from Rhodobacter sphaeroides is only fully functional with a limited set of methoxy-bearing quinones, suggesting that specific interactions with this substituent are required to drive electron transport and the formation of quinol. The nature of these interactions has yet to be determined. Through parameterization of a CHARMM-compatible quinone force field and subsequent molecular dynamics simulations of the quinone-bound RC, in this paper we have investigated and characterized themore » interactions of the protein with the quinones in the QA and QB sites using both equilibrium simulation and thermodynamic integration. In particular, we identify a specific interaction between the 2-methoxy group of ubiquinone in the QB site and the amide nitrogen of GlyL225 that we implicate in locking the orientation of the 2-methoxy group, thereby tuning the redox potential difference between the quinones occupying the QA and QB sites. Finally, disruption of this interaction leads to weaker binding in a ubiquinone analogue that lacks a 2-methoxy group, a finding supported by reverse electron transfer electron paramagnetic resonance experiments of the QA–QB– biradical and competitive binding assays.« less

  9. Localization of Ubiquinone-8 in the Na+-pumping NADH:Quinone Oxidoreductase from Vibrio cholerae*

    PubMed Central

    Casutt, Marco S.; Nedielkov, Ruslan; Wendelspiess, Severin; Vossler, Sara; Gerken, Uwe; Murai, Masatoshi; Miyoshi, Hideto; Möller, Heiko M.; Steuber, Julia

    2011-01-01

    Na+ is the second major coupling ion at membranes after protons, and many pathogenic bacteria use the sodium-motive force to their advantage. A prominent example is Vibrio cholerae, which relies on the Na+-pumping NADH:quinone oxidoreductase (Na+-NQR) as the first complex in its respiratory chain. The Na+-NQR is a multisubunit, membrane-embedded NADH dehydrogenase that oxidizes NADH and reduces quinone to quinol. Existing models describing redox-driven Na+ translocation by the Na+-NQR are based on the assumption that the pump contains four flavins and one FeS cluster. Here we show that the large, peripheral NqrA subunit of the Na+-NQR binds one molecule of ubiquinone-8. Investigations of the dynamic interaction of NqrA with quinones by surface plasmon resonance and saturation transfer difference NMR reveal a high affinity, which is determined by the methoxy groups at the C-2 and C-3 positions of the quinone headgroup. Using photoactivatable quinone derivatives, it is demonstrated that ubiquinone-8 bound to NqrA occupies a functional site. A novel scheme of electron transfer in Na+-NQR is proposed that is initiated by NADH oxidation on subunit NqrF and leads to quinol formation on subunit NqrA. PMID:21885438

  10. Programmed cell death in plants: protective effect of mitochondrial-targeted quinones.

    PubMed

    Vasil'ev, L A; Dzyubinskaya, E V; Kiselevsky, D B; Shestak, A A; Samuilov, V D

    2011-10-01

    Ubiquinone or plastoquinone covalently linked to synthetic decyltriphenylphosphonium (DTPP(+)) or rhodamine cations prevent programmed cell death (PCD) in pea leaf epidermis induced by chitosan or CN(-). PCD was monitored by recording the destruction of cell nuclei. CN(-) induced the destruction of nuclei in both epidermal cells (EC) and guard cells (GC), whereas chitosan destroyed nuclei in EC not in GC. The half-maximum concentrations for the protective effects of the quinone derivatives were within the pico- and nanomolar range. The protective effect of the quinones was removed by a protonophoric uncoupler and reduced by tetraphenylphosphonium cations. CN(-)-Induced PCD was accelerated by the tested quinone derivatives at concentrations above 10(-8)-10(-7) M. Unlike plastoquinone linked to the rhodamine cation (SkQR1), DTPP(+) derivatives of quinones suppressed menadione-induced H(2)O(2) generation in the cells. The CN(-)-induced destruction of GC nuclei was prevented by DTPP(+) derivatives in the dark not in the light. SkQR1 inhibited this process both in the dark and in the light, and its effect in the light was similar to that of rhodamine 6G. The data on the protective effect of cationic quinone derivatives indicate that mitochondria are involved in PCD in plants.

  11. Effects of humic substances and quinones at low concentrations on ferrihydrite reduction by Geobacter metallireducens.

    PubMed

    Wolf, Manfred; Kappler, Andreas; Jiang, Jie; Meckenstock, Rainer U

    2009-08-01

    Humic substances (HS) and quinones can accelerate dissimilatory Fe(III) reduction by electron shuttling between microorganisms and poorly soluble iron(III) (hydr)oxides. The mechanism of electron shuttling for HS is not fully understood, but it is suggested that the most important redox-active components in HS are also quinones. Here we studied the influence of HS and different quinones at low concentrations on ferrihydrite reduction by Geobacter metallireducens. The aquatic HS used were humic and fulvic acids (HA and FA) isolated from groundwater of a deep aquifer in Gorleben (Niedersachsen, Germany). HA stimulated iron reduction stronger than FA down to total HA concentrations as low as 1 mg/L. The quinones studied showed large differences: some had strong accelerating effects, whereas others showed only small effects, no effects, or even inhibitory effects on the kinetics of iron reduction. We found that the redox potentials of the most active quinones fall in a narrow range of -137 to -225 mV vs NHE at pH 7. These results give evidence that the kinetic of microbial iron reduction mediated by electron shuttles is mainly controlled by thermodynamic parameters, i.e., by the redox potential of the shuttle compound, rather than by the proportion of dissolved vs adsorbed compound.

  12. Quinones: reactions with hemoglobin, effects within erythrocytes and potential for antimalarial development

    SciTech Connect

    Denny, B.J.

    1986-01-01

    The focus of this research was to characterize the interactions of some simple quinone like compounds with purified hemoglobin and to study the effects of these compounds within erythrocytes. It is proposed that these sorts of agents can have an antimalarial effect. The simplest compounds chosen for study were benzoquinone, methylquinone (toluquinone) and hydroquinone. When /sup 14/C-quinone was reacted with purified hemoglobin (Hb) there was rapid binding of the first two moles of substrate per Hb molecule. An unusual property of the modified Hb's is that in the presence of a redox sensitive agent such as cytochrome c they are capable of generating superoxide anions. Within erythrocytes, quinone and toluquinone which differ only by a single methyl group have completely different effects. Toluquinone causes the cells to hemolyse and the effect was enhanced when the erythrocyte superoxide dismutase was inhibited; the effect was diminished when scavengers of activated oxygen such as histidine, mannitol and vital E were present. Benzoquinone on the other hand did not cause the cells to hemolyse and instead appeared to protect the cells from certain hemolytic stresses. Growth of malaria parasites in erythrocytes has been shown to be inhibited by activated forms of oxygen, also some quinone like agents in the past have been shown to inhibit the parasite's metabolism. An initial experiment with erythrocytes infected with malaria parasites showed that quinone and toluquinone could both inhibit the growth rate of parasites.

  13. Quinone-related hexacyclic by-products in the production process of exemestane.

    PubMed

    Giovenzana, Giovanni Battista; Masciocchi, Norberto; Negri, Roberto; Palmisano, Giovanni; Penoni, Andrea; Toma, Lucio

    2017-04-01

    Exemestane, a 3rd-generation aromatase inhibitor, is clinically used in the treatment of breast cancer in postmenopausal women. The key step of the industrial synthetic process, i.e., a dehydrogenation to introduce the Δ(1)-unsaturation, is normally performed with quinones such as p-chloranil or DDQ. We observed the formation of two different hexacyclic by-products, depending on the quinone used in the oxidation step. These compounds arise from an initial [4+2] cycloaddition between the precursor 6-methylenandrost-4-ene-3,17-dione and the quinone reagent, followed by a twofold dehydrohalogenation (with p-chloranil) or dehydrogenation (with DDQ). The structures of these unprecedented hexacyclic adducts were determined by a combination of mass spectrometry, NMR techniques and crystallographic analysis.

  14. Function of isoprenoid quinones and chromanols during oxidative stress in plants.

    PubMed

    Kruk, Jerzy; Szymańska, Renata; Nowicka, Beatrycze; Dłużewska, Jolanta

    2016-09-25

    Isoprenoid quinones and chromanols in plants fulfill both signaling and antioxidant functions under oxidative stress. The redox state of the plastoquinol pool (PQ-pool), which is modulated by interaction with reactive oxygen species (ROS) during oxidative stress, has a major regulatory function in both short- and long-term acclimatory responses. By contrast, the scavenging of ROS by prenyllipids affects signaling pathways where ROS play a role as signaling molecules. As the primary antioxidants, isoprenoid quinones and chromanols are synthesized under high-light stress in response to any increased production of ROS. During photo-oxidative stress, these prenyllipids are continuously synthesized and oxidized to other compounds. In turn, their oxidation products (hydroxy-plastochromanol, plastoquinol-C, plastoquinone-B) can still have an antioxidant function. The oxidation products of isoprenoid quinones and chromanols formed specifically in the face of singlet oxygen, can be indicators of singlet oxygen stress.

  15. Experimental and Theoretical Reduction Potentials of Some Biologically Active ortho-Carbonyl para-Quinones.

    PubMed

    Martínez-Cifuentes, Maximiliano; Salazar, Ricardo; Ramírez-Rodríguez, Oney; Weiss-López, Boris; Araya-Maturana, Ramiro

    2017-04-04

    The rational design of quinones with specific redox properties is an issue of great interest because of their applications in pharmaceutical and material sciences. In this work, the electrochemical behavior of a series of four p-quinones was studied experimentally and theoretically. The first and second one-electron reduction potentials of the quinones were determined using cyclic voltammetry and correlated with those calculated by density functional theory (DFT) using three different functionals, BHandHLYP, M06-2x and PBE0. The differences among the experimental reduction potentials were explained in terms of structural effects on the stabilities of the formed species. DFT calculations accurately reproduced the first one-electron experimental reduction potentials with R² higher than 0.94. The BHandHLYP functional presented the best fit to the experimental values (R² = 0.957), followed by M06-2x (R² = 0.947) and PBE0 (R² = 0.942).

  16. [On the electron stabilization within the quinone acceptor part of Rhodobacter sphaeroides photosynthetic reaction centers].

    PubMed

    Noks, P P; Krasil'nikov, P M; Mamonov, P A; Seĭfullina, N Kh; Uchoa, A F; Baptista, M S

    2008-01-01

    The time evolution of the photoinduced differential absorption spectrum of isolated Rhodobacter sphaeroides photosynthetic reaction centers was investigated. The measurements were carried out in the spectral region of 400-500 nm on the time scale of up to 200 microseconds. The spectral changes observed can be interpreted in terms of the effects of proton shift along hydrogen bonds between the primary quinone acceptor and the protein. A theoretical analysis of the spectrum time evolution was performed, which is based on the consideration of the kinetics of proton tunneling along the hydrogen bond. It was shown that the stabilization of the primary quinone electronic state occurs within the first several tens of microseconds after quinone reduction. It slows down upon the deuteration of reaction centers as well as after adding 90% of glycerol; on the other hand, it accelerates as temperature rises up to 40 degrees C.

  17. TC and H NMR studies of PQQ and selected derivatives. [Pyrroloquinoline quinone

    SciTech Connect

    Houck, D.R.; Unkefer, C.J.

    1988-01-01

    The ortho-quinone structure of pyrroloquinoline quinone (PQQ) is famous for its reactivity with nucleophilic species of carbon, nitrogen, and oxygen(Duine et. al. 1987). In fact, the crystal structure of PQQ was solved in the form of the C-5 acetone adduct(Salisbury et. al 1979). The propensity of the ortho-quinone to accept nucleophiles is the chemical basis of the function of PQQ at enzyme active sites. The present study focuses on the NMR of PQQ and various derivatives formed with oxygen and nitrogen nucleophiles. Our goals are to assign the H, TC, and VN NMR spectra and to rigorously confirm the structures of the adducts. Once the NMR data of the relevant adducts are well defined, we will use TC and VN labeled substrates to probe the active sites of PQQ containing enzymes. 7 refs., 2 figs., 1 tab.

  18. Photoinduced electron transfer reactions of ruthenium(II)-complexes containing amino acid with quinones.

    PubMed

    Eswaran, Rajkumar; Kalayar, Swarnalatha; Paulpandian, Muthu Mareeswaran; Seenivasan, Rajagopal

    2014-05-01

    With the aim of mimicking, at basic level the photoinduced electron transfer process in the reaction center of photosystem II, ruthenium(II)-polypyridyl complexes, carrying amino acids were synthesized and studied their photoinduced electron transfer reactions with quinones by steady state and time resolved measurements. The reaction of quinones with excited state of ruthenium(II)-complexes, I-V in acetonitrile has been studied by luminescence quenching technique and the rate constant, k(q), values are close to the diffusion controlled rate. The detection of the semiquinone anion radical in this system using time-resolved transient absorption spectroscopy confirms the electron transfer nature of the reaction. The semiclassical theory of electron transfer has been successfully applied to the photoluminescence quenching of Ru(II)-complexes with quinones.

  19. Mechanism and analyses for extracting photosynthetic electrons using exogenous quinones - what makes a good extraction pathway?

    PubMed

    Longatte, G; Rappaport, F; Wollman, F-A; Guille-Collignon, M; Lemaître, F

    2016-08-04

    Plants or algae take many benefits from oxygenic photosynthesis by converting solar energy into chemical energy through the synthesis of carbohydrates from carbon dioxide and water. However, the overall yield of this process is rather low (about 4% of the total energy available from sunlight is converted into chemical energy). This is the principal reason why recently many studies have been devoted to extraction of photosynthetic electrons in order to produce a sustainable electric current. Practically, the electron transfer occurs between the photosynthetic organism and an electrode and can be assisted by an exogenous mediator, mainly a quinone. In this regard, we recently reported on a method involving fluorescence measurements to estimate the ability of different quinones to extract photosynthetic electrons from a mutant of Chlamydomonas reinhardtii. In the present work, we used the same kind of methodology to establish a zone diagram for predicting the most suitable experimental conditions to extract photoelectrons from intact algae (quinone concentration and light intensity) as a function of the purpose of the study. This will provide further insights into the extraction mechanism of photosynthetic electrons using exogenous quinones. Indeed fluorescence measurements allowed us to model the capacity of photosynthetic algae to donate electrons to an exogenous quinone by considering a numerical parameter called "open center ratio" which is related to the Photosystem II acceptor redox state. Then, using it as a proxy for investigating the extraction of photosynthetic electrons by means of an exogenous quinone, 2,6-DCBQ, we suggested an extraction mechanism that was globally found consistent with the experimentally extracted parameters.

  20. Role of quinones on the ascorbate reduction rates of S-nitrosogluthathione

    PubMed Central

    Sanchez-Cruz, Pedro; Garcia, Carmelo; Alegria, Antonio E.

    2010-01-01

    Quinones are one of the largest class of antitumor agents approved for clinical use and several antitumor quinones are in different stages of clinical and preclinical development. Many of these are metabolites of, or are, environmental toxins. Due to their chemical structure these are known to enhance electron transfer processes such as ascorbate oxidation and NO reduction. The paraquinones 2,6-dimethyl-1,4-benzoquinone (DMBQ), 1,4-benzoquinone (BQ), methyl-1,4-benzoquinone (MBQ), 2,6-dimethoxy-1,4-benzoquinone (DMOBQ), 2-hydroxymethyl-6-methoxy-1,4-benzoquinone (HMOBQ), trimethyl-1,4-benzoquinone (TMQ), tetramethyl-1,4-benzoquinone (DQ), 2,3-dimethoxy-5-methyl-1,4-benzoquinone (UBQ-0), the paranaphthoquinones 1,4-naphthoquinone (NQ), menadione (MNQ), 1,4-naphthoquinone-2-sulfonate (NQ2S), juglone (JQ) and phenanthroquinone (PHQ) all enhance the anaerobic rate of ascorbate reduction of GSNO to produce NO and GSH. Rates of this reaction were much larger for p-benzoquinones and PHQ than for p-naphthoquinone derivatives with similar one-electron redox potentials. The quinone DMBQ also enhances the rate of NO production from S-nitrosylated bovine serum albumin (BSA-NO) upon ascorbate reduction. Density functional theory calculations suggest that stronger interactions between p-benzo- or phenanthrasemiquinones than those of p-naphthosemiquinones with GSNO are the major causes of these differences. Thus, quinones, and especially p-quinones and PHQ, could act as NO release enhancers from GSNO in biomedical systems in the presence of ascorbate. Since quinones are exogenous toxins which could enter the human body via a chemotherapeutic application or as an environmental contaminant, these could boost the release of NO from S-nitrosothiol storages in the body in the presence of ascorbate and thus enhance the responses elicited by a sudden increase in NO levels. PMID:20691779

  1. Towards a modern definition of vitamin E-evidence for a quinone hypothesis.

    PubMed

    Shrader, William D; Amagata, Akiko; Barnes, Adam; Hinman, Andrew; Jankowski, Orion; Lee, Edgar; Kheifets, Viktoria; Komatsuzaki, Ryo; Mollard, Paul; Murase, Katsuyuki; Rioux, Patrice; Wesson, Kieron; Miller, Guy

    2012-01-01

    We report on the synthesis, biological and pharmacological activity of the tocoquinone natural product, α-tocopherol quinone (ATQ); an oxidative metabolite of α-tocopherol. ATQ is a potent cellular protectant against oxidative stress, whose biological activity is dependent upon its ability to undergo reversible two-electron redox cycling. ATQ is orally bioavailable, with a favorable pharmacokinetic profile and has demonstrated a beneficial clinical response in patients with Friedreich's ataxia. ATQ is a member of a broader class of vitamin E derived quinone metabolites which may be ascribable in whole or in part to the activity of vitamin E.

  2. Substituent effects on carbocation stability: the pK(R) for p-quinone methide.

    PubMed

    Toteva, Maria M; Moran, Michael; Amyes, Tina L; Richard, John P

    2003-07-23

    A value of k(H) = 1.5 x 10(-)(3) M(-)(1) s(-)(1) has been determined for the generation of simple p-quinone methide by the acid-catalyzed cleavage of 4-hydroxybenzyl alcohol in water at 25 degrees C and I = 1.0 (NaClO(4)). This was combined with k(s) = 5.8 x 10(6) s(-)(1) for the reverse addition of solvent water to the 4-hydroxybenzyl carbocation [J. Am. Chem. Soc. 2002, 124, 6349-6356] to give pK(R) = -9.6 as the Lewis acidity constant of O-protonated p-quinone methide. Values of pK(R) = 2.3 for the Lewis acidity constant of neutral p-quinone methide and pK(add) = -7.6 for the overall addition of solvent water to p-quinone methide to form 4-hydroxybenzyl alcohol are also reported. The thermodynamic driving force for transfer of the elements of water from formaldehyde hydrate to p-quinone methide to form formaldehyde and p-(hydroxymethyl)phenol (4-hydroxybenzyl alcohol) is determined as 6 kcal/mol. This relatively small driving force represents the balance between the much stronger chemical bonds to oxygen at the reactant formaldehyde hydrate than at the product p-(hydroxymethyl)phenol and the large stabilization of product arising from the aromatization that accompanies solvent addition to p-quinone methide. The Marcus intrinsic barrier for nucleophilic addition of solvent water to the "extended" carbonyl group at p-quinone methide is estimated to be 4.5 kcal/mol larger than that for the addition of water to the simple carbonyl group of formaldehyde. O-Alkylation of p-quinone methide to give the 4-methoxybenzyl carbocation and of formaldehyde to give a simple oxocarbenium ion results in very little change in the relative Marcus intrinsic barriers for the addition of solvent water to these electrophiles.

  3. Quinone-mediated decolorization of sulfonated azo dyes by cells and cell extracts from Sphingomonas xenophaga.

    PubMed

    Jiao, Ling; Lu, Hong; Zhou, Jiti; Wang, Jing

    2009-01-01

    The effects of various quinone compounds on the decolorization rates of sulfonated azo dyes by Sphingomonas xenophaga QYY were investigated. The results showed that anthraquinone-2-sulfonate (AQS) was the most effective redox mediator and AQS reduction was the rate-limited step of AQS-mediated decolorization of sulfonated azo dyes. Based on AQS biological toxicity tests, it was assumed that AQS might enter the cells and kill them. In the cytoplasmic extracts from strain QYY, AQS more effectively increased decolorization rates of sulfonated azo dyes than other quinone compounds. In addition, we found a NADH/FMN-dependent AQS reductase using nondenaturing polyacrylamide gel electrophoresis (Native-PAGE).

  4. Two-electron reduction of quinones by Enterobacter cloacae PB2 pentaerythritol tetranitrate reductase: quantitative structure-activity relationships.

    PubMed

    Miseviciene, Lina; Anusevicius, Zilvinas; Sarlauskas, Jonas; Harris, Richard J; Scrutton, Nigel S; Cenas, Narimantas

    2007-01-01

    In order to clarify the poorly understood mechanisms of two-electron reduction of quinones by flavoenzymes, we examined the quinone reductase reactions of a member of a structurally distinct old yellow enzyme family, Enterobacter cloacae PB2 pentaerythritol tetranitrate reductase (PETNR). PETNR catalyzes two-electron reduction of quinones according to a 'ping-pong' scheme. A multiparameter analysis shows that the reactivity of quinones increases with an increase in their single-electron reduction potential and pK(a) of their semiquinones (a three-step (e(-),H(+),e(-)) hydride transfer scheme), or with an increase in their hydride-transfer potential (E(7)(H(-))) (a single-step (H(-)) hydride transfer scheme), and decreases with a decrease in their van der Waals volume. However, the pH-dependence of PETNR reactivity is more consistent with a single-step hydride transfer. A comparison of X-ray data of PETNR, mammalian NAD(P)H : quinone oxidoreductase (NQO1), and Enterobacter cloacae nitroreductase, which reduce quinones in a two-electron way, and their reactivity revealed that PETNR is much less reactive, and much less sensitive to the quinone substrate steric effects than NQO1. This may be attributed to the lack of pi-pi stacking between quinone and the displaced aromatic amino acid in the active center, e.g., with Phe-178' in NQO1.

  5. Environmental effects on electron transfer from chlorophyll triplet to quinone: role of dielectric constant, viscosity and quinone structure in cellulose acetate films

    SciTech Connect

    Cheddar, G.; Tollin, G.

    1981-01-01

    The effects of environmental parameters on chlorophyll triplet quenching and electron transfer to quinones have been investigated in a system consisting of donor and acceptor incorporated into a cellulose acetate film which was subsequently exposed to solvent. Triplet quenching by a diffusional mechanism was found to occur in the dry film, with steric effects being a major determinant of quencher effectiveness. No formation of separated radicals was found under these conditions, probably because the high viscosity prevented separation of the initially formed radical-ion pair. When the film was subsequently exposed to water, triplet quenching became more effective and separated radical production occurred. This is attributed to effects of decreased microviscosity and increased dielectric constant. Both steric effects and quinone redox potential were found to influence radical yields. Rate constants for reverse electron transfer were independent of quinone redox potential. When solvents other than pure water were used, radical yields were observed to increase with the dielectric constant. This is ascribed to an increase in the ease of separation of the radical-ion pair.

  6. Protonated paramagnetic redox forms of di-o-quinone bridged with p-phenylene-extended TTF: A EPR spectroscopy study

    PubMed Central

    Chalkov, Nikolay O; Cherkasov, Vladimir K; Abakumov, Gleb A; Starikov, Andrey G

    2016-01-01

    The chemical oxidation and reduction processes of deprotonated, direduced o-quinone-exTTF-o-quinone in protic solvents were studied by EPR spectroscopy. The formation of relatively stable paramagnetic protonated redox forms of the parent triad was very surprising. The character of spin-density distribution in the semiquinone–quinone and semiquinone–catechol redox forms indicates that the p-phenylene-extended tetrathiafulvalene connector provides a quite effective electronic communication channel between dioxolene coordination sites. It was found that the deprotonated, direduced o-quinone-exTTF-o-quinone is capable to reduction of the metal copper in solution. The radical anion species formed in this reaction exists in solution as a solvent-separated ion pair with a copper cation. A character of spin-density distribution in a radical anion species leads to the conclusion that the ligand corresponds to type III of the Robin–Day classification. PMID:28144312

  7. Preserving the adhesion of catechol-conjugated hydrogels by thiourea-quinone coupling.

    PubMed

    Xu, Yang J; Wei, Kongchang; Zhao, Pengchao; Feng, Qian; Choi, Chun Kit K; Bian, Liming

    2016-11-15

    Mussel adhesion has inspired the development of catechol-based adhesive polymers. However, conventional strategies require basic pH conditions and lead to the loss of adhesion. To solve the problem, we report the first attempt to use thiourea-functionalized polymers for preserving hydrogel adhesion. We believe that this simple thiourea-quinone coupling chemistry is instrumental to synthetic adhesive materials.

  8. Extraction methods determine the antioxidant capacity and induction of quinone reductase by soy products in vitro

    USDA-ARS?s Scientific Manuscript database

    Gastrointestinal mimic (GI) and organic solvent extracts of whole soybean powder (WSP), soy protein concentrate (SPC), and soy protein isolate (SPI) as well as soy isoflavone concentrate (SIC) were analyzed for total phenols; quinone reductase (QR) induction in hepa1c1c7 cells; antioxidant scavengi...

  9. EXAMINATION OF QUINONE TOXICITY USING YEAST SACCHAROMYCES CEREVISIAE MODEL SYSTEM. (R827352C007)

    EPA Science Inventory

    The toxicity of quinones is generally thought to occur by two mechanisms: the formation of covalent bonds with biological molecules by Michael addition chemistry and the catalytic reduction of oxygen to superoxide and other reactive oxygen species (ROS) (redox cycling). In an ...

  10. Genomic Analysis of the Human Gut Microbiome Suggests Novel Enzymes Involved in Quinone Biosynthesis.

    PubMed

    Ravcheev, Dmitry A; Thiele, Ines

    2016-01-01

    Ubiquinone and menaquinone are membrane lipid-soluble carriers of electrons that are essential for cellular respiration. Eukaryotic cells can synthesize ubiquinone but not menaquinone, whereas prokaryotes can synthesize both quinones. So far, most of the human gut microbiome (HGM) studies have been based on metagenomic analysis. Here, we applied an analysis of individual HGM genomes to the identification of ubiquinone and menaquinone biosynthetic pathways. In our opinion, the shift from metagenomics to analysis of individual genomes is a pivotal milestone in investigation of bacterial communities, including the HGM. The key results of this study are as follows. (i) The distribution of the canonical pathways in the HGM genomes was consistent with previous reports and with the distribution of the quinone-dependent reductases for electron acceptors. (ii) The comparative genomics analysis identified four alternative forms of the previously known enzymes for quinone biosynthesis. (iii) Genes for the previously unknown part of the futalosine pathway were identified, and the corresponding biochemical reactions were proposed. We discuss the remaining gaps in the menaquinone and ubiquinone pathways in some of the microbes, which indicate the existence of further alternate genes or routes. Together, these findings provide further insight into the biosynthesis of quinones in bacteria and the physiology of the HGM.

  11. Enantioselective [4 + 1] cycloaddition of ortho-quinone methides and bromomalonates under phase-transfer catalysis.

    PubMed

    Lian, Xiao-Lei; Adili, Alafate; Liu, Bin; Tao, Zhong-Lin; Han, Zhi-Yong

    2017-05-03

    An enantioselective [4 + 1] cycloaddition reaction of ortho-quinone methides and bromomalonates using a quinine and BINOL derived phase-transfer catalyst is described. With high yields and enantioselectivities, the method provided a variety of optically active dihydrobenzofurans, which represent a valuable structural motif present in numerous naturally occurring and biologically active molecules.

  12. Rat liver mitochondrial and microsomal tests for the assessment of quinone toxicity

    SciTech Connect

    Bramble, L.A.; Boardman, G.D.; Dietrich, A.M. . Dept. of Civil Engineering); Bevan, D.R. . Dept. of Biochemistry)

    1994-02-01

    Short-term toxicity tests using mitochondrial and microsomal metabolism were developed and applied to a series of eight quinones. In the mitochondrial assay, the degree to which test compounds inhibited mitochondrial respiration varied from an effective concentration (EC50) of 9 to 125 [mu]M. In the microsomal assay, the maximum percentage of increase over control oxygen consumption rates elicited by the quinones ranged from 8 to 837%. The ability of the compounds to stimulate microsomal oxygen uptake reflects their capability to redox cycle and form reactive oxygen species. Results of the mitochondrial and microsomal assay were statistically correlated with several quinone physicochemical parameters and qualitatively compared to reduction potential. The biological response observed in both test systems appeared to be most strongly influenced by the reduction potential of the quinone. Biomechanisms of action were suggested on the basis of this relationship. To assess the ability of the mitochondrial and microsomal assays to indicate toxicity of the quinonoid compounds, results were statistically correlated with literature-derived toxicity data. It was concluded that the mitochondrial assay appears to be a valid indicator of acute toxicity, whereas the microsomal assay better portends the potential for chronic toxicity.

  13. Differential antioxidant and quinone reductase inducing activity of American, Asian, and Siberian ginseng

    USDA-ARS?s Scientific Manuscript database

    The antioxidant and quinone reductase (QR) inducing activities of American, Asian, and Siberian ginseng have been reported using various plant materials, solvents, and assays. To directly establish their comparative bioactivity, the effects of extracts obtained from acidified methanol (MeOH), a gas...

  14. EXAMINATION OF QUINONE TOXICITY USING YEAST SACCHAROMYCES CEREVISIAE MODEL SYSTEM. (R827352C007)

    EPA Science Inventory

    The toxicity of quinones is generally thought to occur by two mechanisms: the formation of covalent bonds with biological molecules by Michael addition chemistry and the catalytic reduction of oxygen to superoxide and other reactive oxygen species (ROS) (redox cycling). In an ...

  15. Mechanism of enhanced removal of quinonic intermediates during electrochemical oxidation of Orange II under ultraviolet irradiation.

    PubMed

    Li, Fazhan; Li, Guoting; Zhang, Xiwang

    2014-03-01

    The effect of ultraviolet irradiation on generation of radicals and formation of intermediates was investigated in electrochemical oxidation of the azo-dye Orange II using a TiO2-modified β-PbO2 electrode. It was found that a characteristic absorbance of quinonic compounds at 255 nm, which is responsible for the rate-determining step during aromatics degradation, was formed only in electrocatalytic oxidation. The dye can be oxidized by either HO radicals or direct electron transfer. Quinonic compounds were produced concurrently. The removal of TOC by photo-assisted electrocatalytic oxidation was 1.56 times that of the sum of the other two processes, indicating a significant synergetic effect. In addition, once the ultraviolet irradiation was introduced into the process of electrocatalytic oxidation, the degradation rate of quinonic compounds was enhanced by as much as a factor of two. The more efficient generation of HO radicals resulted from the introduction of ultraviolet irradiation in electrocatalytic oxidation led to the significant synergetic effect as well as the inhibiting effect on the accumulation of quinonic compounds.

  16. Rates of hydroxyl radical production from transition metals and quinones in a surrogate lung fluid

    PubMed Central

    Charrier, Jessica G.; Anastasio, Cort

    2016-01-01

    Hydroxyl radical (.OH) is the most reactive, and perhaps most detrimental to health, of the reactive oxygen species. .OH production in lungs following inhalation of particulate matter (PM) can result from redox-active chemicals, including iron and copper, but the relative importance of these species is unknown. This work investigates .OH production from iron, copper, and quinones, both individually and in mixtures at atmospherically relevant concentrations. Iron, copper and three of the four quinones (1,2-naphthoquinone, phenanthrenequinone and 1,4-naphthoquinone) produce .OH. Mixtures of copper or quinones with iron synergistically produce .OH at a rate 20 - 130% higher than the sum of the rates of the individual redox-active species. We developed a regression equation from 20 mixtures to predict the rate of .OH production from the particle composition. For typical PM compositions, iron and copper account for most .OH production, while quinones are a minor source, although they can contribute if present at very high concentrations. This work shows that Cu contributes significantly to .OH production in ambient PM; other work has shown that Cu appears to be the primary driver of HOOH production and dithiothreitol (DTT) loss in ambient PM extracts. Taken together, these results indicate that copper appears to be the most important individual contributor to direct oxidant production from inhaled PM. PMID:26153923

  17. Differential stress-induced regulation of two quinone reductases in the brown rot Basidiomycete Gloeophyllum trabeum

    Treesearch

    Roni Cohen; Melissa R. Suzuki; Kenneth E. Hammel

    2004-01-01

    Quinone reductases (QRDs) have two important functions in the basidiomycete Gloeophyllum trabeum, which causes brown rot of wood. First, a QRD is required to generate biodegradative hydroxyl radicals via redox cycling between two G. trabeum extracellular metabolites, 2,5-dimethoxyhydroquinone (2,5-DMHQ) and 2,5-dimethoxy-1,4-benzoquinone (2,5- DMBQ). Second, because 2,...

  18. Induction of micronuclei and aneuploidy by the quinone-forming agents benzene and o-phenylphenol.

    PubMed

    Eastmond, D A

    1993-04-01

    A number of carcinogens appear to exert their tumorigenic effects through the formation of quinone metabolites. These quinone-forming carcinogens are generally inactive or weakly active in standard gene mutation assays. Accumulating evidence indicates that this class of compounds may exert their genotoxic and carcinogenic effects through the induction of large-scale gene alterations. This article presents an overview of work that has been performed using recently developed molecular cytogenic techniques to investigate the aneuploidy-inducing and clastogenic properties of the major quinone-forming metabolites of benzene, a widely used industrial chemical, and o-phenylphenol, a fungicide and disinfectant. These metabolites of benzene (hydroquinone, catechol, and benzenetriol) and o-phenylphenol (phenylhydroquinone) have each been shown to be capable of interfering with chromosome segregation and inducing chromosomal breakage. These results indicate that both numerical and structural chromosomal aberrations induced by the quinone metabolites of benzene and o-phenylphenol may play a role in the carcinogenic effects of these two agents.

  19. Mixed donor quinone complexes of nickel, zinc, cobalt, manganese and vanadium

    SciTech Connect

    Scotto, C.S.

    1992-01-01

    Mixed donor complexes of several first row metals have been prepared and examined for variations in redox properties, charge distribution and stability in comparison with homoleptic metal quinone species. Schiff base condensation between 3,5-di-tert-butylcatechol and ammonia provided the 3,5 di-tert-butyl-1,2-quinone-1-(2-hydroxy-3,5-di-tert-butlyphenyl)imine ligand for known M(QNQ)[sub 2] compounds. X-ray diffraction, cyclic voltammetry and solution susceptibility measurements were employed to compare properties with the pure quinone complexes and, in the case of Mn(QNQ)[sub 2] and CO(QNQ)[sub 2], with mixed ligand pyridyl quinone compounds of the two metals. Synthesis of the V(QNQ)[sub 2] analog was undertaken with partial characterization achieved through EPR, cyclic voltammetry and mass spectrometry. The vanadium chemistry was extended to mixed ligand catecholate complexes of V[sup III] and V[sup IV]. Such species are currently of interest in tunicate vanadium studies and in the catalytic oxygenation of pyrocatechols. Tetrachlorocatecholate analogs of known compounds were prepared and fully characterized. The x-ray structure of V(bipyridyl)(tetrachlorocatecholate)[sub 2] provided an unusual example of trigonal prismataic geometry about the metal center. A proposed intermediate in the synthesis of the target complex anion [V(bipyridyl)(tetrachlorocatecholate)[sub 2

  20. Synthesis and Anti-Platelet Activity of Thiosulfonate Derivatives Containing a Quinone Moiety

    PubMed Central

    Bolibrukh, Khrystyna; Polovkovych, Svyatoslav; Khoumeri, Omar; Halenova, Tetyana; Nikolaeva, Irina; Savchuk, Olexiy; Terme, Thierry; Vanelle, Patrice; Lubenets, Vira; Novikov, Volodymyr

    2015-01-01

    Thiosulfonate derivatives based on quinones were synthesized for studying “structure-activity relationship” compounds with an acylated and a free amino-group. Anti-platelet activity of the synthesized compounds was determined and the influence of substituents on the activity of the derivatives was assessed. PMID:26839819

  1. Understanding the cytotoxicity or cytoprotective effects of biological and synthetic quinone derivatives by redox mechanism.

    PubMed

    Borges, Rosivaldo S; Carneiro, Agnaldo S; Barros, Tainá G; Barros, Carlos A L; Neto, Antonio M J Chaves; da Silva, Albérico B F

    2014-12-01

    Quinones represent an important class of biological compounds, but are also involved with toxicological intermediates and among their hazardous effects include cytotoxicity, immunotoxicity, and carcinogenesis. The structure-toxicity relationship for quinone derivatives has been used to cytotoxicity or cytoprotective effects by redox mechanism is determined using quantum chemical calculations through the density functional theory (DFT). According to our DFT study, the electron acceptance is related with LUMO, electron affinity, and stabilization energy values. The highest spin density distribution in the heteroatoms is more favored for the more cytotoxic compounds. The electrophilic capacities of these compounds have been related with LUMO values. The cytotoxic properties of quinones are related to the stabilization energy after electron accepting by redox mechanism. Electron affinity is the most relevant parameter related to toxicity mechanism. Regioisomers has different electrophilic capacity. The electrophilicity increases on molecules containing electron-withdrawing groups (EWG) and reduces on molecules containing electron-donating groups (EDG). These results explain the toxic difference between natural and synthetic quinone derivatives and can be used in the design and study of new drugs.

  2. Theoretical investigation of pillar[4]quinone as a cathode active material for lithium-ion batteries.

    PubMed

    Huan, Long; Xie, Ju; Chen, Ming; Diao, Guowang; Zhao, Rongfang; Zuo, Tongfei

    2017-04-01

    The applicability of a novel macrocyclic multi-carbonyl compound, pillar[4]quinone (P4Q), as the cathode active material for lithium-ion batteries (LIBs) was assessed theoretically. The molecular geometry, electronic structure, Li-binding thermodynamic properties, and the redox potential of P4Q were obtained using density functional theory (DFT) at the M06-2X/6-31G(d,p) level of theory. The results of the calculations indicated that P4Q interacts with Li atoms via three binding modes: Li-O ionic bonding, O-Li···O bridge bonding, and Li···phenyl noncovalent interactions. Calculations also indicated that, during the LIB discharging process, P4Q could yield a specific capacity of 446 mAh g(-1) through the utilization of its many carbonyl groups. Compared with pillar[5]quinone and pillar[6]quinone, the redox potential of P4Q is enhanced by its high structural stability as well as the effect of the solvent. These results should provide the theoretical foundations for the design, synthesis, and application of novel macrocyclic carbonyl compounds as electrode materials in LIBs in the future. Graphical Abstract Schematic representation of the proposed charge-discharge mechanism of Pillar[4]quinone as cathode for lithium-ion batteries.

  3. Quinone-dependent proton transfer pathways in the photosynthetic cytochrome b6f complex.

    PubMed

    Hasan, S Saif; Yamashita, Eiki; Baniulis, Danas; Cramer, William A

    2013-03-12

    As much as two-thirds of the proton gradient used for transmembrane free energy storage in oxygenic photosynthesis is generated by the cytochrome b6f complex. The proton uptake pathway from the electrochemically negative (n) aqueous phase to the n-side quinone binding site of the complex, and a probable route for proton exit to the positive phase resulting from quinol oxidation, are defined in a 2.70-Å crystal structure and in structures with quinone analog inhibitors at 3.07 Å (tridecyl-stigmatellin) and 3.25-Å (2-nonyl-4-hydroxyquinoline N-oxide) resolution. The simplest n-side proton pathway extends from the aqueous phase via Asp20 and Arg207 (cytochrome b6 subunit) to quinone bound axially to heme c(n). On the positive side, the heme-proximal Glu78 (subunit IV), which accepts protons from plastosemiquinone, defines a route for H(+) transfer to the aqueous phase. These pathways provide a structure-based description of the quinone-mediated proton transfer responsible for generation of the transmembrane electrochemical potential gradient in oxygenic photosynthesis.

  4. Quinone-dependent proton transfer pathways in the photosynthetic cytochrome b6f complex

    PubMed Central

    Hasan, S. Saif; Yamashita, Eiki; Baniulis, Danas; Cramer, William A.

    2013-01-01

    As much as two-thirds of the proton gradient used for transmembrane free energy storage in oxygenic photosynthesis is generated by the cytochrome b6f complex. The proton uptake pathway from the electrochemically negative (n) aqueous phase to the n-side quinone binding site of the complex, and a probable route for proton exit to the positive phase resulting from quinol oxidation, are defined in a 2.70-Å crystal structure and in structures with quinone analog inhibitors at 3.07 Å (tridecyl-stigmatellin) and 3.25-Å (2-nonyl-4-hydroxyquinoline N-oxide) resolution. The simplest n-side proton pathway extends from the aqueous phase via Asp20 and Arg207 (cytochrome b6 subunit) to quinone bound axially to heme cn. On the positive side, the heme-proximal Glu78 (subunit IV), which accepts protons from plastosemiquinone, defines a route for H+ transfer to the aqueous phase. These pathways provide a structure-based description of the quinone-mediated proton transfer responsible for generation of the transmembrane electrochemical potential gradient in oxygenic photosynthesis. PMID:23440205

  5. Characterization of cytochrome b from European field isolates of Cercospora beticola with quinone outside inhibitor resistance

    USDA-ARS?s Scientific Manuscript database

    Cercospora leaf spot (CLS), caused by the fungal pathogen Cercospora beticola, is the most important foliar disease of sugar beet worldwide. Control strategies for CLS rely heavily on quinone outside inhibitor (QOI) fungicides. Despite the dependence on QOIs for disease control for more than a de...

  6. LC-MS method for screening unknown microbial carotenoids and isoprenoid quinones.

    PubMed

    Kaiser, Philipp; Geyer, Roland; Surmann, Peter; Fuhrmann, Herbert

    2012-01-01

    The structure of secondary metabolites from microorganisms provides a useful tool for microbial characterization and chemotaxonomic classification. Microbial isoprenoid quinones, for example, are well described and used to distinguish among photosynthetic microorganism groups. In addition, isoprenoid quinones can also be found, together with carotenoids, in non-photosynthetic microorganisms. The aim of the present study was to develop a LC-MS/MS method which can analyze and identify these microbial isoprenoids. Positive atmospheric pressure chemical ionization (APCI) together with collisionally induced dissociation was applied for generation of informative fragment spectra by mass spectrometry. Enhanced product ion (EPI) scan in a linear ion trap with information dependent data acquisition (IDA) enabled generation of MS fragment data even from minor isoprenoids. The developed liquid chromatography method enabled separation of isoprenoid patterns from their ester derivatives. Discovery and structural characterization of isoprenoid quinones and carotenoids were carried out by comparing characteristics of fragment spectra from unknown compounds with fragment spectra of a range of isoprenoid standard compounds and using published data. Throughout the study 17 microorganisms (e.g., Acremonium butyri, Arthrobacter spp., Brevibacterium linens, Bullera variabilis, Exophiala dermatitidis, Lecythophora hoffmannii, Panthoea agglomerans, Rhodotorula spp., Xanthophyllomyces dendrorhous) were screened and probable structures of isoprenoid quinones and carotenoids were suggested. The method lays some foundations on the analysis of yet unknown isoprenoids in microorganisms by using LCMS/MS techniques.

  7. Identification of NAD(P)H quinone oxidoreductase activity in azoreductases from P. aeruginosa: azoreductases and NAD(P)H quinone oxidoreductases belong to the same FMN-dependent superfamily of enzymes.

    PubMed

    Ryan, Ali; Kaplan, Elise; Nebel, Jean-Christophe; Polycarpou, Elena; Crescente, Vincenzo; Lowe, Edward; Preston, Gail M; Sim, Edith

    2014-01-01

    Water soluble quinones are a group of cytotoxic anti-bacterial compounds that are secreted by many species of plants, invertebrates, fungi and bacteria. Studies in a number of species have shown the importance of quinones in response to pathogenic bacteria of the genus Pseudomonas. Two electron reduction is an important mechanism of quinone detoxification as it generates the less toxic quinol. In most organisms this reaction is carried out by a group of flavoenzymes known as NAD(P)H quinone oxidoreductases. Azoreductases have previously been separate from this group, however using azoreductases from Pseudomonas aeruginosa we show that they can rapidly reduce quinones. Azoreductases from the same organism are also shown to have distinct substrate specificity profiles allowing them to reduce a wide range of quinones. The azoreductase family is also shown to be more extensive than originally thought, due to the large sequence divergence amongst its members. As both NAD(P)H quinone oxidoreductases and azoreductases have related reaction mechanisms it is proposed that they form an enzyme superfamily. The ubiquitous and diverse nature of azoreductases alongside their broad substrate specificity, indicates they play a wide role in cellular survival under adverse conditions.

  8. Identification of NAD(P)H Quinone Oxidoreductase Activity in Azoreductases from P. aeruginosa: Azoreductases and NAD(P)H Quinone Oxidoreductases Belong to the Same FMN-Dependent Superfamily of Enzymes

    PubMed Central

    Ryan, Ali; Kaplan, Elise; Nebel, Jean-Christophe; Polycarpou, Elena; Crescente, Vincenzo; Lowe, Edward; Preston, Gail M.; Sim, Edith

    2014-01-01

    Water soluble quinones are a group of cytotoxic anti-bacterial compounds that are secreted by many species of plants, invertebrates, fungi and bacteria. Studies in a number of species have shown the importance of quinones in response to pathogenic bacteria of the genus Pseudomonas. Two electron reduction is an important mechanism of quinone detoxification as it generates the less toxic quinol. In most organisms this reaction is carried out by a group of flavoenzymes known as NAD(P)H quinone oxidoreductases. Azoreductases have previously been separate from this group, however using azoreductases from Pseudomonas aeruginosa we show that they can rapidly reduce quinones. Azoreductases from the same organism are also shown to have distinct substrate specificity profiles allowing them to reduce a wide range of quinones. The azoreductase family is also shown to be more extensive than originally thought, due to the large sequence divergence amongst its members. As both NAD(P)H quinone oxidoreductases and azoreductases have related reaction mechanisms it is proposed that they form an enzyme superfamily. The ubiquitous and diverse nature of azoreductases alongside their broad substrate specificity, indicates they play a wide role in cellular survival under adverse conditions. PMID:24915188

  9. Update of the NAD(P)H:quinone oxidoreductase (NQO) gene family

    PubMed Central

    2006-01-01

    The NAD(P)H:quinone acceptor oxidoreductase (NQO) gene family belongs to the flavoprotein clan and, in the human genome, consists of two genes (NQO1 and NQO2). These two genes encode cytosolic flavoenzymes that catalyse the beneficial two-electron reduction of quinones to hydroquinones. This reaction prevents the unwanted one-electron reduction of quinones by other quinone reductases; one-electron reduction results in the formation of reactive oxygen species, generated by redox cycling of semiquinones in the presence of molecular oxygen. Both the mammalian NQO1 and NQO2 genes are upregulated as a part of the oxidative stress response and are inexplicably overexpressed in particular types of tumours. A non-synonymous mutation in the NQO1 gene, leading to absence of enzyme activity, has been associated with an increased risk of myeloid leukaemia and other types of blood dyscrasia in workers exposed to benzene. NQO2 has a melatonin-binding site, which may explain the anti-oxidant role of melatonin. An ancient NQO3 subfamily exists in eubacteria and the authors suggest that there should be additional divisions of the NQO family to include the NQO4 subfamily in fungi and NQO5 subfamily in archaebacteria. Interestingly, no NQO genes could be identified in the worm, fly, sea squirt or plants; because these taxa carry quinone reductases capable of one- and two-electron reductions, there has been either convergent evolution or redundancy to account for the appearance of these enzyme functions whenever they have been needed during evolution. PMID:16595077

  10. Isolation and Cr(VI) reduction characteristics of quinone respiration in Mangrovibacter plantisponsor strain CR1.

    PubMed

    Lian, Jing; Li, Zifu; Xu, Zhifang; Guo, Jianbo; Hu, Zhenzhen; Guo, Yankai; Li, Min; Yang, Jingliang

    2016-07-01

    A Cr(VI)-reducing Mangrovibacter plantisponsor strain, CR1, was isolated from tannery effluent sludge and had quinone respiration characteristics. Its chromate (CrO4 (2-) ) resistance, quinone respiration characteristics, and Cr(VI) reduction efficiencies were evaluated in detail. Strain CR1 exhibited a high Cr(VI) resistance with a minimal inhibitory concentration (MIC) of 32 mM in LB medium, and its quinone respiration could occur when an electron donor and strain CR1 both existed in the reaction system. Cr(VI) reduction by strain CR1 was significantly enhanced by a factor of 0.4-4.3 with five different quinone compounds: anthraquinone-2,7-disulfonate, anthraquinone-1-sulfonate, anthraquinone-2-sulfonate (AQS), anthraquinone-2,6-disulfonate, and anthraquinone-1,5-disulfonate. AQS was the best electron shuttle among them, and the greatest enhancement to the Cr(VI) bio-reduction was achieved with 0.96 mM AQS. The correlation between the reaction constant k (mg Cr(VI) g(-1) dry cell weight H(-1) ) and thermodynamic temperature T (K) was expressed as an Arrhenius equation lnk=-7662.9/T+27.931(R2=0.9486); the activation energy Ea was 63.71 kJ mol(-1) , and the pre-exponential factor A was 1.35 × 10(12)  mg Cr(VI) g(-1) dry cell weight H(-1) . During the Cr(VI) reduction process, the pH tended to become neutral, and the oxidation-reduction potential decreased to -440 mV. The efficient reduction of Cr(VI) mediated by a quinone respiration strain shows potential for the rapid anaerobic removal of Cr(VI). © 2015 International Union of Biochemistry and Molecular Biology, Inc.

  11. Induction and inhibition of NAD(P)H: quinone reductase in murine and human skin.

    PubMed

    Merk, H; Jugert, F; Bonnekoh, B; Mahrle, G

    1991-01-01

    The purpose of this study was to characterize the human cutaneous NAD(P)H: quinone reductase (NQR) activity by known inhibitors of different reductases and to compare it with the murine skin and liver NQR activity. This enzyme plays a major role in the defence of cells against oxygen stress because it inhibits the 1-electron reduction of quinones to semiquinones and their subsequent oxidation to quinones termed as quinone redox cycle. It belongs to the aromatic hydrocarbon-responsive (Ah) battery. This gene battery includes Cyp1a1 (cytochrome P-450 IA1), Cyp1a2 (cytochrome P-450 IA2) and Nmo-1 [NAD(P)H: quinone reductase]. In the skin cytochrome P-450 IA1-dependent activity is about 1-5% compared to the corresponding activity in the liver, whereas NQR has the same activity in skin and liver. NQR was determined in the cytoplasm of murine skin, liver, and human keratinocytes using 2,6-dichlorophenolindophenol as the substrate. The Ah-receptor binding compounds, such as coal tar constituents, or 3-methylcholanthrene induce cytochrome P-450-dependent activities such as aryl hydrocarbon hydroxylase or 7-ethoxyresorufin-O-de-ethylase and NQR, whereas butyl hydroxytoluol, which does not bind to the Ah receptor, induces only NQR. For inhibition studies several known inhibitors of dihydrodiol dehydrogenase, aldo-keto and carbonyl reductase activities were used. There was a similar pattern of inhibition of the basal and induced activity in all tissues investigated. Pyrazole, progesterone and phenobarbital did not inhibit, whereas dicoumarol, rutin and indomethacin inhibited NQR activity in murine skin and liver as well as in human keratinocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Differential Stress-Induced Regulation of Two Quinone Reductases in the Brown Rot Basidiomycete Gloeophyllum trabeum

    PubMed Central

    Cohen, Roni; Suzuki, Melissa R.; Hammel, Kenneth E.

    2004-01-01

    Quinone reductases (QRDs) have two important functions in the basidiomycete Gloeophyllum trabeum, which causes brown rot of wood. First, a QRD is required to generate biodegradative hydroxyl radicals via redox cycling between two G. trabeum extracellular metabolites, 2,5-dimethoxyhydroquinone (2,5-DMHQ) and 2,5-dimethoxy-1,4-benzoquinone (2,5-DMBQ). Second, because 2,5-DMBQ is cytotoxic and 2,5-DMHQ is not, a QRD is needed to maintain the intracellular pool of these metabolites in the reduced form. Given their importance in G. trabeum metabolism, QRDs could prove useful targets for new wood preservatives. We have identified two G. trabeum genes, each existing in two closely related, perhaps allelic variants, that encode QRDs in the flavodoxin family. Past work with QRD1 and heterologous expression of QRD2 in this study confirmed that both genes encode NADH-dependent, flavin-containing QRDs. Real-time reverse transcription PCR analyses of liquid- and wood-grown cultures showed that qrd1 expression was maximal during secondary metabolism, coincided with the production of 2,5-DMBQ, and was moderately up-regulated by chemical stressors such as quinones. By contrast, qrd2 expression was maximal during fungal growth when 2,5-DMBQ levels were low, yet was markedly up-regulated by chemical stress or heat shock. The total QRD activity in lysates of G. trabeum mycelium was significantly enhanced by induction beforehand with a cytotoxic quinone. The promoter of qrd2 contains likely antioxidant, xenobiotic, and heat shock elements, absent in qrd1, that probably explain the greater response of qrd2 transcription to stress. We conclude from these results that QRD1 is the enzyme G. trabeum routinely uses to detoxify quinones during incipient wood decay and that it could also drive the biodegradative quinone redox cycle. However, QRD2 assumes a more important role when the mycelium is stressed. PMID:14711659

  13. X-ray structural studies of quinone reductase 2 nanomolar range inhibitors

    SciTech Connect

    Pegan, Scott D.; Sturdy, Megan; Ferry, Gilles; Delagrange, Philippe; Boutin, Jean A.; Mesecar, Andrew D.

    2011-09-06

    Quinone reductase 2 (QR2) is one of two members comprising the mammalian quinone reductase family of enzymes responsible for performing FAD mediated reductions of quinone substrates. In contrast to quinone reductase 1 (QR1) which uses NAD(P)H as its co-substrate, QR2 utilizes a rare group of hydride donors, N-methyl or N-ribosyl nicotinamide. Several studies have linked QR2 to the generation of quinone free radicals, several neuronal degenerative diseases, and cancer. QR2 has been also identified as the third melatonin receptor (MT3) through in cellulo and in vitro inhibition of QR2 by traditional MT3 ligands, and through recent X-ray structures of human QR2 (hQR2) in complex with melatonin and 2-iodomelatonin. Several MT3 specific ligands have been developed that exhibit both potent in cellulo inhibition of hQR2 nanomolar, affinity for MT3. The potency of these ligands suggest their use as molecular probes for hQR2. However, no definitive correlation between traditionally obtained MT3 ligand affinity and hQR2 inhibition exists limiting our understanding of how these ligands are accommodated in the hQR2 active site. To obtain a clearer relationship between the structures of developed MT3 ligands and their inhibitory properties, in cellulo and in vitro IC{sub 50} values were determined for a representative set of MT3 ligands (MCA-NAT, 2-I-MCANAT, prazosin, S26695, S32797, and S29434). Furthermore, X-ray structures for each of these ligands in complex with hQR2 were determined allowing for a structural evaluation of the binding modes of these ligands in relation to the potency of MT3 ligands.

  14. FQR1, a Novel Primary Auxin-Response Gene, Encodes a Flavin Mononucleotide-Binding Quinone Reductase1

    PubMed Central

    Laskowski, Marta J.; Dreher, Kate A.; Gehring, Mary A.; Abel, Steffen; Gensler, Arminda L.; Sussex, Ian M.

    2002-01-01

    FQR1 is a novel primary auxin-response gene that codes for a flavin mononucleotide-binding flavodoxin-like quinone reductase. Accumulation of FQR1 mRNA begins within 10 min of indole-3-acetic acid application and reaches a maximum of approximately 10-fold induction 30 min after treatment. This increase in FQR1 mRNA abundance is not diminished by the protein synthesis inhibitor cycloheximide, demonstrating that FQR1 is a primary auxin-response gene. Sequence analysis reveals that FQR1 belongs to a family of flavin mononucleotide-binding quinone reductases. Partially purified His-tagged FQR1 isolated from Escherichia coli catalyzes the transfer of electrons from NADH and NADPH to several substrates and exhibits in vitro quinone reductase activity. Overexpression of FQR1 in plants leads to increased levels of FQR1 protein and quinone reductase activity, indicating that FQR1 functions as a quinone reductase in vivo. In mammalian systems, glutathione S-transferases and quinone reductases are classified as phase II detoxification enzymes. We hypothesize that the auxin-inducible glutathione S-transferases and quinone reductases found in plants also act as detoxification enzymes, possibly to protect against auxin-induced oxidative stress. PMID:11842161

  15. Overexpression of NAD(P)H:quinone oxidoreductase 1 (NQO1) and genomic gain of the NQO1 locus modulates breast cancer cell sensitivity to quinones.

    PubMed

    Glorieux, Christophe; Sandoval, Juan Marcelo; Dejeans, Nicolas; Ameye, Geneviève; Poirel, Hélène Antoine; Verrax, Julien; Calderon, Pedro Buc

    2016-01-15

    Alterations in the expression of antioxidant enzymes are associated with changes in cancer cell sensitivity to chemotherapeutic drugs (menadione and β-lapachone). Mechanisms of acquisition of resistance to pro-oxidant drugs were investigated using a model of oxidative stress-resistant MCF-7 breast cancer cells (Resox cells). FISH experiments were performed in tumor biopsy and breast cancer cells to characterize the pattern of the NQO1 gene. SNP-arrays were conducted to detect chromosomal imbalances. Finally, the importance of NQO1 overexpression in the putative acquisition of either drug resistance or an increased sensitivity to quinones by cancer cells was investigated by immunoblotting and cytotoxicity assays. Genomic gain of the chromosomal band 16q22 was detected in Resox cells compared to parental breast cancer MCF-7 cells and normal human mammary epithelial 250MK cells. This genomic gain was associated with amplification of the NQO1 gene in one tumor biopsy as well as in breast cancer cell lines. Using different breast cell models, we found that NQO1 overexpression was a main determinant for a potential chemotherapy resistance or an increased sensitivity to quinone-bearing compounds. Because NQO1 is frequently modified in tumors at genomic and transcriptomic levels, the impact of NQO1 modulation on breast cancer cell sensitivity places NQO1 as a potential link between cancer redox alterations and resistance to chemotherapy. Thus, the NQO1 gene copy number and NQO1 activity should be considered when quinone-bearing molecules are being utilized as potential drugs against breast tumors. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. 2-Substituted 3-methylnaphtho[1,2-b]furan-4,5-diones as novel L-shaped ortho-quinone substrates for NAD(P)H:quinone oxidoreductase (NQO1).

    PubMed

    Bian, Jinlei; Deng, Bang; Xu, Lili; Xu, Xiaoli; Wang, Nan; Hu, Tianhan; Yao, Zeyu; Du, Jianyao; Yang, Li; Lei, Yonghua; Li, Xiang; Sun, Haopeng; Zhang, Xiaojin; You, Qidong

    2014-07-23

    A series of L-shaped ortho-quinone analogs were designed by analyzing the binding mode with NQO1. Metabolic studies demonstrated that compounds 2m, 2n and 2q exhibited higher metabolic rates than β-lapachone. The docking studies, which supported the rationalization of the metabolic studies, constituted a prospective rational basis for the development of optimized ortho-quinone analogs. Besides, good substrates (2m, 2n and 2r) for NQO1 showed higher selective toxicity than β-lapachone toward A549 (NQO1-rich) cancer cells versus H596 (NQO1-deficient) cells. Determination of superoxide (O2(•-)) production and in vitro cytotoxicity evaluation in the presence of the NQO1 inhibitor dicoumarol confirmed that the ortho-quinones exerted their antitumor activity through NQO1-mediated ROS production by redox cycling. It was suggested that the L-shaped quinone substrates for NQO1 possessed better specificity and safety than β-lapachone.

  17. Photoreactions of p-quinones with dimethyl sulfide and dimethyl sulfoxide in aqueous acetonitrile. goerner@mpi-muelheim.mpg.de.

    PubMed

    Görner, Helmut

    2006-01-01

    The effects of dimethyl sulfide (DMS) and dimethyl sulfoxide (DMSO) on the photoreactions of 1,4-benzoquinone (BQ), 1,4-naphthoquinone (NQ), 9,10-anthraquinone (AQ) and several derivatives in acetonitrile/water were studied. The observed triplet state of the quinones is quenched and the rate constant is close to the diffusion-controlled limit for reactions of most quinones with DMS and lower with DMSO. Semiquinone radical anions (Q*-) produced by electron transfer from sulfur to the triplet quinone were detected. For both DMS and DMSO the yield of Q*- is similar, being generally low for BQ and NQ, substantial for AQ and largest for chloranil. The specific quencher concentrations and the effects of quinone structure and redox potentials on the time-resolved photochemical properties are discussed.

  18. Rates of primary electron transfer reactions in the photosystem I reaction center reconstituted with different quinones as the secondary acceptor

    SciTech Connect

    Kumazaki, Shigeichi; Kandori, Hideki; Yoshihara, Keitaro ); Iwaki, Masayo; Itoh, Shigeru ); Ikegamu, Isamu )

    1994-10-27

    Rates of sequential electron transfer reactions from the primary electron donor chlorophyll dimer (P700) to the electron acceptor chlorophyll a-686 (A[sub 0]) and to the secondary acceptor quinone (Q[sub [phi

  19. Heats of formation and protonation thermochemistry of gaseous benzaldehyde, tropone and quinone methides

    NASA Astrophysics Data System (ADS)

    Bouchoux, Guy

    2010-08-01

    Quantum chemistry calculations using composite G3B3, G3MP2B3 and CBS-QB3 methods were performed for benzaldehyde, 1, tropone, 2, ortho-quinone methide, 3, para-quinone methide, 4, their protonated forms 1H+- 4H+ and the isomeric meta-hydroxybenzyl cation 5H+. The G3B3 298 K heats of formation values obtained in this work are: -39, 61, 52, 39, 661, 679, 699, 680 and 733 kJ mol -1 for 1- 4, 1H+- 5H+, respectively. At the same level of theory, computed proton affinities are equal to 834, 916, 887 and 892 kJ mol -1 for molecules 1- 4. These results allow to correct discrepancies on the previously reported thermochemistry of molecules 2- 4 and cations 2H+- 5H+.

  20. Novel chemistries and materials for grid-scale energy storage: Quinones and halogen catalysis

    NASA Astrophysics Data System (ADS)

    Huskinson, Brian Thomas

    In this work I describe various approaches to electrochemical energy storage at the grid-scale. Chapter 1 provides an introduction to energy storage and an overview of the history and development of flow batteries. Chapter 2 describes work on the hydrogen-chlorine regenerative fuel cell, detailing its development and the record-breaking performance of the device. Chapter 3 dives into catalyst materials for such a fuel cell, focusing on ruthenium oxide based alloys to be used as chlorine redox catalysts. Chapter 4 introduces and details the development of a performance model for a hydrogen-bromine cell. Chapter 5 delves into the more recent work I have done, switching to applications of quinone chemistries in flow batteries. It focuses on the pairing of one particular quinone (2,7-anthraquinone disulfonic acid) with bromine, and highlights the promising performance characteristics of a device based on this type of chemistry.

  1. Evaluating the therapeutic potential of idebenone and related quinone analogues in Leber hereditary optic neuropathy.

    PubMed

    Yu-Wai-Man, Patrick; Soiferman, Devorah; Moore, David G; Burté, Florence; Saada, Ann

    2017-09-01

    Leber hereditary optic neuropathy (LHON) is an important cause of mitochondrial blindness among young adults. In this study, we investigated the potential of four quinone analogues (CoQ1, CoQ10, decylubiquinone and idebenone) in compensating for the deleterious effect of the m.11778G>A mitochondrial DNA mutation. The LHON fibroblast cell lines tested exhibited reduced cell growth, impaired mitochondrial bioenergetics and elevated levels of reactive oxygen species (ROS). Idebenone increased ATP production and reduced ROS levels, but the effect was partial and cell-specific. The remaining quinone analogues had variable effects and a negative impact on certain mitochondrial parameters was observed in some cell lines. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  2. Polyketide Quinones Are Alternate Intermediate Electron Carriers during Mycobacterial Respiration in Oxygen-Deficient Niches.

    PubMed

    Anand, Amitesh; Verma, Priyanka; Singh, Anil Kumar; Kaushik, Sandeep; Pandey, Rajesh; Shi, Ce; Kaur, Harneet; Chawla, Manbeena; Elechalawar, Chandra Kumar; Kumar, Dhirendra; Yang, Yong; Bhavesh, Neel S; Banerjee, Rajkumar; Dash, Debasis; Singh, Amit; Natarajan, Vivek T; Ojha, Anil K; Aldrich, Courtney C; Gokhale, Rajesh S

    2015-11-19

    Mycobacterium tuberculosis (Mtb) adaptation to hypoxia is considered crucial to its prolonged latent persistence in humans. Mtb lesions are known to contain physiologically heterogeneous microenvironments that bring about differential responses from bacteria. Here we exploit metabolic variability within biofilm cells to identify alternate respiratory polyketide quinones (PkQs) from both Mycobacterium smegmatis (Msmeg) and Mtb. PkQs are specifically expressed in biofilms and other oxygen-deficient niches to maintain cellular bioenergetics. Under such conditions, these metabolites function as mobile electron carriers in the respiratory electron transport chain. In the absence of PkQs, mycobacteria escape from the hypoxic core of biofilms and prefer oxygen-rich conditions. Unlike the ubiquitous isoprenoid pathway for the biosynthesis of respiratory quinones, PkQs are produced by type III polyketide synthases using fatty acyl-CoA precursors. The biosynthetic pathway is conserved in several other bacterial genomes, and our study reveals a redox-balancing chemicocellular process in microbial physiology.

  3. Constituents of the stem bark of Pongamia pinnata with the potential to induce quinone reductase.

    PubMed

    Carcache-Blanco, Esperanza J; Kang, Young-Hwa; Park, Eun Jung; Su, Bao-Ning; Kardono, Leonardus B S; Riswan, Soedarsono; Fong, Harry H S; Pezzuto, John M; Kinghorn, A Douglas

    2003-09-01

    Activity-guided fractionation of the petroleum ether and ethyl acetate extracts of the stem bark of Pongamia pinnata, using cultured Hepa 1c1c7 mouse hepatoma cells to evaluate quinone reductase (QR) inducing activity, led to the isolation of four new flavanone derivatives (1-4), one new flavone (5), one new chalcone (6), and 13 known compounds of the flavonoid, terpenoid, and fatty acid types. The structures of 1-6 were characterized on the basis of the interpretation of their spectroscopic data. The absolute stereochemistry of compounds 1-4 was determined from their CD data and by Mosher ester determination. All isolates obtained were evaluated in the quinone reductase induction assay.

  4. Characterizing Anharmonic Vibrational Modes of Quinones with Two-Dimensional Infrared Spectroscopy.

    PubMed

    Cyran, Jenée D; Nite, Jacob M; Krummel, Amber T

    2015-07-23

    Two-dimensional infrared (2D IR) spectroscopy was used to study the vibrational modes of three quinones--benzoquinone, naphthoquinone, and anthraquinone. The vibrations of interest were in the spectral range of 1560-1710 cm(-1), corresponding to the in-plane carbonyl and ring stretching vibrations. Coupling between the vibrational modes is indicated by the cross peaks in the 2D IR spectra. The diagonal and off-diagonal anharmonicities range from 4.6 to 17.4 cm(-1) for the quinone series. In addition, there is significant vibrational coupling between the in-plane carbonyl and ring stretching vibrations. The diagonal anharmonicity, off-diagonal anharmonicity, and vibrational coupling constants are reported for benzoquinone, naphthoquinone, and anthraquinone.

  5. New method for spectrophotometric determination of quinones and barbituric acid through their reaction. A kinetic study

    NASA Astrophysics Data System (ADS)

    Medien, H. A. A.

    1996-11-01

    A new and sensitive spectrophotometric method is described for the determination of p-benzoquinone, p-chloranil and 1.4-naphthoquinone. The method is based on the reaction between quinones and barbituric acid, by which a color is developed with maximum absorption between 485 and 555 nm in 50% methyl alcohol-water mixture. The absorption of the product obeys Beer's law within the concentration range 0.025-05 mM of orginal quinone. The kinetics of the reaction between p-benzoquinone and barbituric acid was studied in a range of methyl alcohol-water mixtures. The reaction follows overall second order kinetics, first order in each of the reactants. The rate increases with increasing dielectric constant. The method was applied for determination of barbituric acid with p-benzoquinone in the concentration range of 0.025-0.345 mM. Other barbiturates do not interfere.

  6. Synthesis and antimalarial activity of quinones and structurally-related oxirane derivatives.

    PubMed

    Carneiro, Paula F; Pinto, Maria C R F; Marra, Roberta K F; da Silva, Fernando de C; Resende, Jackson A L C; Rocha E Silva, Luiz F; Alves, Hilkem G; Barbosa, Gleyce S; de Vasconcellos, Marne C; Lima, Emerson S; Pohlit, Adrian M; Ferreira, Vitor F

    2016-01-27

    A series of eighteen quinones and structurally-related oxiranes were synthesized and evaluated for in vitro inhibitory activity against the chloroquine-sensitive 3D7 clone of the human malaria parasite Plasmodium falciparum. 2-amino and 2-allyloxynaphthoquinones exhibited important antiplasmodial activity (median inhibitory concentrations (IC50) < 10 μM). Oxiranes 6 and 25, prepared respectively by reaction of α-lapachone and tetrachloro-p-quinone with diazomethane in a mixture of ether and ethanol, exhibited the highest antiplasmodial activity and low cytotoxicity against human fibroblasts (MCR-5 cell line). The active compounds could represent a good prototype for an antimalarial lead molecule. Copyright © 2015. Published by Elsevier Masson SAS.

  7. Inhibition of reverse transcriptase by tyrosinase generated quinones related to levodopa and dopamine.

    PubMed

    Wick, M M; Fitzgerald, G

    1981-12-01

    Several derivatives of levodopa have been shown to be potent inhibitors of the sulfhydryl enzyme, RNA dependent DNA polymerase, reverse transcriptase (RT). In the presence of the polyphenol oxidase, tyrosinase, the inhibitory values were between 10(-6) M and 10(-5) M. Structure-activity studies revealed that active oxidation or reduction was necessary for this potent inhibitory response. Spectrophotometric analysis showed that the presence of both the quinone and quinol was required for maximum inhibitory activity. These data suggest that the common intermediate of oxidation of quinols or reduction of quinones (i.e., semiquinone) is the active species. The use of tyrosinase provides a convenient model for the detection of the actual inhibitory interaction of a free-radical (semiquinone) with a biologically important macromolecule, reverse transcriptase.

  8. Proteomic analysis of rat brain mitochondria following exposure to dopamine quinone: implications for Parkinson disease.

    PubMed

    Van Laar, Victor S; Dukes, April A; Cascio, Michael; Hastings, Teresa G

    2008-03-01

    Oxidative stress and mitochondrial dysfunction have been linked to dopaminergic neuron degeneration in Parkinson disease. We have previously shown that dopamine oxidation leads to selective dopaminergic terminal degeneration in vivo and alters mitochondrial function in vitro. In this study, we utilized 2-D difference in-gel electrophoresis to assess changes in the mitochondrial proteome following in vitro exposure to reactive dopamine quinone. A subset of proteins exhibit decreased fluorescence labeling following dopamine oxidation, suggesting a rapid loss of specific proteins. Amongst these proteins are mitochondrial creatine kinase, mitofilin, mortalin, the 75 kDa subunit of NADH dehydrogenase, and superoxide dismutase 2. Western blot analyses for mitochondrial creatine kinase and mitofilin confirmed significant losses in isolated brain mitochondria exposed to dopamine quinone and PC12 cells exposed to dopamine. These results suggest that specific mitochondrial proteins are uniquely susceptible to changes in abundance following dopamine oxidation, and carry implications for mitochondrial stability in Parkinson disease neurodegeneration.

  9. Quinones as dienophiles in the Diels-Alder reaction: history and applications in total synthesis.

    PubMed

    Nawrat, Christopher C; Moody, Christopher J

    2014-02-17

    In the canon of reactions available to the organic chemist engaged in total synthesis, the Diels-Alder reaction is among the most powerful and well understood. Its ability to rapidly generate molecular complexity through the simultaneous formation of two carbon-carbon bonds is almost unrivalled, and this is reflected in the great number of reported applications of this reaction. Historically, the use of quinones as dienophiles is highly significant, being the very first example investigated by Diels and Alder. Herein, we review the application of the Diels-Alder reaction of quinones in the total synthesis of natural products. The highlighted examples span some 60 years from the landmark syntheses of morphine (1952) and reserpine (1956) by Gates and Woodward, respectively, through to the present day examples, such as the tetracyclines. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Highly Efficient Catalysis of Retro-Claisen Reactions: From a Quinone Derivative to Functionalized Imidazolium Salts.

    PubMed

    Visbal, Renso; Laguna, Antonio; Gimeno, M Concepción

    2016-03-14

    A new and efficient method for the preparation of several imidazolium salts containing an ester group in the C4 position of the aromatic ring through a retro-Claisen reaction pathway between a quinone derivative and several alcohols is described. This new organic transformation proceeds in the absence of a catalyst, but it is greatly catalyzed by different Lewis acids, especially with AgOAc at a very low catalyst loading and in very short reaction times. The process takes place by the nucleophilic attack of the carbonyl groups by the alcohol functionality, thus promoting a double C-C bond cleavage and C-H and C-O bond formation. This reaction represents the first example of this type between a quinone derivative and alcohols.

  11. Crystallization of the Na+-translocating NADH:quinone oxidoreductase from Vibrio cholerae

    PubMed Central

    Casutt, Marco S.; Wendelspiess, Severin; Steuber, Julia; Fritz, Günter

    2010-01-01

    The Na+-translocating NADH:quinone oxidoreductase (Na+-NQR) from the human pathogen Vibrio cholerae couples the exergonic oxidation of NADH by membrane-bound quinone to Na+ translocation across the membrane. Na+-NQR consists of six different subunits (NqrA–NqrF) and contains a [2Fe–2S] cluster, a noncovalently bound FAD, a noncovalently bound riboflavin, two covalently bound FMNs and potentially Q8 as cofactors. Initial crystallization of the entire Na+-NQR complex was achieved by the sitting-drop method using a nanolitre dispenser. Optimization of the crystallization conditions yielded flat yellow-coloured crystals with dimensions of up to 200 × 80 × 20 µm. The crystals diffracted to 4.0 Å resolution and belonged to space group P21, with unit-cell parameters a = 94, b = 146, c = 105 Å, α = γ = 90, β = 111°. PMID:21139223

  12. Induction of quinone reductase (QR) by withanolides isolated from Physalis angulata L. var. villosa Bonati (Solanaceae).

    PubMed

    Ding, Hui; Hu, Zhijuan; Yu, Liyan; Ma, Zhongjun; Ma, Xiaoqiong; Chen, Zhe; Wang, Dan; Zhao, Xiaofeng

    2014-08-01

    In the present study, the EtOAc extract of the persistent calyx of Physalis angulata L. var. villosa Bonati (PA) was tested for its potential quinone reductase (QR) inducing activity with glutathione (GSH) as the substrate using an UPLC-ESI-MS method. The result revealed that the PA had electrophiles that could induce quinone reductase (QR) activity, which might be attributed to the modification of the highly reactive cysteine residues in Keap1. Herein, three new withanolides, compounds 3, 6 and 7, together with four known withanolides, compounds 1, 2, 4 and 5 were isolated from PA extract. Their structures were determined by spectroscopic techniques, including (1)H-, (13)C NMR (DEPT), and 2D-NMR (HMBC, HMQC, (1)H, (1)H-COSY, NOESY) experiments, as well as by HR-MS. All the seven compounds were tested for their QR induction activities towards mouse hepa 1c1c7 cells.

  13. Selective Alkylation of C-Rich Bulge Motifs in Nucleic Acids by Quinone Methide Derivatives.

    PubMed

    Lönnberg, Tuomas; Hutchinson, Mark; Rokita, Steven

    2015-09-07

    A quinone methide precursor featuring a bis-cyclen anchoring moiety has been synthesized and its capacity to alkylate oligonucleotide targets quantified in the presence and absence of divalent metal ions (Zn(2+) , Ni(2+) and Cd(2+) ). The oligonucleotides were designed for testing the sequence and secondary structure specificity of the reaction. Gel electrophoretic analysis revealed predominant alkylation of C-rich bulges, regardless of the presence of divalent metal ions or even the bis-cyclen anchor. This C-selectivity appears to be an intrinsic property of the quinone methide electrophile as reflected by its reaction with an equimolar mixture of the 2'-deoxynucleosides. Only dA-N1 and dC-N3 alkylation products were detected initially and only the dC adduct persisted for detection under conditions of the gel electrophoretic analysis.

  14. An antibacterial ortho-quinone diterpenoid and its derivatives from Caryopteris mongolica.

    PubMed

    Saruul, Erdenebileg; Murata, Toshihiro; Selenge, Erdenechimeg; Sasaki, Kenroh; Yoshizaki, Fumihiko; Batkhuu, Javzan

    2015-06-15

    To identify antibacterial components in traditional Mongolian medicinal plant Caryopteris mongolica, an ortho-quinone abietane caryopteron A (1) and three its derivatives caryopteron B-D (2-4) were isolated from the roots of the plant together with three known abietanes demethylcryptojaponol (5), 6α-hydroxydemethyl cryptojaponol (6), and 14-deoxycoleon U (7). The chemical structures of these abietane derivatives were elucidated on the basis of spectroscopic data. Compounds 1-4 had C-13 methylcyclopropane substructures, and 2-4 had a hexanedioic anhydride ring C instead of ortho-quinone in 1. The stereochemistry of these compound was assumed from NOE spectra and ECD Cotton effects. Compounds 1 and 5-7 showed antibacterial activities against the Gram-positive bacteria Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, and Micrococcus luteus, being 1 the more potent.

  15. Quinone exchange at the A{sub 1} site in photosystem I [PSI

    SciTech Connect

    Barkoff, A.; Brunkan, N.; Snyder, S.W.; Ostafin, A.; Werst, M.; Thurnauer, M.C.; Biggins, J.

    1995-12-31

    Quinones play an essential role in light-induced electron transport in photosynthetic reaction centers (RC). Study of quinone binding within the protein matrix of the RC is a focal point of understanding the biological optimization of photosynthesis. In plant and cyanobacterial PSI, phylloquinone (K{sub 1}) is believed to be the secondary electron acceptor, A{sub 1}, similar to Q{sub a} in the purple bacterial RC. Photoinduced electron transfer is initiated by reduction of the electron acceptor (A{sub 0}), a chlorophyll species, by the photoexcited primary donor *P{sub 700}. A{sub 1} acts as a transient redox intermediate between A{sub 0} and the iron-sulfur centers (FeS). We have examined the characteristic PSI electron spin polarized (ESP) electron paramagnetic resonance (EPR) signal as a marker of the interacting radical pairs developed during electron transfer.

  16. Interaction of chlorinated phenolics and quinones with the mitochondrial respiration: a comparison of the o- and p-chlorinated quinones and hydroquinones

    SciTech Connect

    Pritsos, C.A.; Pointon, M.; Pardini, R.S.

    1987-05-01

    Interest in the environmental toxicology of chlorinated catechols and their analogous quinones was prompted by their acute toxicity towards fish and other aquatic organisms. Chlorophenols, such as pentachlorophenol, as well as tetrachlorocatechol have been suggested to uncouple mitochondrial oxidative phosphorylation while chloranil and tetrachloro-o-benzoquinone have been shown to inhibit liver mitochondrial respiration, which may be related to their cytotoxicity. Another chlorinated quinone fungicide, 2,3 dichloro-1,4-naphthoquinone (CNQ) has been studied and shown to both uncouple oxidative phosphorylation and inhibit respiration in liver and heart mitochondria. CNQ was shown to undergo redox cycling with mitochondria, with a concomitant production of toxic oxygen species including superoxide and hydrogen peroxide. These reactive oxygen species were associated with the generation of mitochondrial oxidative stress, and were related to the toxic action of CNQ. Based upon these previous findings, the authors examined the interaction of both the ortho and para isomers of tetrachloro-benzoquinone and their corresponding hydroquinones with mitochondria in order to prove their mechanism of actions and compare the reactions of the various isomers.

  17. A Catalyst-Controlled Aerobic Coupling of ortho-Quinones and Phenols Applied to the Synthesis of Aryl Ethers.

    PubMed

    Huang, Zheng; Lumb, Jean-Philip

    2016-09-12

    ortho-Quinones are underutilized six-carbon-atom building blocks. We herein describe an approach for controlling their reactivity with copper that gives rise to a catalytic aerobic cross-coupling with phenols. The resulting aryl ethers are generated in high yield across a broad substrate scope under mild conditions. This method represents a unique example where the covalent modification of an ortho-quinone is catalyzed by a transition metal, creating new opportunities for their utilization in synthesis.

  18. Copper-Catalyzed Borylative Aromatization of p-Quinone Methides: Enantioselective Synthesis of Dibenzylic Boronates

    PubMed Central

    2015-01-01

    In this report, we establish that DM-Segphos copper(I) complexes are efficient catalysts for the enantioselective borylation of para-quinone methides. This method provides straightforward access to chiral monobenzylic and dibenzylic boronic esters, with enantiomeric ratios up to 96:4, using a commercially available chiral phosphine. Standard manipulations of the C–B bond afford a variety of chiral diaryl derivatives. PMID:27088045

  19. Comparative Studies on Plastoquinones: V. Changes in Lipophilic Chloroplast Quinones during Development.

    PubMed

    Barr, R; Crane, F L; Peak, S M

    1970-01-01

    Changes of lipophilic chloroplast quinones in corn, oats, peas, and Vicia faba are reported after 0, 4, 8, 12, 16, 20, 24, 48, 72, or 96 hours of exposure to light. There is a pronounced increase in plastoquinone A and chlorophyll levels and slight increase, in plastoquinone C(1-6), vitamin K(1), and alpha-tocopherylquinone content. Coenzyme Q levels, on the other hand, show little change upon exposure to light.THE SEQUENCE IN WHICH INDIVIDUAL QUINONES APPEAR DURING DEVELOPMENT IS AS FOLLOWS: plastoquinone A instantaneously after exposure to light, plastoquinone C(1-6) from 4 to 24 hours, vitamin K(1) from 12 to 24 hours, alpha-tocopherylquinone from 0 to 24 hours of illumination. Small amounts (<0.01 mumole/g, dry wt) of plastoquinone A and plastoquinone B are found in seeds and etiolated tissues. After exposure to light, the quinone tentatively identified as a member of the plastoquinone B series by reverse phase thin layer chromatography disappears and can be detected again in small amounts during maturity and toward senescence of the leaf.

  20. Antioxidant and quinone reductase-inducing constituents of black chokeberry (Aronia melanocarpa) fruits.

    PubMed

    Li, Jie; Deng, Ye; Yuan, Chunhua; Pan, Li; Chai, Heebyung; Keller, William J; Kinghorn, A Douglas

    2012-11-21

    Using in vitro hydroxyl radical-scavenging and quinone reductase-inducing assays, bioactivity-guided fractionation of an ethyl acetate-soluble extract of the fruits of the botanical dietary supplement, black chokeberry (Aronia melanocarpa), led to the isolation of 27 compounds, including a new depside, ethyl 2-[(3,4-dihydroxybenzoyloxy)-4,6-dihydroxyphenyl] acetate (1), along with 26 known compounds (2-27). The structures of the isolated compounds were identified by analysis of their physical and spectroscopic data ([α](D), NMR, IR, UV, and MS). Altogether, 17 compounds (1-4, 9, 15-17, and 19-27) showed significant antioxidant activity in the hydroxyl radical-scavenging assay, with hyperin (24, ED(50) = 0.17 μM) being the most potent. The new compound (1, ED(50) = 0.44 μM) also exhibited potent antioxidant activity in this assay. Three constituents of black chokeberry fruits doubled quinone reductase activity at concentrations <20 μM, namely, protocatechuic acid [9, concentration required to double quinone reductase activity (CD) = 4.3 μM], neochlorogenic acid methyl ester (22, CD = 6.7 μM), and quercetin (23, CD = 3.1 μM).

  1. Crystal structures of Pseudomonas syringae pv. tomato DC3000 quinone oxidoreductase and its complex with NADPH

    SciTech Connect

    Pan, Xiaowei; Zhang, Hongmei; Gao, Yu; Li, Mei; Chang, Wenrui

    2009-12-18

    Zeta-crystallin-like quinone oxidoreductase is NAD(P)H-dependent and catalyzes one-electron reduction of certain quinones to generate semiquinone. Here we present the crystal structures of zeta-crystallin-like quinone oxidoreductase from Pseudomonas syringae pv. tomato DC3000 (PtoQOR) and its complexes with NADPH determined at 2.4 and 2.01 A resolutions, respectively. PtoQOR forms as a homologous dimer, each monomer containing two domains. In the structure of the PtoQOR-NADPH complex, NADPH locates in the groove between the two domains. NADPH binding causes obvious conformational changes in the structure of PtoQOR. The putative substrate-binding site of PtoQOR is wider than that of Escherichia coli and Thermus thermophilus HB8. Activity assays show that PtoQOR has weak 1,4-benzoquinone catalytic activity, and very strong reduction activity towards large substrates such as 9,10-phenanthrenequinone. We propose a model to explain the conformational changes which take place during reduction reactions catalyzed by PtoQOR.

  2. Density Functional Theory-Based First Principles Calculations of Rhododendrol-Quinone Reactions: Preference to Thiol Binding over Cyclization

    NASA Astrophysics Data System (ADS)

    Kishida, Ryo; Kasai, Hideaki; Meñez Aspera, Susan; Lacdao Arevalo, Ryan; Nakanishi, Hiroshi

    2017-02-01

    Using density functional theory-based first principles calculations, we investigated the changes in the energetics and electronic structures of rhododendrol (RD)-quinone for the initial step of two important reactions, viz., cyclization and thiol binding, to give significant insights into the mechanism of the cause of cytotoxic effects. We found that RD-quinone in the electroneutral structure cannot undergo cyclization, indicating a slow cyclization of RD-quinone at neutral pH. Furthermore, using methane thiolate ion as a model thiol, we found that the oxidized form of the cyclized RD-quinone, namely RD-cyclic quinone, exhibited a reduced binding energy for thiols. However, this reduction of binding energy is clearly smaller than the case of dopaquinone, which is a molecule originally involved in the melanin synthesis. This study clearly shows that RD-quinone has a preference toward thiol bindings than cyclization compared to the case of dopaquinone. Considering that thiol bindings have been reported to induce cytotoxic effects in various ways, the preference toward thiol bindings is an important chemical property for the cytotoxicity caused by RD.

  3. Quinone 1 e(-) and 2 e(-)/2 H(+) Reduction Potentials: Identification and Analysis of Deviations from Systematic Scaling Relationships.

    PubMed

    Huynh, Mioy T; Anson, Colin W; Cavell, Andrew C; Stahl, Shannon S; Hammes-Schiffer, Sharon

    2016-12-14

    Quinones participate in diverse electron transfer and proton-coupled electron transfer processes in chemistry and biology. To understand the relationship between these redox processes, an experimental study was carried out to probe the 1 e(-) and 2 e(-)/2 H(+) reduction potentials of a number of common quinones. The results reveal a non-linear correlation between the 1 e(-) and 2 e(-)/2 H(+) reduction potentials. This unexpected observation prompted a computational study of 134 different quinones, probing their 1 e(-) reduction potentials, pKa values, and 2 e(-)/2 H(+) reduction potentials. The density functional theory calculations reveal an approximately linear correlation between these three properties and an effective Hammett constant associated with the quinone substituent(s). However, deviations from this linear scaling relationship are evident for quinones that feature intramolecular hydrogen bonding, halogen substituents, charged substituents, and/or sterically bulky substituents. These results, particularly the different substituent effects on the 1 e(-) versus 2 e(-)/2 H(+) reduction potentials, have important implications for designing quinones with tailored redox properties.

  4. Electron transfer capacity dependence of quinone-mediated Fe(III) reduction and current generation by Klebsiella pneumoniae L17.

    PubMed

    Li, Xiaomin; Liu, Liang; Liu, Tongxu; Yuan, Tian; Zhang, Wei; Li, Fangbai; Zhou, Shungui; Li, Yongtao

    2013-06-01

    Quinone groups in exogenous electron shuttles can accelerate extracellular electron transfer (EET) from bacteria to insoluble terminal electron acceptors, such as Fe(III) oxides and electrodes, which are important in biogeochemical redox processes and microbial electricity generation. However, the relationship between quinone-mediated EET performance and electron-shuttling properties of the quinones remains incompletely characterized. This study investigates the effects of a series of synthetic quinones (SQs) on goethite reduction and current generation by a fermenting bacterium Klebsiella pneumoniae L17. In addition, the voltammetric behavior and electron transfer capacities (ETCs) of SQ, including electron accepting (EAC) and donating (EDC) capacities, is also examined using electrochemical methods. The results showed that SQ can significantly increase both the Fe(III) reduction rates and current outputs of L17. Each tested SQ reversibly accepted and donated electrons as indicated by the cyclic voltammograms. The EAC and EDC results showed that Carmine and Alizarin had low relative capacities of electron transfer, whereas 9,10-anthraquinone-2,6-disulfonic acid (AQDS), 2-hydroxy-1,4-naphthoquinone (2-HNQ), and 5-hydroxy-1,4-naphthoquinone (5-HNQ) showed stronger relative ETC, and 9,10-anthraquinone-2-carboxylic acid (AQC) and 9,10-anthraquinone-2-sulfonic acid (AQS) had high relative ETC. Enhancement of microbial goethite reduction kinetics and current outputs by SQ had a good linear relationship with their ETC, indicating that the effectiveness of quinone-mediated EET may be strongly dependent on the ETC of the quinones. Therefore, the presence of quinone compounds and fermenting microorganisms may increase the diversity of microbial populations that contribute to element transformation in natural environments. Moreover, ETC determination of different SQ would help to evaluate their performance for microbial EET under anoxic conditions. Copyright © 2013 Elsevier

  5. Complete Phenotypic Recovery of an Alzheimer's Disease Model by a Quinone-Tryptophan Hybrid Aggregation Inhibitor

    PubMed Central

    Scherzer-Attali, Roni; Pellarin, Riccardo; Convertino, Marino; Frydman-Marom, Anat; Egoz-Matia, Nirit; Peled, Sivan; Levy-Sakin, Michal; Shalev, Deborah E.; Caflisch, Amedeo; Gazit, Ehud; Segal, Daniel

    2010-01-01

    The rational design of amyloid oligomer inhibitors is yet an unmet drug development need. Previous studies have identified the role of tryptophan in amyloid recognition, association and inhibition. Furthermore, tryptophan was ranked as the residue with highest amyloidogenic propensity. Other studies have demonstrated that quinones, specifically anthraquinones, can serve as aggregation inhibitors probably due to the dipole interaction of the quinonic ring with aromatic recognition sites within the amyloidogenic proteins. Here, using in vitro, in vivo and in silico tools we describe the synthesis and functional characterization of a rationally designed inhibitor of the Alzheimer's disease-associated β-amyloid. This compound, 1,4-naphthoquinon-2-yl-L-tryptophan (NQTrp), combines the recognition capacities of both quinone and tryptophan moieties and completely inhibited Aβ oligomerization and fibrillization, as well as the cytotoxic effect of Aβ oligomers towards cultured neuronal cell line. Furthermore, when fed to transgenic Alzheimer's disease Drosophila model it prolonged their life span and completely abolished their defective locomotion. Analysis of the brains of these flies showed a significant reduction in oligomeric species of Aβ while immuno-staining of the 3rd instar larval brains showed a significant reduction in Aβ accumulation. Computational studies, as well as NMR and CD spectroscopy provide mechanistic insight into the activity of the compound which is most likely mediated by clamping of the aromatic recognition interface in the central segment of Aβ. Our results demonstrate that interfering with the aromatic core of amyloidogenic peptides is a promising approach for inhibiting various pathogenic species associated with amyloidogenic diseases. The compound NQTrp can serve as a lead for developing a new class of disease modifying drugs for Alzheimer's disease. PMID:20559435

  6. Directly probing redox-linked quinones in photosystem II membrane fragments via UV resonance Raman scattering.

    PubMed

    Chen, Jun; Yao, Mingdong; Pagba, Cynthia V; Zheng, Yang; Fei, Liping; Feng, Zhaochi; Barry, Bridgette A

    2015-01-01

    In photosynthesis, photosystem II (PSII) harvests sunlight with bound pigments to oxidize water and reduce quinone to quinol, which serves as electron and proton mediators for solar-to-chemical energy conversion. At least two types of quinone cofactors in PSII are redox-linked: QA, and QB. Here, we for the first time apply 257-nm ultraviolet resonance Raman (UVRR) spectroscopy to acquire the molecular vibrations of plastoquinone (PQ) in PSII membranes. Owing to the resonance enhancement effect, the vibrational signal of PQ in PSII membranes is prominent. A strong band at 1661 cm(-1) is assigned to ring CC/CO symmetric stretch mode (ν8a mode) of PQ, and a weak band at 469 cm(-1) to ring stretch mode. By using a pump-probe difference UVRR method and a sample jet technique, the signals of QA and QB can be distinguished. A frequency difference of 1.4 cm(-1) in ν8a vibrational mode between QA and QB is observed, corresponding to ~86 mV redox potential difference imposed by their protein environment. In addition, there are other PQs in the PSII membranes. A negligible anharmonicity effect on their combination band at 2130 cm(-1) suggests that the 'other PQs' are situated in a hydrophobic environment. The detection of the 'other PQs' might be consistent with the view that another functional PQ cofactor (not QA or QB) exists in PSII. This UVRR approach will be useful to the study of quinone molecules in photosynthesis or other biological systems.

  7. Modification of photosystem I reaction center by the extraction and exchange of chlorophylls and quinones.

    PubMed

    Itoh, S; Iwaki, M; Ikegami, I

    2001-10-30

    The photosystem (PS) I photosynthetic reaction center was modified thorough the selective extraction and exchange of chlorophylls and quinones. Extraction of lyophilized photosystem I complex with diethyl ether depleted more than 90% chlorophyll (Chl) molecules bound to the complex, preserving the photochemical electron transfer activity from the primary electron donor P700 to the acceptor chlorophyll A(0). The treatment extracted all the carotenoids and the secondary acceptor phylloquinone (A(1)), and produced a PS I reaction center that contains nine molecules of Chls including P700 and A(0), and three Fe-S clusters (F(X), F(A) and F(B)). The ether-extracted PS I complex showed fast electron transfer from P700 to A(0) as it is, and to FeS clusters if phylloquinone or an appropriate artificial quinone was reconstituted as A(1). The ether-extracted PS I enabled accurate detection of the primary photoreactions with little disturbance from the absorbance changes of the bulk pigments. The quinone reconstitution created the new reactions between the artificial cofactors and the intrinsic components with altered energy gaps. We review the studies done in the ether-extracted PS I complex including chlorophyll forms of the core moiety of PS I, fluorescence of P700, reaction rate between A(0) and reconstituted A(1), and the fast electron transfer from P700 to A(0). Natural exchange of chlorophyll a to 710-740 nm absorbing chlorophyll d in PS I of the newly found cyanobacteria-like organism Acaryochloris marina was also reviewed. Based on the results of exchange studies in different systems, designs of photosynthetic reaction centers are discussed.

  8. Potential gastroprotective effect of novel cyperenoic acid/quinone derivatives in human cell cultures.

    PubMed

    Theoduloz, Cristina; Carrión, Ivanna Bravo; Pertino, Mariano Walter; Valenzuela, Daniela; Schmeda-Hirschmann, Guillermo

    2012-11-01

    The stem bark of Tabebuia species and the rhizomes of Jatropha isabelii are used in Paraguayan traditional medicine to treat gastric lesions and as anti-inflammatory agents. The sesquiterpene cyperenoic acid obtained from J. isabelii has been shown to display a gastroprotective effect in animal models of induced gastric ulcers while the quinone lapachol shows several biological effects associated with the use of the crude drug. The aim of this work was to prepare hybrid molecules presenting a terpene and a quinone moiety and to obtain an assessment of the gastroprotective activity of the new compounds using human cell cultures (MRC-5 fibroblasts and AGS epithelial gastric cells). Eight compounds, including the natural products and semisynthetic derivatives were assessed for proliferation of MRC-5 fibroblasts, protection against sodium taurocholate-induced damage, prostaglandin E2 content, and stimulation of cellular-reduced glutathione synthesis in AGS cells. The following antioxidant assays were performed: DPPH discoloration, scavenging of the superoxide anion, and inhibition of induced lipoperoxidation in erythrocyte membranes. 3-Hydroxy-β-lapachone (3) and cyperenoic acid (4) stimulated fibroblast proliferation. Lapachol (1), dihydroprenyl lapachol (2), 3-hydroxy-β-lapachone (3), and lapachoyl cyperenate (6) protected against sodium taurocholate-induced damage in AGS cells. Lapachol (1) and dihydroprenyl lapachoyl cyperenate (7) significantly stimulated prostaglandin E2 synthesis in AGS cells. Compounds 3, 4, and 7 raised reduced glutathione levels in AGS cells. The hybrid compounds presented activities different than those of the starting sesquiterpene or quinones. Georg Thieme Verlag KG Stuttgart · New York.

  9. Redox potential tuning through differential quinone binding in the photosynthetic reaction center of Rhodobacter sphaeroides

    SciTech Connect

    Vermaas, Josh V.; Taguchi, Alexander T.; Dikanov, Sergei A.; Wraight, Colin A.; Tajkhorshid, Emad

    2015-03-03

    Ubiquinone forms an integral part of the electron transport chain in cellular respiration and photosynthesis across a vast number of organisms. Prior experimental results have shown that the photosynthetic reaction center (RC) from Rhodobacter sphaeroides is only fully functional with a limited set of methoxy-bearing quinones, suggesting that specific interactions with this substituent are required to drive electron transport and the formation of quinol. The nature of these interactions has yet to be determined. Through parameterization of a CHARMM-compatible quinone force field and subsequent molecular dynamics simulations of the quinone-bound RC, in this paper we have investigated and characterized the interactions of the protein with the quinones in the QA and QB sites using both equilibrium simulation and thermodynamic integration. In particular, we identify a specific interaction between the 2-methoxy group of ubiquinone in the QB site and the amide nitrogen of GlyL225 that we implicate in locking the orientation of the 2-methoxy group, thereby tuning the redox potential difference between the quinones occupying the QA and QB sites. Finally, disruption of this interaction leads to weaker binding in a ubiquinone analogue that lacks a 2-methoxy group, a finding supported by reverse electron transfer electron paramagnetic resonance experiments of the QA–QB– biradical and competitive binding assays.

  10. Structural and Functional insights into the catalytic mechanism of the Type II NADH:quinone oxidoreductase family

    PubMed Central

    Marreiros, Bruno C.; Sena, Filipa V.; Sousa, Filipe M.; Oliveira, A. Sofia F.; Soares, Cláudio M.; Batista, Ana P.; Pereira, Manuela M.

    2017-01-01

    Type II NADH:quinone oxidoreductases (NDH-2s) are membrane proteins involved in respiratory chains. These proteins contribute indirectly to the establishment of the transmembrane difference of electrochemical potential by catalyzing the reduction of quinone by oxidation of NAD(P)H. NDH-2s are widespread enzymes being present in the three domains of life. In this work, we explored the catalytic mechanism of NDH-2 by investigating the common elements of all NDH-2s, based on the rationale that conservation of such elements reflects their structural/functional importance. We observed conserved sequence motifs and structural elements among 1762 NDH-2s. We identified two proton pathways possibly involved in the protonation of the quinone. Our results led us to propose the first catalytic mechanism for NDH-2 family, in which a conserved glutamate residue, E172 (in NDH-2 from Staphylococcus aureus) plays a key role in proton transfer to the quinone pocket. This catalytic mechanism may also be extended to the other members of the two-Dinucleotide Binding Domains Flavoprotein (tDBDF) superfamily, such as sulfide:quinone oxidoreductases. PMID:28181562

  11. Structural and Functional insights into the catalytic mechanism of the Type II NADH:quinone oxidoreductase family.

    PubMed

    Marreiros, Bruno C; Sena, Filipa V; Sousa, Filipe M; Oliveira, A Sofia F; Soares, Cláudio M; Batista, Ana P; Pereira, Manuela M

    2017-02-09

    Type II NADH:quinone oxidoreductases (NDH-2s) are membrane proteins involved in respiratory chains. These proteins contribute indirectly to the establishment of the transmembrane difference of electrochemical potential by catalyzing the reduction of quinone by oxidation of NAD(P)H. NDH-2s are widespread enzymes being present in the three domains of life. In this work, we explored the catalytic mechanism of NDH-2 by investigating the common elements of all NDH-2s, based on the rationale that conservation of such elements reflects their structural/functional importance. We observed conserved sequence motifs and structural elements among 1762 NDH-2s. We identified two proton pathways possibly involved in the protonation of the quinone. Our results led us to propose the first catalytic mechanism for NDH-2 family, in which a conserved glutamate residue, E172 (in NDH-2 from Staphylococcus aureus) plays a key role in proton transfer to the quinone pocket. This catalytic mechanism may also be extended to the other members of the two-Dinucleotide Binding Domains Flavoprotein (tDBDF) superfamily, such as sulfide:quinone oxidoreductases.

  12. Phospholipid-derived fatty acids and quinones as markers for bacterial biomass and community structure in marine sediments.

    PubMed

    Kunihiro, Tadao; Veuger, Bart; Vasquez-Cardenas, Diana; Pozzato, Lara; Le Guitton, Marie; Moriya, Kazuyoshi; Kuwae, Michinobu; Omori, Koji; Boschker, Henricus T S; van Oevelen, Dick

    2014-01-01

    Phospholipid-derived fatty acids (PLFA) and respiratory quinones (RQ) are microbial compounds that have been utilized as biomarkers to quantify bacterial biomass and to characterize microbial community structure in sediments, waters, and soils. While PLFAs have been widely used as quantitative bacterial biomarkers in marine sediments, applications of quinone analysis in marine sediments are very limited. In this study, we investigated the relation between both groups of bacterial biomarkers in a broad range of marine sediments from the intertidal zone to the deep sea. We found a good log-log correlation between concentrations of bacterial PLFA and RQ over several orders of magnitude. This relationship is probably due to metabolic variation in quinone concentrations in bacterial cells in different environments, whereas PLFA concentrations are relatively stable under different conditions. We also found a good agreement in the community structure classifications based on the bacterial PLFAs and RQs. These results strengthen the application of both compounds as quantitative bacterial biomarkers. Moreover, the bacterial PLFA- and RQ profiles revealed a comparable dissimilarity pattern of the sampled sediments, but with a higher level of dissimilarity for the RQs. This means that the quinone method has a higher resolution for resolving differences in bacterial community composition. Combining PLFA and quinone analysis as a complementary method is a good strategy to yield higher resolving power in bacterial community structure.

  13. Phospholipid-Derived Fatty Acids and Quinones as Markers for Bacterial Biomass and Community Structure in Marine Sediments

    PubMed Central

    Kunihiro, Tadao; Veuger, Bart; Vasquez-Cardenas, Diana; Pozzato, Lara; Le Guitton, Marie; Moriya, Kazuyoshi; Kuwae, Michinobu; Omori, Koji; Boschker, Henricus T. S.; van Oevelen, Dick

    2014-01-01

    Phospholipid-derived fatty acids (PLFA) and respiratory quinones (RQ) are microbial compounds that have been utilized as biomarkers to quantify bacterial biomass and to characterize microbial community structure in sediments, waters, and soils. While PLFAs have been widely used as quantitative bacterial biomarkers in marine sediments, applications of quinone analysis in marine sediments are very limited. In this study, we investigated the relation between both groups of bacterial biomarkers in a broad range of marine sediments from the intertidal zone to the deep sea. We found a good log-log correlation between concentrations of bacterial PLFA and RQ over several orders of magnitude. This relationship is probably due to metabolic variation in quinone concentrations in bacterial cells in different environments, whereas PLFA concentrations are relatively stable under different conditions. We also found a good agreement in the community structure classifications based on the bacterial PLFAs and RQs. These results strengthen the application of both compounds as quantitative bacterial biomarkers. Moreover, the bacterial PLFA- and RQ profiles revealed a comparable dissimilarity pattern of the sampled sediments, but with a higher level of dissimilarity for the RQs. This means that the quinone method has a higher resolution for resolving differences in bacterial community composition. Combining PLFA and quinone analysis as a complementary method is a good strategy to yield higher resolving power in bacterial community structure. PMID:24769853

  14. A quinone-assisted photoformation of energy-rich chemical bonds

    NASA Technical Reports Server (NTRS)

    Fox, S. W.; Adachi, T.; Stillwell, W.

    1980-01-01

    In a study of biochemical means of solar energy conversion, ADP and inorganic phosphates were converted to ATP by white light in the nonaqueous solvent dimethylformamide in the presence of tetrachloro-p-quinone or ubiquinone. Conversion of ADP to ATP has been accomplished in aqueous suspension by the use of cell-like structures aggregated from poly(aspartic acid, glutamic acid, tyrosine). This is believed to occur through the formation of dopaquinone in the peptide structure during illumination. The way in which the quantitative yield of ATP has been influenced by pH and by added substances, such as FeCl2, was studied.

  15. Chemoselective methylation of phenolic hydroxyl group prevents quinone methide formation and repolymerization during lignin depolymerization

    DOE PAGES

    Kim, Kwang Ho; Dutta, Tanmoy; Walter, Eric D.; ...

    2017-03-22

    Chemoselective blocking of the phenolic hydroxyl (Ar–OH) group by methylation was found to suppress secondary repolymerization and charring during lignin depolymerization. Methylation of Ar–OH prevents formation of reactive quinone methide intermediates, which are partly responsible for undesirable secondary repolymerization reactions. Instead, this structurally modified lignin produces more relatively low molecular weight products from lignin depolymerization compared to unmodified lignin. This result demonstrates that structural modification of lignin is desirable for production of low molecular weight phenolic products. Finally, this approach could be directed toward alteration of natural lignification processes to produce biomass that is more amenable to chemical depolymerization.

  16. Homologation of α-aryl amino acids through quinone-catalyzed decarboxylation/Mukaiyama-Mannich addition.

    PubMed

    Haugeberg, Benjamin J; Phan, Johnny H; Liu, Xinyun; O'Connor, Thomas J; Clift, Michael D

    2017-03-09

    A new method for amino acid homologation by way of formal C-C bond functionalization is reported. This method utilizes a 2-step/1-pot protocol to convert α-amino acids to their corresponding N-protected β-amino esters through quinone-catalyzed oxidative decarboxylation/in situ Mukaiyama-Mannich addition. The scope and limitations of this chemistry are presented. This methodology provides an alternative to the classical Arndt-Eistert homologation for accessing β-amino acid derivatives. The resulting N-protected amine products can be easily deprotected to afford the corresponding free amines.

  17. Novel prenylated bichalcone and chalcone from Humulus lupulus and their quinone reductase induction activities.

    PubMed

    Yu, Liyan; Zhang, Fuxian; Hu, Zhijuan; Ding, Hui; Tang, Huifang; Ma, Zhongjun; Zhao, Xiaofeng

    2014-03-01

    A new prenylated chalcone xanthohumol M (1), a novel prenylated bichalcone humulusol (2) and six known chalcones (3-8) were found from Humulus lupulus. Their structures were determined by spectroscopic methods. All the chalcones' electrophilic abilities were assessed by GSH (glutathione) rapid screening, and their QR (quinone reductase) induction activities were evaluated using hepa 1c1c7 cells. The results of electrophilic assay and QR induction activity assay were quite well. New compounds 1 and 2, along with some known prenylated chalcones, displayed certain QR induction activity.

  18. A quinone-assisted photoformation of energy-rich chemical bonds

    NASA Technical Reports Server (NTRS)

    Fox, S. W.; Adachi, T.; Stillwell, W.

    1980-01-01

    In a study of biochemical means of solar energy conversion, ADP and inorganic phosphates were converted to ATP by white light in the nonaqueous solvent dimethylformamide in the presence of tetrachloro-p-quinone or ubiquinone. Conversion of ADP to ATP has been accomplished in aqueous suspension by the use of cell-like structures aggregated from poly(aspartic acid, glutamic acid, tyrosine). This is believed to occur through the formation of dopaquinone in the peptide structure during illumination. The way in which the quantitative yield of ATP has been influenced by pH and by added substances, such as FeCl2, was studied.

  19. Michael Additions of Highly Basic Enolates to ortho-Quinone Methides.

    PubMed

    Lewis, Robert S; Garza, Christopher J; Dang, Ann T; Pedro, Te Kie A; Chain, William J

    2015-05-01

    A protocol by which ketone or ester enolates and ortho-quinone methides (o-QMs) are generated in situ in a single reaction flask from silylated precursors under the action of anhydrous fluoride is reported. The reaction partners are joined to give a variety of β-(2-hydroxyphenyl)-carbonyl compounds in 32-94% yield in a single laboratory operation. The intermediacy of o-QMs is supported by control experiments utilizing enolate precursors and conventional alkyl halides as competitive alkylating agents and the isolation of 1,5-dicarbonyl products resulting from conjugate additions that do not restore the aromatic system.

  20. Michael Additions of Highly Basic Enolates to ortho-Quinone Methides

    PubMed Central

    Lewis, Robert S.; Garza, Christopher J.; Dang, Ann T.; Pedro, Te Kie A.; Chain, William J.

    2015-01-01

    A protocol by which ketone or ester enolates and ortho-quinone methides (o-QMs) are generated in situ in a single reaction flask from silylated precursors under the action of anhydrous fluoride is reported. The reaction partners are joined to give a variety of β-(2-hydroxyphenyl)-carbonyl compounds in 32–94% yield in a single laboratory operation. The intermediacy of o-QMs is supported by control experiments utilizing enolate precursors and conventional alkyl halides as competitive alkylating agents and the isolation of 1,5-dicarbonyl products resulting from conjugate additions that do not restore the aromatic system. PMID:25906358

  1. α-Tocotrienol quinone modulates oxidative stress response and the biochemistry of aging.

    PubMed

    Shrader, William D; Amagata, Akiko; Barnes, Adam; Enns, Gregory M; Hinman, Andrew; Jankowski, Orion; Kheifets, Viktoria; Komatsuzaki, Ryo; Lee, Edgar; Mollard, Paul; Murase, Katsuyuki; Sadun, Alfredo A; Thoolen, Martin; Wesson, Kieron; Miller, Guy

    2011-06-15

    We report that α-tocotrienol quinone (ATQ3) is a metabolite of α-tocotrienol, and that ATQ3 is a potent cellular protectant against oxidative stress and aging. ATQ3 is orally bioavailable, crosses the blood-brain barrier, and has demonstrated clinical response in inherited mitochondrial disease in open label studies. ATQ3 activity is dependent upon reversible 2e-redox-cycling. ATQ3 may represent a broader class of unappreciated dietary-derived phytomolecular redox motifs that digitally encode biochemical data using redox state as a means to sense and transfer information essential for cellular function.

  2. Analytical ultracentrifugation and preliminary X-ray studies of the chloroplast envelope quinone oxidoreductase homologue from Arabidopsis thaliana

    PubMed Central

    Mas y mas, Sarah; Giustini, Cécile; Ferrer, Jean-Luc; Rolland, Norbert; Curien, Gilles; Cobessi, David

    2015-01-01

    Quinone oxidoreductases reduce a broad range of quinones and are widely distributed among living organisms. The chloroplast envelope quinone oxidoreductase homologue (ceQORH) from Arabidopsis thaliana binds NADPH, lacks a classical N-terminal and cleavable chloroplast transit peptide, and is transported through the chloroplast envelope membrane by an unknown alternative pathway without cleavage of its internal chloroplast targeting sequence. To unravel the fold of this targeting sequence and its substrate specificity, ceQORH from A. thaliana was overexpressed in Escherichia coli, purified and crystallized. Crystals of apo ceQORH were obtained and a complete data set was collected at 2.34 Å resolution. The crystals belonged to space group C2221, with two molecules in the asymmetric unit. PMID:25849509

  3. Unexpected Reduction of Iminoquinone and Quinone Derivatives in Positive Electrospray Ionization Mass Spectrometry and Possible Mechanism Exploration

    NASA Astrophysics Data System (ADS)

    Pei, Jiying; Hsu, Cheng-Chih; Zhang, Ruijie; Wang, Yinghui; Yu, Kefu; Huang, Guangming

    2017-08-01

    Unexpected reduction of iminoquinone (IQ) and quinone derivatives was first reported during positive electrospray ionization mass spectrometry. Upon increasing spray voltage, the intensities of IQ and quinone derivatives decreased drastically, accompanying the increase of the intensities of the reduction products, amodiaquine (AQ) and phenol derivatives. To gain more insight into the mechanism of such reduction, we explored the experimental factors that are influential to corona discharge (CD). The results show that experimental parameters that favor severe CD, including metal spray emitter, using water as spray solvent, sheath gas with low dielectric strength (e.g., nitrogen), and shorter spray tip-to-mass spectrometer inlet distance, facilitated the reduction of IQ and quinone derivatives, implying that the reduction should be closely related to CD in the gas phase. [Figure not available: see fulltext.

  4. Measuring protection of aromatic wine thiols from oxidation by competitive reactions vs wine preservatives with ortho-quinones.

    PubMed

    Nikolantonaki, Maria; Magiatis, Prokopios; Waterhouse, Andrew L

    2014-11-15

    Quinones are central intermediates in wine oxidation that can degrade the quality of wine by reactions with varietal thiols, such as 3-sulfanylhexanol, decreasing desirable aroma. Protection by wine preservatives (sulphur dioxide, glutathione, ascorbic acid and model tannin, phloroglucinol) was assessed by competitive sacrificial reactions with 4-methyl-1,2-benzoquinone, quantifying products and ratios by HPLC-UV-MS. Regioselectivity was assessed by product isolation and identification by NMR spectroscopy. Nucleophilic addition reactions compete with two electron reduction of quinones by sulphur dioxide or ascorbic acid, and both routes serve as effective quenching pathways, but minor secondary products from coupled redox reactions between the products and reactants are also observed. The wine preservatives were all highly reactive and thus all very protective against 3-sulfanylhexanol loss to the quinone, but showed only additive antioxidant effects. Confirmation of these reaction rates and pathways in wine is needed to assess the actual protective action of each tested preservative.

  5. Structural analysis and molecular docking of trypanocidal aryloxy-quinones in trypanothione and glutathione reductases: a comparison with biochemical data.

    PubMed

    Vera, Brenda; Vázquez, Karina; Mascayano, Carolina; Tapia, Ricardo A; Espinosa, Victoria; Soto-Delgado, Jorge; Salas, Cristian O; Paulino, Margot

    2016-07-15

    A set of aryloxy-quinones, previously synthesized and evaluated against Trypanosoma cruzi epimastigotes cultures, were found more potent and selective than nifurtimox. One of the possible mechanisms of the trypanocidal activity of these quinones could be inhibition of trypanothione reductase (TR). Considering that glutathione reductase (GR) is the equivalent of TR in humans, biochemical, kinetic, and molecular docking studies in TR and GR were envisaged and compared with the trypanocidal and cytotoxic data of a set of aryloxy-quinones. Biochemical assays indicated that three naphthoquinones (Nq-h, Nq-g, and Nq-d) selectively inhibit TR and the TR kinetic analyses indicated that Nq-h inhibit TR in a noncompetitive mechanism. Molecular dockings were performed in TR and GR in the following three putative binding sites: the catalytic site, the dimer interface, and the nicotinamide adenine dinucleotide phosphate-binding site. In TR and GR, the aryloxy-quinones were found to exhibit high affinity for a site near it cognate-binding site in a place in which the noncompetitive kinetics could be justified. Taking as examples the three compounds with TR specificity (TRS) (Nq-h, Nq-g, and Nq-d), the presence of a network of contacts with the quinonic ring sustained by the triad of Lys62, Met400', Ser464' residues, seems to contribute hardly to the TRS. Compound Nq-b, a naphthoquinone with nitrophenoxy substituent, proved to be the best scaffold for the design of trypanocidal compounds with low toxicity. However, the compound displayed only a poor and non-selective effect toward TR indicating that TR inhibition is not the main reason for the antiparasitic activity of the aryloxy-quinones.

  6. Identification of the Binding Position of Amilorides in the Quinone Binding Pocket of Mitochondrial Complex I.

    PubMed

    Ito, Takeshi; Murai, Masatoshi; Morisaka, Hironobu; Miyoshi, Hideto

    2015-06-16

    We previously demonstrated that amilorides bind to the quinone binding pocket of bovine mitochondrial complex I, not to the hitherto suspected Na⁺/H⁺ antiporter-like subunits (ND2, ND4, and ND5) [Murai, M., et al. (2015) Biochemistry 54, 2739-2746]. To characterize the binding position of amilorides within the pocket in more detail, we conducted specific chemical labeling [alkynylation (-C≡CH)] of complex I via ligand-directed tosyl (LDT) chemistry using a newly synthesized amide-type amiloride AAT as a LDT chemistry reagent. The inhibitory potency of AAT, in terms of its IC50 value, was markedly higher (∼1000-fold) than that of prototypical guanidine-type amilorides such as commercially available EIPA and benzamil. Detailed proteomic analyses in combination with click chemistry revealed that the chemical labeling occurred at Asp160 of the 49 kDa subunit (49 kDa Asp160). This labeling was significantly suppressed in the presence of an excess amount of other amilorides or ordinary inhibitors such as quinazoline and acetogenin. Taking into consideration the fact that 49 kDa Asp160 was also specifically labeled by LDT chemistry reagents derived from acetogenin [Masuya, T., et al. (2014) Biochemistry 53, 2307-2317, 7816-7823], we found this aspartic acid to elicit very strong nucleophilicity in the local protein environment. The structural features of the quinone binding pocket in bovine complex I are discussed on the basis of this finding.

  7. Determination of total proteins: a study of reaction between quinones and proteins.

    PubMed

    Zaia, D A; Verri, W A; Zaia, C T

    1999-06-14

    A previous study was undertaken to test the reaction of several quinones (p-benzoquinone; 2,5-dichloro and 2,6-dichloro p-benzoquinone; tetrachloro-p-benzoquinone; tetrachloro-o-benzoquinone; 2,5-dichloro-3,6-dihydroxy-p-benzoquinone; benz[a]anthracene-7,12-dione) with bovine serum albumin (BSA). From this study, we have devised a spectrophotometric method for determination of total proteins. The quinone, tetrachloro-p-benzoquinone (p-chloranil), showed the best result. The product of reaction between proteins and p-chloranil absorbed at 360 nm and Beer's law was followed up to 200 mug ml(-1) of BSA. The product of reaction of BSA/p-chloranil was stable for 30 min, after that the absorbance increased 16% and kept stable for 24 h. The p-chloranil method showed a limit of detection (1.25 mug ml(-1)) lower than the biuret method (52.0 mug ml(-1)) or p-benzoquinone (PBQ) method (2.6-4.0 mug ml(-1)). The method was applied to spectrophotometric determination of total proteins in blood plasma; the results were compared with the biuret method that is widely used in clinical analysis.

  8. Identification of lactate dehydrogenase as a mammalian pyrroloquinoline quinone (PQQ)-binding protein

    PubMed Central

    Akagawa, Mitsugu; Minematsu, Kenji; Shibata, Takahiro; Kondo, Tatsuhiko; Ishii, Takeshi; Uchida, Koji

    2016-01-01

    Pyrroloquinoline quinone (PQQ), a redox-active o-quinone, is an important nutrient involved in numerous physiological and biochemical processes in mammals. Despite such beneficial functions, the underlying molecular mechanisms remain to be established. In the present study, using PQQ-immobilized Sepharose beads as a probe, we examined the presence of protein(s) that are capable of binding PQQ in mouse NIH/3T3 fibroblasts and identified five cellular proteins, including l-lactate dehydrogenase (LDH) A chain, as potential mammalian PQQ-binding proteins. In vitro studies using a purified rabbit muscle LDH show that PQQ inhibits the formation of lactate from pyruvate in the presence of NADH (forward reaction), whereas it enhances the conversion of lactate to pyruvate in the presence of NAD+ (reverse reaction). The molecular mechanism underlying PQQ-mediated regulation of LDH activity is attributed to the oxidation of NADH to NAD+ by PQQ. Indeed, the PQQ-bound LDH oxidizes NADH, generating NAD+, and significantly catalyzes the conversion of lactate to pyruvate. Furthermore, PQQ attenuates cellular lactate release and increases intracellular ATP levels in the NIH/3T3 fibroblasts. Our results suggest that PQQ, modulating LDH activity to facilitate pyruvate formation through its redox-cycling activity, may be involved in the enhanced energy production via mitochondrial TCA cycle and oxidative phosphorylation. PMID:27230956

  9. Another unusual type of citric acid cycle enzyme in Helicobacter pylori: the malate:quinone oxidoreductase.

    PubMed

    Kather, B; Stingl, K; van der Rest, M E; Altendorf, K; Molenaar, D

    2000-06-01

    The only enzyme of the citric acid cycle for which no open reading frame (ORF) was found in the Helicobacter pylori genome is the NAD-dependent malate dehydrogenase. Here, it is shown that in this organism the oxidation of malate to oxaloacetate is catalyzed by a malate:quinone oxidoreductase (MQO). This flavin adenine dinucleotide-dependent membrane-associated enzyme donates electrons to quinones of the electron transfer chain. Similar to succinate dehydrogenase, it is part of both the electron transfer chain and the citric acid cycle. MQO activity was demonstrated in isolated membranes of H. pylori. The enzyme is encoded by the ORF HP0086, which is shown by the fact that expression of the HP0086 sequence from a plasmid induces high MQO activity in mqo deletion mutants of Escherichia coli or Corynebacterium glutamicum. Furthermore, this plasmid was able to complement the phenotype of the C. glutamicum mqo deletion mutant. Interestingly, the protein predicted to be encoded by this ORF is only distantly related to known or postulated MQO sequences from other bacteria. The presence of an MQO shown here and the previously demonstrated presence of a 2-ketoglutarate:ferredoxin oxidoreductase and a succinyl-coenzyme A (CoA):acetoacetyl-CoA transferase indicate that H. pylori possesses a complete citric acid cycle, but one which deviates from the standard textbook example in three steps.

  10. Solid-State Thermolytic Epimerization and Polymerization of (+)-Catechin and (-)-Epicatechin Proceed through Quinone Methide Intermediates.

    PubMed

    Oomah, B Dave; Quigley, Nicole; Latorre, Marie-Laure; Rayne, Sierra; Mazza, Giuseppe

    2008-06-04

    A mechanism involving a quinone methide intermediate is proposed for the thermally driven epimerization and polymerization reactions of solid-state catechin and epicatechin. Epimerization of catechin to epicatechin maximized after heating at 180 degrees C for 30 min (0.76:1, epicatechin/catechin ratio), whereas maximum epicatechin to catechin epimerization occurred after heating at 250 degrees C for 2 min at a ratio of 1.34:1 (catechin/epicatechin). These results imply that the conversion of epicatechin to catechin is the thermodynamically favored process. Conversion to nonepimerized products was optimal (99%) after 8 min at 220 degrees C for catechin and after 2 min at 265 degrees C for epicatechin (99.8%). Pyrocatechol was identified by HPLC as a degradation product in both catechin and epicatechin. Heating catechin at 220 degrees C for 8 min produced a 5-fold increase in chromatographic peak area at 450 nm, indicative of quinone methide formation that was thermally stable over time and degraded in the presence of sodium borohydride.

  11. Oxidized quinones signal onset of darkness directly to the cyanobacterial circadian oscillator.

    PubMed

    Kim, Yong-Ick; Vinyard, David J; Ananyev, Gennady M; Dismukes, G Charles; Golden, Susan S

    2012-10-30

    Synchronization of the circadian clock in cyanobacteria with the day/night cycle proceeds without an obvious photoreceptor, leaving open the question of its specific mechanism. The circadian oscillator can be reconstituted in vitro, where the activities of two of its proteins, KaiA and KaiC, are affected by metabolites that reflect photosynthetic activity: KaiC phosphorylation is directly influenced by the ATP/ADP ratio, and KaiA stimulation of KaiC phosphorylation is blocked by oxidized, but not reduced, quinones. Manipulation of the ATP/ADP ratio can reset the timing of KaiC phosphorylation peaks in the reconstituted in vitro oscillator. Here, we show that pulses of oxidized quinones reset the cyanobacterial circadian clock both in vitro and in vivo. Onset of darkness causes an abrupt oxidation of the plastoquinone pool in vivo, which is in contrast to a gradual decrease in the ATP/ADP ratio that falls over the course of hours until the onset of light. Thus, these two metabolic measures of photosynthetic activity act in concert to signal both the onset and duration of darkness to the cyanobacterial clock.

  12. Oxidized quinones signal onset of darkness directly to the cyanobacterial circadian oscillator

    PubMed Central

    Kim, Yong-Ick; Vinyard, David J.; Ananyev, Gennady M.; Dismukes, G. Charles; Golden, Susan S.

    2012-01-01

    Synchronization of the circadian clock in cyanobacteria with the day/night cycle proceeds without an obvious photoreceptor, leaving open the question of its specific mechanism. The circadian oscillator can be reconstituted in vitro, where the activities of two of its proteins, KaiA and KaiC, are affected by metabolites that reflect photosynthetic activity: KaiC phosphorylation is directly influenced by the ATP/ADP ratio, and KaiA stimulation of KaiC phosphorylation is blocked by oxidized, but not reduced, quinones. Manipulation of the ATP/ADP ratio can reset the timing of KaiC phosphorylation peaks in the reconstituted in vitro oscillator. Here, we show that pulses of oxidized quinones reset the cyanobacterial circadian clock both in vitro and in vivo. Onset of darkness causes an abrupt oxidation of the plastoquinone pool in vivo, which is in contrast to a gradual decrease in the ATP/ADP ratio that falls over the course of hours until the onset of light. Thus, these two metabolic measures of photosynthetic activity act in concert to signal both the onset and duration of darkness to the cyanobacterial clock. PMID:23071342

  13. Staphylococcus aureus lactate- and malate-quinone oxidoreductases contribute to nitric oxide resistance and virulence.

    PubMed

    Spahich, Nicole A; Vitko, Nicholas P; Thurlow, Lance R; Temple, Brenda; Richardson, Anthony R

    2016-06-01

    Staphylococcus aureus is a Gram-positive pathogen that resists many facets of innate immunity including nitric oxide (NO·). Staphylococcus aureus NO-resistance stems from its ability to evoke a metabolic state that circumvents the negative effects of reactive nitrogen species. The combination of l-lactate and peptides promotes S. aureus growth at moderate NO-levels, however, neither nutrient alone suffices. Here, we investigate the staphylococcal malate-quinone and l-lactate-quinone oxidoreductases (Mqo and Lqo), both of which are critical during NO-stress for the combined utilization of peptides and l-lactate. We address the specific contributions of Lqo-mediated l-lactate utilization and Mqo-dependent amino acid consumption during NO-stress. We show that Lqo conversion of l-lactate to pyruvate is required for the formation of ATP, an essential energy source for peptide utilization. Thus, both Lqo and Mqo are essential for growth under these conditions making them attractive candidates for targeted therapeutics. Accordingly, we exploited a modelled Mqo/Lqo structure to define the catalytic and substrate-binding residues.We also compare the S. aureus Mqo/Lqo enzymes to their close relatives throughout the staphylococci and explore the substrate specificities of each enzyme. This study provides the initial characterization of the mechanism of action and the immunometabolic roles for a newly defined staphylococcal enzyme family. © 2016 John Wiley & Sons Ltd.

  14. On the importance of anion-π interactions in the mechanism of sulfide:quinone oxidoreductase.

    PubMed

    Bauzá, Antonio; Quiñonero, David; Deyà, Pere M; Frontera, Antonio

    2013-11-01

    Sulfide:quinone oxidoreductase (SQR) is a flavin-dependent enzyme that plays a physiological role in two important processes. First, it is responsible for sulfide detoxification by oxidizing sulfide ions (S(2-) and HS(-)) to elementary sulfur and the electrons are first transferred to flavin adenine dinucleotide (FAD), which in turn passes them to the quinone pool in the membrane. Second, in sulfidotrophic bacteria, SQRs play a key role in the sulfide-dependent respiration and anaerobic photosynthesis, deriving energy for their growth from reduced sulfur. Two mechanisms of action for SQR have been proposed: first, nucleophilic attack of a Cys residue on the C4 of FAD, and second, an alternate anionic radical mechanism by direct electron transfer from Cys to the isoalloxazine ring of FAD. Both mechanisms involve a common anionic intermediate that it is stabilized by a relevant anion-π interaction and its previous formation (from HS(-) and Cys-S-S-Cys) is also facilitated by reducing the transition-state barrier, owing to an interaction that involves the π system of FAD. By analyzing the X-ray structures of SQRs available in the Protein Data Bank (PDB) and using DFT calculations, we demonstrate the relevance of the anion-π interaction in the enzymatic mechanism.

  15. Direct and quinone-mediated palladium reduction by Geobacter sulfurreducens: mechanisms and modeling.

    PubMed

    Pat-Espadas, Aurora M; Razo-Flores, Elías; Rangel-Mendez, J Rene; Cervantes, Francisco J

    2014-01-01

    Palladium(II) reduction to Pd(0) nanoparticles by Geobacter sulfurreducens was explored under conditions of neutral pH, 30 °C and concentrations of 25, 50, and 100 mg of Pd(II)/L aiming to investigate the effect of solid species of palladium on their microbial reduction. The influence of anthraquinone-2,6-disulfonate was reported to enhance the palladium reaction rate in an average of 1.7-fold and its addition is determining to achieve the reduction of solid species of palladium. Based on the obtained results two mechanisms are proposed: (1) direct, which is fully described considering interactions of amide, sulfur, and phosphoryl groups associated to proteins from bacteria on palladium reduction reaction, and (2) quinone-mediated, which implies multiheme c-type cytochromes participation. Speciation analysis and kinetic results were considered and integrated into a model to fit the experimental data that explain both mechanisms. This work provides elements for a better understanding of direct and quinone-mediated palladium reduction by G. sulfurreducens, which could facilitate metal recovery with concomitant formation of valuable palladium nanoparticles in industrial processes.

  16. Induction of quinone reductase (QR) by withanolides isolated from Physalis pubescens L. (Solanaceae).

    PubMed

    Ji, Long; Yuan, Yonglei; Ma, Zhongjun; Chen, Zhe; Gan, Lishe; Ma, Xiaoqiong; Huang, Dongsheng

    2013-09-01

    In the present study, it was demonstrated that the dichloromethane extract of Physalis pubescens L. (DEPP) had weak potential quinone reductase (QR) inducing activity, but an UPLC-ESI-MS method with glutathione (GSH) as the substrate revealed that the DEPP had electrophiles (with an α,β-unsaturated ketone moiety). These electrophiles could induce quinone reductase (QR) activity, which might be attributed to the modification of the highly reactive cysteine residues in Keap1. Herein, four withanolides, including three new compounds physapubescin B (2), physapubescin C (3), physapubescin D (4), together with one known steroidal compound physapubescin (1) were isolated. Structures of these compounds were determined by spectroscopic analysis and that of physapubescin C (3) was confirmed by a combination of molecular modeling and quantum chemical DFT-GIAO calculations. Evaluation of the QR inducing activities of all withanolides indicated potent activities of compounds 1 and 2, which had a common α,β-unsaturated ketone moiety. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Lactococcus lactis catalyses electricity generation at microbial fuel cell anodes via excretion of a soluble quinone.

    PubMed

    Freguia, Stefano; Masuda, Masaki; Tsujimura, Seiya; Kano, Kenji

    2009-09-01

    Lactococcus lactis is a gram-positive, normally homolactic fermenter that is known to produce several kinds of membrane associated quinones, which are able to mediate electron transfer to extracellular electron acceptors such as Fe(3+), Cu(2+) and hexacyanoferrate. Here we show that this bacterium is also capable of performing extracellular electron transfer to anodes by utilizing at least two soluble redox mediators, as suggested by the two-step catalytic current developed. One of these two mediators was herein suggested to be 2-amino-3-dicarboxy-1,4-naphthoquinone (ACNQ), via evaluation of standard redox potential, ability of the bacterium to exploit the quinone when exogenously provided, as well as by high performance liquid chromatography coupled with UV spectrum analysis. During electricity generation, L. lactis slightly deviated from its normal homolactic metabolism by excreting acetate and pyruvate in stoichiometric amounts with respect to the electrical current. In this metabolism, the anode takes on the role of electron sink for acetogenic fermentation. The finding that L. lactis self-catalyses anodic electron transfer by excretion of redox mediators is remarkable as the mechanisms of extracellular electron transfer by pure cultures of gram-positive bacteria had previously never been elucidated.

  18. Identification of lactate dehydrogenase as a mammalian pyrroloquinoline quinone (PQQ)-binding protein.

    PubMed

    Akagawa, Mitsugu; Minematsu, Kenji; Shibata, Takahiro; Kondo, Tatsuhiko; Ishii, Takeshi; Uchida, Koji

    2016-05-27

    Pyrroloquinoline quinone (PQQ), a redox-active o-quinone, is an important nutrient involved in numerous physiological and biochemical processes in mammals. Despite such beneficial functions, the underlying molecular mechanisms remain to be established. In the present study, using PQQ-immobilized Sepharose beads as a probe, we examined the presence of protein(s) that are capable of binding PQQ in mouse NIH/3T3 fibroblasts and identified five cellular proteins, including l-lactate dehydrogenase (LDH) A chain, as potential mammalian PQQ-binding proteins. In vitro studies using a purified rabbit muscle LDH show that PQQ inhibits the formation of lactate from pyruvate in the presence of NADH (forward reaction), whereas it enhances the conversion of lactate to pyruvate in the presence of NAD(+) (reverse reaction). The molecular mechanism underlying PQQ-mediated regulation of LDH activity is attributed to the oxidation of NADH to NAD(+) by PQQ. Indeed, the PQQ-bound LDH oxidizes NADH, generating NAD(+), and significantly catalyzes the conversion of lactate to pyruvate. Furthermore, PQQ attenuates cellular lactate release and increases intracellular ATP levels in the NIH/3T3 fibroblasts. Our results suggest that PQQ, modulating LDH activity to facilitate pyruvate formation through its redox-cycling activity, may be involved in the enhanced energy production via mitochondrial TCA cycle and oxidative phosphorylation.

  19. Role of glutathione in augmenting the anticancer activity of pyrroloquinoline quinone (PQQ).

    PubMed

    Shankar, Bhavani S; Pandey, Ruchi; Amin, Prayag; Misra, Hari S; Sainis, Krishna B

    2010-01-01

    Pyrroloquinoline quinone (PQQ), a bacterial redox co-factor and antioxidant, is highly reactive with nucleophilic compounds present in biological fluids. PQQ induced apoptosis in human promonocytic leukemia U937 cells and this was accompanied by depletion of the major cellular antioxidant glutathione and increase in intracellular reactive oxygen species (ROS). Treatment with glutathione (GSH) or N-acetyl-L-cysteine (NAC) did not spare PQQ toxicity but resulted in a 2-5-fold increase in PQQ-induced apoptosis in U937 cells. Cellular GSH levels increased following treatment by NAC alone but were severely depleted by co-treatment with NAC and PQQ. This was accompanied by an increase in intracellular ROS. Alternatively, depletion of glutathione also resulted in increased PQQ cytotoxicity. However, the cells underwent necrosis as evidenced by dual labeling with annexin V and propidium iodide. PQQ-induced cytotoxicity is thus critically regulated by the cellular redox status. An increase in GSH can augment apoptosis and its depletion can switch the mode of cell death to necrosis in the presence of PQQ. Our data suggest that modulation of intracellular GSH can be used as an effective strategy to potentiate cytotoxicity of quinones like PQQ.

  20. Synthesis and crystal structure of pyrroloquinoline quinol (PQQH2) and pyrroloquinoline quinone (PQQ).

    PubMed

    Ikemoto, Kazuto; Mori, Shigeki; Mukai, Kazuo

    2017-06-01

    Pyrroloquinoline quinone (PQQ) is a water-soluble quinone compound first identified as a cofactor of alcohol- and glucose-dehydrogenases (ADH and GDH) in bacteria. For example, in the process of ADH reaction, alcohol is oxidized to the corresponding aldehyde, and inversely PQQ is reduced to pyrroloquinoline quinol (PQQH2). PQQ and PQQH2 molecules play an important role as a cofactor in ADH and GDH reactions. However, crystal structure analysis has not been performed for PQQ and PQQH2. In the present study, the synthesis of PQQH2 powder crystals was performed under air, by utilizing vitamin C as a reducing agent. By reacting a trihydrate of disodium salt of PQQ (PQQNa2·3H2O) with excess vitamin C in H2O at 293 and 343 K, yellowish brown and black powder crystals of PQQH2 having different properties were obtained in high yield, respectively. The former was PQQH2 trihydrate (PQQH2·3H2O) and the latter was PQQH2 anhydrate (PQQH2). Furthermore, sodium-free red PQQ powder crystal (a monohydrate of PQQ, PQQ·H2O) was prepared by the reaction of PQQNa2·3H2O with HCl in H2O. Single crystals of PQQH2 and PQQ were prepared from Me2SO/CH3CN mixed solvent, and we have succeeded in the crystal structure analyses of PQQH2 and PQQ for the first time.

  1. Effect of the Antioxidant Supplement Pyrroloquinoline Quinone Disodium Salt (BioPQQ™) on Cognitive Functions.

    PubMed

    Itoh, Yuji; Hine, Kyoko; Miura, Hiroshi; Uetake, Tatsuo; Nakano, Masahiko; Takemura, Naohiro; Sakatani, Kaoru

    2016-01-01

    Pyrroloquinoline quinone (PQQ) is a quinone compound first identified in 1979. It has been reported that rats fed a PQQ-supplemented diet showed better learning ability than controls, suggesting that PQQ may be useful for improving memory in humans. In the present study, a randomized, placebo-controlled, double-blinded study to examine the effect of PQQ disodium salt (BioPQQ™) on cognitive functions was conducted with 41 elderly healthy subjects. Subjects were orally given 20 mg of BioPQQ™ per day or placebo, for 12 weeks. For cognitive functions, selective attention by the Stroop and reverse Stroop test, and visual-spatial cognitive function by the laptop tablet Touch M, were evaluated. In the Stroop test, the change of Stroop interference ratios (SIs) for the PQQ group was significantly smaller than for the placebo group. In the Touch M test, the stratification analyses dividing each group into two groups showed that only in the lower group of the PQQ group (initial score<70), did the score significantly increase. Measurements of physiological parameters indicated no abnormal blood or urinary adverse events, nor adverse internal or physical examination findings at any point in the study. The preliminary experiment using near-infrared spectrometry (NIRS) suggests that cerebral blood flow in the prefrontal cortex was increased by the administration of PQQ. The results suggest that PQQ can prevent reduction of brain function in aged persons, especially in attention and working memory.

  2. Antineoplastic Isoflavonoids Derived from Intermediate ortho-Quinone Methides Generated from Mannich Bases.

    PubMed

    Frasinyuk, Mykhaylo S; Mrug, Galyna P; Bondarenko, Svitlana P; Khilya, Volodymyr P; Sviripa, Vitaliy M; Syrotchuk, Oleksandr A; Zhang, Wen; Cai, Xianfeng; Fiandalo, Michael V; Mohler, James L; Liu, Chunming; Watt, David S

    2016-03-17

    The regioselective condensations of various 7-hydroxyisoflavonoids with bis(N,N-dimethylamino)methane in a Mannich reaction provided C-8 N,N-dimethylaminomethyl-substituted isoflavonoids in good yield. Similar condensations of 7-hydroxy-8-methylisoflavonoids led to the C-6-substituted analogs. Thermal eliminations of dimethylamine from these C-6 or C-8 N,N-dimethylaminomethyl-substituted isoflavonoids generated ortho-quinone methide intermediates within isoflavonoid frameworks for the first time. Despite other potential competing outcomes, these ortho-quinone methide intermediates trapped dienophiles including 2,3-dihydrofuran, 3,4-dihydro-2H-pyran, 3-(N,N-dimethylamino)-5,5-dimethyl-2-cyclohexen-1-one, 1-morpholinocyclopentene, and 1-morpholinocyclohexene to give various inverse electron-demand Diels-Alder adducts. Several adducts derived from 8-N,N-dimethylaminomethyl-substituted isoflavonoids displayed good activity in the 1-10 μm concentration range in an in vitro proliferation assay using the PC-3 prostate cancer cell line.

  3. Structure-function studies of the photosynthetic reaction center using herbicides that compete for the quinone binding site

    SciTech Connect

    Bylina, E.J.

    1995-12-31

    Certain classes of herbicides act as competitive inhibitors of the photosynthetic reaction center. Genetic engineering techniques can be used to generate photosynthetic reaction centers which contain altered quinone binding sites. A genetic system for rapidly screening herbicides developed in the photosynthetic bacterium Rhodobacter capsulatus has been used to examine the effect of different s-triazine herbicides on the growth of bacteria containing reaction centers with altered quinone binding sites. Structural insights into herbicide binding have been obtained by determining the level of resistance or sensitivity to structurally related herbicides in these modified reaction centers.

  4. Investigating the thermostability of succinate: quinone oxidoreductase enzymes by direct electrochemistry at SWNTs-modified electrodes and FTIR spectroscopy

    PubMed Central

    Melin, Frederic; Noor, Mohamed R.; Pardieu, Elodie; Boulmedais, Fouzia; Banhart, Florian; Cecchini, Gary; Soulimane, Tewfik

    2015-01-01

    Succinate Quinone reductases (SQRs) are the enzymes which couple the oxidation of succinate and the reduction of quinones in the respiratory chain of prokaryotes and eukaryotes. We compare herein the temperature-dependent activity and structural stability of two SQRs, the first one from the mesophilic bacterium E. coli and the second one from the thermophilic bacterium T. thermophilus by a combined electrochemical and infrared spectroscopy approach. Direct electron transfer was achieved with the full membrane protein complexes at SWNTs-modified electrodes. The possible structural factors which contribute to the temperature-dependent activity of the enzymes and to the thermostability of the T. thermophiles SQR in particular, are discussed. PMID:25139263

  5. Synergistic Rhodium/Phosphoric Acid Catalysis for the Enantioselective Addition of Oxonium Ylides to ortho-Quinone Methides.

    PubMed

    Alamsetti, Santosh Kumar; Spanka, Matthias; Schneider, Christoph

    2016-02-12

    We report herein a powerful and highly stereoselective protocol for the domino-type reaction of diazoesters with ortho-quinone methides generated in situ to furnish densely functionalized chromans with three contiguous stereogenic centers. A transition-metal and a Brønsted acid catalyst were shown to act synergistically to produce a transient oxonium ylide and ortho-quinone methide, respectively, in two distinct cycles. These intermediates underwent subsequent coupling in a conjugate-addition-hemiacetalization event in generally good yield with excellent diastereo- and enantioselectivity.

  6. Monitoring of BHT-quinone and BHT-CHO in the gas of capsules of Asclepias physocarpa.

    PubMed

    Ma, Bing-Ji; Peng, Hua; Liu, Ji-Kai

    2006-01-01

    Three volatile components, namely benzoic acid ethyl ester (1), 2,6-di-tert-butyl-p-benzoquinone (BHT-quinone) (2), and 3,5-di-tert-butyl-4-hydroxybenzaldehyde (BHT-CHO) (3), were detected from the gas in the capsules of Asclepias physocarpa by means of GC/MS analysis. BHT-quinone and BHT-CHO as organic pollutants are the degradation products of the antioxidant 2,6-di-tert-butyl-4-methylphenol (BHT). Ground water, lake water and/or rain water are a source of BHT metabolites in the plant Asclepias physocarpa.

  7. Antineoplastic agents 552. Oxidation of combretastatin A-1: Trapping the o-Quinone intermediate considered metabolic product of the corresponding phosphate prodrug

    USDA-ARS?s Scientific Manuscript database

    The very unstable (< 10 min at rt) o-quinone derived from the vicinol diphenol anticancer drug combretastatin A-1 has been obtained by careful oxidation with NaIO4 employing tetrabutylammonium bromide in water/dichloromethane. Immediate reaction with phenylenediamine allowed o-quinone 5 to be trapp...

  8. The Role of Human Aldo-Keto Reductases in the Metabolic Activation and Detoxication of Polycyclic Aromatic Hydrocarbons: Interconversion of PAH Catechols and PAH o-Quinones.

    PubMed

    Zhang, Li; Jin, Yi; Huang, Meng; Penning, Trevor M

    2012-01-01

    Polycyclic aromatic hydrocarbons (PAH) are ubiquitous environmental pollutants. They are procarcinogens requiring metabolic activation to elicit their deleterious effects. Aldo-keto reductases (AKR) catalyze the oxidation of proximate carcinogenic PAH trans-dihydrodiols to yield electrophilic and redox-active PAH o-quinones. AKRs are also found to be capable of reducing PAH o-quinones to form PAH catechols. The interconversion of o-quinones and catechols results in the redox-cycling of PAH o-quinones to give rise to the generation of reactive oxygen species and subsequent oxidative DNA damage. On the other hand, PAH catechols can be intercepted through phase II metabolism by which PAH o-quinones could be detoxified and eliminated. The aim of the present review is to summarize the role of human AKRs in the metabolic activation/detoxication of PAH and the relevance of phase II conjugation reactions to human lung carcinogenesis.

  9. Time-Resolved Electron Paramagnetic Resonance Study of Photoinduced Electron Transfer in Pd Porphyrin-Quinone and Zn Porphyrin-Quinone Dyads with a Cyclohexylene Spacer.

    PubMed

    Perchanova, Maya; Kurreck, Harry; Berg, Alexander

    2015-07-23

    Peculiarities of the light induced intramolecular electron transfer processes in two ensembles where Pd porphyrin and Zn porphyrin donors with similar peripheral substituents are covalently linked via cyclohexylene spacer with a quinone acceptor, were studied by time-resolved electron paramagnetic resonance spectroscopy in different phases of the magnetically oriented nematic liquid crystal E-7. In the photoexcited PdP-Q the net absorptive signal was observed and ascribed to the thermally equilibrated spectrum of (3)*(PdP(•+)-Q(•-)). In ZnP-Q photoinduced intramolecular electron transfer was also found. It was demonstrated that the multiplet spectrum of the charge-separated state (3)*(ZnP(•+)-Q(•-)) consists of two signals with different widths and decay times. The signals were assigned to two spin-polarized triplets of the radical pairs formed in "stretched" and "folded" ensemble conformers, corresponding to different configurations of the cyclohexylene spacer. These findings were discussed in terms of differences in the properties of the porphyrin metal cores, macrocycle peripheral substituents and geometry of the donor-acceptor cyclohexylene spacer.

  10. Kinetics and mechanism of bimolecular electron transfer reaction in quinone-amine systems in micellar solution

    SciTech Connect

    Kumbhakar, Manoj; Nath, Sukhendu; Mukherjee, Tulsi; Pal, Haridas

    2005-02-22

    Photoinduced electron transfer (ET) reactions between anthraquinone derivatives and aromatic amines have been investigated in sodium dodecyl sulphate (SDS) micellar solutions. Significant static quenching of the quinone fluorescence due to high amine concentration in the micellar phase has been observed in steady-state measurements. The bimolecular rate constants for the dynamic quenching in the present systems k{sub q}{sup TR}, as estimated from the time-resolved measurements, have been correlated with the free energy changes {delta}G{sup 0} for the ET reactions. Interestingly it is seen that the k{sub q}{sup TR} vs {delta}G{sup 0} plot displays an inversion behavior with maximum k{sub q}{sup TR} at around 0.7 eV, a trend similar to that predicted in Marcus ET theory. Like the present results, Marcus inversion in the k{sub q}{sup TR} values was also observed earlier in coumarin-amine systems in SDS and TX-100 micellar solutions, with maximum k{sub q}{sup TR} at around the same exergonicity. These results thus suggest that Marcus inversion in bimolecular ET reaction is a general phenomenon in micellar media. Present observations have been rationalized on the basis of the two-dimensional ET (2DET) theory, which seems to be more suitable for micellar ET reactions than the conventional ET theory. For the quinone-amine systems, it is interestingly seen that k{sub q}{sup TR} vs {delta}G{sup 0} plot is somewhat wider in comparison to that of the coumarin-amine systems, even though the maxima in the k{sub q}{sup TR} vs {delta}G{sup 0} plots appear at almost similar exergonicity for both the acceptor-donor systems. These observations have been rationalized on the basis of the differences in the reaction windows along the solvation axis, as envisaged within the framework of the 2DET theory, and arise due to the differences in the locations of the quinones and coumarin dyes in the micellar phase.

  11. Molecular characterization of dopamine-derived quinones reactivity toward NADH and glutathione: implications for mitochondrial dysfunction in Parkinson disease.

    PubMed

    Bisaglia, Marco; Soriano, Maria Eugenia; Arduini, Irene; Mammi, Stefano; Bubacco, Luigi

    2010-09-01

    Oxidative stress and mitochondrial dysfunction, especially at the level of complex I of the electronic transport chain, have been proposed to be involved in the pathogenesis of Parkinson disease (PD). A plausible source of oxidative stress in nigral dopaminergic neurons is the redox reactions that specifically involve dopamine (DA) and produce various toxic molecules, i.e., free radicals and quinone species (DAQ). It has been shown that DA oxidation products can induce various forms of mitochondrial dysfunction, such as mitochondrial swelling and decreased electron transport chain activity. In the present work, we analyzed the potentially toxic effects of DAQ on mitochondria and, specifically, on the NADH and GSH pools. Our results demonstrate that the generation of DAQ in isolated respiring mitochondria triggers the opening of the permeability transition pore most probably by inducing oxidation of NADH, while GSH levels are not affected. We then characterized in vitro, by UV and NMR spectroscopy, the reactivity of different DA-derived quinones, i.e., dopamine-o-quinone (DQ), aminochrome (AC) and indole-quinone (IQ), toward NADH and GSH. Our results indicate a very diverse reactivity for the different DAQ studied that may contribute to unravel the complex molecular mechanisms underlying oxidative stress and mitochondria dysfunction in the context of PD.

  12. Oxidation of 3,4-dihydroxyphenylacetaldehyde, a toxic dopaminergic metabolite, to a semiquinone radical and an ortho-quinone.

    PubMed

    Anderson, David G; Mariappan, S V Santhana; Buettner, Garry R; Doorn, Jonathan A

    2011-07-29

    The oxidation and toxicity of dopamine is believed to contribute to the selective neurodegeneration associated with Parkinson disease. The formation of reactive radicals and quinones greatly contributes to dopaminergic toxicity through a variety of mechanisms. The physiological metabolism of dopamine to 3,4-dihydroxyphenylacetaldehyde (DOPAL) via monoamine oxidase significantly increases its toxicity. To more adequately explain this enhanced toxicity, we hypothesized that DOPAL is capable of forming radical and quinone species upon oxidation. Here, two unique oxidation products of DOPAL are identified. Several different oxidation methods gave rise to a transient DOPAL semiquinone radical, which was characterized by electron paramagnetic resonance spectroscopy. NMR identified the second oxidation product of DOPAL as the ortho-quinone. Also, carbonyl hydration of DOPAL in aqueous media was evident via NMR. Interestingly, the DOPAL quinone exists exclusively in the hydrated form. Furthermore, the enzymatic and chemical oxidation of DOPAL greatly enhance protein cross-linking, whereas auto-oxidation results in the production of superoxide. Also, DOPAL was shown to be susceptible to oxidation by cyclooxygenase-2 (COX-2). The involvement of this physiologically relevant enzyme in both oxidative stress and Parkinson disease underscores the potential importance of DOPAL in the pathogenesis of this condition.

  13. The effect of glassy carbon surface oxides in non-aqueous voltammetry: the case of quinones in acetonitrile.

    PubMed

    Staley, Patrick A; Newell, Christina M; Pullman, David P; Smith, Diane K

    2014-11-04

    Glassy carbon (GC) electrodes are well-known to contain oxygenated functional groups such as phenols, carbonyls, and carboxylic acids on their surface. The effects of these groups on voltammetry in aqueous solution are well-studied, but there has been little discussion of their possible effects in nonaqueous solution. In this study, we show that the acidic functional groups, particularly phenols, are likely causes of anomalous features often seen in the voltammetry of quinones in nonaqueous solution. These features, a too small second cyclic voltammetric wave and extra current between the two waves that sometimes appears to be a small, broad third voltammetric wave, have previously been attributed to different types of dimerization. In this work, concentration-dependent voltammetry in acetonitrile rules out dimerization with a series of alkyl-benzoquinones because the anomalous features get larger as the concentration decreases. At low concentrations, solution bimolecular reactions will be relatively less important than reactions with surface groups. Addition of substoichiometric amounts of naphthol at higher quinone concentrations produces almost identical behavior as seen at low quinone concentrations with no added naphthol. This implicates hydrogen bonding and proton transfer from the surface phenolic groups as the cause of the anomalous features in quinone voltammetry at GC electrodes. This conclusion is supported by the perturbation of surface oxide coverage on GC electrodes through different electrode pretreatments.

  14. Coupling of cytochrome and quinone turnovers in the photocycle of reaction centers from the photosynthetic bacterium Rhodobacter sphaeroides.

    PubMed Central

    Osváth, S; Maróti, P

    1997-01-01

    A minimal kinetic model of the photocycle, including both quinone (Q-6) reduction at the secondary quinone-binding site and (mammalian) cytochrome c oxidation at the cytochrome docking site of isolated reaction centers from photosynthetic purple bacteria Rhodobacter sphaeroides, was elaborated and tested by cytochrome photooxidation under strong continuous illumination. The typical rate of photochemical excitation by a laser diode at 810 nm was 2.200 s-1, and the rates of stationary turnover of the reaction center (one-half of that of cytochrome photooxidation) were 600 +/- 70 s-1 at pH 6 and 400 +/- 50 s-1 at pH 8. The rate of turnover showed strong pH dependence, indicating the contribution of different rate-limiting processes. The kinetic limitation of the photocycle was attributed to the turnover of the cytochrome c binding site (pH < 6), light intensity and quinone/quinol exchange (6 < pH < 8), and proton-coupled second electron transfer in the quinone acceptor complex (pH > 8). The analysis of the double-reciprocal plot of the rate of turnover versus light intensity has proved useful in determining the light-independent (maximum) turnover rate of the reaction center (445 +/- 50 s-1 at pH 7.8). PMID:9251814

  15. KefF, the regulatory subunit of the potassium efflux system KefC, shows quinone oxidoreductase activity.

    PubMed

    Lyngberg, Lisbeth; Healy, Jessica; Bartlett, Wendy; Miller, Samantha; Conway, Stuart J; Booth, Ian R; Rasmussen, Tim

    2011-09-01

    Escherichia coli and many other Gram-negative pathogenic bacteria protect themselves from the toxic effects of electrophilic compounds by using a potassium efflux system (Kef). Potassium efflux is coupled to the influx of protons, which lowers the internal pH and results in immediate protection. The activity of the Kef system is subject to complex regulation by glutathione and its S conjugates. Full activation of KefC requires a soluble ancillary protein, KefF. This protein has structural similarities to oxidoreductases, including human quinone reductases 1 and 2. Here, we show that KefF has enzymatic activity as an oxidoreductase, in addition to its role as the KefC activator. It accepts NADH and NADPH as electron donors and quinones and ferricyanide (in addition to other compounds) as acceptors. However, typical electrophilic activators of the Kef system, e.g., N-ethyl maleimide, are not substrates. If the enzymatic activity is disrupted by site-directed mutagenesis while retaining structural integrity, KefF is still able to activate the Kef system, showing that the role as an activator is independent of the enzyme activity. Potassium efflux assays show that electrophilic quinones are able to activate the Kef system by forming S conjugates with glutathione. Therefore, it appears that the enzymatic activity of KefF diminishes the redox toxicity of quinones, in parallel with the protection afforded by activation of the Kef system.

  16. Double hetero-Michael addition of N-substituted hydroxylamines to quinone monoketals: synthesis of bridged isoxazolidines.

    PubMed

    Yin, Zhiwei; Zhang, Jinzhu; Wu, Jing; Liu, Che; Sioson, Kate; Devany, Matthew; Hu, Chunhua; Zheng, Shengping

    2013-07-19

    A general synthesis of bridged isoxazolidines from a double hetero-Michael addition of N-substituted hydroxylamines to quinone monoketals has been developed. The different addition order of N-benzylhydroxylamine and N-Boc hydroxylamine is also discussed. Moreover, the various functionalities in the isoxazolidine products allow facile derivatization.

  17. Cathodic Voltammetric Behavior of Pillar[5]quinone in Nonaqueous Media. Symmetry Effects on the Electron Uptake Sequence.

    PubMed

    Cheng, Beijun; Kaifer, Angel E

    2015-08-12

    The cathodic voltammetric behavior of pillar[5]quinone was investigated in dichloromethane solution. Our data show that the symmetry of the macrocycle has a pronounced effect on the electron uptake sequence. The uptake of the first five electrons follows a 2-1-2 pattern, and only a total of eight electrons could be injected into the macrocycle under our experimental conditions.

  18. Synthesis of o-Chlorophenols via an Unexpected Nucleophilic Chlorination of Quinone Monoketals Mediated by N, N′-Dimethylhydrazine Dihydrochloride

    PubMed Central

    Yin, Zhiwei; Zhang, Jinzhu; Wu, Jing; Green, Riana; Li, Sihan; Zheng, Shengping

    2014-01-01

    An unexpected nucleophilic chlorination of a quinone monoketal while carrying out a pyrazolidine synthesis has led to a general preparation of multisubstituted phenols. The products are obtained in good to high yields under mild conditions. The bridged pyrazolidines that were the original targets are obtained in the presence of a protic solvent. PMID:24675905

  19. Anti-inflammatory and Quinone Reductase Inducing Compounds from Fermented Noni (Morinda citrifolia) Juice Exudates.

    PubMed

    Youn, Ui Joung; Park, Eun-Jung; Kondratyuk, Tamara P; Sang-Ngern, Mayuramas; Wall, Marisa M; Wei, Yanzhang; Pezzuto, John M; Chang, Leng Chee

    2016-06-24

    A new fatty acid ester disaccharide, 2-O-(β-d-glucopyranosyl)-1-O-(2E,4Z,7Z)-deca-2,4,7-trienoyl-β-d-glucopyranose (1), a new ascorbic acid derivative, 2-caffeoyl-3-ketohexulofuranosonic acid γ-lactone (2), and a new iridoid glycoside, 10-dimethoxyfermiloside (3), were isolated along with 13 known compounds (4-16) from fermented noni fruit juice (Morinda citrifolia). The structures of the new compounds, together with 4 and 5, were determined by 1D and 2D NMR experiments, as well as comparison with published values. Compounds 2 and 7 showed moderate inhibitory activities in a TNF-α-induced NF-κB assay, and compounds 4 and 6 exhibited considerable quinone reductase-1 (QR1) inducing effects.

  20. Mathematical description of pH-stat kinetic traces measured during photochemical quinone decomposition.

    PubMed

    Kiss, Virág; Lehoczki, Gábor; Ősz, Katalin

    2017-04-12

    Substituted 1,4-benzoquinone (QR) derivatives are photosensitive in aqueous solution and form hydroquinones (QR-H2) and hydroxy-quinones (QR-OH), two weak acids in their photoreaction. For this reason, the kinetics of the photoreaction can be conveniently followed by the pH-stat titration technique. The mathematical description of the kinetic traces measured provides the two main parameters of the photoreaction: the differential quantum yield of the reaction (Φ) and the ratio of the two photo-products, i.e. the fraction of QR that is converted to QR-OH (α). These values are described in this paper for 2,5-dichloro-1,4-benzoquinone at different pH values, together with the detailed mathematical evaluation of the application limits of the pH-stat method for such reactions.

  1. Persistent and widespread occurrence of bioactive quinone pigments during post-Paleozoic crinoid diversification

    PubMed Central

    Wolkenstein, Klaus

    2015-01-01

    Secondary metabolites often play an important role in the adaptation of organisms to their environment. However, little is known about the secondary metabolites of ancient organisms and their evolutionary history. Chemical analysis of exceptionally well-preserved colored fossil crinoids and modern crinoids from the deep sea suggests that bioactive polycyclic quinones related to hypericin were, and still are, globally widespread in post-Paleozoic crinoids. The discovery of hypericinoid pigments both in fossil and in present-day representatives of the order Isocrinida indicates that the pigments remained almost unchanged since the Mesozoic, also suggesting that the original color of hypericinoid-containing ancient crinoids may have been analogous to that of their modern relatives. The persistent and widespread occurrence, spatially as well as taxonomically, of hypericinoid pigments in various orders during the adaptive radiation of post-Paleozoic crinoids suggests a general functional importance of the pigments, contributing to the evolutionary success of the Crinoidea. PMID:25730856

  2. Peltomexicanin, a Peltogynoid Quinone Methide from Peltogyne Mexicana Martínez Purple Heartwood.

    PubMed

    Gutiérrez-Macías, Paulina; Peralta-Cruz, Javier; Borja-de-la-Rosa, Amparo; Barragán-Huerta, Blanca E

    2016-02-04

    Peltomexicanin (7,10-dihydroxy-6,12-dioxa-5H-tetraphen-3-one) is a new peltogynoid quinone methide isolated from Palo Morado (Peltogyne mexicana Martínez) heartwood by column chromatography. Its chemical structure was elucidated by IR, NMR (¹H, (13)C), 2D NMR experiments (COSY, NOESY, HMQC, and HSQC), ESI-MS, and UV-Vis spectroscopic analysis. According to HPLC quantification, this compound is the main pigment and accounts for 1.21% of Palo Morado heartwood material. The antioxidant activity of peltomexicanin and dried methanolic extract (DEx) of purple heartwood was evaluated using the radical of 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) assay, and the corresponding values expressed as Trolox equivalents (µmol TE/mg sample) were 4.25 and 4.57, respectively.

  3. Crystal Structure of ChrR -- A Quinone Reductase with the Capacity to Reduce Chromate

    SciTech Connect

    Eswaramoorthy S.; Poulain, S.; Hienerwadel, R.; Bremond, N.; Sylvester, M. D.; Zhang, Y.-B.; Berthomieu, C.; van der Lelie, D.; Matin, A.

    2012-04-01

    The Escherichia coli ChrR enzyme is an obligatory two-electron quinone reductase that has many applications, such as in chromate bioremediation. Its crystal structure, solved at 2.2 {angstrom} resolution, shows that it belongs to the flavodoxin superfamily in which flavin mononucleotide (FMN) is firmly anchored to the protein. ChrR crystallized as a tetramer, and size exclusion chromatography showed that this is the oligomeric form that catalyzes chromate reduction. Within the tetramer, the dimers interact by a pair of two hydrogen bond networks, each involving Tyr128 and Glu146 of one dimer and Arg125 and Tyr85 of the other; the latter extends to one of the redox FMN cofactors. Changes in each of these amino acids enhanced chromate reductase activity of the enzyme, showing that this network is centrally involved in chromate reduction.

  4. Photoinduced reduction of divalent mercury by quinones in the presence of formic acid under anaerobic conditions.

    PubMed

    Berkovic, Andrea M; Bertolotti, Sonia G; Villata, Laura S; Gonzalez, Mónica C; Pis Diez, Reinaldo; Mártire, Daniel O

    2012-11-01

    The laser flash photolysis technique (λ(exc)=355 nm) was used to investigate the mechanism of the HgCl(2) reduction mediated by CO(2)(-) radicals generated from quenching of the triplet states of 1,4-naphthoquinone (NQ) by formic acid. Kinetic simulations of the experimental signals support the proposed reaction mechanism. This system is of potential interest in the development of UV-A photoinduced photolytic procedures for the treatment of Hg(II) contaminated waters. The successful replacement of NQ with a commercial fulvic acid, as a model compound of dissolved organic matter, showed that the method is applicable to organic matter-containing waters without the addition of quinones.

  5. Reactions of oxygen radicals with the quinone ring of coenzyme Q.

    PubMed

    Fiorentini, D; Cabrini, L; Sechi, A M; Landi, L

    1991-01-01

    Coenzyme Q, besides its role in electron transfer reactions, may act as a radical scavenger. The effect of oxygen radicals produced by ultrasonic irradiation on the quinone ring was investigated. Aqueous solutions of a Q homologue, completely lacking the side chain, were irradiated and the modifications were spectrophotometrically followed. The experimental results show that both degradation and reduction of the benzoquinone ring took place when the irradiation was performed in water. Data obtained when ultrasonic irradiation was carried out in the presence of OH. scavengers, as formate, organic and inorganic buffers, suggest: a) the responsible species for most the ubiquinol generated by sonication appeared to be the superoxide radical b) addition reactions of OH. radicals with the aromatic ring led probably to the degradation of Coenzyme Q molecules.

  6. Quinones and aromatic chemical compounds in particulate matter induce mitochondrial dysfunction: implications for ultrafine particle toxicity.

    PubMed

    Xia, Tian; Korge, Paavo; Weiss, James N; Li, Ning; Venkatesen, M Indira; Sioutas, Constantinos; Nel, Andre

    2004-10-01

    Particulate pollutants cause adverse health effects through the generation of oxidative stress. A key question is whether these effects are mediated by the particles or their chemical compounds. In this article we show that aliphatic, aromatic, and polar organic compounds, fractionated from diesel exhaust particles (DEPs), exert differential toxic effects in RAW 264.7 cells. Cellular analyses showed that the quinone-enriched polar fraction was more potent than the polycyclic aromatic hydrocarbon (PAH)-enriched aromatic fraction in O2 .- generation, decrease of membrane potential (Delta-Psi m), loss of mitochondrial membrane mass, and induction of apoptosis. A major effect of the polar fraction was to promote cyclosporin A (CsA)-sensitive permeability transition pore (PTP) opening in isolated liver mitochondria. This opening effect is dependent on a direct effect on the PTP at low doses as well as on an effect on Delta-Psi m at high doses in calcium (Ca2+)-loaded mitochondria. The direct PTP effect was mimicked by redox-cycling DEP quinones. Although the aliphatic fraction failed to perturb mitochondrial function, the aromatic fraction increased the Ca2+ retention capacity at low doses and induced mitochondrial swelling and a decrease in Delta-Psi m at high doses. This swelling effect was mostly CsA insensitive and could be reproduced by a mixture of PAHs present in DEPs. These chemical effects on isolated mitochondria could be reproduced by intact DEPs as well as ambient ultrafine particles (UFPs). In contrast, commercial polystyrene nanoparticles failed to exert mitochondrial effects. These results suggest that DEP and UFP effects on the PTP and Delta-Psi m are mediated by adsorbed chemicals rather than the particles themselves.

  7. Quinones and Aromatic Chemical Compounds in Particulate Matter Induce Mitochondrial Dysfunction: Implications for Ultrafine Particle Toxicity

    PubMed Central

    Xia, Tian; Korge, Paavo; Weiss, James N.; Li, Ning; Venkatesen, M. Indira; Sioutas, Constantinos; Nel, Andre

    2004-01-01

    Particulate pollutants cause adverse health effects through the generation of oxidative stress. A key question is whether these effects are mediated by the particles or their chemical compounds. In this article we show that aliphatic, aromatic, and polar organic compounds, fractionated from diesel exhaust particles (DEPs), exert differential toxic effects in RAW 264.7 cells. Cellular analyses showed that the quinone-enriched polar fraction was more potent than the polycyclic aromatic hydrocarbon (PAH)–enriched aromatic fraction in O2•− generation, decrease of membrane potential (ΔΨm), loss of mitochondrial membrane mass, and induction of apoptosis. A major effect of the polar fraction was to promote cyclosporin A (CsA)–sensitive permeability transition pore (PTP) opening in isolated liver mitochondria. This opening effect is dependent on a direct effect on the PTP at low doses as well as on an effect on ΔΨm at high doses in calcium (Ca2+)-loaded mitochondria. The direct PTP effect was mimicked by redox-cycling DEP quinones. Although the aliphatic fraction failed to perturb mitochondrial function, the aromatic fraction increased the Ca2+ retention capacity at low doses and induced mitochondrial swelling and a decrease in ΔΨm at high doses. This swelling effect was mostly CsA insensitive and could be reproduced by a mixture of PAHs present in DEPs. These chemical effects on isolated mitochondria could be reproduced by intact DEPs as well as ambient ultrafine particles (UFPs). In contrast, commercial polystyrene nanoparticles failed to exert mitochondrial effects. These results suggest that DEP and UFP effects on the PTP and ΔΨm are mediated by adsorbed chemicals rather than the particles themselves. PMID:15471724

  8. Quinone Induced Activation of Keap1/Nrf2 Signaling by Aspirin Prodrugs Masquerading as Nitric Oxide

    PubMed Central

    Dunlap, Tareisha; Piyankarage, Sujeewa C.; Wijewickrama, Gihani T.; Abdul-Hay, Samer; Vanni, Michael; Litosh, Vladislav; Luo, Jia; Thatcher, Gregory R. J.

    2013-01-01

    The promising therapeutic potential of the NO-donating hybrid aspirin prodrugs (NO-ASA), includes induction of chemopreventive mechanisms, and has been reported in almost 100 publications. One example, NCX-4040 (pNO-ASA), is bioactivated by esterase to a quinone methide (QM) electrophile. In cell cultures, pNO-ASA and QM-donating X-ASA prodrugs that cannot release NO rapidly depleted intracellular GSH and caused DNA damage; however, induction of Nrf2 signaling elicited cellular defense mechanisms including upregulation of NAD(P)H:quinone oxidoreductase-1 (NQO1) and glutamate-cysteine ligase (GCL). In HepG2 cells, the “NO-specific” 4,5-diaminofluorescein reporter, DAF-DA, responded to NO-ASA and X-ASA, with QM-induced oxidative stress masquerading as NO. LC-MS/MS analysis demonstrated efficient alkylation of Cys residues of proteins including glutathione-S-transferase-P1 (GST-P1) and Kelch-like ECH-associated protein 1 (Keap1). Evidence was obtained for alkylation of Keap1 Cys residues associated with Nrf2 translocation to the nucleus, nuclear translocation of Nrf2, activation of antioxidant response element (ARE), and upregulation of cytoprotective target genes. At least in cell culture, pNO-ASA acts as a QM-donor, bioactivated by cellular esterase activity to release salicylates, NO3−, and an electrophilic QM. Finally, two novel aspirin prodrugs were synthesized, both potent activators of ARE, designed to release only the QM and salicylates on bioactivation. Current interest in electrophilic drugs acting via Nrf2 signaling suggests that QM-donating hybrid drugs can be designed as informative chemical probes in drug discovery. PMID:23035985

  9. Photochemical formation and chemistry of long-lived adamantylidene-quinone methides and 2-adamantyl cations.

    PubMed

    Basarić, Nikola; Zabcić, Ivana; Mlinarić-Majerski, Kata; Wan, Peter

    2010-01-01

    Hydroxymethylphenols strategically substituted with the 2-hydroxy-2-adamantyl moiety, AdPh 8-10, were synthesized, and their photochemical reactivity was investigated. On excitation to the singlet excited state, AdPh 8 undergoes intramolecular proton transfer coupled with a loss of H(2)O giving quinone methide 8QM. The presence of 8QM has been detected by laser flash photolysis (CH(3)CN-H(2)O 1:1, tau = 0.55 s) and UV-vis spectroscopy. Singlet excited states of AdPh 9 and 10 in the presence of H(2)O dehydrate giving 9QM and 10QM. Photochemically formed QMs are trapped by nucleophiles giving the addition products (e.g., Phi for methanolysis of 8 is 0.55). In addition, the zwitterionic 9QM undergoes an unexpected rearrangement involving transformation of the 2-phenyl-2-adamantyl cation into the 4-phenyl-2-adamantyl cation (Phi approximately 0.03). An analogous rearrangement was observed with methoxy derivatives 9a and 10a. Zwitterionic 9QM was characterized by LFP in 2,2,2-trifluoroethanol (tau = 1 mus). In TFE, in the ground state, AdPh 10 is in equilibrium with 10QM, which allowed for recording the (1)H and (13)C NMR spectra of the QM. Introduction of the adamantyl substituent into the o-hydroxymethylphenol moiety increased the quantum yield of the associated QM formation by up to 3-fold and significantly prolonged their lifetimes. Furthermore, adamantyl substituent made the study of the alkyl-substituted quinone methides easier by LFP by prolonging their lifetimes and increasing the quantum yields of formation.

  10. Sulfide Consumption in Sulfurimonas denitrificans and Heterologous Expression of Its Three Sulfide-Quinone Reductase Homologs.

    PubMed

    Han, Yuchen; Perner, Mirjam

    2016-04-01

    Sulfurimonas denitrificans is a sulfur-oxidizing epsilonproteobacterium. It has been reported to grow with sulfide and to harbor genes that encode sulfide-quinone reductases (SQRs) (catalyze sulfide oxidation). However, the actual sulfide concentrations at which S. denitrificans grows and whether its SQRs are functional remain enigmatic. Here, we illustrate the sulfide concentrations at which S. denitrificans exhibits good growth, namely, 0.18 mM to roughly 1.7 mM. Around 2.23 mM, sulfide appears to inhibit growth. S. denitrificans harbors three SQR homolog genes on its genome (Suden_2082 for type II SQR, Suden_1879 for type III SQR, and Suden_619 for type IV SQR). They are all transcribed in S. denitrificans. According to our experiments, they appear to be loosely bound to the membrane. Each individual S. denitrificans SQR was heterologously expressed in the Rhodobacter capsulatus SB1003 sqr deletion mutant, and all exhibited SQR activities individually. This suggests that all of these three genes encode functional SQRs. This study also provides the first experimental evidence of a functional bacterial type III SQR. Although the epsilonproteobacterium Sulfurimonas denitrificans has been described as using many reduced sulfur compounds as electron donors, there is little knowledge about its growth with sulfide. In many bacteria, the sulfide-quinone reductase (SQR) is responsible for catalyzing sulfide oxidation. S. denitrificans has an array of different types of sqr genes on its genome and so do several other sulfur-oxidizing Epsilonproteobacteria. However, whether these SQRs are functional has remained unknown. Here, we shed light on sulfide metabolism in S. denitrificans. Our study provides the first experimental evidence of active epsilonproteobacterial SQRs and also gives the first report of a functional bacterial type III SQR. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  11. Subunit functional studies of NAD(P)H:quinone oxidoreductase with a heterodimer approach.

    PubMed

    Cui, K; Lu, A Y; Yang, C S

    1995-02-14

    NAD(P)H:quinone oxidoreductase (NQOR; EC 1.6.99.2) is a homodimeric enzyme which catalyzes the reduction of quinones, azo dyes, and other electron acceptors by NADPH or NADH. To pursue subunit functional studies, we expressed a wild-type/mutant heterodimer of NQOR in Escherichia coli. The wild-type subunit of the heterodimer was tagged with polyhistidine and the other subunit contained a His-194-->Ala mutation (H194A), a change known to dramatically increase the Km for NADPH. This approach enabled us to efficiently purify the heterodimer (H194A/HNQOR) from the homodimers by stepwise elution with imidazole from a nickel nitrilotriacetate column under nondenaturing conditions. The composition of the purified heterodimer was confirmed by SDS and nondenaturing polyacrylamide gel electrophoresis and immunoblot analysis. The enzyme kinetics of the purified heterodimer were studied with two two-electron acceptors, 2,6-dichloroindophenol and menadione, and a four-electron acceptor, methyl red, as the substrates. With two-electron acceptors, the Km(NADPH) and Km(NADH) values of the heterodimer H194A/HNQOR were virtually identical to those of the wild-type homodimer, but the kcat-(NADPH) and kcat(NADH) values were only about 50% those of the wild-type homodimer. With the four-electron acceptor, the Km and kcat values of H194A/HNQOR for NADPH and NADH were similar to those of the low-efficiency mutant homodimer. These results suggest that the subunits of NQOR function independently with two-electron acceptors, but dependently with a four-electron acceptor. This heterodimer approach may have general applications for studying the functional and structural relationships of subunits in dimeric or oligomeric proteins.

  12. Metabolomic Profiling Unravels DNA Adducts in Human Breast That Are Formed from Peroxidase Mediated Activation of Estrogens to Quinone Methides

    PubMed Central

    Gaikwad, Nilesh W.

    2013-01-01

    Currently there are three major hypotheses that have been proposed for estrogen induced carcinogenicity, however exact etiology remains unknown. Based on the chemical logic, studies were undertaken to investigate if estrogens could generate quinone methides in an oxidative environment which then could cause DNA damage in humans. In presence of MnO2 estrogens were oxidized to quinone methides. Surprisingly quinone methides were found to be stable with t1/2 of 20.8 and 4.5 min respectively. Incubation of estrogens with lactoperoxidase (LPO) and H2O2 resulted in formation of respective quinone methides (E1(E2)-QM). Subsequent addition of adenine to the assay mixture lead to trapping of E1(E2)-QM, resulting in formation of adenine adducts of estrogens, E1(E2)-9-N-Ade. Targeted ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) based metabolomic analysis of the breast tissue extracts showed the presence of adenine adducts of estrogens, E1(E2)-9-N-Ade, along with other estrogen related metabolites. Identity of E1(E2)-N-Ade in LPO assay extracts and breast tissue extracts were confirmed by comparing them to pure synthesized E1(E2)-9-N-Ade standards. From these results, it is evident that peroxidase enzymes or peroxidase-like activity in human breast tissue could oxidize estrogens to electrophilic and stable quinone methides in a single step that covalently bind to DNA to form adducts. The error prone repair of the damaged DNA can result in mutation of critical genes and subsequently cancer. This article reports evidence for hitherto unknown estrogen metabolic pathway in human breast, catalyzed by peroxidase, which could initiate cancer. PMID:23762435

  13. Studies using structural analogs and inbred strain differences to support a role for quinone methide metabolites of butylated hydroxytoluene (BHT) in mouse lung tumor promotion.

    PubMed

    Thompson, J A; Carlson, T J; Sun, Y; Dwyer-Nield, L D; Malkinson, A M

    2001-03-07

    Chronic treatment of BALB and GRS mice with BHT (2,6-di-tert-butyl-4-methylphenol) following a single urethane injection increases lung tumor multiplicity, but this does not occur in CXB4 mice. Previous data suggest that promotion requires the conversion of BHT to a tert-butyl-hydroxylated metabolite (BHTOH) in lung and the subsequent oxidation of this species to an electrophilic quinone methide. To obtain additional evidence for the importance of quinone methide formation, structural analogs that form less reactive quinone methides were tested and found to lack promoting activity in BHT-responsive mice. The possibility that promotion-unresponsive strains are unable to form BHTOH was tested by substituting this compound for BHT in the promotion protocol using CXB4 mice. No promotion occurred, and in-vitro work demonstrated that CXB4 mice are, in fact, capable of producing BHTOH and its quinone methide, albeit in smaller quantities. Incubations with BALB lung microsomes and radiolabeled substrates confirmed that more covalent binding to protein occurs with BHTOH than with BHT and, in addition, BHTOH quinone methide is considerably more toxic to mouse lung epithelial cells than BHT quinone methide. These data are consistent with the hypothesis that a two-step oxidation process, i.e. hydroxylation and quinone methide formation, is required for the promotion of mouse lung tumors by BHT.

  14. Structure and function of quinones in biological solar energy transduction: a differential pulse voltammetry, EPR, and hyperfine sublevel correlation (HYSCORE) spectroscopy study of model benzoquinones.

    PubMed

    Weyers, Amanda M; Chatterjee, Ruchira; Milikisiyants, Sergey; Lakshmi, K V

    2009-11-19

    Quinones are widely used electron transport cofactors in photosynthetic reaction centers. Previous studies have suggested that the structure of the quinone cofactors and the protein interactions or "smart" matrix effects from the surrounding environment govern the redox potential and hence the function of quinones in photosynthesis. In the present study, a series of 1,4-benzoquinone models are examined via differential pulse voltammetry to provide relative redox potentials. In parallel, CW and pulsed EPR methods are used to directly determine the electronic properties of each benzoquinone in aprotic and protic environments. The shifts in the redox potential of the quinones are found to be dependent on the nature of the substituent group and the number of substituent groups on the quinone molecule. Further, we establish a direct correlation between the nature of the substituent group and the change in electronic properties of the benzosemiquinone by analysis of the isotropic and anisotropic components of the electron-nuclear hyperfine interactions observed by CW and pulsed EPR studies, respectively. Examination of an extensive library of model quinones in both aprotic and protic solvents indicates that hydrogen-bonding interactions consistently accentuate the effects of the substituent groups of the benzoquinones. This study provides direct support for the tuning and control of quinone cofactors in biological solar energy transduction through interactions with the surrounding protein matrix.

  15. Crystal structure of sulfide:quinone oxidoreductase from Acidithiobacillus ferrooxidans: insights into sulfidotrophic respiration and detoxification.

    PubMed

    Cherney, Maia M; Zhang, Yanfei; Solomonson, Matthew; Weiner, Joel H; James, Michael N G

    2010-04-30

    Sulfide:quinone oxidoreductase from the acidophilic and chemolithotrophic bacterium Acidithiobacillus ferrooxidans was expressed in Escherichia coli and crystallized, and its X-ray molecular structure was determined to 2.3 A resolution for native unbound protein in space group P4(2)2(1)2 . The decylubiquinone-bound structure and the Cys160Ala variant structure were subsequently determined to 2.3 A and 2.05 A resolutions, respectively, in space group P6(2)22 . The enzymatic reaction catalyzed by sulfide:quinone oxidoreductase includes the oxidation of sulfide compounds H(2)S, HS(-), and S(2-) to soluble polysulfide chains or to elemental sulfur in the form of octasulfur rings; these oxidations are coupled to the reduction of ubiquinone or menaquinone. The enzyme comprises two tandem Rossmann fold domains and a flexible C-terminal domain encompassing two amphipathic helices that are thought to provide for membrane anchoring. The second amphipathic helix unwinds and changes its orientation in the hexagonal crystal form. The protein forms a dimer that could be inserted into the membrane to a depth of approximately 20 A. It has an endogenous flavin adenine dinucleotide (FAD) cofactor that is noncovalently bound in the N-terminal domain. Several wide channels connect the FAD cofactor to the exterior of the protein molecule; some of the channels would provide access to the membrane. The ubiquinone molecule is bound in one of these channels; its benzoquinone ring is stacked between the aromatic rings of two conserved Phe residues, and it closely approaches the isoalloxazine moiety of the FAD cofactor. Two active-site cysteine residues situated on the re side of the FAD cofactor form a branched polysulfide bridge. Cys356 disulfide acts as a nucleophile that attacks the C4A atom of the FAD cofactor in electron transfer reaction. The third essential cysteine Cys128 is not modified in these structures; its role is likely confined to the release of the polysulfur product. (c

  16. Biochemical and biophysical characterization of succinate: quinone reductase from Thermus thermophilus.

    PubMed

    Kolaj-Robin, Olga; O'Kane, Sarah R; Nitschke, Wolfgang; Léger, Christophe; Baymann, Frauke; Soulimane, Tewfik

    2011-01-01

    Enzymes serving as respiratory complex II belong to the succinate:quinone oxidoreductases superfamily that comprises succinate:quinone reductases (SQRs) and quinol:fumarate reductases. The SQR from the extreme thermophile Thermus thermophilus has been isolated, identified and purified to homogeneity. It consists of four polypeptides with apparent molecular masses of 64, 27, 14 and 15kDa, corresponding to SdhA (flavoprotein), SdhB (iron-sulfur protein), SdhC and SdhD (membrane anchor proteins), respectively. The existence of [2Fe-2S], [4Fe-4S] and [3Fe-4S] iron-sulfur clusters within the purified protein was confirmed by electron paramagnetic resonance spectroscopy which also revealed a previously unnoticed influence of the substrate on the signal corresponding to the [2Fe-2S] cluster. The enzyme contains two heme b cofactors of reduction midpoint potentials of -20mV and -160mV for b(H) and b(L), respectively. Circular dichroism and blue-native polyacrylamide gel electrophoresis revealed that the enzyme forms a trimer with a predominantly helical fold. The optimum temperature for succinate dehydrogenase activity is 70°C, which is in agreement with the optimum growth temperature of T. thermophilus. Inhibition studies confirmed sensitivity of the enzyme to the classical inhibitors of the active site, as there are sodium malonate, sodium diethyl oxaloacetate and 3-nitropropionic acid. Activity measurements in the presence of the semiquinone analog, nonyl-4-hydroxyquinoline-N-oxide (NQNO) showed that the membrane part of the enzyme is functionally connected to the active site. Steady-state kinetic measurements showed that the enzyme displays standard Michaelis-Menten kinetics at a low temperature (30°C) with a K(M) for succinate of 0.21mM but exhibits deviation from it at a higher temperature (70°C). This is the first example of complex II with such a kinetic behavior suggesting positive cooperativity with k' of 0.39mM and Hill coefficient of 2.105. While the crystal

  17. Bioactivation of Nevirapine to a Reactive Quinone Methide: Implications for Liver Injury

    PubMed Central

    2012-01-01

    Nevirapine (NVP) treatment is associated with a significant incidence of liver injury. We developed an anti-NVP antiserum to determine the presence and pattern of covalent binding of NVP to mouse, rat, and human hepatic tissues. Covalent binding to hepatic microsomes from male C57BL/6 mice and male Brown Norway rats was detected on Western blots; the major protein had a mass of ∼55 kDa. Incubation of NVP with rat CYP3A1 and 2C11 or human CYP3A4 also led to covalent binding. Treatment of female Brown Norway rats or C57BL/6 mice with NVP led to extensive covalent binding to a wide range of proteins. Co-treatment with 1-aminobenzotriazole dramatically changed the pattern of binding. The covalent binding of 12-hydroxy-NVP, the pathway that leads to a skin rash, was much less than that of NVP, both in vitro and in vivo. An analogue of NVP in which the methyl hydrogens were replaced by deuterium also produced less covalent binding than NVP. These data provide strong evidence that covalent binding of NVP in the liver is due to a quinone methide formed by oxidation of the methyl group. Attempts were made to develop an animal model of NVP-induced liver injury in mice. There was a small increase in ALT in some NVP-treated male C57BL/6 mice at 3 weeks that resolved despite continued treatment. Male Cbl-b–/– mice dosed with NVP had an increase in ALT of >200 U/L, which also resolved despite continued treatment. Liver histology in these animals showed focal areas of complete necrosis, while most of the liver appeared normal. This is a different pattern from the histology of NVP-induced liver injury in humans. This is the first study to report hepatic covalent binding of NVP and also liver injury in mice. It is likely that the quinone methide metabolite is responsible for NVP-induced liver injury. PMID:22793666

  18. Selective, nontoxic CB(2) cannabinoid o-quinone with in vivo activity against triple-negative breast cancer.

    PubMed

    Morales, Paula; Blasco-Benito, Sandra; Andradas, Clara; Gómez-Cañas, María; Flores, Juana María; Goya, Pilar; Fernández-Ruiz, Javier; Sánchez, Cristina; Jagerovic, Nadine

    2015-03-12

    Triple-negative breast cancer (TNBC) represents a subtype of breast cancer characterized by high aggressiveness. There is no current targeted therapy for these patients whose prognosis, as a group, is very poor. Here, we report the synthesis and evaluation of a potent antitumor agent in vivo for this type of breast cancer designed as a combination of quinone/cannabinoid pharmacophores. This new compound (10) has been selected from a series of chromenopyrazolediones with full selectivity for the nonpsychotropic CB2 cannabinoid receptor and with efficacy in inducing death of human TNBC cell lines. The dual concept quinone/cannabinoid was supported by the fact that compound 10 exerts antitumor effect by inducing cell apoptosis through activation of CB2 receptors and through oxidative stress. Notably, it did not show either cytotoxicity on noncancerous human mammary epithelial cells nor toxic effects in vivo, suggesting that it may be a new therapeutic tool for the management of TNBC.

  19. Design, Synthesis, and Biological Evaluation of Potent Quinoline and Pyrroloquinoline Ammosamide Analogues as Inhibitors of Quinone Reductase 2†

    PubMed Central

    Reddy, P. V. Narasimha; Jensen, Katherine C.; Mesecar, Andrew D.; Fanwick, Phillip E.; Cushman, Mark

    2012-01-01

    A variety of ammosamide B analogues have been synthesized and evaluated as inhibitors of quinone reductase 2 (QR2). The potencies of the resulting series of QR2 inhibitors range from 4.1 to 25,200 nM. The data provide insight into the structural parameters necessary for QR2 inhibitory activity. The natural product ammosamide B proved to be a potent QR2 inhibitor, and the potencies of the analogues generally decreased as their structures became more distinct from that of ammosamide B. Methylation of the 8-amino group of ammosamide B was an exception, resulting in an increase in quinone reductase 2 inhibitory activity from IC50 of 61 nM to IC50 4.1 nM. PMID:22206487

  20. The sodium pumping NADH:quinone oxidoreductase (Na⁺-NQR), a unique redox-driven ion pump.

    PubMed

    Barquera, Blanca

    2014-08-01

    The Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR) is a unique Na(+) pumping respiratory complex found only in prokaryotes, that plays a key role in the metabolism of marine and pathogenic bacteria, including Vibrio cholerae and other human pathogens. Na(+)-NQR is the main entrance for reducing equivalents into the respiratory chain of these bacteria, catalyzing the oxidation of NADH and the reduction of quinone, the free energy of this redox reaction drives the selective translocation of Na(+) across the cell membrane, which energizes key cellular processes. In this review we summarize the unique properties of Na(+)-NQR in terms of its redox cofactor composition, electron transfer reactions and a possible mechanism of coupling and pumping.

  1. Inhibition of the water oxidizing complex of photosystem II and the reoxidation of the quinone acceptor QA- by Pb2+.

    PubMed

    Belatik, Ahmed; Hotchandani, Surat; Carpentier, Robert

    2013-01-01

    The action of the environmental toxic Pb(2+) on photosynthetic electron transport was studied in thylakoid membranes isolated from spinach leaves. Fluorescence and thermoluminescence techniques were performed in order to determine the mode of Pb(2+) action in photosystem II (PSII). The invariance of fluorescence characteristics of chlorophyll a (Chl a) and magnesium tetraphenylporphyrin (MgTPP), a molecule structurally analogous to Chl a, in the presence of Pb(2+) confirms that Pb cation does not interact directly with chlorophyll molecules in PSII. The results show that Pb interacts with the water oxidation complex thus perturbing charge recombination between the quinone acceptors of PSII and the S2 state of the Mn4Ca cluster. Electron transfer between the quinone acceptors QA and QB is also greatly retarded in the presence of Pb(2+). This is proposed to be owing to a transmembrane modification of the acceptor side of the photosystem.

  2. 3-Methoxy-2-methyl-carbazole-1,4-quinone, carbazomycins D and F from Streptomyces sp. CMU-JT005.

    PubMed

    Ruanpanun, Pornthip; Dame, Zerihun Teklemariam; Laatsch, Hartmut; Lumyong, Saisamorn

    2011-09-01

    3-Methoxy-2-methyl-carbazole-1,4-quinone (1) together with carbazomycins D (2) and F (3) were isolated from the crude extract of Streptomyces CMU-JT005, an actinomycete with nematicidal activity. 3-Methoxy-2-methyl-carbazole-1,4-quinone is reported here for the first time from nature. In this paper, we describe the isolation and structure elucidation of the compounds together with the characterization of the Streptomyces strain CMU-JT005.

  3. Transition metal-free direct C-H functionalization of quinones and naphthoquinones with diaryliodonium salts: synthesis of aryl naphthoquinones as β-secretase inhibitors.

    PubMed

    Wang, Dawei; Ge, Bingyang; Li, Liang; Shan, Jie; Ding, Yuqiang

    2014-09-19

    A novel ligand-free, transition metal-free direct C-H functionalization of quinones with diaryliodonium salts has been developed for the first time. The transformation was promoted only through the use of a base and gave aryl quinone derivatives in moderate to good yields. This methodology provided an effective and easy way to synthesize β-secretase inhibitors. The radical trapping experiments showed that this progress was the radical mechanism.

  4. Rapid and Complete Surface Modification with Strain‐Promoted Oxidation‐Controlled Cyclooctyne‐1,2‐Quinone Cycloaddition (SPOCQ)

    PubMed Central

    Sen, Rickdeb; Escorihuela, Jorge; van Delft, Floris

    2017-01-01

    Abstract Strain‐promoted oxidation‐controlled cyclooctyne‐1,2‐quinone cycloaddition (SPOCQ) between functionalized bicyclo[6.1.0]non‐4‐yne (BCN) and surface‐bound quinones revealed an unprecedented 100 % conjugation efficiency. In addition, monitoring by direct analysis in real time mass spectrometry (DART‐MS) revealed the underlying kinetics and activation parameters of this immobilization process in dependence on its microenvironment. PMID:28198134

  5. The key role of glutamate 172 in the mechanism of type II NADH:quinone oxidoreductase of Staphylococcus aureus.

    PubMed

    Sousa, Filipe M; Sena, Filipa V; Batista, Ana P; Athayde, Diogo; Brito, José A; Archer, Margarida; Oliveira, A Sofia F; Soares, Cláudio M; Catarino, Teresa; Pereira, Manuela M

    2017-10-01

    Type II NADH:quinone oxidoreductases (NDH-2s) are membrane bound enzymes that deliver electrons to the respiratory chain by oxidation of NADH and reduction of quinones. In this way, these enzymes also contribute to the regeneration of NAD(+), allowing several metabolic pathways to proceed. As for the other members of the two-Dinucleotide Binding Domains Flavoprotein (tDBDF) superfamily, the enzymatic mechanism of NDH-2s is still little explored and elusive. In this work we addressed the role of the conserved glutamate 172 (E172) residue in the enzymatic mechanism of NDH-2 from Staphylococcus aureus. We aimed to test our earlier hypothesis that E172 plays a key role in proton transfer to allow the protonation of the quinone. For this we performed a complete biochemical characterization of the enzyme's variants E172A, E172Q and E172S. Our steady state kinetic measurements show a clear decrease in the overall reaction rate, and our substrate interaction studies indicate the binding of the two substrates is also affected by these mutations. Interestingly our fast kinetic results show quinone reduction is more affected than NADH oxidation. We have also determined the X-ray crystal structure of the E172S mutant (2.55Ǻ) and compared it with the structure of the wild type (2.32Ǻ). Together these results support our hypothesis for E172 being of central importance in the catalytic mechanism of NDH-2, which may be extended to other members of the tDBDF superfamily. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Brønsted Acid-Catalyzed Synthesis of N-Arylindoles from 2-Vinylanilines and Quinones.

    PubMed

    Zhang, Han-Ming; Gao, Zhong-Hua; Yi, Liang; Ye, Song

    2016-10-06

    In the presence of a quinone, Brønsted acid-catalyzed intramolecular C-N bond formation of o-vinylanilines by electrophilic cyclization was developed, giving the corresponding N-arylindoles in good to high yields. The reaction worked well for o-vinylanilines with terminal and internal C=C double bonds. © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Examining the Role of Quinone Moieties in the Photochemistry of Colored Dissolved Organic Matter in Coastal Waters

    DTIC Science & Technology

    2002-09-30

    ring substituents. Ubiquinone 50 is a naturally occurring complex quinone compound with a 50-unit C side chain that is found in the mitochondria of...were completed in collaboration with Dr. Rod Zika at RSMAS over the last year and two manuscript published on the methodology for CDOM in natural...February 2002, Honolulu). My co-conveners were Dr. Paula Coble (USF) and Dr. Rod Zika (RSMAS). This session served as a focused venue for results

  8. Synthesis of isoxazoles en route to semi-aromatized polyketides: dehydrogenation of benzonitrile oxide-para-quinone acetal cycloadducts.

    PubMed

    Hashimoto, Yoshimitsu; Takada, Akiomi; Takikawa, Hiroshi; Suzuki, Keisuke

    2012-08-14

    A variety of highly functionalized polycyclic isoxazoles are prepared by a two-step protocol: (1) 1,3-dipolar cycloaddition of o,o'-disubstituted benzonitrile oxides to para-quinone mono-acetals, then (2) dehydrogenation. The cycloaddition proceeds in a regioselective manner, favouring the formation of the 4-acyl cycloadducts, which are suitable intermediates for the synthesis of semi-aromatized polycyclic targets derived from polyketide type-II biosynthesis.

  9. The development of 3D-QSAR study and recursive partitioning of heterocyclic quinone derivatives with antifungal activity.

    PubMed

    Choi, Su-Young; Shin, Jae Hong; Ryu, Chung Kyu; Nam, Ky-Youb; No, Kyoung Tai; Park Choo, Hea-Young

    2006-03-01

    It was reported that some 1,4-quinone derivatives such as 6-(N-arylamino)-7-chloro/6,7-bis[S-(aryl)thio]-5,8-quinolinedione and 6-arylthio-/5,6-arylamino-4,7-dioxobenzothiazoles have antifungal effects. To understand the structural basis for antifungal activity and guide in the design of more potent agents, we performed three-dimensional quantitative structure-activity relationship studies for a series of compounds using comparative molecular field analysis (CoMFA). The MIC values of 1,4-quinone derivatives on Aspergillus niger exhibited a strong correlation with steric and electrostatic factors of the 3D structure of molecules. The statistical results of the training set, cross-validated q(2) (0.683) and conventional r(2) (0.877) values, gave reliability to the prediction of inhibitory activity of a series of compounds. We also performed recursive partitioning (RP) analysis, used for the classification of molecules with activity using CART methods. Physicochemical, structural, and topological connectivity indices and E-state key descriptors were used for obtaining the decision tree models. The decision tree could classify the inhibitory activity of 1,4-quinone derivatives and its essential descriptors were S_aaN, Hbond donor, and Kappa-3.

  10. Modification of quinone electrochemistry by the proteins in the biological electron transfer chains: examples from photosynthetic reaction centers

    PubMed Central

    Gunner, M. R.; Madeo, Jennifer; Zhu, Zhenyu

    2009-01-01

    Quinones such as ubiquinone are the lipid soluble electron and proton carriers in the membranes of mitochondria, chloroplasts and oxygenic bacteria. Quinones undergo controlled redox reactions bound to specific sites in integral membrane proteins such as the cytochrome bc1 oxidoreductase. The quinone reactions in bacterial photosynthesis are amongst the best characterized, presenting a model to understand how proteins modulate cofactor chemistry. The free energy of ubiquinone redox reactions in aqueous solution and in the QA and QB sites of the bacterial photosynthetic reaction centers (RCs) are compared. In the primary QA site ubiquinone is reduced only to the anionic semiquinone (Q•−) while in the secondary QB site the product is the doubly reduced, doubly protonated quinol (QH2). The ways in which the protein modifies the relative energy of each reduced and protonated intermediate are described. For example, the protein stabilizes Q•− while destabilizing Q= relative to aqueous solution through electrostatic interactions. In addition, kinetic and thermodynamic mechanisms for stabilizing the intermediate semiquinones are compared. Evidence for the protein sequestering anionic compounds by slowing both on and off rates as well as by binding the anion more tightly is reviewed. PMID:18979192

  11. Quinone-reactive proteins devoid of haem b form widespread membrane-bound electron transport modules in bacterial respiration.

    PubMed

    Simon, Jörg; Kern, Melanie

    2008-10-01

    Many quinone-reactive enzyme complexes that are part of membrane-integral eukaryotic or prokaryotic respiratory electron transport chains contain one or more haem b molecules embedded in the membrane. In recent years, various novel proteins have emerged that are devoid of haem b but are thought to fulfil a similar function in bacterial anaerobic respiratory systems. These proteins are encoded by genes organized in various genomic arrangements and are thought to form widespread membrane-bound quinone-reactive electron transport modules that exchange electrons with redox partner proteins located at the outer side of the cytoplasmic membrane. Prototypic representatives are the multihaem c-type cytochromes NapC, NrfH and TorC (NapC/NrfH family), the putative iron-sulfur protein NapH and representatives of the NrfD/PsrC family. Members of these protein families vary in the number of their predicted transmembrane segments and, consequently, diverse quinone-binding sites are expected. Only a few of these enzymes have been isolated and characterized biochemically and high-resolution structures are limited. This mini-review briefly summarizes predicted and experimentally demonstrated properties of the proteins in question and discusses their role in electron transport and bioenergetics of anaerobic respiration.

  12. ArsH from the cyanobacterium Synechocystis sp. PCC 6803 is an efficient NADPH-dependent quinone reductase.

    PubMed

    Hervás, Manuel; López-Maury, Luis; León, Pilar; Sánchez-Riego, Ana M; Florencio, Francisco J; Navarro, José A

    2012-02-14

    The cyanobacterium Synechocystis sp. PCC 6803 possesses an arsenic resistance operon that encodes, among others, an ArsH protein. ArsH is a flavin mononucleotide (FMN)-containing protein of unknown function and a member of the family of NADPH-dependent FMN reductases. The nature of its final electron acceptor and the role of ArsH in the resistance to arsenic remained to be clarified. Here we have expressed and purified Synechocystis ArsH and conducted an intensive biochemical study. We present kinetic evidence supporting a quinone reductase activity for ArsH, with a preference for quinones with hydrophobic substituents. By using steady-state activity measurements, as well as stopped-flow and laser-flash photolysis kinetic analyses, it has been possible to establish the mechanism of the process and estimate the values of the kinetic constants. Although the enzyme is able to stabilize the anionic semiquinone form of the FMN, reduction of quinones involves the hydroquinone form of the flavin cofactor, and the enzymatic reaction occurs through a ping-pong-type mechanism. ArsH is able to catalyze one-electron reactions (oxygen and cytocrome c reduction), involving the FMN semiquinone form, but with lower efficiency. In addition, arsH mutants are sensitive to the oxidizing agent menadione, suggesting that ArsH plays a role in the response to oxidative stress caused by arsenite.

  13. Reduction of quinones and nitroaromatic compounds by Escherichia coli nitroreductase A (NfsA): Characterization of kinetics and substrate specificity.

    PubMed

    Valiauga, Benjaminas; Williams, Elsie M; Ackerley, David F; Čėnas, Narimantas

    2017-01-15

    NfsA, a major FMN-associated nitroreductase of E. coli, reduces nitroaromatic compounds via consecutive two-electron transfers. NfsA has potential applications in the biodegradation of nitroaromatic environment pollutants, e.g. explosives, and is also of interest for the anticancer strategy gene-directed enzyme prodrug therapy. However, the catalytic mechanism of NfsA is poorly characterized. Here we examined the NADPH-dependent reduction of quinones (n = 16) and nitroaromatic compounds (n = 12) by NfsA. We confirmed a general "ping-pong" reaction scheme, and preliminary rapid reaction studies of the enzyme reduction by NADPH showed that this step is much faster than the steady-state turnover number, i.e., the enzyme turnover is limited by the oxidative half-reaction. The reactivity of nitroaromatic compounds (log kcat/Km) followed a linear dependence on their single-electron reduction potential (E(1)7), indicating a limited role for compound structure or active site flexibility in their reactivity. The reactivity of quinones was lower than that of nitroaromatics having similar E(1)7 values, except for the significantly enhanced reactivity of 2-OH-1,4-naphthoquinones, consistent with observations previously made for the group B nitroreductase of Enterobacter cloacae. We present evidence that the reduction of quinones by NfsA is most consistent with a single-step (H(-)) hydride transfer mechanism.

  14. Switching Futile para-Quinone to Efficient Reactive Oxygen Species Generator: Ubiquitin-Specific Protease-2 Inhibition, Electrocatalysis, and Quantification.

    PubMed

    Gopinath, Pushparathinam; Mahammed, Atif; Eilon-Shaffer, Tal; Nawatha, Mickal; Ohayon, Shimrit; Shabat, Doron; Gross, Zeev; Brik, Ashraf

    2017-09-05

    Understanding the correlation between structural features of small-molecule drugs and their mode of action is a fascinating topic and crucial for the drug-discovery process. However, in many cases, knowledge of the exact parameters that dictate the mode of action is still lacking. Following a large screening for ubiquitin specific protease 2 (USP2) inhibition, an effective para-quinone-based inhibitor with an unclear mode of action was identified. To gain a deeper understanding of the mechanism of inhibition, a set of para-quinones were prepared and studied for USP2 inhibition, electrocatalysis, and reactive oxygen species (ROS) quantification. The excellent correlation obtained from the above-mentioned studies disclosed a distinct pattern of "N-C=O-N" in the bicyclic para-quinones to be a crucial factor for ROS generation, and demonstrated that minor changes in such a skeleton drastically altered the ROS-generating ability. The knowledge acquired herein would serve as an important guideline for future medicinal chemistry optimization of related structures to select the preferred mode of action. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. Insight into the kinetics and thermodynamics of the hydride transfer reactions between quinones and lumiflavin: a density functional theory study.

    PubMed

    Reinhardt, Clorice R; Jaglinski, Tanner C; Kastenschmidt, Ashly M; Song, Eun H; Gross, Adam K; Krause, Alyssa J; Gollmar, Jonathan M; Meise, Kristin J; Stenerson, Zachary S; Weibel, Tyler J; Dison, Andrew; Finnegan, Mackenzie R; Griesi, Daniel S; Heltne, Michael D; Hughes, Tom G; Hunt, Connor D; Jansen, Kayla A; Xiong, Adam H; Hati, Sanchita; Bhattacharyya, Sudeep

    2016-09-01

    The kinetics and equilibrium of the hydride transfer reaction between lumiflavin and a number of substituted quinones was studied using density functional theory. The impact of electron withdrawing/donating substituents on the redox potentials of quinones was studied. In addition, the role of these substituents on the kinetics of the hydride transfer reaction with lumiflavin was investigated in detail under the transition state (TS) theory assumption. The hydride transfer reactions were found to be more favorable for an electron-withdrawing substituent. The activation barrier exhibited a quadratic relationship with the driving force of these reactions as derived under the formalism of modified Marcus theory. The present study found a significant extent of electron delocalization in the TS that is stabilized by enhanced electrostatic, polarization, and exchange interactions. Analysis of geometry, bond-orders, and energetics revealed a predominant parallel (Leffler-Hammond) effect on the TS. Closer scrutiny reveals that electron-withdrawing substituents, although located on the acceptor ring, reduce the N-H bond order of the donor fragment in the precursor complex. Carried out in the gas-phase, this is the first ever report of a theoretical study of flavin's hydride transfer reactions with quinones, providing an unfiltered view of the electronic effect on the nuclear reorganization of donor-acceptor complexes.

  16. Redox-active quinones and ascorbate: an innovative cancer therapy that exploits the vulnerability of cancer cells to oxidative stress.

    PubMed

    Verrax, J; Beck, R; Dejeans, N; Glorieux, C; Sid, B; Pedrosa, R Curi; Benites, J; Vásquez, D; Valderrama, J A; Calderon, P Buc

    2011-02-01

    Cancer cells are particularly vulnerable to treatments impairing redox homeostasis. Reactive oxygen species (ROS) can indeed play an important role in the initiation and progression of cancer, and advanced stage tumors frequently exhibit high basal levels of ROS that stimulate cell proliferation and promote genetic instability. In addition, an inverse correlation between histological grade and antioxidant enzyme activities is frequently observed in human tumors, further supporting the existence of a redox dysregulation in cancer cells. This biochemical property can be exploited by using redox-modulating compounds, which represent an interesting approach to induce cancer cell death. Thus, we have developed a new strategy based on the use of pharmacologic concentrations of ascorbate and redox-active quinones. Ascorbate-driven quinone redox cycling leads to ROS formation and provoke an oxidative stress that preferentially kill cancer cells and spare healthy tissues. Cancer cell death occurs through necrosis and the underlying mechanism implies an energetic impairment (ATP depletion) that is likely due to glycolysis inhibition. Additional mechanisms that participate to cell death include calcium equilibrium impairment and oxidative cleavage of protein chaperone Hsp90. Given the low systemic toxicity of ascorbate and the impairment of crucial survival pathways when associated with redox-active quinones, these combinations could represent an original approach that could be combined to standard cancer therapy.

  17. Dopamine quinones activate microglia and induce a neurotoxic gene expression profile: relationship to methamphetamine-induced nerve ending damage.

    PubMed

    Kuhn, Donald M; Francescutti-Verbeem, Dina M; Thomas, David M

    2006-08-01

    Methamphetamine (METH) intoxication leads to persistent damage of dopamine (DA) nerve endings of the striatum. Recently, we and others have suggested that the neurotoxicity associated with METH is mediated by extensive microglial activation. DA itself has been shown to play an obligatory role in METH neurotoxicity, possibly through the formation of quinone species. We show presently that DA-quinones (DAQ) cause a time-dependent activation of cultured microglial cells. Microarray analysis of the effects of DAQ on microglial gene expression revealed that 101 genes were significantly changed in expression, with 73 genes increasing and 28 genes decreasing in expression. Among those genes differentially regulated by DAQ were those often associated with neurotoxic conditions including inflammation, cytokines, chemokines, and prostaglandins. In addition, microglial genes associated with a neuronally protective phenotype were among those that were downregulated by DAQ. These results implicate DAQ as one species that could cause early activation of microglial cells in METH intoxication, manifested as an alteration in the expression of a broad biomarker panel of genes. These results also link oxidative stress, chemical alterations in DA to its quinone, and microglial activation as part of a cascade of glial-neuronal crosstalk that can amplify METH-induced neurotoxicity.

  18. Towards configurationally stable [4]helicenes: enantioselective synthesis of 12-substituted 7,8-dihydro[4]helicene quinones.

    PubMed

    Carreño, M Carmen; Enríquez, Alvaro; García-Cerrada, Susana; Sanz-Cuesta, M Jesús; Urbano, Antonio; Maseras, Feliu; Nonell-Canals, Alfons

    2008-01-01

    The synthesis of enantiopure C-12 methoxy- or alkyl-substituted 5,7,8,12b-tetrahydro[4]helicene quinones 16 and 17 and the 7,8-dihydroaromatic analogues 4 and 5 has been achieved from (SS)-2-(p-tolylsulfinyl)-1,4-benzoquinone. In the first series, with a structure containing both central and helical chiralities, the R absolute configuration of the stereogenic carbon atom was defined after the asymmetric cycloaddition step, whereas the P or M helicity was shown to be dependent on the nature of the C-12 substituent. The size of this group was also defining the configurational stability of the final (P)-7,8-dihydro[4]helicene quinones 4 and 5. The interconversion barriers between the P and M helimers in the latter, computed with a DFT B3LYP method, matched well with the experimentally observed stability. Our study provided evidence that, in addition to steric effects, a small but significant role of electronic effects is governing the configurational stability of such helical quinones.

  19. Arsenic redox changes by microbially and chemically formed semiquinone radicals and hydroquinones in a humic substance model quinone.

    PubMed

    Jiang, Jie; Bauer, Iris; Paul, Andrea; Kappler, Andreas

    2009-05-15

    Arsenic is a redox-active metalloid whose toxicity and mobility strongly depends on its oxidation state, with arsenite (As(III)) being more toxic and mobile than arsenate (As(V)). Humic substances (HS) are also redox-active and can potentially react with arsenic and change its redox state. In this study we show that semiquinone radicals produced during microbial or chemical reduction of a HS model quinone (AQDS, 9,10-anthraquinone-2,6-disulfonic acid) are strong oxidants. They oxidize arsenite to arsenate, thus decreasing As toxicity and mobility. This reaction depends strongly on pH with more arsenite (up to 67.3%) being oxidized at pH 11 compared to pH 7 (12.6% oxidation) and pH 3 (0.5% oxidation). In addition to As(III) oxidation by semiquinone radicals, hydroquinones that were also produced during quinone reduction reduced As(V) to As(III) at neutral and acidic pH values (less than 12%) but not at alkaline pH. In order to understand redox reactions between arsenite/arsenate and reduced/oxidized HS, we quantified the radical content in reduced quinone solutions and constructed Eh-pH diagrams that explain the observed redox reactions. The results from this study can be used to better predict the fate of arsenic in the environment and potentially explain the occurrence of oxidized As(V) in anoxic environments.

  20. Enhanced dechlorination of carbon tetrachloride by Geobacter sulfurreducens in the presence of naturally occurring quinones and ferrihydrite.

    PubMed

    Doong, Ruey-an; Lee, Chun-chi; Lien, Chia-min

    2014-02-01

    The effect of naturally occurring quinones including lawsone (LQ), ubiquinone (UQ), juglone (JQ), and 1,4-naphthoquinone (NQ) on the biotransformation of carbon tetrachloride (CT) in the presence of Geobacter sulfurreducens and ferrihydrite was investigated. AQDS was used as the model compound for comparison. The reductive dissolution of ferrihydrite by G. sulfurreducens was enhanced by AQDS, NQ, and LQ. However, addition of UQ and JQ had little enhancement effect on Fe(II) production. The bioreduction efficiency and rate of ferrihydrite was highly dependent on the natural property and concentration of quinone compounds and the addition of low concentrations of LQ and NQ significantly accelerated the biotransformation rate of CT. The pseudo-first-order rate constants for CT dechlorination (kobsCT) in AQDS-, LQ- and NQ-amended batches were 5.4-5.8, 4.6-7.4 and 2.4-5.8 times, respectively, higher than those in the absence of quinone. A good relationship between kobsCT for CT dechlorination and bioreduction ratio of ferrihydrite was observed, indicating the important role of biogenic Fe(II) in dechlorination of CT under iron-reducing conditions. Spectroscopic analysis showed that AQDS and NQ could be reduced to semiquinones and hydroquinones, while only hydroquinones were generated in LQ-amended batches.

  1. A new approach to evaluating the extent of Michael adduct formation to PAH quinones: tetramethylammonium hydroxide (TMAH) thermochemolysis with GC/MS.

    PubMed

    Briggs, Mary K; Desavis, Emmanuel; Mazzer, Paula A; Sunoj, R B; Hatcher, Susan A; Hadad, Christopher M; Hatcher, Patrick G

    2003-11-01

    Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants that are converted to cytotoxic and carcinogenic metabolites, quinones, by detoxifying enzyme systems in animals. PAH metabolites such as the quinones can form Michael adducts with biological macromolecules containing reactive nucleophiles, making detection of exposure to PAHs difficult using conventional techniques. A technique has been developed for detecting exposure to PAHs. Tetramethylammonium hydroxide (TMAH) thermochemolysis coupled with GC/MS is proposed as an assay method for PAH quinones that have formed Michael adducts with biological molecules. Three PAH quinones (1,4-naphthoquinone, 1,2-naphthoquinone, and 1,4-anthraquinone) and 1,4-benzoquinone were reacted with cysteine, and the TMAH thermochemolysis method was used to assay for both thiol and amine adduction between the quinones and the cysteine. Additional studies with 1,4-naphthoquinone adducts to glutathione and bovine serum albumin showed the same thiol and amine TMAH thermochemolysis products with larger peptides as was observed with cysteine adducts. The TMAH GC/MS method clearly shows great promise for detecting PAH quinones, produced by enzymatic conversion of PAHs in biological systems, that have been converted to respective Michael adducts.

  2. Inducible Alkylation of DNA by a Quinone Methide-Peptide Nucleic Acid Conjugate†

    PubMed Central

    Liu, Yang; Rokita, Steven E.

    2012-01-01

    The reversibility of alkylation by a quinone methide intermediate (QM) avoids the irreversible consumption that plagues most reagents based on covalent chemistry and allows for site specific reaction that is controlled by the thermodynamics rather than kinetics of target association. This characteristic was originally examined with an oligonucleotide QM conjugate but broad application depends on alternative derivatives that are compatible with a cellular environment. Now, a peptide nucleic acid (PNA) derivative has been constructed and shown to exhibit an equivalent ability to delivery the reactive QM in a controlled manner. This new conjugate demonstrates high selectivity for a complementary sequence of DNA even when challenged with an alternative sequence containing a single T/T mismatch. Alkylation of non-complementary sequences is only possible when a template strand is present to co-localize the conjugate and its target. For efficient alkylation in this example, a single-stranded region of the target is required adjacent to the QM conjugate. Most importantly, the intrastrand self adducts formed between the PNA and its attached QM remained active and reversible over more than eight days in aqueous solution prior to reaction with a chosen target added subsequently. PMID:22243337

  3. Quinone-formaldehyde polymer as an active material in Li-ion batteries

    NASA Astrophysics Data System (ADS)

    Pirnat, Klemen; Mali, Gregor; Gaberscek, Miran; Dominko, Robert

    2016-05-01

    A benzoquinone polymer is synthesized by the polymerisation of hydrobenzoquinone and formaldehyde, followed by oxidation process using a hydrogen peroxide to convert hydroquinone to quinone. As prepared materials are characterized with FTIR, 1H-13C CPMAS NMR, pyrolysis coupled with gas chromatography (GC) and mass spectrometer (MS), TGA-MS analysis, EDX, elemental analysis, XRD, SEM and TEM microscopies and BET nitrogen adsorption. The benzoquinone polymer shows an excellent electrochemical performance when used as a positive electrode material in Li-ion secondary batteries. Using an electrolyte consisting 1 M bis(trifluoromethane)-sulfonimide lithium salt dissolved in 1,3-dioxolane and dimethoxyethane in a vol. ratio 1:1 (1 M LiTFSI/DOL + DME = 1:1) a stable capacity close to 150 mAh/g can be obtained. Compared to other electroactive materials based on benzoquinones it has a supreme capacity stability and is prepared by a simple synthesis using easily accessible starting materials. Further improvements in the capacity value (up to the theoretical value of 406 mAh/g) can be foreseen by achieving a higher degree of oxidation and by modification of polymerization process to enhance the electronic and ionic conductivity.

  4. Enhanced rat sciatic nerve regeneration through silicon tubes filled with pyrroloquinoline quinone.

    PubMed

    Liu, Shiqing; Li, Haohuan; Ou Yang, Jingping; Peng, Hao; Wu, Ke; Liu, Yongming; Yang, Jingwei

    2005-01-01

    Pyrroloquinoline quinone (PQQ) is an antioxidant that also stimulates nerve growth factor (NGF) synthesis and secretion. In an earlier pilot study in our laboratory, Schwann cell growth was accelerated, and NGF mRNA expression and NGF secretion were promoted. The present study was designed to explore the possible nerve-inducing effect of PQQ on a nerve tube model over a 1-cm segmental deficit. An 8-mm sciatic nerve deficit was created in a rat model and bridged by a 1-cm silicone tube. Then,10 mul of 0.03 mmol/l PQQ were perfused into the silicone chamber in the PQQ group. The same volume of normal saline was delivered in the control group. Each animal underwent functional observation (SFI) at 2-week intervals and electrophysiological studies at 4-week intervals for 12 weeks. Histological and morphometrical analyses were performed at the end of the experiment, 12 weeks after tube implantation. Using a digital image-analysis system, thickness of the myelin sheath was measured, and total numbers of regenerated axons were counted. There was a significant difference in SFI, electrophysiological index (motor-nerve conduct velocity and amplitude of activity potential), and morphometrical results (regenerated axon number and thickness of myelin sheath) in nerve regeneration between the PQQ group and controls (P < 0.05). More mature, high-density, newly regenerated nerve was observed in the PQQ group. We conclude that PQQ is a potent enhancer for the regeneration of peripheral nerves.

  5. Quinone molecules encapsulated in SWCNTs for low-temperature Na ion batteries

    NASA Astrophysics Data System (ADS)

    Li, Canghao; Ishii, Yosuke; Inayama, Shunya; Kawasaki, Shinji

    2017-09-01

    We have performed Li and Na ion charge-discharge experiments of 9,10-phenanthrene quinone (PhQ) molecules encapsulated in single-walled carbon nanotubes (SWCNTs) with mean tube diameters of 1.5 and 2.5 nm at room temperature and also at low temperatures. The Na ion reversible capacity of PhQ encapsulated in the larger diameter SWCNTs, measured at a low temperature of 0 °C, remained as high as that measured at room temperature (RT), while the capacity of PhQ in the smaller diameter SWCNTs at 0 °C was about a half of that at RT. The diameter dependence of the capacity should be attributed to the difference in the interactions between the encapsulated PhQ molecules and the host SWCNTs, which was revealed by Raman peak profile analysis. Charge-transfer reaction from metallic tubes to PhQ molecules encapsulated in the smaller diameter SWCNTs was detected by Raman measurements. The electrostatic interaction between charged SWCNTs and PhQ molecules, induced by the charge-transfer reaction, would partly contribute to the stabilization of PhQ molecules in the smaller diameter SWCNTs, while only van der Waals interaction stabilizes PhQ molecules in the larger diameter SWCNTs. The difference in stability was confirmed by thermogravimetric, x-ray photoelectron spectroscopy, and Raman measurements. Charge-discharge curves of PhQ encapsulated in SWCNTs were also discussed based on the stability difference.

  6. Pyrroloquinoline quinone-conferred neuroprotection in rotenone models of Parkinson's disease.

    PubMed

    Qin, Jiaojiao; Wu, Meilong; Yu, Shu; Gao, Xiaorong; Zhang, Jingjing; Dong, Xingyue; Ji, Jinyan; Zhang, Yuxi; Zhou, Lin; Zhang, Qi; Ding, Fei

    2015-11-04

    Pyrroloquinoline quinone (PQQ), a redox cofactor in the mitochondrial respiratory chain, has proven to protect neurons against glutamate-induced damage both in vitro and in vivo. This study was aimed to investigate the possible neuroprotective effects of PQQ in rotenone-induced Parkinson's disease (PD) model. Pre-treatment with PQQ prevented cultured SH-SY5Y cells from rotenone-induced apoptosis, accompanied by modulation of apoptosis-related proteins (Bcl-2, Bax and Smac), restoration of the mitochondrial membrane potential, inhibition of intracellular reactive oxygen species (ROS) production, suppression of tyrosine residues nitration, and dopamine redistribution. PQQ also exerted protective effects in an in vivo PD model, which was created by rotenone injection into the medial forebrain bundle of rats. Co-injection with PQQ and rotenone improved the apomorphine-evoked rotation, decreased neuronal loss, increased the ROS-scavenging ability, regulated intracellular expressions of mitochondrial complex subunits (Ndufs1-4), tyrosine hydroxylase, and vesicular monoamine transporter 2. Taken together, our results collectively suggest that PQQ confers neuroprotection in rotenone-induced PD model probably through complex and multifaceted mechanisms, at least involving oxidative stress, mitochondrial integrity, and dopamine functions. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Pyrroloquinoline quinone ameliorates l-thyroxine-induced hyperthyroidism and associated problems in rats.

    PubMed

    Kumar, Narendra; Kar, Anand; Panda, Sunanda

    2014-08-01

    Pyrroloquinoline quinone (PQQ) is believed to be a strong antioxidant. In this study, we have evaluated its hitherto unknown role in l-thyroxin (L-T4 )-induced hyperthyroidism considering laboratory rat as a model. Alterations in the serum concentration of thyroxin (T4 ) and triiodothyronine (T3 ); lipid peroxidation (LPO) of liver, kidney, heart, muscles and brain; in the endogenous antioxidants such as superoxide dismutase, catalase and glutathione and in serum total cholesterol, high-density lipoprotien, triglycerides, serum glutamate pyruvate transaminase (SGPT), serum glutamate oxaloacetate transaminase (SGOT) and urea were evaluated. Administration of l-T4 (500-µg kg(-1) body weight) enhanced not only the serum T3 and T4 levels but also the tissue LPO, serum SGOT, SGPT and urea with a parallel decrease in the levels of antioxidants and serum lipids. However, on simultaneous administration of PQQ (5 mg kg(-1) for 6 days), all these adverse effects were ameliorated, indicating the potential of PQQ in the amelioration of hyperthyroidism and associated problems. Possibly, the curative effects were mediated through inhibition of oxidative stress. We suggest that PQQ may be considered for therapeutic use for hyperthyroidism after dose standardization.

  8. Laccase-catalyzed synthesis of 2,3-ethylenedithio-1,4-quinones

    SciTech Connect

    Cannatelli, Mark D.; Ragauskas, Arthur J.

    2015-06-05

    Laccases (benzenediol:oxygen oxidoreductase EC 1.10.3.2) are part of a family of multicopper oxidases. These environmentally friendly enzymes require O2 as their only co-substrate and produce H2O as their sole by-product. As a result, they have acquired increasing use in biotechnological applications, particularly in the field of organic synthesis. In the current study, laccases have been employed to successfully couple 1,2-ethanedithiol to various substituted hydroquinones to produce novel 2,3-ethylenedithio-1,4-quinones in good yields via an oxidation–addition–oxidation–addition–oxidation mechanism. The reactions proceeded in one-pot under mild conditions (room temperature, pH 5.0). This study further supports the use of laccases as green tools in organic chemistry. Furthermore, it provides evidence that laccase-catalyzed cross-coupling reactions involving small thiols are possible, in spite of research that suggests small thiols are potent inhibitors of laccases.

  9. All-solid-state lithium organic battery with composite polymer electrolyte and pillar[5]quinone cathode.

    PubMed

    Zhu, Zhiqiang; Hong, Meiling; Guo, Dongsheng; Shi, Jifu; Tao, Zhanliang; Chen, Jun

    2014-11-26

    The cathode capacity of common lithium ion batteries (LIBs) using inorganic electrodes and liquid electrolytes must be further improved. Alternatively, all-solid-state lithium batteries comprising the electrode of organic compounds can offer much higher capacity. Herein, we successfully fabricated an all-solid-state lithium battery based on organic pillar[5]quinone (C35H20O10) cathode and composite polymer electrolyte (CPE). The poly(methacrylate) (PMA)/poly(ethylene glycol) (PEG)-LiClO4-3 wt % SiO2 CPE has an optimum ionic conductivity of 0.26 mS cm(-1) at room temperature. Furthermore, pillar[5]quinine cathode in all-solid-state battery rendered an average operation voltage of ∼2.6 V and a high initial capacity of 418 mAh g(-1) with a stable cyclability (94.7% capacity retention after 50 cycles at 0.2C rate) through the reversible redox reactions of enolate/quinonid carbonyl groups, showing favorable prospect for the device application with high capacity.

  10. Laccase-catalyzed synthesis of 2,3-ethylenedithio-1,4-quinones

    DOE PAGES

    Cannatelli, Mark D.; Ragauskas, Arthur J.

    2015-06-05

    Laccases (benzenediol:oxygen oxidoreductase EC 1.10.3.2) are part of a family of multicopper oxidases. These environmentally friendly enzymes require O2 as their only co-substrate and produce H2O as their sole by-product. As a result, they have acquired increasing use in biotechnological applications, particularly in the field of organic synthesis. In the current study, laccases have been employed to successfully couple 1,2-ethanedithiol to various substituted hydroquinones to produce novel 2,3-ethylenedithio-1,4-quinones in good yields via an oxidation–addition–oxidation–addition–oxidation mechanism. The reactions proceeded in one-pot under mild conditions (room temperature, pH 5.0). This study further supports the use of laccases as green tools in organicmore » chemistry. Furthermore, it provides evidence that laccase-catalyzed cross-coupling reactions involving small thiols are possible, in spite of research that suggests small thiols are potent inhibitors of laccases.« less

  11. Quinone molecules encapsulated in SWCNTs for low-temperature Na ion batteries.

    PubMed

    Li, Canghao; Ishii, Yosuke; Inayama, Shunya; Kawasaki, Shinji

    2017-09-01

    We have performed Li and Na ion charge-discharge experiments of 9,10-phenanthrene quinone (PhQ) molecules encapsulated in single-walled carbon nanotubes (SWCNTs) with mean tube diameters of 1.5 and 2.5 nm at room temperature and also at low temperatures. The Na ion reversible capacity of PhQ encapsulated in the larger diameter SWCNTs, measured at a low temperature of 0 °C, remained as high as that measured at room temperature (RT), while the capacity of PhQ in the smaller diameter SWCNTs at 0 °C was about a half of that at RT. The diameter dependence of the capacity should be attributed to the difference in the interactions between the encapsulated PhQ molecules and the host SWCNTs, which was revealed by Raman peak profile analysis. Charge-transfer reaction from metallic tubes to PhQ molecules encapsulated in the smaller diameter SWCNTs was detected by Raman measurements. The electrostatic interaction between charged SWCNTs and PhQ molecules, induced by the charge-transfer reaction, would partly contribute to the stabilization of PhQ molecules in the smaller diameter SWCNTs, while only van der Waals interaction stabilizes PhQ molecules in the larger diameter SWCNTs. The difference in stability was confirmed by thermogravimetric, x-ray photoelectron spectroscopy, and Raman measurements. Charge-discharge curves of PhQ encapsulated in SWCNTs were also discussed based on the stability difference.

  12. Cation transport by the respiratory NADH:quinone oxidoreductase (complex I): facts and hypotheses.

    PubMed

    Steffen, Wojtek; Steuber, Julia

    2013-10-01

    The respiratory complex I (electrogenic NADH:quinone oxidoreductase) has been considered to act exclusively as a H+ pump. This was questioned when the search for the NADH-driven respiratory Na+ pump in Klebsiella pneumoniae initiated by Peter Dimroth led to the discovery of a Na+-translocating complex in this enterobacterium. The 3D structures of complex I from different organisms support the idea that the mechanism of cation transport by complex I involves conformational changes of the membrane-bound NuoL, NuoM and NuoN subunits. In vitro methods to follow Na+ transport were compared with in vivo approaches to test whether complex I, or its individual NuoL, NuoM or NuoN subunits, extrude Na+ from the cytoplasm to the periplasm of bacterial host cells. The truncated NuoL subunit of the Escherichia coli complex I which comprises amino acids 1-369 exhibits Na+ transport activity in vitro. This observation, together with an analysis of putative cation channels in NuoL, suggests that there exists in NuoL at least one continuous pathway for cations lined by amino acid residues from transmembrane segments 3, 4, 5, 7 and 8. Finally, we discuss recent studies on Na+ transport by mitochondrial complex I with respect to its putative role in the cycling of Na+ ions across the inner mitochondrial membrane.

  13. Pyrroloquinoline Quinone (PQQ) Prevents Cognitive Deficit Caused by Oxidative Stress in Rats

    PubMed Central

    Ohwada, Kei; Takeda, Hironobu; Yamazaki, Makiko; Isogai, Hirosi; Nakano, Masahiko; Shimomura, Masao; Fukui, Koji; Urano, Shiro

    2008-01-01

    The effects of pyrroloquinoline quinone (PQQ) and coenzyme Q10 (Co Q10), either alone or together, on the learning ability and memory function of rats were investigated. Rats fed a PQQ-supplemented diet showed better learning ability than rats fed a CoQ10-supplemented diet at the early stage of the Morris water maze test. The combination of both compounds resulted in no significant improvement in the learning ability compared with the supplementation of PQQ alone. At the late stage of the test, rats fed PQQ-, CoQ10- and PQQ + CoQ10-supplemented diets showed similar improved learning abilities. When all the groups were subjected to hyperoxia as oxidative stress for 48 h, rats fed the PQQ- and CoQ10 supplemented diets showed better memory function than the control rats. The concurrent diet markedly improved the memory deficit of the rats caused by oxidative stress. Although the vitamin E-deficient rats fed PQQ or CoQ10 improved their learning function even when subjected to hyperoxia, their memory function was maintained by PQQ rather than by CoQ10 after the stress. These results suggest that PQQ is potentially effective for preventing neurodegeneration caused by oxidative stress, and that its effect is independent of either antioxidant’s interaction with vitamin E. PMID:18231627

  14. Determination of oxygen radical absorbance capacity of black cumin (Nigella sativa) seed quinone compounds.

    PubMed

    Tesarova, Hana; Svobodova, Blanka; Kokoska, Ladislav; Marsik, Petr; Pribylova, Marie; Landa, Premysl; Vadlejch, Jaroslav

    2011-02-01

    In this study, the antioxidant capacities of main quinone constituents of Nigella sativa seeds, namely dithymoquinone (1), thymohydroquinone (2) and thymoquinone (3), were compared using DPPH and ORAC methods. The best scavenging activity was produced by 2, which showed a remarkable activity of 2.60 Trolox equivalents (TE) in a concentration range between 1.6 and 6.4 microg/mL and IC50 value of 2.4 microg/mL in ORAC and DPPH assays, respectively. Contrastingly, 3 possessed only weak DPPH scavenging efficacy (IC50 = 170 microg/mL) but significant antioxidative action of 1.91 TE in ORAC assay. No effect has been observed for 1. Additionally, modified protocol for synthesis of 2 has been developed with aim to enhance its availability for further studies as well as for its future potential use. Based on the results of this study, we conclude that 2 could be considered as a compound with prospective antioxidative properties.

  15. Transient Kinetic Analysis of Hydrogen Sulfide Oxidation Catalyzed by Human Sulfide Quinone Oxidoreductase.

    PubMed

    Mishanina, Tatiana V; Yadav, Pramod K; Ballou, David P; Banerjee, Ruma

    2015-10-09

    The first step in the mitochondrial sulfide oxidation pathway is catalyzed by sulfide quinone oxidoreductase (SQR), which belongs to the family of flavoprotein disulfide oxidoreductases. During the catalytic cycle, the flavin cofactor is intermittently reduced by sulfide and oxidized by ubiquinone, linking H2S oxidation to the electron transfer chain and to energy metabolism. Human SQR can use multiple thiophilic acceptors, including sulfide, sulfite, and glutathione, to form as products, hydrodisulfide, thiosulfate, and glutathione persulfide, respectively. In this study, we have used transient kinetics to examine the mechanism of the flavin reductive half-reaction and have determined the redox potential of the bound flavin to be -123 ± 7 mV. We observe formation of an unusually intense charge-transfer (CT) complex when the enzyme is exposed to sulfide and unexpectedly, when it is exposed to sulfite. In the canonical reaction, sulfide serves as the sulfur donor and sulfite serves as the acceptor, forming thiosulfate. We show that thiosulfate is also formed when sulfide is added to the sulfite-induced CT intermediate, representing a new mechanism for thiosulfate formation. The CT complex is formed at a kinetically competent rate by reaction with sulfide but not with sulfite. Our study indicates that sulfide addition to the active site disulfide is preferred under normal turnover conditions. However, under pathological conditions when sulfite concentrations are high, sulfite could compete with sulfide for addition to the active site disulfide, leading to attenuation of SQR activity and to an alternate route for thiosulfate formation.

  16. Organization of the human [zeta]-crystallin/quinone reductase gene (CRYZ)

    SciTech Connect

    Gonzalez, P.; Rao, P.V.; Zigler, J.S. Jr. )

    1994-05-15

    [zeta]-Crystallin is a protein highly expressed in the lens of guinea pigs and camels, where it comprises about 10% of the total soluble protein. It has recently been characterized as a novel quinone oxidoreductase present in a variety of mammalian tissues. The authors report here the isolation and characterization of the human [zeta]-crystallin gene (CRYZ) and its processed pseudogene. The functional gene is composed of nine exons and spans about 20 kb. The 5[prime]-flanking region of the gene is rich in G and C (58%) and lacks TATA and CAAT boxes. Previous analysis of the guinea pig gene revealed the presence of two different promoters, one responsible for the high lens-specific expression and the other for expression at the enzymatic level in numerous tissues. Comparative analysis with the guinea pig gene shows that a region of [approximately]2.5 kb that includes the promoter responsible for the high expression in the lens in guinea pig is not present in the human gene. 34 refs., 6 figs., 1 tab.

  17. Complex and charge transfer between TiO2 and pyrroloquinoline quinone.

    PubMed

    Dimitrijevic, Nada M; Poluektov, Oleg G; Saponjic, Zoran V; Rajh, Tijana

    2006-12-21

    Pyrroloquinoline quinone (PQQ) forms a tridentate complex with coordinatively unsaturated titanium atoms on the surface of approximately 4.5 nm TiO2 particles; an association constant of K = 550 M-1 per Ti(IV)surf has been determined. Low-temperature electron paramagnetic resonance was employed in identification of localized charges and consequently produced radicals and in determination of charge-transfer processes. The photoexcitation of the PQQ-TiO2 complex results in the transfer of conduction band electrons from TiO2 to bound PQQ and the formation of the semiquinone radical. Attaching dopamine (DA) as an electron donor and PQQ as an electron acceptor on the surface of TiO2 results in spatial separation of photogenerated charges; the holes localize on dopamine and electrons on PQQ, with higher yields than for each component separately. In this triad-type assembly (PQQ-TiO2/DA) the PQQ that is bound to the particles acts as a sink for electrons allowing their almost complete scavenging even at temperature as low as 4 K.

  18. Ebselen: A thioredoxin reductase-dependent catalyst for {alpha}-tocopherol quinone reduction

    SciTech Connect

    Fang Jianguo; Zhong Liangwei; Zhao Rong; Holmgren, Arne . E-mail: arne.holmgren@mbb.ki.se

    2005-09-01

    The thioredoxin system, composed of thioredoxin (Trx), thioredoxin reductase (TrxR), and NADPH, is a powerful protein disulfide reductase system with a broad substrate specificity. Recently the selenazol drug ebselen was shown to be a substrate for both mammalian TrxR and Trx. We examined if {alpha}-tocopherol quinone (TQ), a product of {alpha}-tocopherol oxidation, is reduced by ebselen in the presence of TrxR, since TQ was not a substrate for the enzyme itself. Ebselen reduction of TQ in the presence of TrxR was caused by ebselen selenol, generated from fast reduction of ebselen by the enzyme. TQ has no intrinsic antioxidant activity, while the product of reduction of TQ, {alpha}-tocopherolhydroquinone (TQH{sub 2}), is a potent antioxidant. The thioredoxin system dependence of ebselen to catalyze reduction of other oxidized species, such as hydrogen peroxide, dehydroascorbate, and peroxynitrite, is discussed. The ability of ebselen to reduce TQ via the thioredoxin system is a novel mechanism to explain the effects of the drug as an antioxidant in vivo.

  19. Pyrroloquinoline quinone prevents MK-801-induced stereotypical behavior and cognitive deficits in mice.

    PubMed

    Zhou, Xingqin; Chen, Quancheng; Hu, Xindai; Mao, Shishi; Kong, Yanyan

    2014-01-01

    Pyrroloquinoline quinone (PQQ), an essential nutrient, antioxidant, redox modulator, and nerve growth factor, prevents cognitive deficits associated with oxidative stress-induced neurodegeneration. Previous molecular imaging studies also demonstrate that PQQ binds to N-methyl D-aspartate (NMDA) receptors. In this study, we investigated the effects of PQQ on stereotypical behaviors and cognitive deficits induced by MK-801, a non-competitive NMDA antagonist used to model schizophrenia. Mice were given repeated injections of MK-801 (0.5mg/kg/d) and PQQ (0.2, 2.0, or 20 μg/kg/d) for 60 days. Behavior was evaluated using a variety of motor, social, and cognitive tests. We found that PQQ administration significantly attenuated MK-801-induced increases in stereotypical behavior and ataxia, suggesting a protective role of PQQ against MK-801-induced neuronal dysfunction and psychiatric disorders. Future studies are necessary to elucidate the underlying mechanisms of PQQ. Copyright © 2013 Elsevier B.V. All rights reserved.

  20. Overexpression of quinone reductase from Salix matsudana Koidz enhances salt tolerance in transgenic Arabidopsis thaliana.

    PubMed

    Song, Xixi; Fang, Jie; Han, Xiaojiao; He, Xuelian; Liu, Mingying; Hu, Jianjun; Zhuo, Renying

    2016-01-15

    Quinone reductase (QR) is an oxidative-related gene and few studies have focused on its roles concerning salt stress tolerance in plants. In this study, we cloned and analyzed the QR gene from Salix matsudana, a willow with tolerance of moderate salinity. The 612-bp cDNA corresponding to SmQR encodes 203 amino acids. Expression of SmQR in Escherichia coli cells enhanced their tolerance under salt stress. In addition, transgenic Arabidopsis thaliana lines overexpressing SmQR exhibited higher salt tolerance as compared with WT, with higher QR activity and antioxidant enzyme activity as well as higher chlorophyll content, lower methane dicarboxylic aldehyde (MDA) content and electric conductivity under salt stress. Nitro blue tetrazolium (NBT) and 3,3'-diaminobenzidine (DAB) staining also indicated that the transgenic plants accumulated less reactive oxygen species compared to WT when exposed to salt stress. Overall, our results suggested that SmQR plays a significant role in salt tolerance and that this gene may be useful for biotechnological development of plants with improved tolerance of salinity.

  1. Pyrroloquinoline quinone-dependent carbohydrate dehydrogenase: activity enhancement and the role of artificial electron acceptors.

    PubMed

    Kulys, Juozas; Tetianec, Lidija; Bratkovskaja, Irina

    2010-08-01

    Pyrroloquinoline quinone (PQQ)-dependent glucose dehydrogenase (PQQ-GDH) offers a variety of opportunities for applications, e.g. in highly sensitive biosensors and electrosynthetic reactions. Here we report on the acceleration (up to 4.9 x 10(4)-fold) of enzymatic ferricyanide reduction by artificial redox mediators (enhancers). The reaction mechanism includes reduction of the PQQ-GDH by glucose followed by oxidation of the reduced PQQ cofactor with either ferricyanide or a redox mediator. A synergistic effect occurs through the oxidation of a reduced mediator by ferricyanide. Using kinetic description of the coupled reaction, the second order rate constant for the reaction of an oxidized mediator with the reduced enzyme cofactor (k(ox)) can be calculated. For different mediators this value is 2.2 x 10(6)-1.6 x 10(8) M(-1)s(-1) at pH 7.2 and 25 degrees C. However, no correlation of the rate constant with the midpoint redox potential of the mediator could be established. For low-potential mediators the synergistic effect is proportional to the ratio of k(ox(med))/k(ox(ferricyanide)), whereas for the high-potential mediators the effect depends on both this ratio and the concentration of the oxidized mediator, which can be calculated from the Nernst equation. The described effect can be applied in various ways, e.g. for substrate reactivity determination, electrosynthetic PQQ cofactor regeneration or building of new highly sensitive biosensors.

  2. Mitochondrial Sulfide Quinone Oxidoreductase Prevents Activation of the Unfolded Protein Response in Hydrogen Sulfide*

    PubMed Central

    Horsman, Joseph W.

    2016-01-01

    Hydrogen sulfide (H2S) is an endogenously produced gaseous molecule with important roles in cellular signaling. In mammals, exogenous H2S improves survival of ischemia/reperfusion. We have previously shown that exposure to H2S increases the lifespan and thermotolerance in Caenorhabditis elegans, and improves protein homeostasis in low oxygen. The mitochondrial SQRD-1 (sulfide quinone oxidoreductase) protein is a highly conserved enzyme involved in H2S metabolism. SQRD-1 is generally considered important to detoxify H2S. Here, we show that SQRD-1 is also required to maintain protein translation in H2S. In sqrd-1 mutant animals, exposure to H2S leads to phosphorylation of eIF2α and inhibition of protein synthesis. In contrast, global protein translation is not altered in wild-type animals exposed to lethally high H2S or in hif-1(ia04) mutants that die when exposed to low H2S. We demonstrate that both gcn-2 and pek-1 kinases are involved in the H2S-induced phosphorylation of eIF2α. Both ER and mitochondrial stress responses are activated in sqrd-1 mutant animals exposed to H2S, but not in wild-type animals. We speculate that SQRD-1 activity in H2S may coordinate proteostasis responses in multiple cellular compartments. PMID:26677221

  3. Catalytic reaction of cytokinin dehydrogenase: preference for quinones as electron acceptors.

    PubMed Central

    Frébortová, Jitka; Fraaije, Marco W; Galuszka, Petr; Sebela, Marek; Pec, Pavel; Hrbác, Jan; Novák, Ondrej; Bilyeu, Kristin D; English, James T; Frébort, Ivo

    2004-01-01

    The catalytic reaction of cytokinin oxidase/dehydrogenase (EC 1.5.99.12) was studied in detail using the recombinant flavoenzyme from maize. Determination of the redox potential of the covalently linked flavin cofactor revealed a relatively high potential dictating the type of electron acceptor that can be used by the enzyme. Using 2,6-dichlorophenol indophenol, 2,3-dimethoxy-5-methyl-1,4-benzoquinone or 1,4-naphthoquinone as electron acceptor, turnover rates with N6-(2-isopentenyl)adenine of approx. 150 s(-1) could be obtained. This suggests that the natural electron acceptor of the enzyme is quite probably a p-quinone or similar compound. By using the stopped-flow technique, it was found that the enzyme is rapidly reduced by N6-(2-isopentenyl)adenine (k(red)=950 s(-1)). Re-oxidation of the reduced enzyme by molecular oxygen is too slow to be of physiological relevance, confirming its classification as a dehydrogenase. Furthermore, it was established for the first time that the enzyme is capable of degrading aromatic cytokinins, although at low reaction rates. As a result, the enzyme displays a dual catalytic mode for oxidative degradation of cytokinins: a low-rate and low-substrate specificity reaction with oxygen as the electron acceptor, and high activity and strict specificity for isopentenyladenine and analogous cytokinins with some specific electron acceptors. PMID:14965342

  4. Wired pyrroloquinoline quinone soluble glucose dehydrogenase enzyme electrodes operating at unprecedented low redox potential.

    PubMed

    Flexer, Victoria; Mano, Nicolas

    2014-03-04

    We report unprecedented high current densities for the enzymatic oxidation of glucose already at 0 V versus Ag/AgCl. The modified electrodes were made by assembling pyrroloquinoline quinone (PQQ)-soluble glucose dehydrogenase (PQQ-sGDH) from Acinetobacter calcoaceticus with osmium-based redox polymers and a cross-linker. Both redox mediators are made of a poly(4-vinylpyridine) (PVP) polymer with Os complexes tethered to the polymer backbone via long C chains, giving the Os complexes flexibility and mobility inside the redox hydrogels. Current densities larger than 1 mA cm(-2) were measured already below 0 V with a plateau value of 4.4 mA cm(-2). Similar hydrogel electrodes comprising the same redox polymers and glucose oxidase (GOx) showed less than half the current densities of the PQQ-sGDH electrodes. The current versus potential curve dependence showed a sigmoidal shape characteristic of mediated enzyme catalysis but with a current increase versus potential less sharp than expected. Surprisingly, the midwave redox potential was positively shifted with respect to the potential of the redox mediator.

  5. Pyrroloquinoline Quinone (PQQ) Prevents Cognitive Deficit Caused by Oxidative Stress in Rats.

    PubMed

    Ohwada, Kei; Takeda, Hironobu; Yamazaki, Makiko; Isogai, Hirosi; Nakano, Masahiko; Shimomura, Masao; Fukui, Koji; Urano, Shiro

    2008-01-01

    The effects of pyrroloquinoline quinone (PQQ) and coenzyme Q(10) (Co Q(10)), either alone or together, on the learning ability and memory function of rats were investigated. Rats fed a PQQ-supplemented diet showed better learning ability than rats fed a CoQ(10)-supplemented diet at the early stage of the Morris water maze test. The combination of both compounds resulted in no significant improvement in the learning ability compared with the supplementation of PQQ alone. At the late stage of the test, rats fed PQQ-, CoQ(10)- and PQQ + CoQ(10)-supplemented diets showed similar improved learning abilities. When all the groups were subjected to hyperoxia as oxidative stress for 48 h, rats fed the PQQ- and CoQ(10) supplemented diets showed better memory function than the control rats. The concurrent diet markedly improved the memory deficit of the rats caused by oxidative stress. Although the vitamin E-deficient rats fed PQQ or CoQ(10) improved their learning function even when subjected to hyperoxia, their memory function was maintained by PQQ rather than by CoQ(10) after the stress. These results suggest that PQQ is potentially effective for preventing neurodegeneration caused by oxidative stress, and that its effect is independent of either antioxidant's interaction with vitamin E.

  6. A subchronic oral toxicity study on pyrroloquinoline quinone (PQQ) disodium salt in rats.

    PubMed

    Liang, Chunlai; Zhang, Xin; Wang, Wei; Song, Yan; Jia, Xudong

    2015-01-01

    A subchronic oral toxicity study on pyrroloquinoline quinone (PQQ) disodium salt was performed in rats. Sprague-Dawley rats were randomly divided into four groups (10 rats/sex/group) and administered with PQQ disodium salt at doses of 0 (control), 100, 200 and 400 mg/kg bw/day by gavage for 13 weeks. Daily clinical observations and weekly measurement of body weights and food consumption were conducted. Blood samples were obtained on day 46 and day 91 for measurement of hematology and serum biochemical parameters. Animals were euthanized for necropsy, selected organs were weighted and recorded. Histological examination was performed on all tissues from animals in the control and PQQ disodium salt treatment groups. No mortality or toxicologically significant changes in clinical signs, body weight, food consumption, necropsy findings or organ weights was observed. Differences between treated and control groups in some hematological and serum biochemical examinations and histopathological examination were not considered treatment-related. The no-observed-adverse-effect-level (NOAEL) of PQQ disodium salt in rats was considered to be 400 mg/kg bw/day for both sexes, the highest dose tested. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Acute and subchronic toxicity studies of pyrroloquinoline quinone (PQQ) disodium salt (BioPQQ™) in rats.

    PubMed

    Nakano, Masahiko; Takahashi, Hisaaki; Koura, Seiko; Chung, Catherine; Tafazoli, Shahrzad; Roberts, Ashley

    2014-10-01

    The potential use of pyrroloquinoline quinone disodium salt (BioPQQ™), as a supplemental food ingredient, was evaluated in a range of oral toxicity studies in rats including an acute study, a 14-day preliminary and a 28-day repeated-dose study, and a 13-week subchronic study. The median lethal dose of BioPQQ™ was shown to be 1000-2000mg/kg body weight (bw) in male and 500-1000mg/kgbw in female rats. In the 14-day study, high doses of BioPQQ™ resulted in increases in relative kidney weights with associated histopathology in female rats only, while a follow-up 28-day study in female animals resulted in increases in urinary protein and crystals. These findings were reversible, and resolved during the recovery period. In the 13-week study, a number of clinical chemistry findings and histopathological changes were noted, which were deemed to be of no toxicological significance, as the levels were within the historical control range, were not dose-dependent, occurred at a similar frequency in control groups, or only occurred in the control group. Based on these findings, a no-observed-adverse-effect level of 100mg/kgbw/day was determined for BioPQQ™ in rats, the highest dose tested in the 13-week study. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Cloning and expression of pyrroloquinoline quinone (PQQ) genes from a phosphate-solubilizing bacterium Enterobacter intermedium.

    PubMed

    Kim, Chul Hong; Han, Song Hee; Kim, Kil Yong; Cho, Baik Ho; Kim, Yong Hwan; Koo, Bon Sung; Kim, Young Cheol

    2003-12-01

    A grass rhizosphere bacterium, Enterobacter intermedium (60-2G), has a strong ability to solubilize insoluble phosphate. Certain phosphate-solubilizing bacteria secrete gluconic acid for this process. The gluconic acid is produced by direct extracellular oxidation of glucose by a glucose dehydrogenase equipped with pyrroloquinoline quinone (PQQ) as a cofactor. A pqq gene cluster producing PQQ was detected in E. intermedium and this sequence conferred phosphate-solubilizing activity to Escherichia coli DH5alpha. The 6,783-bp pqq sequence had six open reading frames (pqqA, B, C, D, E, and F) and showed 50-95% homology to pqq genes of other bacteria. E. coli DH5alpha expressing the E. intermedium pqq genes solubilized phosphate from hydroxyapatite after a pH drop to pH 4.0, which paralleled in time the secretion of gluconic acid. We speculate that production of PQQ in E. coli DH5alpha expressing the pqq cluster activates an endogenous glucose dehydrogenase to permit gluconic acid secretion that solubilizes the insoluble phosphate.

  9. Protective Effect of Pyrroloquinoline Quinone (PQQ) in Rat Model of Intracerebral Hemorrhage.

    PubMed

    Lu, Hongjian; Shen, Jiabing; Song, Xinjian; Ge, Jianbin; Cai, Rixin; Dai, Aihua; Jiang, Zhongli

    2015-10-01

    Pyrroloquinoline quinone (PQQ) has invoked considerable interest because of its presence in foods, antioxidant properties, cofactor of dehydrogenase, and amine oxidase. Protective roles of PQQ in central nervous system diseases, such as experimental stroke and spinal cord injury models have been emerged. However, it is unclear whether intracerebral hemorrhage (ICH), as an acute devastating disease, can also benefit from PQQ in experimental conditions. Herein, we examined the possible effect of PQQ on neuronal functions following ICH in the adult rats. The results showed that rats pretreated with PQQ at 10 mg/kg effectively improved the locomotor functions, alleviated the hematoma volumes, and reduced the expansion of brain edema after ICH. Also, pretreated rats with PQQ obviously reduced the production of reactive oxygen species after ICH, probably due to its antioxidant properties. Further, we found that, Bcl-2/Bax, the important indicator of oxidative stress insult in mitochondria after ICH, exhibited increasing ratio in PQQ-pretreated groups. Moreover, activated caspase-3, the apoptotic executor, showed coincident alleviation in PQQ groups after ICH. Collectively, we speculated that PQQ might be an effective and potential neuroprotectant in clinical therapy for ICH.

  10. Biological effects of pyrroloquinoline quinone on liver damage in Bmi-1 knockout mice

    PubMed Central

    HUANG, YUANQING; CHEN, NING; MIAO, DENGSHUN

    2015-01-01

    Pyrroloquinoline quinone (PQQ) has been demonstrated to function as an antioxidant by scavenging free radicals and subsequently protecting the mitochondria from oxidative stress-induced damage. The aim of the present study was to investigate whether PQQ is able to rescue premature senescence in the liver, induced by the deletion of B cell-specific Moloney MLV insertion site-1 (Bmi-1), by inhibiting oxidative stress. In vivo, the mice were allocated into three groups that underwent the following treatment protocols. WT mice received a normal diet, while BKO mice also received a normal diet. An additional group of BKO mice were fed a PQQ-supplemented diet (BKO + PQQ; 4 mg PQQ/kg in the normal diet). The results indicated that PQQ partially rescued the liver damage induced by the deletion of Bmi-1. PQQ was demonstrated to exhibit these therapeutic effects on liver damage through multiple aspects, including the promotion of proliferation, antiapoptotic effects, the inhibition of senescence, the upregulation of antioxidant ability, the downregulation of cell cycle protein expression, the scavenging of reactive oxygen species and the reduction of DNA damage. The results of these experiments indicated that treatment of BKO mice with a moderate dose of PQQ significantly protected the liver from deleterious effects by inhibiting oxidative stress and participating in DNA damage repair. Therefore, PQQ has great potential as a therapeutic agent against oxidative stress during liver damage. PMID:26622336

  11. The Effect of Pyrroloquinoline Quinone on the Expression of WISP1 in Traumatic Brain Injury

    PubMed Central

    Ye, Yongqi; Zhang, Pengju; Qian, Yuhang; Yin, Baoxin

    2017-01-01

    WISP1, as a member of the CCN4 protein family, has cell protective effects of promoting cell proliferation and inhibiting cell apoptosis. Although some studies have confirmed that WISP1 is concerned with colon cancer and lung cancer, there is little report about the influence of WISP1 in traumatic brain injury. Here, we found that the expression of WISP1 mRNA and protein decreased at 3 d and then increased at 5 d after traumatic brain injury (TBI). Meanwhile, immunofluorescence demonstrated that there was little colocation of WISP1 with GFAP, Iba1, and WISP1 colocalized with NeuN partly. WISP1 colocalized with LC3, but there was little of colocation about WISP1 with cleaved caspase-3. Subsequent study displayed that the expression of β-catenin protein was identical to that of WISP1 after TBI. WISP1 was mainly located in cytoplasm of PC12 or SHSY5Y cells. Compared with the negative control group, WISP1 expression reduced obviously in SHSY5Y cells transfected with WISP1 si-RNA. CCK-8 assay showed that pyrroloquinoline quinone (PQQ) had little influence on viability of PC12 and SHSY5Y cells. These results suggested that WISP1 played a protective role after traumatic brain injury in rats, and this effect might be relative to autophagy caused by traumatic brain injury. PMID:28883836

  12. Intestinal absorption and tissue distribution of ( sup 14 C)pyrroloquinoline quinone in mice

    SciTech Connect

    Smidt, C.R.; Unkefer, C.J.; Houck, D.R.; Rucker, R.B. )

    1991-05-01

    Pyrroloquinoline quinone (PQQ) functions as a cofactor for prokaryotic oxidoreductases, such as methanol dehydrogenase and membrane-bound glucose dehydrogenase. In animals fed chemically defined diets, PQQ improves reproductive outcome and neonatal growth. Consequently, the present study was undertaken to determine the extent to which PQQ is absorbed by the intestine, its tissue distribution, and route of excretion. About 28 micrograms of PQQ (0.42 microCi/mumol), labeled with {sup 14}C derived from L-tyrosine, was administered orally to Swiss-Webster mice (18-20 g) to estimate absorption. PQQ was readily absorbed (62%, range 19-89%) in the lower intestine, and was excreted by the kidneys (81% of the absorbed dose) within 24 hr. The only tissues that retained significant amounts of ({sup 14}C)PQQ at 24 hr were skin and kidney. For kidney, it was assumed that retention of ({sup 14}C)PQQ represented primarily PQQ destined for excretion. For skin, the concentration of ({sup 14}C)PQQ increased from 0.3% of the absorbed dose at 6 hr to 1.3% at 24 hr. Furthermore, most of the ({sup 14}C)PQQ in blood (greater than 95%) was associated with the blood cell fraction, rather than plasma.

  13. Cytotoxicity of a Quinone-containing Cockroach Sex Pheromone in Human Lung Adenocarcinoma Cells.

    PubMed

    Ma, Bennett; Carr, Brian A; Krolikowski, Paul; Chang, Frank N

    2007-01-01

    The cytotoxic effects of blattellaquinone (BTQ), a sex pheromone produced by adult female German cockroaches, have been studied using human lung adenocarcinoma A549 cells. 1,4-Benzoquinone (BQ), a toxic chemical implicated in benzene toxicity, was used as a reference compound. Both BQ and BTQ showed comparable toxicity toward A549 cells, with LD50 values estimated to be 14 and 19 microM, respectively. These two compounds increased the formation of an oxidized fluorescent probe, 2',7'-dichlorofluorescein, but had no effect on the cellular GSSG level. Interestingly, BTQ increased the level of 8-epi-prostaglandin F2alpha and was 4-fold more efficient in depleting cellular GSH content than BQ. Of the five GSH adducts of BTQ isolated, three were identified as mono-GSH conjugates, and the other two were di-conjugates. Mass spectrometric and NMR analyses of the di-conjugates showed that the second GSH molecule displaced the isovaleric acid moiety, potentially via a nucleophilic substitution reaction. The ability of BTQ to conjugate a second GSH molecule without quinone regeneration indicated that it may be a more effective cross-linking agent than BQ. Future experiments may be needed to evaluate the overall safety of BTQ before the commercialization of the compound as a cockroach attractant.

  14. NAD(P)H:quinone oxidoreductase 1 inducer activity of some novel anilinoquinazoline derivatives

    PubMed Central

    Ghorab, Mostafa M; Alsaid, Mansour S; Higgins, Maureen; Dinkova-Kostova, Albena T; Shahat, Abdelaaty A; Elghazawy, Nehal H; Arafa, Reem K

    2016-01-01

    The Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response elements pathway enables cells to survive oxidative stress conditions through regulating the expression of cytoprotective enzymes such as NAD(P)H:quinone oxidoreductase 1 (NQO1). This work presents the design and synthesis of novel anilinoquinazoline derivatives (2–16a) and evaluation of their NQO1 inducer activity in murine cells. Molecular docking of the new compounds was performed to assess their ability to inhibit Keap1–Nrf2 protein–protein interaction through occupying the Keap1–Nrf2-binding domain, which leads to Nrf2 accumulation and enhanced gene expression of NQO1. Docking results showed that all compounds can potentially interact with Keap1; however, 1,5-dimethyl-2-phenyl-4-(2-phenylquinazolin-4-ylamino)-1,2-dihydropyrazol-3-one (9), the most potent inducer, showed the largest number of interactions with key amino acids in the binding pocket (Arg483, Tyr525, and Phe478) compared to the native ligand or any other compound in this series. PMID:27540279

  15. Purification and properties of a quinone-dependent p-nitrophenylphosphatase from Clostridium sticklandii.

    PubMed

    Davis, J N; Stadtman, T C

    1985-06-01

    A highly specialized phosphatase that depends on both a quinone (e.g., 2-methyl-1,4-napthoquinone) and a sulfhydryl compound for activity was purified to homogeneity from extracts of Clostridium sticklandii. Selective adsorption to Cibacron Blue-Sepharose 4B followed by elution with p-nitrophenylphosphate was an effective enrichment procedure. An affinity matrix containing vitamin K5 (4-amino-2-methyl-1-naphthol) covalently attached to Sepharose 4B selectively retained the enzyme and was also used in its purification. The only known substate for the enzyme, p-nitrophenylphosphate, is hydrolyzed to equivalent amounts of orthophosphate and p-nitrophenol. Although a protein phosphotyrosine residue seemed a likely candidate as the natural substrate, the enzyme failed to hydrolyze 32P-labeled phosphotyrosine residues in casein, in vinculin, or in denatured glutamine synthetase. Also, free O-phosphotyrosine and numerous phosphate esters that serve as substrates for common phosphomonoesterases were not hydrolyzed. The molecular weight of the native enzyme, estimated by Sephacryl-S-200 gel chromatography, is 27,600. Sodium dodecyl sulfate-polyacrylamide gel electrophoretic analysis showed a single component with a molecular weight of 28,600. From the amino acid composition, a minimum molecular weight of 28,000 was calculated.

  16. Hydrolysis of the quinone methide of butylated hydroxytoluene in aqueous solutions.

    PubMed

    Willcockson, Maren Gulsrud; Toteva, Maria M; Stella, Valentino J

    2013-10-01

    Butylated hydroxytoluene or BHT is an antioxidant commonly used in pharmaceutical formulations. BHT upon oxidation forms a quinone methide (QM). QM is a highly reactive electrophilic species that can undergo nucleophilic addition. Here, the kinetic reactivity of QM with water at various apparent pH values in a 50% (v/v) water-acetonitrile solution at constant ionic strength of I = 0.5 (NaCl)4 , was studied. The hydrolysis of QM in the presence of added acid, base, sodium chloride, and phosphate buffer resulted in the formation of only one product--the corresponding 3,5-di-tert-butyl-4-hydroxybenzyl alcohol (BA). The rate of BA formation was catalyzed by the addition of acid and base, but not chloride and phosphate species. Nucleophilic excipients, used in the pharmaceutical formulation, or nucleophilic groups on active pharmaceutical ingredient molecule may form adducts with QM, the immediate oxidative product of BHT degradation, thus having implications for drug product impurity profiles. Because of these considerations, BHT should be used with caution in formulations containing drugs or excipients capable of acting as nucleophiles. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association.

  17. Formation of Aza-ortho-quinone Methides Under Room Temperature Conditions: Cs2CO3 Effect.

    PubMed

    Walden, Daniel M; Jaworski, Ashley A; Johnston, Ryne C; Hovey, M Todd; Baker, Hannah V; Meyer, Matthew P; Scheidt, Karl A; Cheong, Paul Ha-Yeon

    2017-07-21

    Since the first report of a facile, room temperature process to access aza-ortho-quinone methides (aoQMs) by Corey in 1999, this chemistry has remained dormant until our report of an enantioselective catalytic example in 2014. We report a theoretical and experimental study of the key to success behind these successful examples to enable broader exploitation of this useful intermediate. We have discovered that transformations involving the aoQM are remarkably facile with barriers <17 kcal/mol. The main difficulty of exploiting aoQM in synthesis is that they are unstable (ΔG > 30 kcal/mol), precluding their formation under mild conditions. The use of Cs2CO3 as base is critical. It provides a thermodynamically and kinetically favorable means to form aoQMs, independent of the salt solubility and base strength. The exothermic formation of salt byproducts provides a driving force (average ΔG = -30.8 kcal/mol) compensating for the majority of the inherent unfavorable thermodynamics of aoQM formation.

  18. Antimalarial Quinones for Prophylaxis Based on a Rationale of Inhibition of Electron Transfer in Plasmodium*

    PubMed Central

    Wan, Yieh-Ping; Porter, Thomas H.; Folkers, Karl

    1974-01-01

    Knowledge of the biochemistry of Plasmodium is emerging as a new field. Previous studies showed that the parasite apparently requires electron transfer for energy, and techniques to study such energy mechanisms are available. The discovery of the existence of coenzyme Q8 in Plasmodium implies an indispensable functionality for this redox entity in the electron transfer of the parasite, as coenzyme Qn similarily functions in other forms of life. Effective antimalarial activity in prophylaxis has been demonstrated in sporozoite-induced infections by Plasmodium gallinaceum in chicks by several representatives of 7-alkylmercapto-6-hydroxy-5,8-quinolinequinones. The absence of toxicity in this assay even at greatly elevated dosage underscores the achievement of selectivity and safety to the host for the potential utilization of antimetabolites of coenzyme Qn as medicinals. Seven new 7-alkylmercapto-6-hydroxy-5,8-quinoline-quinones were synthesized. The structural variations of the 7-alkylmercapto group in relationship to the antimalarial activities reveal substantial differences in biological activities, which can reflect molecular specificities of enzyme sites and which are not evident from the deceptively minor structural differences in the alkylmercapto groups. These analogs of coenzyme Q8 having effective antimalarial activity are known to inhibit mammalian coenzyme Qn enzymes, and could be useful in elucidation of the basic electron transfer mechanisms of Plasmodium. PMID:4595578

  19. A cannabigerol quinone alleviates neuroinflammation in a chronic model of multiple sclerosis.

    PubMed

    Granja, Aitor G; Carrillo-Salinas, Francisco; Pagani, Alberto; Gómez-Cañas, María; Negri, Roberto; Navarrete, Carmen; Mecha, Miriam; Mestre, Leyre; Fiebich, Bend L; Cantarero, Irene; Calzado, Marco A; Bellido, Maria L; Fernandez-Ruiz, Javier; Appendino, Giovanni; Guaza, Carmen; Muñoz, Eduardo

    2012-12-01

    Phytocannabinoids like ∆(9)-tetrahydrocannabinol (THC) and cannabidiol (CBD) show a beneficial effect on neuroinflammatory and neurodegenerative processes through cell membrane cannabinoid receptor (CBr)-dependent and -independent mechanisms. Natural and synthetic cannabinoids also target the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ), an attractive molecular target for the treatment of neuroinflammation. As part of a study on the SAR of phytocannabinoids, we have investigated the effect of the oxidation modification in the resorcinol moiety of cannabigerol (CBG) on CB(1), CB(2) and PPARγ binding affinities, identifying cannabigerol quinone (VCE-003) as a potent anti-inflammatory agent. VCE-003 protected neuronal cells from excitotoxicity, activated PPARγ transcriptional activity and inhibited the release of pro-inflammatory mediators in LPS-stimulated microglial cells. Theiler's murine encephalomyelitis virus (TMEV) model of multiple sclerosis (MS) was used to investigate the anti-inflammatory activity of this compound in vivo. Motor function performance was evaluated and the neuroinflammatory response and gene expression pattern in brain and spinal cord were studied by immunostaining and qRT-PCR. We found that VCE-003 ameliorated the symptoms associated to TMEV infection, decreased microglia reactivity and modulated the expression of genes involved in MS pathophysiology. These data lead us to consider VCE-003 to have high potential for drug development against MS and perhaps other neuroinflammatory diseases.

  20. Quinone-mediated microbial synthesis of reduced graphene oxide with peroxidase-like activity.

    PubMed

    Liu, Guangfei; Zhang, Xin; Zhou, Jiti; Wang, Aijie; Wang, Jing; Jin, Ruofei; Lv, Hong

    2013-12-01

    The effects of different quinones on graphene oxide (GO) reduction by Shewanella oneidensis MR-1 and the peroxidase activity of the resultant reduced graphene oxide (QRGO) were studied. The presence of 100 μM anthraquinone-2-sulfonate (AQS), anthraquinone-2,6-disulfonate and 5-hydroxy-1,4-naphthoquinone could lead to 1.6-2.8-fold increase in GO reduction rate, whereas anthraquinone-2-carboxylate slowed down the reduction. The stimulating effects of AQS increased with the increase of its concentration (10-100 μM). The mediated effects were proved by direct GO reduction by microbially reduced AQS. The mediated reduction of GO to QRGO was characterized by UV-vis, XRD, FTIR, Raman spectra, XPS, TEM and AFM, respectively. The as-prepared QRGO possessed peroxidase-like activity, which could catalyze the oxidation of 3,3'5,5'-tetramethylbenzidine by H2O2, and followed Michealis-Menten kinetics. A colorimetric sensor for quantitative determination of glucose based on the peroxidase activity of QRGO was developed over a range of 1-120 μM with a detection limit of 1 μM. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Functional analysis of three sulfide:quinone oxidoreductase homologs in Chlorobaculum tepidum.

    PubMed

    Chan, Leong-Keat; Morgan-Kiss, Rachael M; Hanson, Thomas E

    2009-02-01

    Sulfide:quinone oxidoreductase (SQR) catalyzes sulfide oxidation during sulfide-dependent chemo- and phototrophic growth in bacteria. The green sulfur bacterium Chlorobaculum tepidum (formerly Chlorobium tepidum) can grow on sulfide as the sole electron donor and sulfur source. C. tepidum contains genes encoding three SQR homologs: CT0117, CT0876, and CT1087. This study examined which, if any, of the SQR homologs possess sulfide-dependent ubiquinone reduction activity and are required for growth on sulfide. In contrast to CT0117 and CT0876, transcripts of CT1087 were detected only when cells actively oxidized sulfide. Mutation of CT0117 or CT1087 in C. tepidum decreased SQR activity in membrane fractions, and the CT1087 mutant could not grow with >or=6 mM sulfide. Mutation of both CT0117 and CT1087 in C. tepidum completely abolished SQR activity, and the double mutant failed to grow with >or=4 mM sulfide. A C-terminal His(6)-tagged CT1087 protein was membrane localized, as was SQR activity. Epitope-tagged CT1087 was detected only when sulfide was actively consumed by cells. Recombinantly produced CT1087 and CT0117 proteins had SQR activity, while CT0876 did not. In summary, we conclude that, under the conditions tested, both CT0117 and CT1087 function as SQR proteins in C. tepidum. CT0876 may support the growth of C. tepidum at low sulfide concentrations, but no evidence was found for SQR activity associated with this protein.

  2. The mechanism of catalysis by type-II NADH:quinone oxidoreductases

    PubMed Central

    Blaza, James N.; Bridges, Hannah R.; Aragão, David; Dunn, Elyse A.; Heikal, Adam; Cook, Gregory M.; Nakatani, Yoshio; Hirst, Judy

    2017-01-01

    Type II NADH:quinone oxidoreductase (NDH-2) is central to the respiratory chains of many organisms. It is not present in mammals so may be exploited as an antimicrobial drug target or used as a substitute for dysfunctional respiratory complex I in neuromuscular disorders. NDH-2 is a single-subunit monotopic membrane protein with just a flavin cofactor, yet no consensus exists on its mechanism. Here, we use steady-state and pre-steady-state kinetics combined with mutagenesis and structural studies to determine the mechanism of NDH-2 from Caldalkalibacillus thermarum. We show that the two substrate reactions occur independently, at different sites, and regardless of the occupancy of the partner site. We conclude that the reaction pathway is determined stochastically, by the substrate/product concentrations and dissociation constants, and can follow either a ping-pong or ternary mechanism. This mechanistic versatility provides a unified explanation for all extant data and a new foundation for the development of therapeutic strategies. PMID:28067272

  3. NADPH:Quinone Oxidoreductase 1 Regulates Host Susceptibility to Ozone via Isoprostane Generation*

    PubMed Central

    Kummarapurugu, Apparao B.; Fischer, Bernard M.; Zheng, Shuo; Milne, Ginger L.; Ghio, Andrew J.; Potts-Kant, Erin N.; Foster, W. Michael; Soderblom, Erik J.; Dubois, Laura G.; Moseley, M. Arthur; Thompson, J. Will; Voynow, Judith A.

    2013-01-01

    NADPH:quinone oxidoreductase 1 (NQO1) is recognized as a major susceptibility gene for ozone-induced pulmonary toxicity. In the absence of NQO1 as can occur by genetic mutation, the human airway is protected from harmful effects of ozone. We recently reported that NQO1-null mice are protected from airway hyperresponsiveness and pulmonary inflammation following ozone exposure. However, NQO1 regenerates intracellular antioxidants and therefore should protect the individual from oxidative stress. To explain this paradox, we tested whether in the absence of NQO1 ozone exposure results in increased generation of A2-isoprostane, a cyclopentenone isoprostane that blunts inflammation. Using GC-MS, we found that NQO1-null mice had greater lung tissue levels of D2- and E2-isoprostanes, the precursors of J2- and A2-isoprostanes, both at base line and following ozone exposure compared with congenic wild-type mice. We confirmed in primary cultures of normal human bronchial epithelial cells that A2-isoprostane inhibited ozone-induced NF-κB activation and IL-8 regulation. Furthermore, we determined that A2-isoprostane covalently modified the active Cys179 domain in inhibitory κB kinase in the presence of ozone in vitro, thus establishing the biochemical basis for A2-isoprostane inhibition of NF-κB. Our results demonstrate that host factors may regulate pulmonary susceptibility to ozone by regulating the generation of A2-isoprostanes in the lung. These observations provide the biochemical basis for the epidemiologic observation that NQO1 regulates pulmonary susceptibility to ozone. PMID:23275341

  4. NADPH:quinone oxidoreductase 1 regulates host susceptibility to ozone via isoprostane generation.

    PubMed

    Kummarapurugu, Apparao B; Fischer, Bernard M; Zheng, Shuo; Milne, Ginger L; Ghio, Andrew J; Potts-Kant, Erin N; Foster, W Michael; Soderblom, Erik J; Dubois, Laura G; Moseley, M Arthur; Thompson, J Will; Voynow, Judith A

    2013-02-15

    NADPH:quinone oxidoreductase 1 (NQO1) is recognized as a major susceptibility gene for ozone-induced pulmonary toxicity. In the absence of NQO1 as can occur by genetic mutation, the human airway is protected from harmful effects of ozone. We recently reported that NQO1-null mice are protected from airway hyperresponsiveness and pulmonary inflammation following ozone exposure. However, NQO1 regenerates intracellular antioxidants and therefore should protect the individual from oxidative stress. To explain this paradox, we tested whether in the absence of NQO1 ozone exposure results in increased generation of A(2)-isoprostane, a cyclopentenone isoprostane that blunts inflammation. Using GC-MS, we found that NQO1-null mice had greater lung tissue levels of D(2)- and E(2)-isoprostanes, the precursors of J(2)- and A(2)-isoprostanes, both at base line and following ozone exposure compared with congenic wild-type mice. We confirmed in primary cultures of normal human bronchial epithelial cells that A(2)-isoprostane inhibited ozone-induced NF-κB activation and IL-8 regulation. Furthermore, we determined that A(2)-isoprostane covalently modified the active Cys(179) domain in inhibitory κB kinase in the presence of ozone in vitro, thus establishing the biochemical basis for A(2)-isoprostane inhibition of NF-κB. Our results demonstrate that host factors may regulate pulmonary susceptibility to ozone by regulating the generation of A(2)-isoprostanes in the lung. These observations provide the biochemical basis for the epidemiologic observation that NQO1 regulates pulmonary susceptibility to ozone.

  5. NAD(P)H quinone oxidoreductase 1 regulates neutrophil elastase-induced mucous cell metaplasia

    PubMed Central

    Meyer, Marisa L.; Potts-Kant, Erin N.; Ghio, Andrew J.; Fischer, Bernard M.; Foster, W. Michael

    2012-01-01

    Mucous cell metaplasia (MCM) and neutrophil-predominant airway inflammation are pathological features of chronic inflammatory airway diseases. A signature feature of MCM is increased expression of a major respiratory tract mucin, MUC5AC. Neutrophil elastase (NE) upregulates MUC5AC in primary airway epithelial cells by generating reactive oxygen species, and this response is due in part to upregulation of NADPH quinone oxidoreductase 1 (NQO1) activity. Delivery of NE directly to the airway triggers inflammation and MCM and increases synthesis and secretion of MUC5AC protein from airway epithelial cells. We hypothesized that NE-induced MCM is mediated in vivo by NQO1. Male wild-type and Nqo1-null mice (C57BL/6 background) were exposed to human NE (50 μg) or vehicle via oropharyngeal aspiration on days 1, 4, and 7. On days 8 and 11, lung tissues and bronchoalveolar lavage (BAL) samples were obtained and evaluated for MCM, inflammation, and oxidative stress. MCM, inflammation, and production of specific cytokines, granulocyte-macrophage colony-stimulating factor, macrophage inflammatory protein-2, interleukin-4, and interleukin-5 were diminished in NE-treated Nqo1-null mice compared with NE-treated wild-type mice. However, in contrast to the role of NQO1 in vitro, we demonstrate that NE-treated Nqo1-null mice had greater levels of BAL and lung tissue lipid carbonyls and greater BAL iron on day 11, all consistent with increased oxidative stress. NQO1 is required for NE-induced inflammation and MCM. This model system demonstrates that NE-induced MCM directly correlates with inflammation, but not with oxidative stress. PMID:22659878

  6. Exogenous methyl jasmonate treatment increases glucosinolate biosynthesis and quinone reductase activity in kale leaf tissue.

    PubMed

    Ku, Kang-Mo; Jeffery, Elizabeth H; Juvik, John A

    2014-01-01

    Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties 'Dwarf Blue Curled Vates' and 'Red Winter' in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar 'Red Winter' in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r = 0.800, P<0.001). Concentrations required to double the specific QR activity (CD values) of I3C was calculated at 230 µM, which is considerably weaker at induction than other isothiocyanates like sulforphane. To confirm relationships between GS hydrolysis products and QR activity, a range of concentrations of MeJA sprays were applied to kale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to combined

  7. Induction of immunogenic cell death of tumors by newly synthesized heterocyclic quinone derivative

    PubMed Central

    Ryu, Chung-Kyu; Lee, Seog Jae; Kim, Ho Jeong

    2017-01-01

    Many cancer types are serious diseases causing mortality, and new therapeutics with improved efficacy and safety are required. Immuno-(cell)-therapy is considered as one of the promising therapeutic strategies for curing intractable cancer. In this study, we tested R2016, a newly developed heterocyclic quinone derivative, for induction of immunogenic tumor cell death and as a possible novel immunochemotherapeutic. We studied the anti-cancer effects of R2016 against LLC, a lung cancer cell line and B16F10, a melanoma cell line. LLC (non-immunogenic) and B16F10 (immunogenic) cells were killed by R2016 in dose-dependent manner. R2016 reduced the viability of both LLC and B16F10 tumor cells by inducing apoptosis and necrosis, while it demonstrated no cytotoxicity against normal splenocytes. Expression of immunogenic death markers on the cell surface of R2016 treated tumor cells including calreticulin (CRT) and heat shock proteins (HSPs) was increased along with the induction of their genes. Increased CRT expression correlated with dendritic cell (DC) uptake of dying tumor cells: the proportion of CRT+CD11c+cells was increased in the R2016-treated group. The gene transcription of Calr3, Hspb1, and Tnfaip6, which are related to immunogenicity induction of dead cells, was up-regulated in the R2016 treated tumor cells. On the other hand, ANGPT1, FGF7, and URGCP gene levels were down-regulated by R2016 treatment. This data suggests that R2016 induced immunogenic tumor cell death, and suggests R2016 as an effective anti-tumor immunochemotherapeutic modality. PMID:28282460

  8. Anaerobic Mineralization of Toluene by Enriched Sediments with Quinones and Humus as Terminal Electron Acceptors

    PubMed Central

    Cervantes, Francisco J.; Dijksma, Wouter; Duong-Dac, Tuan; Ivanova, Anna; Lettinga, Gatze; Field, Jim A.

    2001-01-01

    The anaerobic microbial oxidation of toluene to CO2 coupled to humus respiration was demonstrated by use of enriched anaerobic sediments from the Amsterdam petroleum harbor (APH) and the Rhine River. Both highly purified soil humic acids (HPSHA) and the humic quinone moiety model compound anthraquinone-2,6-disulfonate (AQDS) were utilized as terminal electron acceptors. After 2 weeks of incubation, 50 and 85% of added uniformly labeled [13C]toluene were recovered as 13CO2 in HPSHA- and AQDS-supplemented APH sediment enrichment cultures, respectively; negligible recovery occurred in unsupplemented cultures. The conversion of [13C]toluene agreed with the high level of recovery of electrons as reduced humus or as anthrahydroquinone-2,6-disulfonate. APH sediment was also able to use nitrate and amorphous manganese dioxide as terminal electron acceptors to support the anaerobic biodegradation of toluene. The addition of substoichiometric amounts of humic acids to bioassay reaction mixtures containing amorphous ferric oxyhydroxide as a terminal electron acceptor led to more than 65% conversion of toluene (1 mM) after 11 weeks of incubation, a result which paralleled the partial recovery of electron equivalents as acid-extractable Fe(II). Negligible conversion of toluene and reduction of Fe(III) occurred in these bioassay reaction mixtures when humic acids were omitted. The present study provides clear quantitative evidence for the mineralization of an aromatic hydrocarbon by humus-respiring microorganisms. The results indicate that humic substances may significantly contribute to the intrinsic bioremediation of anaerobic sites contaminated with priority pollutants by serving as terminal electron acceptors. PMID:11571145

  9. Induction of immunogenic cell death of tumors by newly synthesized heterocyclic quinone derivative.

    PubMed

    Son, Keum-Joo; Choi, Ki Ryung; Ryu, Chung-Kyu; Lee, Seog Jae; Kim, Ho Jeong; Lee, Hyunah

    2017-01-01

    Many cancer types are serious diseases causing mortality, and new therapeutics with improved efficacy and safety are required. Immuno-(cell)-therapy is considered as one of the promising therapeutic strategies for curing intractable cancer. In this study, we tested R2016, a newly developed heterocyclic quinone derivative, for induction of immunogenic tumor cell death and as a possible novel immunochemotherapeutic. We studied the anti-cancer effects of R2016 against LLC, a lung cancer cell line and B16F10, a melanoma cell line. LLC (non-immunogenic) and B16F10 (immunogenic) cells were killed by R2016 in dose-dependent manner. R2016 reduced the viability of both LLC and B16F10 tumor cells by inducing apoptosis and necrosis, while it demonstrated no cytotoxicity against normal splenocytes. Expression of immunogenic death markers on the cell surface of R2016 treated tumor cells including calreticulin (CRT) and heat shock proteins (HSPs) was increased along with the induction of their genes. Increased CRT expression correlated with dendritic cell (DC) uptake of dying tumor cells: the proportion of CRT+CD11c+cells was increased in the R2016-treated group. The gene transcription of Calr3, Hspb1, and Tnfaip6, which are related to immunogenicity induction of dead cells, was up-regulated in the R2016 treated tumor cells. On the other hand, ANGPT1, FGF7, and URGCP gene levels were down-regulated by R2016 treatment. This data suggests that R2016 induced immunogenic tumor cell death, and suggests R2016 as an effective anti-tumor immunochemotherapeutic modality.

  10. Altering Pyrroloquinoline Quinone Nutritional Status Modulates Mitochondrial, Lipid, and Energy Metabolism in Rats

    PubMed Central

    Bauerly, Kathryn; Harris, Calliandra; Chowanadisai, Winyoo; Graham, James; Havel, Peter J.; Tchaparian, Eskouhie; Satre, Mike; Karliner, Joel S.; Rucker, Robert B.

    2011-01-01

    We have reported that pyrroloquinoline quinone (PQQ) improves reproduction, neonatal development, and mitochondrial function in animals by mechanisms that involve mitochondrial related cell signaling pathways. To extend these observations, the influence of PQQ on energy and lipid relationships and apparent protection against ischemia reperfusion injury are described herein. Sprague-Dawley rats were fed a nutritionally complete diet with PQQ added at either 0 (PQQ−) or 2 mg PQQ/Kg diet (PQQ+). Measurements included: 1) serum glucose and insulin, 2) total energy expenditure per metabolic body size (Wt3/4), 3) respiratory quotients (in the fed and fasted states), 4) changes in plasma lipids, 5) the relative mitochondrial amount in liver and heart, and 6) indices related to cardiac ischemia. For the latter, rats (PQQ− or PQQ+) were subjected to left anterior descending occlusions followed by 2 h of reperfusion to determine PQQ's influence on infarct size and myocardial tissue levels of malondialdehyde, an indicator of lipid peroxidation. Although no striking differences in serum glucose, insulin, and free fatty acid levels were observed, energy expenditure was lower in PQQ− vs. PQQ+ rats and energy expenditure (fed state) was correlated with the hepatic mitochondrial content. Elevations in plasma di- and triacylglyceride and β-hydroxybutryic acid concentrations were also observed in PQQ− rats vs. PQQ+ rats. Moreover, PQQ administration (i.p. at 4.5 mg/kg BW for 3 days) resulted in a greater than 2-fold decrease in plasma triglycerides during a 6-hour fast than saline administration in a rat model of type 2 diabetes. Cardiac injury resulting from ischemia/reperfusion was more pronounced in PQQ− rats than in PQQ+ rats. Collectively, these data demonstrate that PQQ deficiency impacts a number of parameters related to normal mitochondrial function. PMID:21814553

  11. Crystal Structure and Function of PqqF Protein in the Pyrroloquinoline Quinone Biosynthetic Pathway*

    PubMed Central

    Wei, Qiaoe; Ran, Tingting; Ma, Chencui; He, Jianhua; Xu, Dongqing; Wang, Weiwu

    2016-01-01

    Pyrroloquinoline quinone (PQQ) has received considerable attention due to its numerous important physiological functions. PqqA is a precursor peptide of PQQ with two conserved residues: glutamate and tyrosine. After linkage of the Cγ of glutamate and Cϵ of tyrosine by PqqE, these two residues are hypothesized to be cleaved from PqqA by PqqF. The linked glutamate and tyrosine residues are then used to synthesize PQQ. Here, we demonstrated that the pqqF gene is essential for PQQ biosynthesis as deletion of it eliminated the inhibition of prodigiosin production by glucose. We further determined the crystal structure of PqqF, which has a closed clamshell-like shape. The PqqF consists of two halves composed of an N- and a C-terminal lobe. The PqqF-N and PqqF-C lobes form a chamber with the volume of the cavity of ∼9400 Å3. The PqqF structure conforms to the general structure of inverzincins. Compared with the most thoroughly characterized inverzincin insulin-degrading enzyme, the size of PqqF chamber is markedly smaller, which may define the specificity for its substrate PqqA. Furthermore, the 14-amino acid-residue-long tag formed by the N-terminal tag from expression vector precisely protrudes into the counterpart active site; this N-terminal tag occupies the active site and stabilizes the closed, inactive conformation. His-48, His-52, Glu-129 and His-14 from the N-terminal tag coordinate with the zinc ion. Glu-51 acts as a base catalyst. The observed histidine residue-mediated inhibition may be applicable for the design of a peptide for the inhibition of M16 metalloproteases. PMID:27231346

  12. A Novel Pyrroloquinoline Quinone-Dependent 2-Keto-d-Glucose Dehydrogenase from Pseudomonas aureofaciens

    PubMed Central

    Umezawa, Kiwamu; Takeda, Kouta; Ishida, Takuya; Sunagawa, Naoki; Makabe, Akiko; Isobe, Kazuo; Koba, Keisuke; Ohno, Hiroyuki; Samejima, Masahiro; Nakamura, Nobuhumi; Igarashi, Kiyohiko

    2015-01-01

    A gene encoding an enzyme similar to a pyrroloquinoline quinone (PQQ)-dependent sugar dehydrogenase from filamentous fungi, which belongs to new auxiliary activities (AA) family 12 in the CAZy database, was cloned from Pseudomonas aureofaciens. The deduced amino acid sequence of the cloned enzyme showed only low homology to previously characterized PQQ-dependent enzymes, and multiple-sequence alignment analysis showed that the enzyme lacks one of the three conserved arginine residues that function as PQQ-binding residues in known PQQ-dependent enzymes. The recombinant enzyme was heterologously expressed in an Escherichia coli expression system for further characterization. The UV-visible (UV-Vis) absorption spectrum of the oxidized form of the holoenzyme, prepared by incubating the apoenzyme with PQQ and CaCl2, revealed a broad peak at approximately 350 nm, indicating that the enzyme binds PQQ. With the addition of 2-keto-d-glucose (2KG) to the holoenzyme solution, a sharp peak appeared at 331 nm, attributed to the reduction of PQQ bound to the enzyme, whereas no effect was observed upon 2KG addition to authentic PQQ. Enzymatic assay showed that the recombinant enzyme specifically reacted with 2KG in the presence of an appropriate electron acceptor, such as 2,6-dichlorophenol indophenol, when PQQ and CaCl2 were added. 1H nuclear magnetic resonance (1H-NMR) analysis of reaction products revealed 2-keto-d-gluconic acid (2KGA) as the main product, clearly indicating that the recombinant enzyme oxidizes the C-1 position of 2KG. Therefore, the enzyme was identified as a PQQ-dependent 2KG dehydrogenase (Pa2KGDH). Considering the high substrate specificity, the physiological function of Pa2KGDH may be for production of 2KGA. PMID:25645559

  13. Pyrroloquinoline quinone protects mouse brain endothelial cells from high glucose-induced damage in vitro

    PubMed Central

    Wang, Zhong; Chen, Guo-qiang; Yu, Gui-ping; Liu, Chang-jian

    2014-01-01

    Aim: To investigate the effects of pyrroloquinoline quinone (PQQ), an oxidoreductase cofactor, on high glucose-induced mouse endothelial cell damage in vitro. Methods: Mouse brain microvascular endothelial bEND.3 cells were exposed to different glucose concentrations (5.56, 25 and 40 mmol/L) for 24 or 48 h. The cell viability was examined using MTT assay. Flow cytometry was used to analyze the apoptosis and ROS levels in the cells. MitoTracker Green staining was used to examine the mitochondria numbers in the cells. Western blot analysis was used to analyze the expression of HIF-1α and the proteins in JNK pathway. Results: Treatment of bEND.3 cells with high glucose significantly decreased the cell viability, while addition of PQQ (1 and 10 μmol/L) reversed the high glucose-induced cell damage in a concentration-dependent manner. Furthermore, PQQ (100 μmol/L) significantly suppressed the high glucose-induced apoptosis and ROS production in the cells. PQQ significantly reversed the high glucose-induced reduction in both the mitochondrial membrane potential and mitochondria number in the cells. The high glucose treatment significantly increased the expression of HIF-1α and JNK phosphorylation in the cells, and addition of PQQ led to a further increase of HIF-1α level and a decrease of JNK phosphorylation. Addition of JNK inhibitor SP600125 (10 μmol/L) also significantly suppressed high glucose-induced apoptosis and JNK phosphorylation in bEND.3 cells. Conclusion: PQQ protects mouse brain endothelial cells from high glucose damage in vitro by suppressing intracellular ROS and apoptosis via inhibiting JNK signaling pathway. PMID:25283505

  14. Neuroprotection by pyrroloquinoline quinone (PQQ) in reversible middle cerebral artery occlusion in the adult rat.

    PubMed

    Zhang, Yonghua; Feustel, Paul J; Kimelberg, Harold K

    2006-06-13

    Pyrroloquinoline quinone (PQQ) is a naturally occurring redox cofactor that acts as an essential nutrient, antioxidant, and redox modulator. It has previously been reported to reduce infarct size in 7-day-old rat pups with an in vivo cerebral hypoxia/ischemia model (Jensen et al., 1994). In this study, we tested whether improvement is found in both behavioral measures of protection and by histological measures of infarcted tissue at 72 h after reversible middle cerebral artery occlusion (rMCAo) in adult rats. Two-hour rMCAo was induced in adult rats using the intraluminal suture technique. PQQ (10, 3, and 1 mg/kg) was given once by intravenous injection at the initiation, or 3 h after the initiation, of 2 h rMCAo. Neurobehavioral deficits were evaluated daily for 3 days followed by infarct volumes measurements by 2,3,5-triphenyltetrazolium chloride (TTC) staining. PQQ at 10 mg/kg infused at the initiation, or 3 h after the initiation, of rMCAo was effective in reducing cerebral infarct volumes measured 72 h later. At 3 h after ischemia, a dose of 3 mg/kg significantly reduced infarct volume compared to vehicle-treated animals, but 1 mg/kg was ineffective. Neurobehavioral scores were also significantly better in the PQQ-treated group compared to the vehicle controls when PQQ was given at 10 and 3 mg/kg, but not at 1 mg/kg. Thus, PQQ is neuroprotective when given as a single administration at least 3 h after initiation of rMCAo. These data indicate that PQQ may be a useful neuroprotectant in stroke therapy.

  15. Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects.

    PubMed

    Harris, Calliandra B; Chowanadisai, Winyoo; Mishchuk, Darya O; Satre, Mike A; Slupsky, Carolyn M; Rucker, Robert B

    2013-12-01

    Pyrroloquinoline quinone (PQQ) influences energy-related metabolism and neurologic functions in animals. The mechanism of action involves interactions with cell signaling pathways and mitochondrial function. However, little is known about the response to PQQ in humans. Using a crossover study design, 10 subjects (5 females, 5 males) ingested PQQ added to a fruit-flavored drink in two separate studies. In study 1, PQQ was given in a single dose (0.2 mg PQQ/kg). Multiple measurements of plasma and urine PQQ levels and changes in antioxidant potential [based on total peroxyl radical-trapping potential and thiobarbituric acid reactive product (TBAR) assays] were made throughout the period of 48 h. In study 2, PQQ was administered as a daily dose (0.3 mg PQQ/kg). After 76 h, measurements included indices of inflammation [plasma C-reactive protein, interleukin (IL)-6 levels], standard clinical indices (e.g., cholesterol, glucose, high-density lipoprotein, low-density lipoprotein, triglycerides, etc.) and (1)H-nuclear magnetic resonance estimates of urinary metabolites related in part to oxidative metabolism. The standard clinical indices were normal and not altered by PQQ supplementation. However, dietary PQQ exposure (Study 1) resulted in apparent changes in antioxidant potential based on malonaldehyde-related TBAR assessments. In Study 2, PQQ supplementation resulted in significant decreases in the levels of plasma C-reactive protein, IL-6 and urinary methylated amines such as trimethylamine N-oxide, and changes in urinary metabolites consistent with enhanced mitochondria-related functions. The data are among the first to link systemic effects of PQQ in animals to corresponding effects in humans. © 2013.

  16. Binding of DNA-Intercalating Agents to Oxidized and Reduced Quinone Reductase 2.

    PubMed

    Leung, Kevin K K; Shilton, Brian H

    2015-12-29

    Quinone reductase 2 (NQO2) is an enzyme that might have intracellular signaling functions. NQO2 can exist in either an oxidized state or a reduced state, and binding of compounds to one or both of these states inhibits enzymatic activity and could also affect intracellular signaling. A wide range of planar aromatic compounds bind NQO2, and we have identified three DNA-intercalating agents [ethidium bromide, acridine orange (AO), and doxorubicin] as novel nanomolar inhibitors of NQO2. Ethidium and AO, which carry a positive charge in their aromatic ring systems, bound reduced NQO2 with an affinity 50-fold higher than that of oxidized NQO2, while doxorubicin bound only oxidized NQO2. Crystallographic analyses of oxidized NQO2 in complex with the inhibitors indicated that the inhibitors were situated deep in the active site. The aromatic faces were sandwiched between the isoalloxazine ring of FAD and the phenyl ring of F178, with their edges making direct contact with residues lining the active site. In reduced NQO2, ethidium and AO occupied a more peripheral position in the active site, allowing several water molecules to interact with the polar end of the negatively charged isoalloxazine ring. We also showed that AO inhibited NQO2 at a nontoxic concentration in cells while ethidium was less effective at inhibiting NQO2 in cells. Together, this study shows that reduced NQO2 has structural and electrostatic properties that yield a preference for binding of planar, aromatic, and positively charged molecules that can also function as DNA-intercalating agents.

  17. Coregulated genes link sulfide:quinone oxidoreductase and arsenic metabolism in Synechocystis sp. strain PCC6803.

    PubMed

    Nagy, Csaba I; Vass, Imre; Rákhely, Gábor; Vass, István Zoltán; Tóth, András; Duzs, Agnes; Peca, Loredana; Kruk, Jerzy; Kós, Péter B

    2014-10-01

    Although the biogeochemistry of the two environmentally hazardous compounds arsenic and sulfide has been extensively investigated, the biological interference of these two toxic but potentially energy-rich compounds has only been hypothesized and indirectly proven. Here we provide direct evidence for the first time that in the photosynthetic model organism Synechocystis sp. strain PCC6803 the two metabolic pathways are linked by coregulated genes that are involved in arsenic transport, sulfide oxidation, and probably in sulfide-based alternative photosynthesis. Although Synechocystis sp. strain PCC6803 is an obligate photoautotrophic cyanobacterium that grows via oxygenic photosynthesis, we discovered that specific genes are activated in the presence of sulfide or arsenite to exploit the energy potentials of these chemicals. These genes form an operon that we termed suoRSCT, located on a transposable element of type IS4 on the plasmid pSYSM of the cyanobacterium. suoS (sll5036) encodes a light-dependent, type I sulfide:quinone oxidoreductase. The suoR (sll5035) gene downstream of suoS encodes a regulatory protein that belongs to the ArsR-type repressors that are normally involved in arsenic resistance. We found that this repressor has dual specificity, resulting in 200-fold induction of the operon upon either arsenite or sulfide exposure. The suoT gene encodes a transmembrane protein similar to chromate transporters but in fact functioning as an arsenite importer at permissive concentrations. We propose that the proteins encoded by the suoRSCT operon might have played an important role under anaerobic, reducing conditions on primordial Earth and that the operon was acquired by the cyanobacterium via horizontal gene transfer. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  18. Identification of a Lactate-Quinone Oxidoreductase in Staphylococcus aureus that is Essential for Virulence

    PubMed Central

    Fuller, James R.; Vitko, Nicholas P.; Perkowski, Ellen F.; Scott, Eric; Khatri, Dal; Spontak, Jeffrey S.; Thurlow, Lance R.; Richardson, Anthony R.

    2011-01-01

    Staphylococcus aureus is an important human pathogen commonly infecting nearly every host tissue. The ability of S. aureus to resist innate immunity is critical to its success as a pathogen, including its propensity to grow in the presence of host nitric oxide (NO·). Upon exogenous NO· exposure, S. aureus immediately excretes copious amounts of L-lactate to maintain redox balance. However, after prolonged NO·-exposure, S. aureus reassimilates L-lactate specifically and in this work, we identify the enzyme responsible for this L-lactate-consumption as a L-lactate-quinone oxidoreductase (Lqo, SACOL2623). Originally annotated as Mqo2 and thought to oxidize malate, we show that this enzyme exhibits no affinity for malate but reacts specifically with L-lactate (KM = ∼330 μM). In addition to its requirement for reassimilation of L-lactate during NO·-stress, Lqo is also critical to respiratory growth on L-lactate as a sole carbon source. Moreover, Δlqo mutants exhibit attenuation in a murine model of sepsis, particularly in their ability to cause myocarditis. Interestingly, this cardiac-specific attenuation is completely abrogated in mice unable to synthesize inflammatory NO· (iNOS−/−). We demonstrate that S. aureus NO·-resistance is highly dependent on the availability of a glycolytic carbon sources. However, S. aureus can utilize the combination of peptides and L-lactate as carbon sources during NO·-stress in an Lqo-dependent fashion. Murine cardiac tissue has markedly high levels of L-lactate in comparison to renal or hepatic tissue consistent with the NO·-dependent requirement for Lqo in S. aureus myocarditis. Thus, Lqo provides S. aureus with yet another means of replicating in the presence of host NO·. PMID:22919585

  19. The quinone-reactive Ni/Fe-hydrogenase of Wolinella succinogenes.

    PubMed

    Dross, F; Geisler, V; Lenger, R; Theis, F; Krafft, T; Fahrenholz, F; Kojro, E; Duchêne, A; Tripier, D; Juvenal, K

    1992-05-15

    The hydrogenase (Hyd) isolated from the cytoplasmic membrane of Wolinella succinogenes consists of three polypeptides (HydA, HydB and HydC) and contains cytochrome b (6.4 mumol/g protein), which was reduced upon the addition of H2. The enzyme catalyzed the reduction of 2,3-dimethyl-1,4-naphthoquinone with H2, in contrast to an earlier preparation which was made up of HydA and HydB only and did not contain cytochrome b (Unden, G., Böcher, R., Knecht, J. & Kröger, A. (1982) FEBS Lett. 145, 230-234). This suggests that HydC is a cytochrome b which serves as a mediator in the electron transfer from H2 to the quinone. The hydrogenase genes were cloned, sequenced and identified by sequence comparison with the N-termini of the three subunits. The three genes were arranged in the order hydA, hydB, hydC, with the transcription start site in front of hydA, and were present only once on the genome. Separated by an intergene region of 69 nucleotides, hydC was followed by at least two more open reading frames of unknown function. The amino acid sequences derived from hydA, hydB and hydC were similar to those of the membrane Ni-hydrogenases of seven other bacteria. HydA and HydB also showed similarity to the small and the large subunits of periplasmic Ni-hydrogenases. HydC was predicted to contain four hydrophobic segments which might span the bacterial membrane. Two histidine residues located in hydrophobic segments are conserved in the corresponding sequences of the other membrane hydrogenases and might ligate the haem B.

  20. Water oxidation chemistry of a synthetic dinuclear ruthenium complex containing redox-active quinone ligands.

    PubMed

    Isobe, Hiroshi; Tanaka, Koji; Shen, Jian-Ren; Yamaguchi, Kizashi

    2014-04-21

    We investigated theoretically the catalytic mechanism of electrochemical water oxidation in aqueous solution by a dinuclear ruthenium complex containing redox-active quinone ligands, [Ru2(X)(Y)(3,6-tBu2Q)2(btpyan)](m+) [X, Y = H2O, OH, O, O2; 3,6-tBu2Q = 3,6-di-tert-butyl-1,2-benzoquinone; btpyan =1,8-bis(2,2':6',2″-terpyrid-4'-yl)anthracene] (m = 2, 3, 4) (1). The reaction involves a series of electron and proton transfers to achieve redox leveling, with intervening chemical transformations in a mesh scheme, and the entire molecular structure and motion of the catalyst 1 work together to drive the catalytic cycle for water oxidation. Two substrate water molecules can bind to 1 with simultaneous loss of one or two proton(s), which allows pH-dependent variability in the proportion of substrate-bound structures and following pathways for oxidative activation of the aqua/hydroxo ligands at low thermodynamic and kinetic costs. The resulting bis-oxo intermediates then undergo endothermic O-O radical coupling between two Ru(III)-O(•) units in an anti-coplanar conformation leading to bridged μ-peroxo or μ-superoxo intermediates. The μ-superoxo species can liberate oxygen with the necessity for the preceding binding of a water molecule, which is possible only after four-electron oxidation is completed. The magnitude of catalytic current would be limited by the inherent sluggishness of the hinge-like bending motion of the bridged μ-superoxo complex that opens up the compact, hydrophobic active site of the catalyst and thereby allows water entry under dynamic conditions. On the basis of a newly proposed mechanism, we rationalize the experimentally observed behavior of electrode kinetics with respect to potential and discuss what causes a high overpotential for water oxidation by 1.

  1. Mitochondrial NADH-quinone oxidoreductase of the outer membrane is responsible for paraquat cytotoxicity in rat livers.

    PubMed

    Shimada, H; Hirai, K; Simamura, E; Pan, J

    1998-03-01

    We investigated the existence of an NADH-dependent paraquat (PQ) reduction system in rat liver mitochondria (Mt) in respect to the cytotoxic mechanisms of PQ. The outer membrane fractions, free from the contamination of inner membranes but with a few microsomes, catalyzed rotenone-insensitive NADH, but not NADPH, oxidation by menadione or PQ. Anti-NADH-cytochrome b5 reductase antibody and its inhibitor p-hydroxymercuribenzonate did not inhibit the NADH-PQ reduction activity. Therefore, the respiratory systems of the inner membranes and microsomal cytochrome P450 systems could not have been responsible for the reaction. Dicoumarol, an inhibitor of NAD(P)H-quinone oxidoreductase (NQO), dose dependently suppressed the NADH oxidation in the outer membrane via PQ as well as menadione, with I50 values of 190 (for menadione) and 150 microM (for PQ). Because of a lower sensitivity to NADPH and the higher doses of dicoumarol required for its inhibition, the activity in the outer membrane may be an "NADH-quinone oxidoreductase" which partly differs from the NQO previously reported. This outer membrane enzyme produced superoxide anions in the presence of both NADH and PQ and was too tightly membrane-bound to be extracted by Triton X-100 and deoxycholate. From these results, we concluded that the free radical-producing mitochondrial NADH-quinone oxidoreductase is a novel oxidation-reduction system participating in PQ toxicity. This is in good agreement with our previous results showing that PQ selectively damaged Mt in vivo and in vitro, resulting in cell death (K.-I. Hirai et al., 1992, Toxicology 72, 1-16).

  2. Quinone Reduction by the Na+-Translocating NADH Dehydrogenase Promotes Extracellular Superoxide Production in Vibrio cholerae▿ †

    PubMed Central

    Lin, Po-Chi; Türk, Karin; Häse, Claudia C.; Fritz, Günter; Steuber, Julia

    2007-01-01

    The pathogenicity of Vibrio cholerae is influenced by sodium ions which are actively extruded from the cell by the Na+-translocating NADH:quinone oxidoreductase (Na+-NQR). To study the function of the Na+-NQR in the respiratory chain of V. cholerae, we examined the formation of organic radicals and superoxide in a wild-type strain and a mutant strain lacking the Na+-NQR. Upon reduction with NADH, an organic radical was detected in native membranes by electron paramagnetic resonance spectroscopy which was assigned to ubisemiquinones generated by the Na+-NQR. The radical concentration increased from 0.2 mM at 0.08 mM Na+ to 0.4 mM at 14.7 mM Na+, indicating that the concentration of the coupling cation influences the redox state of the quinone pool in V. cholerae membranes. During respiration, V. cholerae cells produced extracellular superoxide with a specific activity of 10.2 nmol min−1 mg−1 in the wild type compared to 3.1 nmol min−1 mg−1 in the NQR deletion strain. Raising the Na+ concentration from 0.1 to 5 mM increased the rate of superoxide formation in the wild-type V. cholerae strain by at least 70%. Rates of respiratory H2O2 formation by wild-type V. cholerae cells (30.9 nmol min−1 mg−1) were threefold higher than rates observed with the mutant strain lacking the Na+-NQR (9.7 nmol min−1 mg−1). Our study shows that environmental Na+ could stimulate ubisemiquinone formation by the Na+-NQR and hereby enhance the production of reactive oxygen species formed during the autoxidation of reduced quinones. PMID:17322313

  3. Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2

    PubMed Central

    CALAMINI, Barbara; SANTARSIERO, Bernard D.; BOUTIN, Jean A.; MESECAR, Andrew D.

    2011-01-01

    Melatonin exerts its biological effects through at least two transmembrane G-protein-coupled receptors, MT1 and MT2, and a lower-affinity cytosolic binding site, designated MT3. MT3 has recently been identified as QR2 (quinone reductase 2) (EC 1.10.99.2) which is of significance since it links the antioxidant effects of melatonin to a mechanism of action. Initially, QR2 was believed to function analogously to QR1 in protecting cells from highly reactive quinones. However, recent studies indicate that QR2 may actually transform certain quinone substrates into more highly reactive compounds capable of causing cellular damage. Therefore it is hypothesized that inhibition of QR2 in certain cases may lead to protection of cells against these highly reactive species. Since melatonin is known to inhibit QR2 activity, but its binding site and mode of inhibition are not known, we determined the mechanism of inhibition of QR2 by melatonin and a series of melatonin and 5-hydroxytryptamine (serotonin) analogues, and we determined the X-ray structures of melatonin and 2-iodomelatonin in complex with QR2 to between 1.5 and 1.8 Å (1 Å =0.1 nm) resolution. Finally, the thermodynamic binding constants for melatonin and 2-iodomelatonin were determined by ITC (isothermal titration calorimetry). The kinetic results indicate that melatonin is a competitive inhibitor against N-methyldihydronicotinamide (Ki = 7.2 μM) and uncompetitive against menadione (Ki = 92 μM), and the X-ray structures shows that melatonin binds in multiple orientations within the active sites of the QR2 dimer as opposed to an allosteric site. These results provide new insights into the binding mechanisms of melatonin and analogues to QR2. PMID:18254726

  4. Kinetic, thermodynamic and X-ray structural insights into the interaction of melatonin and analogues with quinone reductase 2

    SciTech Connect

    Calamini, Barbara; Santarsiero, Bernard D.; Boutin, Jean A.; Mesecar, Andrew D.

    2008-09-12

    Melatonin exerts its biological effects through at least two transmembrane G-protein-coupled receptors, MT1 and MT2, and a lower-affinity cytosolic binding site, designated MT3. MT3 has recently been identified as QR2 (quinone reductase 2) (EC 1.10.99.2) which is of significance since it links the antioxidant effects of melatonin to a mechanism of action. Initially, QR2 was believed to function analogously to QR1 in protecting cells from highly reactive quinones. However, recent studies indicate that QR2 may actually transform certain quinone substrates into more highly reactive compounds capable of causing cellular damage. Therefore it is hypothesized that inhibition of QR2 in certain cases may lead to protection of cells against these highly reactive species. Since melatonin is known to inhibit QR2 activity, but its binding site and mode of inhibition are not known, we determined the mechanism of inhibition of QR2 by melatonin and a series of melatonin and 5-hydroxytryptamine (serotonin) analogues, and we determined the X-ray structures of melatonin and 2-iodomelatonin in complex with QR2 to between 1.5 and 1.8 {angstrom} (1 {angstrom} = 0.1 nm) resolution. Finally, the thermodynamic binding constants for melatonin and 2-iodomelatonin were determined by ITC (isothermal titration calorimetry). The kinetic results indicate that melatonin is a competitive inhibitor against N-methyldihydronicotinamide (K{sub i} = 7.2 {mu}M) and uncompetitive against menadione (K{sub i} = 92 {mu}M), and the X-ray structures shows that melatonin binds in multiple orientations within the active sites of the QR2 dimer as opposed to an allosteric site. These results provide new insights into the binding mechanisms of melatonin and analogues to QR2.

  5. The Three-Dimensional Structure of NAD(P)H:Quinone Reductase, a Flavoprotein Involved in Cancer Chemoprotection and Chemotherapy: Mechanism of the Two-Electron Reduction

    NASA Astrophysics Data System (ADS)

    Li, Rongbao; Bianchet, Mario A.; Talalay, Paul; Amzel, L. Mario

    1995-09-01

    Quinone reductase [NAD(P)H:(quinone acceptor) oxidoreductase, EC 1.6.99.2], also called DT diaphorase, is a homodimeric FAD-containing enzyme that catalyzes obligatory NAD(P)H-dependent two-electron reductions of quinones and protects cells against the toxic and neoplastic effects of free radicals and reactive oxygen species arising from one-electron reductions. These two-electron reductions participate in the reductive bioactivation of cancer chemotherapeutic agents such as mitomycin C in tumor cells. Thus, surprisingly, the same enzymatic reaction that protects normal cells activates cytotoxic drugs used in cancer chemotherapy. The 2.1-Å crystal structure of rat liver quinone reductase reveals that the folding of a portion of each monomer is similar to that of flavodoxin, a bacterial FMN-containing protein. Two additional portions of the polypeptide chains are involved in dimerization and in formation of the two identical catalytic sites to which both monomers contribute. The crystallographic structures of two FAD-containing enzyme complexes (one containing NADP^+, the other containing duroquinone) suggest that direct hydride transfers from NAD(P)H to FAD and from FADH_2 to the quinone [which occupies the site vacated by NAD(P)H] provide a simple rationale for the obligatory two-electron reductions involving a ping-pong mechanism.

  6. Biphasic Kinetic Behavior of E. coli WrbA, an FMN-Dependent NAD(P)H:Quinone Oxidoreductase

    PubMed Central

    Kishko, Iryna; Harish, Balasubramanian; Zayats, Vasilina; Reha, David; Tenner, Brian; Beri, Dhananjay; Gustavsson, Tobias; Ettrich, Rüdiger; Carey, Jannette

    2012-01-01

    The E. coli protein WrbA is an FMN-dependent NAD(P)H:quinone oxidoreductase that has been implicated in oxidative defense. Three subunits of the tetrameric enzyme contribute to each of four identical, cavernous active sites that appear to accommodate NAD(P)H or various quinones, but not simultaneously, suggesting an obligate tetramer with a ping-pong mechanism in which NAD departs before oxidized quinone binds. The present work was undertaken to evaluate these suggestions and to characterize the kinetic behavior of WrbA. Steady-state kinetics results reveal that WrbA conforms to a ping-pong mechanism with respect to the constancy of the apparent Vmax to Km ratio with substrate concentration. However, the competitive/non-competitive patterns of product inhibition, though consistent with the general class of bi-substrate reactions, do not exclude a minor contribution from additional forms of the enzyme. NMR results support the presence of additional enzyme forms. Docking and energy calculations find that electron-transfer-competent binding sites for NADH and benzoquinone present severe steric overlap, consistent with the ping-pong mechanism. Unexpectedly, plots of initial velocity as a function of either NADH or benzoquinone concentration present one or two Michaelis-Menten phases depending on the temperature at which the enzyme is held prior to assay. The effect of temperature is reversible, suggesting an intramolecular conformational process. WrbA shares these and other details of its kinetic behavior with mammalian DT-diaphorase, an FAD-dependent NAD(P)H:quinone oxidoreductase. An extensive literature review reveals several other enzymes with two-plateau kinetic plots, but in no case has a molecular explanation been elucidated. Preliminary sedimentation velocity analysis of WrbA indicates a large shift in size of the multimer with temperature, suggesting that subunit assembly coupled to substrate binding may underlie the two-plateau behavior. An additional aim of

  7. Biosynthesis of pyrroloquinoline quinone. 1. Identification of biosynthetic precursors using /sup 13/C labeling and NMR spectroscopy

    SciTech Connect

    Houck, D.R.; Hanners, J.L.; Unkefer, C.J.

    1988-09-28

    The biosynthesis of pyrroloquinoline quinone (PQQ) in the methylotropic bacterium methylobacterium AM1 has been investigated using /sup 13/C-labelling of the products and NMR spectroscopy. The data indicated that the quinoline portion of PQQ is formed by a novel condensation of N-1, C-2, -3, and -4 of glutamate with a symmetrical six-carbon ring derived from the shikimate pathway. It is postulated that tyrosine is the shikimate-derived percursor, since pyrrole could be formed by the internal cyclization of the amino acid backbone. 18 references, 2 figures, 2 tables.

  8. Exogenous Methyl Jasmonate Treatment Increases Glucosinolate Biosynthesis and Quinone Reductase Activity in Kale Leaf Tissue

    PubMed Central

    Ku, Kang-Mo; Jeffery, Elizabeth H.; Juvik, John A.

    2014-01-01

    Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties ‘Dwarf Blue Curled Vates’ and ‘Red Winter’ in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar ‘Red Winter’ in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r = 0.800, P<0.001). Concentrations required to double the specific QR activity (CD values) of I3C was calculated at 230 µM, which is considerably weaker at induction than other isothiocyanates like sulforphane. To confirm relationships between GS hydrolysis products and QR activity, a range of concentrations of MeJA sprays were applied to kale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to

  9. Cytoplasmic Localization of Sulfide:Quinone Oxidoreductase and Persulfide Dioxygenase of Cupriavidus pinatubonensis JMP134.

    PubMed

    Gao, Rui; Liu, Honglei; Xun, Luying

    2017-09-22

    Heterotrophic bacteria have recently been reported to oxidize sulfide by using sulfide:quinone oxidoreductase (SQR) and persulfide dioxygenase (PDO) to sulfite and thiosulfate. In chemolithotrophic bacteria, both SQR and PDO have been reported to function in the periplasmic space with SQR as a peripheral membrane protein whose C-terminus inserts into the cytoplasmic membrane and PDO as a soluble protein. Cupriavidus pinatubonensis JMP134, best known for its ability to degrade 2,4-dichlorophenoxyacetic acid and other aromatic pollutants, has a gene cluster of sqr and pdo encoding CpSQR and CpPDO2. When cloned in Escherichia coli, the enzymes are functional. Here we investigated whether they are functioning in the periplasmic space or in the cytoplasm in heterotrophic bacteria. By performing sequence analysis, biochemical detection and GFP/PhoA fusion proteins, we found that CpSQR was located on the cytoplasmic side of the membrane and CpPDO2 was a soluble protein in the cytoplasm with a tendency of being peripherally located near the membrane. The location proximity of these proteins near the membrane in the cytoplasm may facilitate sulfide oxidation in heterotrophic bacteria. The information may guide the use of heterotrophic bacteria in bioremediation of organic pollutants as well as H2S.IMPORTANCE Sulfide (H2S, HS(-), and S(2-)), common in natural gas and wastewater, is a serious malodor at low levels and deadly at high levels. Microbial oxidation of sulfide is a valid bioremediation method, in which chemolithotrophic bacteria that use sulfide as the energy source are often used to remove sulfide. Heterotrophic bacteria with SQR and PDO have recently been reported to oxidize sulfide to sulfite and thiosulfate. Cupriavidus pinatubonensis JMP134 has been extensively characterized for its ability to degrade organic pollutants, and it also contains SQR and PDO. This paper shows the localization of SQR and PDO inside the cytoplasm in the vicinity of the membrane. The

  10. Regional NAD(P)H:quinone oxidoreductase activity in Alzheimer's disease.

    PubMed

    SantaCruz, Karen S; Yazlovitskaya, Eugenia; Collins, Julie; Johnson, Jeff; DeCarli, Charles

    2004-01-01

    Converging evidence supports the role of oxidative stress in the pathology of Alzheimer's disease (AD). This notion is further supported by recent findings of increased NAD(P)H:quinone oxidodreductase (NQO1) activity, a potent antioxidant system, in association with hippocampal AD pathology. If increased NQO1 activity is truly related to the AD process, however, we would expect to see regional co-localization of NQO1 activity with AD pathology throughout affected brain regions and the absence of NQO1 activity in regions unaffected by AD. We examined this hypothesis by measuring NQO1 enzymatic activity and NQO1 immunohistochemical staining in regions commonly affected by the AD process such as frontal cortex and compared this to regions generally unaffected by the AD process such as occipital cortex, cerebellum, and substantia nigra for a group of AD patients and controls. The ratio of frontal to cerebellar NQO1 enzymatic activity was significantly increased in patients with AD (2.07 +/- 1.90) versus controls (0.60 +/- 0.31; P < 0.03). Moreover, regional immunohistochemical staining revealed specific localization of NQO1 staining to astrocytes and neurites surrounding senile plaques. The extent of immunohistochemical staining also closely correlated with the extent of local AD pathology across the various brain regions examined. Neuronal NQO1 staining seen in frontal cortex of AD patients was absent in frontal cortex of controls, but was found to the same extent in neurons of the substantia nigra of both AD patients and controls. We conclude that NQO1 activity co-localizes closely with AD pathology supporting a presumed role as an antioxidant system upregulated in response to the oxidative stress of the AD process. The antioxidant role for NQO1 is further supported by finding increased neuronal NQO1 activity in substantia nigra neurons of both AD patients and controls as this neuronal population is known to be under constant oxidative stress. While requiring further

  11. Induction of NAD(P)H quinone oxidoreductase by vegetables widely consumed in Catalonia, Spain.

    PubMed

    Laso, Nuria; Mas, Sergi; Lafuente, M Jose; Llobet, Joan M; Molina, Rafael; Ballesta, Antonio; Kensler, Thomas W; Lafuente, Amalia

    2005-01-01

    Monofunctional inducers (MIs) enhance phase 2 enzymes such as nicotinamide-adenine-dinucleotide-phosphate [NAD(P)H] quinone oxidoreductase (NQO1) without modifying oxidation enzymes. The induction of these protective enzymes appears to be mediated by genetic regulatory elements in their promoter regions known as the antioxidant response element (ARE). The aim of this study was to identify, through an in vitro study, which of the 30 fruits and vegetables commonly consumed in Catalonia, Spain, contain MIs of NQO1. We assayed the capacity of extracts of these fruits and vegetables to induce NQO1 [by more than 1.5-fold: ratio of induction (cells treated/control) >1.5, 8-mg/ml dose] in two murine hepatoma cell lines: Hepa 1c1c7 and BPrC1, a modified cell line that possesses a nonfunctional aryl hydrocarbon receptor nuclear translocator system and is thus nonresponsive to bifunctional inducers. We also used a third cell line, papiloma (PE) murine keratinocytes, a stably transfected cell line with an ARE-luc+ plasmid (AREPE cell line) for verifying induction through the ARE with a simple luminescence screening assay. Broccoli (Hepa 1c1c7, ratio=5.5; BPrC1, ratio=2.3), calcot (Allium cepa L.) (Hepa 1c1c7, ratio=4.7; BPrC1, ratio=.5), green onion (Hepa 1c1c7, ratio=4.6; BPrC1, ratio=2), green cabbage (Hepa 1c1c7, ratio=3.6; BPrC1, ratio=2.7), purple cabbage (Hepa 1c1c7, ratio=3.4; BPrC1, ratio=2), and black cabbage (Hepa 1c1c7, ratio=3; BPrC1, ratio=3) were active NQO1 inducers in both murine hepatoma cell lines. Extracts from broccoli (ratio=3.5), calcot (ratio=4.8), cauliflower (ratio=4.2), cabbage (ratio=2.2), green onion (ratio=3.2), green cabbage (ratio=3.6), black cabbage (ratio=4.5), and purple cabbage (ratio=3.7) were confirmed to contain MIs in the AREPE cell line. These results are very similar to those described for vegetables consumed in the United States, with the exception of calcot, which is common in Catalonia but is not grown or consumed widely in the

  12. A partition experimental evidence of molecular complex formation of some quinones with sodium dodecyl sulphate anion in aqueous phase by spectrophotometric method

    NASA Astrophysics Data System (ADS)

    Ray, Asim K.; Saha, Avijit; Mukherjee, Asok K.

    2005-01-01

    In an experiment involving partition of four different quinones between their saturated solutions in CCl 4 and aqueous solution of sodium dodecyl sulphate (SDS), done spectrophotometrically, it was observed that below the critical micellisation concentration (c.m.c.) of SDS, the solubility of each quinone in aqueous phase increased linearly with [SDS], just above c.m.c. it dropped sharply and then again increased, becoming nearly constant at very high [SDS]. The absorption λmax of each quinone (excepting o-chloranil) in aqueous SDS showed a red shift relative to that in CCl 4 and the red-shifted λmax is independent of [SDS]. These observations were rationalised by considering complexation and phase equilibria.

  13. Differentiation of Gram-Negative, Nonfermentative Bacteria Isolated from Biofilters on the Basis of Fatty Acid Composition, Quinone System, and Physiological Reaction Profiles

    PubMed Central

    Lipski, André; Klatte, Stefan; Bendinger, Bernd; Altendorf, Karlheinz

    1992-01-01

    Gram-negative, nonfermentative bacteria isolated from biofilters for off-gas treatment of animal-rendering-plant emissions were differentiated by whole-cell fatty acid analysis, quinone analysis, and numerical taxonomy based on their physiological reaction profiles. The last system consisted of 60 physiological tests and was arranged as a microtest system on microtitration plates. Based on fatty acid analyses, 31 isolates were separated into six clusters and five single-member clusters. The isolates of two clusters were identified as Alcaligenes faecalis and Pseudomonas diminuta. The remaining nine clusters were characterized by their fatty acid profiles, quinone systems, and physiological reaction profiles. Clusters resulting from fatty acid analyses were compared with those resulting from physiological reaction profiles. Six clusters could be confirmed this way. The efficiency of the physiological test system was increased by the prearrangement of the isolates according to their quinone type. PMID:16348724

  14. New sterically-hindered o-quinones annelated with metal-dithiolates: regiospecificity in oxidative addition reactions of a bifacial ligand to the Pd and Pt complexes.

    PubMed

    Martyanov, K A; Cherkasov, V K; Abakumov, G A; Samsonov, M A; Khrizanforova, V V; Budnikova, Y H; Kuropatov, V A

    2016-04-25

    An unusual reactivity of sterically hindered o-quinones with an annelated dithiete ring towards coordination at a dithiolene site has been discovered. New Pd and Pt dithiolate complexes have been synthesized. The reaction proceeds regioselectively, and the quinone site of the parent ligand is not affected even while using an excess of the metal complex. Both Pt and Pd complexes display a square planar surrounding for the metal ion and have very similar NMR, IR and UV/Vis spectra. Surprisingly, being coordinated at the dithiolene site to the metal, the ligand exhibits activity like an o-quinone, it could be reduced with different metals resulting in the corresponding o-semiquinonates which were confirmed by EPR spectroscopy. It was shown that an unpaired electron exhibits HFC with the phosphorus nuclei of phosphine ligands coordinated to the metal ions at the dithiolene site of the molecule.

  15. Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis

    SciTech Connect

    Dong, Hui; Shi, Qiong; Song, Xiufang; Fu, Juanli; Hu, Lihua; Xu, Demei; Su, Chuanyang; Xia, Xiaomin; Song, Erqun; Song, Yang

    2015-07-01

    Our previous studies demonstrated that polychlorinated biphenyl (PCB) quinone induced oxidative DNA damage in HepG2 cells. To promote genomic integrity, DNA damage response (DDR) coordinates cell-cycle transitions, DNA repair and apoptosis. PCB quinone-induced cell cycle arrest and apoptosis have been documented, however, whether PCB quinone insult induce DNA repair signaling is still unknown. In this study, we identified the activation of DDR and corresponding signaling events in HepG2 cells upon the exposure to a synthetic PCB quinone, PCB29-pQ. Our data illustrated that PCB29-pQ induces the phosphorylation of p53, which was mediated by ataxia telangiectasia mutated (ATM) protein kinase. The observed phosphorylated histone H2AX (γ-H2AX) foci and the elevation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) indicated that DDR was stimulated by PCB29-pQ treatment. Additionally, we found PCB29-pQ activates non-homologous end joining (NHEJ), base excision repair (BER) and nucleotide excision repair (NER) signalings. However, these repair pathways are not error-free processes and aberrant repair of DNA damage may cause the potential risk of carcinogenesis and mutagenesis. - Highlights: • Polychlorinated biphenyl quinone induces oxidative DNA damage in HepG2 cells. • The elevation of γ-H2AX and 8-OHdG indicates the activation of DNA damage response. • ATM-p53 signaling acts as the DNA damage sensor and effector. • Polychlorinated biphenyl quinone activates NHEJ, BER and NER signalings.

  16. Synthesis of phenol and quinone metabolites of benzo[a]pyrene, a carcinogenic component of tobacco smoke implicated in lung cancer.

    PubMed

    Xu, Daiwang; Penning, Trevor M; Blair, Ian A; Harvey, Ronald G

    2009-01-16

    Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants produced in the combustion of organic matter. PAHs are present in automobile exhaust and tobacco smoke, and they have recently been designated as human carcinogens. Current evidence indicates that PAHs are activated enzymatically to mutagenic metabolites that interact with DNA. There is evidence for three pathways of activation: the diol epoxide path, the radical-cation path, and the quinone path. The relative importance of these paths for human lung cancer has not been established. We now report syntheses of the principal phenol and quinone isomers of the prototype PAH carcinogen benzo[a]pyrene (BP) that are known or are suspected to be formed as metabolites of BP in human bronchoalveolar cells. The methods of synthesis were designed to be adaptable to the preparation of the (13)C-labeled analogues of the BP metabolites. These compounds are needed as standards for sensitive LC-MS/MS methods for analysis of BP metabolites formed in lung cells. Efficient novel syntheses of the 1-, 3-, 6-, 9-, and 12-BP phenols and the BP 1,6-, 3,6-, 6,12-, and 9,10-quinones are now reported. The syntheses of the BP phenols (except 6-HO-BP) involve the key steps of Pd-catalyzed Suzuki-Miyaura cross-coupling of a naphthalene boronate ester with a substituted aryl bromide or triflate ester. The BP quinones were synthesized from the corresponding BP phenols by direct oxidation with the hypervalent iodine reagents IBX or TBI. These reagents exhibited different regiospecificities. IBX oxidation of the 7- and 9-BP phenols provided the ortho-quinone isomers (BP 7,8- and 9,10-diones, respectively), whereas TBI oxidation of the 1-, 3-, and 12-BP phenols furnished BP quinone isomers with carbonyl functions in separate rings (BP 1,6-, 3,6-, and 6,12-diones, respectively).

  17. Synthesis of Phenol and Quinone Metabolites of Benzo[a]pyrene, a Carcinogenic Component of Tobacco Smoke Implicated in Lung Cancer

    PubMed Central

    Xu, Daiwang; Penning, Trevor M.; Blair, Ian A.; Harvey, Ronald G.

    2009-01-01

    Polycyclic aromatic hydrocarbons (PAHs) are widespread environmental pollutants produced in the combustion of organic matter. PAHs are present in automobile exhaust and tobacco smoke, and they have recently been designated as human carcinogens. Current evidence indicates that PAHs are activated enzymatically to mutagenic metabolites that interact with DNA. There is evidence for three pathways of activation, the diol epoxide path, the radical-cation path, and the quinone path. The relative importance of these paths for human lung cancer has not been established. We now report syntheses of the principal phenol and quinone isomers of the prototype PAH carcinogen benzo[a]pyrene (BP) that are known or are suspected to be formed as metabolites of BP in human bronchoalveolar cells. The methods of synthesis were designed to be adaptable to preparation of the 13C-labelled analogues of the BP metabolites. These compounds are needed as standards for sensitive LC-MS/MS methods for analysis of BP metabolites formed in lung cells. Efficient novel syntheses of the 1-, 3-, 6-, 9-, and 12-BP phenols, and the BP 1,6-, 3,6-, 6,12-, and 9,10-quinones are now reported. The syntheses of the BP phenols (except 6-HO-BP) involve in the key steps Pd-catalyzed Suzuki-Miyaura cross-coupling of a naphthalene boronate ester with a substituted aryl bromide or triflate ester. The BP quinones were synthesized from the corresponding BP phenols by direct oxidation with the hypervalent iodine reagents IBX or TBI. These reagents exhibited different regiospecificities. IBX oxidation of the 7- and 9- BP phenols provided the ortho-quinone isomers (BP 7,8-, and 9.10-dione), whereas TBI oxidation of the 1-, 3-, and 12-BP phenols furnished BP quinone isomers with carbonyl functions in separate rings (BP 1,6-, 3,6-, and 6,12-dione). PMID:19132942

  18. In vitro antifungal effect of black cumin seed quinones against dairy spoilage yeasts at different acidity levels.

    PubMed

    Halamova, Katerina; Kokoska, Ladislav; Flesar, Jaroslav; Sklenickova, Olga; Svobodova, Blanka; Marsik, Petr

    2010-12-01

    The antiyeast activity of the black cumin seed (Nigella sativa) quinones dithymoquinone, thymohydroquinone (THQ), and thymoquinone (TQ) were evaluated in vitro with a broth microdilution method against six dairy spoilage yeast species. Antifungal effects of the quinones were compared with those of preservatives commonly used in milk products (calcium propionate, natamycin, and potassium sorbate) at two pH levels (4.0 and 5.5). THQ and TQ possessed significant antiyeast activity and affected the growth of all strains tested at both pH levels, with MICs ranging from 8 to 128 μg/ml. With the exception of the antibiotic natamycin, the inhibitory effects of all food preservatives against the yeast strains tested in this study were strongly affected by differences in pH, with MICs of ≥16 and ≥512 μg/ml at pH 4.0 and 5.5, respectively. These findings suggest that HQ and TQ are effective antiyeast agents that could be used in the dairy industry as chemical preservatives of natural origin.

  19. Redox potential of the terminal quinone electron acceptor QB in photosystem II reveals the mechanism of electron transfer regulation

    PubMed Central

    Kato, Yuki; Nagao, Ryo; Noguchi, Takumi

    2016-01-01

    Photosystem II (PSII) extracts electrons from water at a Mn4CaO5 cluster using light energy and then transfers them to two plastoquinones, the primary quinone electron acceptor QA and the secondary quinone electron acceptor QB. This forward electron transfer is an essential process in light energy conversion. Meanwhile, backward electron transfer is also significant in photoprotection of PSII proteins. Modulation of the redox potential (Em) gap of QA and QB mainly regulates the forward and backward electron transfers in PSII. However, the full scheme of electron transfer regulation remains unresolved due to the unknown Em value of QB. Here, for the first time (to our knowledge), the Em value of QB reduction was measured directly using spectroelectrochemistry in combination with light-induced Fourier transform infrared difference spectroscopy. The Em(QB−/QB) was determined to be approximately +90 mV and was virtually unaffected by depletion of the Mn4CaO5 cluster. This insensitivity of Em(QB−/QB), in combination with the known large upshift of Em(QA−/QA), explains the mechanism of PSII photoprotection with an impaired Mn4CaO5 cluster, in which a large decrease in the Em gap between QA and QB promotes rapid charge recombination via QA−. PMID:26715751

  20. Chemical constituents from the rice fermented with the edible mushroom Pleurotus eryngii and their quinone oxidoreductase 1 inducing effect.

    PubMed

    Liu, Shun; Dong, Yanan; Li, Yongxia; Bao, Li; Liu, Hongwei; Li, Heran

    2013-12-01

    The fruiting bodies or mycelia of mushrooms have been used as food and food-flavoring material for centuries due to their nutritional and medicinal values and the diversity of their bioactive components. The present research was the first to study the chemical components in rice fermented with the edible mushroom Pleurotus eryngii and the quinone oxidoreductase 1 inducing effect of these compounds. Through chemical investigation, one new compound, ((6S,7S)-6,7-dihydroxy-6-methyl-2-(3-methylbutanoyl)-4,5,6,7-tetrahydrobenzofuran-3-yl)methyl acetate (1) and eight known compounds (2-9) were isolated from the P. eryngii-fermented rice. All of these compounds were isolated from rice fermented with the edible mushroom P. eryngii for the first time. Their structures were elucidated by MS and NMR data analyses. Alternariol-5-O-methyl ether (2) showed strong quinone oxidoreductase 1 inducing effect with an IR value of 2.58 at the concentration of 20 μg/ml. The content of adenosine (8) in the fermented rice (175.64 μg/g) is much higher than that of non-fermented rice (14.38 μg/g). © 2013.

  1. Supercritical fluid extraction and ultra performance liquid chromatography of respiratory quinones for microbial community analysis in environmental and biological samples.

    PubMed

    Hanif, Muhammad; Atsuta, Yoichi; Fujie, Koichi; Daimon, Hiroyuki

    2012-03-05

    Microbial community structure plays a significant role in environmental assessment and animal health management. The development of a superior analytical strategy for the characterization of microbial community structure is an ongoing challenge. In this study, we developed an effective supercritical fluid extraction (SFE) and ultra performance liquid chromatography (UPLC) method for the analysis of bacterial respiratory quinones (RQ) in environmental and biological samples. RQ profile analysis is one of the most widely used culture-independent tools for characterizing microbial community structure. A UPLC equipped with a photo diode array (PDA) detector was successfully applied to the simultaneous determination of ubiquinones (UQ) and menaquinones (MK) without tedious pretreatment. Supercritical carbon dioxide (scCO(2)) extraction with the solid-phase cartridge trap proved to be a more effective and rapid method for extracting respiratory quinones, compared to a conventional organic solvent extraction method. This methodology leads to a successful analytical procedure that involves a significant reduction in the complexity and sample preparation time. Application of the optimized methodology to characterize microbial communities based on the RQ profile was demonstrated for a variety of environmental samples (activated sludge, digested sludge, and compost) and biological samples (swine and Japanese quail feces).

  2. A novel coumarin-quinone derivative SV37 inhibits CDC25 phosphatases, impairs proliferation, and induces cell death.

    PubMed

    Bana, Emilie; Sibille, Estelle; Valente, Sergio; Cerella, Claudia; Chaimbault, Patrick; Kirsch, Gilbert; Dicato, Mario; Diederich, Marc; Bagrel, Denyse

    2015-03-01

    Cell division cycle (CDC) 25 proteins are key phosphatases regulating cell cycle transition and proliferation by regulating CDK/cyclin complexes. Overexpression of these enzymes is frequently observed in cancer and is related to aggressiveness, high-grade tumors and poor prognosis. Thus, targeting CDC25 by compounds, able to inhibit their activity, appears a good therapeutic approach. Here, we describe the synthesis of a new inhibitor (SV37) whose structure is based on both coumarin and quinone moieties. An analytical in vitro approach shows that this compound efficiently inhibits all three purified human CDC25 isoforms (IC50 1-9 µM) in a mixed-type mode. Moreover, SV37 inhibits growth of breast cancer cell lines. In MDA-MB-231 cells, reactive oxygen species generation is followed by pCDK accumulation, a mark of CDC25 dysfunction. Eventually, SV37 treatment leads to activation of apoptosis and DNA cleavage, underlining the potential of this new type of coumarin-quinone structure.

  3. Hydroquinone and Quinone-Grafted Porous Carbons for Highly Selective CO2 Capture from Flue Gases and Natural Gas Upgrading.

    PubMed

    Wang, Jun; Krishna, Rajamani; Yang, Jiangfeng; Deng, Shuguang

    2015-08-04

    Hydroquinone and quinone functional groups were grafted onto a hierarchical porous carbon framework via the Friedel-Crafts reaction to develop more efficient adsorbents for the selective capture and removal of carbon dioxide from flue gases and natural gas. The oxygen-doped porous carbons were characterized with scanning electron microscopy, transmission electron microscopy, X-ray powder diffraction, Fourier transform infrared spectroscopy, and Raman spectroscopy. CO2, CH4, and N2 adsorption isotherms were measured and correlated with the Langmuir model. An ideal adsorbed solution theory (IAST) selectivity for the CO2/N2 separation of 26.5 (298 K, 1 atm) was obtained on the hydroquinone-grafted carbon, which is 58.7% higher than that of the pristine porous carbon, and a CO2/CH4 selectivity value of 4.6 (298 K, 1 atm) was obtained on the quinone-grafted carbon (OAC-2), which represents a 28.4% improvement over the pristine porous carbon. The highest CO2 adsorption capacity on the oxygen-doped carbon adsorbents is 3.46 mmol g(-1) at 298 K and 1 atm. In addition, transient breakthrough simulations for CO2/CH4/N2 mixture separation were conducted to demonstrate the good separation performance of the oxygen-doped carbons in fixed bed adsorbers. Combining excellent adsorption separation properties and low heats of adsorption, the oxygen-doped carbons developed in this work appear to be very promising for flue gas treatment and natural gas upgrading.

  4. Lactococcus lactis produces short-chain quinones that cross-feed Group B Streptococcus to activate respiration growth.

    PubMed

    Rezaïki, Lahcen; Lamberet, Gilles; Derré, Aurélie; Gruss, Alexandra; Gaudu, Philippe

    2008-03-01

    Quinones are essential components of the respiration chain that shuttle electrons between oxidoreductases. We characterized the quinones synthesized by Lactococcus lactis, a fermenting bacterium that activates aerobic respiration when a haem source is provided. Two distinct subgroups were characterized: Menaquinones (MK) MK-8 to MK-10, considered as hallmarks of L. lactis, are produced throughout growth. MK-3 and demethylMK-3 [(D)MK-3] are newly identified and are present only late in growth. Production of (D)MK-3 was conditional on the carbon sugar and on the presence of carbon catabolite regulator gene ccpA. Electron flux driven by both (D)MK fractions was shared between the quinol oxidase and extracellular acceptors O(2), iron and, with remarkable efficiency, copper. Purified (D)MK-3, but not MK-8-10, complemented a menB defect in L. lactis. We previously showed that a respiratory metabolism is activated in Group B Streptococcus (GBS) by exogenous haem and MK, and that this activity is implicated in virulence. Here we show that growing lactococci donate (D)MK to GBS to activate respiration and stimulate growth of this opportunist pathogen. We propose that conditions favouring (D)MK production in dense microbial ecosystems, as present in the intestinal tract, could favour implantation of (D)MK-scavengers like GBS within the complex.

  5. Remote position substituents as modulators of conformational and reactive properties of quinones. Relevance of the pi/pi intramolecular interaction.

    PubMed

    Roura-Pérez, Guillermo; Quiróz, Beatriz; Aguilar-Martínez, Martha; Frontana, Carlos; Solano, Alejandro; Gonzalez, Ignacio; Bautista-Martínez, José Antonio; Jiménez-Barbero, Jesús; Cuevas, Gabriel

    2007-03-16

    Several studies have described that quinoid rings with electron-rich olefins at remote position experience changes in their redox potential. Since the original description of these changes, different approaches have been developed to describe the properties of the binding sites of ubiquinones. The origin of this phenomenon has been attributed to lateral chain flexibility and its effect on the recognition between proteins and substrates associated with their important biological activity. The use of electrochemical-electron spin resonance (EC-ESR) assays and theoretical calculations at MP2/6-31G(d,p) and MP2/6-31++G(d,p)//MP2/6-31G(d,p) levels of several conformers of perezone [(2-(1,5-dimethyl-4-hexenyl)-3-hydroxy-5-methyl-1,4-benzoquinone] established that a weak pi-pi interaction controls not only the molecular conformation but also its diffusion coefficient and electrochemical properties. An analogous interaction can be suggested as the origin of similar properties of ubiquinone Q10. The use of nuclear magnetic resonance rendered, for the first time, direct evidence of the participation of different perezone conformers in solution and explained the cycloaddition process observed when the aforementioned quinone is heated to form pipitzols, sesquiterpenes with a cedrene skeleton. The fact that biological systems can modulate the redox potential of this type of quinones depending on the conformer recognized by an enzyme during a biological transformation is of great relevance.

  6. Quinone-rich polydopamine functionalization of yttria stabilized zirconia for apatite biomineralization: The effects of coating temperature

    NASA Astrophysics Data System (ADS)

    Zain, Norhidayu Muhamad; Hussain, Rafaqat; Abdul Kadir, Mohammed Rafiq

    2015-08-01

    The use of yttria stabilized zirconia (YSZ) as biomedical implants is often offset by its bioinert nature that prevents its osseointegration to occur. Therefore, the functionalization of YSZ surface by polydopamine to facilitate the biomineralization of apatite layer on top of the coated film has incessantly been studied. In this study YSZ discs were first immersed in 2 mg/mL of stirred dopamine solution at coating temperatures between 25 and 80 °C. The specimens were then incubated for 7d in 1.5 SBF. The effect of coating temperature on the properties (chemical compositions and wettability) and the apatite mineralization on top of the generated films was investigated. It was found that at 50 °C, the specimen displayed the highest intensity of Ca 2p peak (1.55 ± 0.42 cps) with Ca/P ratio of 1.67 due to the presence of abundant quinone groups (Cdbnd O). However, the hydrophilicity (40.9 ± 01.7°) was greatly improved at 60 °C accompanied by the highest film thickness of 306 nm. Therefore, it was concluded that the presence of high intensity of quinone groups (Cdbnd O) in polydopamine film at elevated temperature affects the chelation of Ca2+ ions and thus enhance the growth of apatite layer on top of the functionalized YSZ surface.

  7. Electrochemical study of quinone redox cycling: A novel application of DNA-based biosensors for monitoring biochemical reactions.

    PubMed

    Ensafi, Ali A; Jamei, Hamid Reza; Heydari-Bafrooei, Esmaeil; Rezaei, B

    2016-10-01

    This paper presents the results of an experimental investigation of voltammetric and impedimetric DNA-based biosensors for monitoring biological and chemical redox cycling reactions involving free radical intermediates. The concept is based on associating the amounts of radicals generated with the electrochemical signals produced, using differential pulse voltammetry (DPV) and electrochemical impedance spectroscopy (EIS). For this purpose, a pencil graphite electrode (PGE) modified with multiwall carbon nanotubes and poly-diallydimethlammonium chloride decorated with double stranded fish sperm DNA was prepared to detect DNA damage induced by the radicals generated from a redox cycling quinone (i.e., menadione (MD; 2-methyl-1,4-naphthoquinone)). Menadione was employed as a model compound to study the redox cycling of quinones. A direct relationship was found between free radical production and DNA damage. The relationship between MD-induced DNA damage and free radical generation was investigated in an attempt to identify the possible mechanism(s) involved in the action of MD. Results showed that DPV and EIS were appropriate, simple and inexpensive techniques for the quantitative and qualitative comparisons of different reducing reagents. These techniques may be recommended for monitoring DNA damages and investigating the mechanisms involved in the production of redox cycling compounds.

  8. The structure of a biosynthetic intermediate of pyrroloquinoline quinone (PQQ) and elucidation of the final step of PQQ biosynthesis.

    PubMed

    Magnusson, Olafur T; Toyama, Hirohide; Saeki, Megumi; Schwarzenbacher, Robert; Klinman, Judith P

    2004-05-05

    Pyrroloquinoline quinone (PQQ) is a tricyclic o-quinone, which serves as a cofactor in several enzyme-catalyzed redox reactions in certain bacteria. PQQ is also important for human health, and its role as a vitamin in mammals has recently been suggested. Although much is known about the function of enzymes that use PQQ as cofactor, relatively little is known about the biosynthesis of this coenzyme. Six gene products in Klebsiella pneumoniae (PqqA-F) are involved in PQQ biosynthesis, and PqqC has been shown to catalyze the last step in the pathway. The chemical structure of the substrate for PqqC has remained elusive and has hampered our understanding of the nature of this reaction. In this report we describe the purification and structure of the substrate as deduced by a number of spectroscopic and chemical methods. The substrate is 3a-(2-amino-2-carboxyethyl)-4,5-dioxo-4,5,6,7,8,9-hexahydroquinoline-7,9-dicarboxylic acid-a fully reduced derivative of PQQ, which has not undergone ring cyclization. These results show that PqqC catalyzes a novel reaction, which involves ring closure and an amazing eight-electron oxidation of the substrate.

  9. KETONE AND QUINONE-SUBSTITUTED POLYCYCLIC AROMATIC HYDROCARBONS IN MUSSEL TISSUE, SEDIMENT, URBAN DUST, AND DIESEL PARTICULATE MATRICES

    PubMed Central

    Layshock, Julie A.; Wilson, Glenn; Anderson, Kim A.

    2013-01-01

    Polycyclic aromatic hydrocarbons (PAHs) substituted with a ketone or quinone functionality (OPAHs) may be important environmental contaminants. The OPAHs from environmental samples have demonstrated toxicity and may be more harmful than PAHs. Knowledge gaps concerning the occurrence of OPAHs in the total environment arise from analytical difficulties, as well as limited standards and methodologies. An optimized method was developed to quantify five ketone and four quinone OPAHs from matrices ranging from biological tissue to diesel particulates. Five National Institute of Standards and Technology Standard Reference Materials (SRMs) were analyzed. This is the first report of OPAH quantitation in SRM 2977 (mussel tissue), SRM 1944 (New York /New Jersey, USA waterway sediment), SRM 1975 (diesel extract) and SRM 1650b (diesel particulate matter) and among the few to report concentrations from SRM 1649 (urban dust). Furthermore, this is one of the first reports of OPAHs in biological tissue. Σ9OPAHs were 374 ± 59 μg/kg (mussel tissue), 5.4 ± 0.5 mg/kg (sediment), 16.9 ± 1.6 mg/kg (urban dust), 33.4 ± 0.4 mg/kg (diesel extract), and 150 ± 43 mg/kg (diesel particulate matter). In all SRMs, the levels of OPAHs were similar to or exceeded levels of PAHs. Of the OPAHs tested, the most frequently occurring in the environmental matrices were 9-fluorenone, 9,10-anthraquinone, benzofluorenone, and 7,12-benz[a]anthracenequinone. PMID:20830751

  10. Effective covalent immobilization of quinone and aptamer onto a gold electrode via thiol addition for sensitive and selective protein biosensing.

    PubMed

    Su, Zhaohong; Xu, Haitao; Xu, Xiaolin; Zhang, Yi; Ma, Yan; Li, Chaorong; Xie, Qingji

    2017-03-01

    Effective covalent immobilization of quinone and aptamer onto a gold electrode via thiol addition (a Michael addition) for sensitive and selective protein (with thrombin as the model) biosensing is reported, with a detection limit down to 20 fM for thrombin. Briefly, the thiol addition reaction of a gold electrode-supported 1,6-hexanedithiol (HDT) with p-benzoquinone (BQ) yielded BQ-HDT/Au, and the similar reaction of thiolated thrombin aptamer (TTA) with activated BQ-HDT/Au under 0.3V led to formation of a gold electrode-supported novel electrochemical probe TTA-BQ-HDT/Au. The thus-prepared TTA-BQ-HDT/Au exhibits a pair of well-defined redox peaks of quinone moiety, and the TTA-thrombin interaction can sensitively decrease the electrochemical signal. Herein the thiol addition acts as an effective and convenient binding protocols for aptasensing, and a new method (electrochemical conversion of Michael addition complex for signal generation) for the fabrication of biosensor is presented. The cyclic voltammetry (CV) was used to characterize the film properties. In addition, the proposed amperometric aptasensor exhibits good sensitivity, selectivity, and reproducibility. The aptasensor also has acceptable recovery for detection in complex protein sample.

  11. Constituents of Musa x paradisiaca cultivar with the potential to induce the phase II enzyme, quinone reductase.

    PubMed

    Jang, Dae Sik; Park, Eun Jung; Hawthorne, Michael E; Vigo, Jose Schunke; Graham, James G; Cabieses, Fernando; Santarsiero, Bernard D; Mesecar, Andrew D; Fong, Harry H S; Mehta, Rajendra G; Pezzuto, John M; Kinghorn, A Douglas

    2002-10-23

    A new bicyclic diarylheptanoid, rel-(3S,4aR,10bR)-8-hydroxy-3-(4-hydroxyphenyl)-9-methoxy-4a,5,6,10b-tetrahydro-3H-naphtho[2,1-b]pyran (1), as well as four known compounds, 1,2-dihydro-1,2,3-trihydroxy-9-(4-methoxyphenyl)phenalene (2), hydroxyanigorufone (3), 2-(4-hydroxyphenyl)naphthalic anhydride (4), and 1,7-bis(4-hydroxyphenyl)hepta-4(E),6(E)-dien-3-one (5), were isolated from an ethyl acetate-soluble fraction of the methanol extract of the fruits of Musa x paradisiaca cultivar, using a bioassay based on the induction of quinone reductase (QR) in cultured Hepa1c1c7 mouse hepatoma cells to monitor chromatographic fractionation. The structure and relative stereochemistry of compound 1 were elucidated unambiguously by one- and two-dimensional NMR experiments ((1)H NMR, (13)C NMR, DEPT, COSY, HMQC, HMBC, and NOESY) and single-crystal X-ray diffraction analysis. Isolates 1-5 were evaluated for their potential cancer chemopreventive properties utilizing an in vitro assay to determine quinone reductase induction and a mouse mammary organ culture assay.

  12. Crystal structure of quinone-dependent alcohol dehydrogenase from Pseudogluconobacter saccharoketogenes. A versatile dehydrogenase oxidizing alcohols and carbohydrates.

    PubMed

    Rozeboom, Henriëtte J; Yu, Shukun; Mikkelsen, Rene; Nikolaev, Igor; Mulder, Harm J; Dijkstra, Bauke W

    2015-12-01

    The quinone-dependent alcohol dehydrogenase (PQQ-ADH, E.C. 1.1.5.2) from the Gram-negative bacterium Pseudogluconobacter saccharoketogenes IFO 14464 oxidizes primary alcohols (e.g. ethanol, butanol), secondary alcohols (monosaccharides), as well as aldehydes, polysaccharides, and cyclodextrins. The recombinant protein, expressed in Pichia pastoris, was crystallized, and three-dimensional (3D) structures of the native form, with PQQ and a Ca(2+) ion, and of the enzyme in complex with a Zn(2+) ion and a bound substrate mimic were determined at 1.72 Å and 1.84 Å resolution, respectively. PQQ-ADH displays an eight-bladed β-propeller fold, characteristic of Type I quinone-dependent methanol dehydrogenases. However, three of the four ligands of the Ca(2+) ion differ from those of related dehydrogenases and they come from different parts of the polypeptide chain. These differences result in a more open, easily accessible active site, which explains why PQQ-ADH can oxidize a broad range of substrates. The bound substrate mimic suggests Asp333 as the catalytic base. Remarkably, no vicinal disulfide bridge is present near the PQQ, which in other PQQ-dependent alcohol dehydrogenases has been proposed to be necessary for electron transfer. Instead an associated cytochrome c can approach the PQQ for direct electron transfer. © 2015 The Protein Society.

  13. Redox potential of the terminal quinone electron acceptor QB in photosystem II reveals the mechanism of electron transfer regulation.

    PubMed

    Kato, Yuki; Nagao, Ryo; Noguchi, Takumi

    2016-01-19

    Photosystem II (PSII) extracts electrons from water at a Mn4CaO5 cluster using light energy and then transfers them to two plastoquinones, the primary quinone electron acceptor QA and the secondary quinone electron acceptor QB. This forward electron transfer is an essential process in light energy conversion. Meanwhile, backward electron transfer is also significant in photoprotection of PSII proteins. Modulation of the redox potential (Em) gap of QA and QB mainly regulates the forward and backward electron transfers in PSII. However, the full scheme of electron transfer regulation remains unresolved due to the unknown Em value of QB. Here, for the first time (to our knowledge), the Em value of QB reduction was measured directly using spectroelectrochemistry in combination with light-induced Fourier transform infrared difference spectroscopy. The Em(QB (-)/QB) was determined to be approximately +90 mV and was virtually unaffected by depletion of the Mn4CaO5 cluster. This insensitivity of Em(QB (-)/QB), in combination with the known large upshift of Em(QA (-)/QA), explains the mechanism of PSII photoprotection with an impaired Mn4CaO5 cluster, in which a large decrease in the Em gap between QA and QB promotes rapid charge recombination via QA (-).

  14. Characterization of estrogen quinone-derived protein adducts and their identification in human serum albumin derived from breast cancer patients and healthy controls.

    PubMed

    Chen, Dar-Ren; Chen, Shou-Tung; Wang, Tzu-Wen; Tsai, Chen-His; Wei, Hz-Han; Chen, Guan-Jie; Yang, Tsung-Chou; Lin, Che; Lin, Po-Hsiung

    2011-05-10

    Both 17β-estradiol-2,3-quinone (E₂-2,3-Q) and 17β-estradiol-3,4-quinone (E₂-3,4-Q) are reactive metabolites of estrogen that are thought to be responsible for the estrogen-induced genotoxicity. The aim of this study was to establish a methodology to analyze estrogen quinone-derived protein adducts and to measure the background levels of these adducts in human serum albumin (Alb) derived from female blood donors in Taiwan. Results from in vitro experiments confirmed that the production of estrogen quinone-derived adducts on serum Alb increased with increased concentration of estrogen quinones. Time-course experiments suggested that both E₂-2,3-Q- and E₂-3,4-Q-derived adducts rapidly reached maximum values at 10 min mark and remained constant thereafter for up to 24 h. Additionally, with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) pretreatment, the production of estrogen quinone-derived protein adducts was detected in human MCF-7 breast cancer cells exposed to estrogen. Co-treatment of a catechol-O-methyl transferase inhibitor further enhanced the production of estrogen quinone-derived adducts in all cases. When we investigated the levels of estrogen quinone-derived adducts in human serum Alb, cysteinyl adducts of E₂-2,3-Q-1-S-Alb, E₂-2,3-Q-4-S-Alb, and E₂-3,4-Q-2-S-Alb were detected in all healthy female controls (n=10) with median levels at 147 (range 14.1-533), 197 (range 30.0-777), and 65.6 (range 17.6-1360) (pmol/g), respectively. We noticed that levels of E₂-2,3-Q-derived adducts were 2-fold greater than those of E₂-3,4-Q-2-S-Alb in controls whereas levels of E₂-3,4-Q-2-S-Alb were 2-fold higher than those of E₂-2,3-Q-derived adducts in patients (n = 20). Additionally, levels of E₂-2,3-Q-4-S-Alb correlated significantly with those of E₂-3,4-Q-2-S-Alb (correlation coefficient r = 0.684-0.850, p < 0.05). Overall, we conclude that cumulative body burden of E₂-3,4-Q is a significant predictor of breast cancer.

  15. Aziridinyl-substituted benzo-1,4-quinones: A preliminary investigation on the theoretical and experimental studies of their structure and spectroscopic properties.

    PubMed

    Šarlauskas, Jonas; Tamulienė, Jelena; Čėnas, Narimantas

    2017-05-05

    The detailed structure, chemical and spectroscopic properties of the derivatives of the selected 2,5-bis(1-aziridinyl)-benzo-1,4-quinone conformers were studied by applying quantum chemical and experimental methods. The relationship between the structure and chemical activity of the selected 3 bifunctional bioreductive quinonic anticancer agents - aziridinyl benzoquinones (AzBQ compounds) was obtained. The results obtained showed that the position of aziridine rings influenced by the chemical activity of the investigated compound were more significant than the substitutions of the benzene ring of the AzBQ compounds. The solvents influencing this activity were obtained, too.

  16. Identification of a quinone dehydrogenase from a Bacillus sp. involved in the decolourization of the lignin-model dye, Azure B.

    PubMed

    Bandounas, Luaine; Pinkse, Martijn; de Winde, Johannes H; Ruijssenaars, Harald J

    2013-01-25

    In this study we have investigated the molecular background of the previously reported dye decolourization potential of Bacillus sp. LD003. Strain LD003 was previously isolated on Kraft lignin and was able to decolourize various lignin model dyes. Specifically Azure B (AB) was decolourized efficiently. Proteins possibly involved in AB decolourization were partially purified, fractionated by gel electrophoresis and identified via mass spectrometry. Five candidate enzymes were selected and expressed in Escherichia coli. Of these, only a quinone dehydrogenase was shown to decolourize AB. Thus, this quinone dehydrogenase was identified as an AB decolourizing enzyme of Bacillus sp. LD003.

  17. Catalytic properties of NAD(P)H:quinone oxidoreductase-2 (NQO2), a dihydronicotinamide riboside dependent oxidoreductase.

    PubMed

    Wu, K; Knox, R; Sun, X Z; Joseph, P; Jaiswal, A K; Zhang, D; Deng, P S; Chen, S

    1997-11-15

    Human NAD(P)H:quinone acceptor oxidoreductase-2 (NQO2) has been prepared using an Escherichia coli expression method. NQO2 is thought to be an isoform of DT-diaphorase (EC 1.6.99.2) [also referred to as NAD(P)H:quinone acceptor oxidoreductase] because there is a 49% identity between their amino acid sequences. The present investigation has revealed that like DT-diaphorase, NQO2 is a dimer enzyme with one FAD prosthetic group per subunit. Interestingly, NQO2 uses dihydronicotinamide riboside (NRH) rather than NAD(P)H as an electron donor. It catalyzes a two-electron reduction of quinones and oxidation-reduction dyes. One-electron acceptors, such as potassium ferricyanide, cannot be reduced by NQO2. This enzyme also catalyzes a four-electron reduction, using methyl red as the electron acceptor. The NRH-methyl red reductase activity of NQO2 is 11 times the NADH-methyl red reductase activity of DT-diaphorase. In addition, through a four-electron reduction reaction, NQO2 can catalyze nitroreduction of cytotoxic compound CB 1954 [5-(aziridin-1-yl)-2,4-dinitrobenzamide]. NQO2 is 3000 times more effective than DT-diaphorase in the reduction of CB 1954. Therefore, NQO2 is a NRH-dependent oxidoreductase which catalyzes two- and four-electron reduction reactions. NQO2 is resistant to typical inhibitors of DT-diaphorase, such as dicumarol, Cibacron blue, and phenindone. Flavones are inhibitors of NQO2. However, structural requirements of flavones for the inhibition of NQO2 are different from those for DT-diaphorase. The most potent flavone inhibitor tested so far is quercetin (3,5,7,3',4'-. 6pentahydroxyflavone). It has been found that quercetin is a competitive inhibitor with respect to NRH (Ki = 21 nM). NQO2 is 43 amino acids shorter than DT-diaphorase, and it has been suggested that the carboxyl terminus of DT-diaphorase plays a role in substrate binding (S. Chen et al., Protein Sci. 3, 51-57, 1994). In order to understand better the basis of catalytic differences between

  18. N-Heterocyclic Carbene-Catalyzed [4 + 2] Cyclization of Saturated Carboxylic Acid with o-Quinone Methides through in Situ Activation: Enantioselective Synthesis of Dihydrocoumarins.

    PubMed

    Wang, Yuanfeng; Pan, Jian; Dong, Jingjiao; Yu, Chenxia; Li, Tuanjie; Wang, Xiang-Shan; Shen, Shide; Yao, Changsheng

    2017-02-03

    An N-heterocyclic carbene (NHC)-catalyzed formal [4 + 2] synthesis of dihydrocoumarins was realized from saturated carboxylic acids and o-quinone methides via an in situ activation strategy. This protocol results in excellent diastereoselectivity and enantioselectivity and good yields and uses readily available and inexpensive starting materials.

  19. REACTIONS OF BENZO[A]PYRENE-7,8-QUINONE WITH DEOXYGUANOSINE AND DEOXYADENOSINE AT PHYSIOLOGICAL pH: IDENTIFICATION AND CHARACTERIZATION OF STABLE ADDUCTS

    EPA Science Inventory

    Reactions of Benzo[a]pyrene-7,8-quinone with Deoxyguanosine and Deoxyadenosine at Physiological pH: Identification and Characterization of Stable Adducts

    Narayanan Balu, William T. Padgett, Guy Lambert, Adam E. Swank,
    Ann M. Richard, and Stephen Nesnow

    Environmen...

  20. Bifunctional squaramide-catalyzed synthesis of chiral dihydrocoumarins via ortho-quinone methides generated from 2-(1-tosylalkyl)phenols.

    PubMed

    Zhou, Ji; Wang, Mao-Lin; Gao, Xiang; Jiang, Guo-Fang; Zhou, Yong-Gui

    2017-03-23

    A bifunctional squaramide-catalyzed reaction of azlactones with o-quinone methides in situ generated from 2-(1-tosylalkyl)-phenols has been successfully developed under basic conditions, providing an efficient and mild access to chiral dihydrocoumarins bearing adjacent tertiary and quaternary stereogenic centers in high yields with excellent diastereo- and enantioselectivities.

  1. Metabolism of a representative oxygenated polycyclic aromatic hydrocarbon (PAH) phenanthrene-9,10-quinone in human hepatoma (HepG2) cells.

    PubMed

    Huang, Meng; Zhang, Li; Mesaros, Clementina; Zhang, Suhong; Blaha, Michael A; Blair, Ian A; Penning, Trevor M

    2014-05-19

    Exposure to polycyclic aromatic hydrocarbons (PAHs) in the food chain is the major human health hazard associated with the Deepwater Horizon oil spill. Phenanthrene is a representative PAH present in crude oil, and it undergoes biological transformation, photooxidation, and chemical oxidation to produce its signature oxygenated derivative, phenanthrene-9,10-quinone. We report the downstream metabolic fate of phenanthrene-9,10-quinone in HepG2 cells. The structures of the metabolites were identified by HPLC-UV-fluorescence detection and LC-MS/MS. O-mono-Glucuronosyl-phenanthrene-9,10-catechol was identified, as reported previously. A novel bis-conjugate, O-mono-methyl-O-mono-sulfonated-phenanthrene-9,10-catechol, was discovered for the first time, and evidence for both of its precursor mono conjugates was obtained. The identities of these four metabolites were unequivocally validated by comparison to authentic enzymatically synthesized standards. Evidence was also obtained for a minor metabolic pathway of phenanthrene-9,10-quinone involving bis-hydroxylation followed by O-mono-sulfonation. The identification of 9,10-catechol conjugates supports metabolic detoxification of phenanthrene-9,10-quinone through interception of redox cycling by UGT, COMT, and SULT isozymes and indicates the possible use of phenanthrene-9,10-catechol conjugates as biomarkers of human exposure to oxygenated PAH.

  2. All Three Endogenous Quinone Species of Escherichia coli Are Involved in Controlling the Activity of the Aerobic/Anaerobic Response Regulator ArcA

    PubMed Central

    van Beilen, Johan W. A.; Hellingwerf, Klaas J.

    2016-01-01

    The enteron Escherichia coli is equipped with a branched electron transfer chain that mediates chemiosmotic electron transfer, that drives ATP synthesis. The components of this electron transfer chain couple the oxidation of available electron donors from cellular metabolism (e.g., NADH, succinate, lactate, formate, etc.) to the reduction of electron acceptors like oxygen, nitrate, fumarate, di-methyl-sulfoxide, etc. Three different quinones, i.e., ubiquinone, demethyl-menaquinone and menaquinone, couple the transfer of electrons between the dehydrogenases and reductases/oxidases that constitute this electron transfer chain, whereas, the two-component regulation system ArcB/A regulates gene expression, to allow the organism to adapt itself to the ambient conditions of available electron donors and acceptors. Here, we report that E. coli can grow and adjust well to transitions in the availability of oxygen, with any of the three quinones as its single quinone. In all three ‘single-quinone’ E. coli strains transitions in the activity of ArcB are observed, as evidenced by changes in the level of phosphorylation of the response regulator ArcA, upon depletion/readmission of oxygen. These results lead us to conclude that all quinol species of E. coli can reduce (i.e., activate) the sensor ArcB and all three quinones oxidize (i.e., de-activate) it. These results also confirm our earlier conclusion that demethyl-menaquinone can function in aerobic respiration. PMID:27656164

  3. REACTIONS OF BENZO[A]PYRENE-7,8-QUINONE WITH DEOXYGUANOSINE AND DEOXYADENOSINE AT PHYSIOLOGICAL pH: IDENTIFICATION AND CHARACTERIZATION OF STABLE ADDUCTS

    EPA Science Inventory

    Reactions of Benzo[a]pyrene-7,8-quinone with Deoxyguanosine and Deoxyadenosine at Physiological pH: Identification and Characterization of Stable Adducts

    Narayanan Balu, William T. Padgett, Guy Lambert, Adam E. Swank,
    Ann M. Richard, and Stephen Nesnow

    Environmen...

  4. LC/MSMS STUDY OF BENZO[A]PYRENE-7,8-QUINONE ADDUCTION TO GLOBIN TRYPTIC PEPTIDES AND N-ACETYLAMINO ACIDS

    EPA Science Inventory

    Benzo[a]pyrene-7,8-quinone (BPQ) is regarded as a reactive genotoxic compound enzymatically formed from a xenobiotic precursor benzo[a]pyrene-7,8-diol by aldo-keto-reductase family of enzymes. Because BPQ, a Michael electrophile, was previously shown to react with oligonucleotide...

  5. LC/MSMS STUDY OF BENZO[A]PYRENE-7,8-QUINONE ADDUCTION TO GLOBIN TRYPTIC PEPTIDES AND N-ACETYLAMINO ACIDS

    EPA Science Inventory

    Benzo[a]pyrene-7,8-quinone (BPQ) is regarded as a reactive genotoxic compound enzymatically formed from a xenobiotic precursor benzo[a]pyrene-7,8-diol by aldo-keto-reductase family of enzymes. Because BPQ, a Michael electrophile, was previously shown to react with oligonucleotide...

  6. Electronic structure and energy decomposition analyses as a tool to interpret the redox potential ranking of naphtho-, biphenyl- and biphenylene-quinone isomers.

    PubMed

    Tomerini, D; Politano, O; Gatti, C; Frayret, C

    2016-09-29

    By calling on modelling approaches we have performed a comparative study on the redox properties of various naphtho-, biphenyl- and biphenylene-quinone isomers. These different compounds exhibit as a whole a redox potential range between 2.09 and 2.90 V vs. Li(+)/Li. A specific methodology was used to decrypt the interplay among isomerism, aromaticity and antiaromaticity modifications and the stabilization/destabilization effects due to other molecular components on this key electrochemical feature for electrode materials of batteries. In particular, energy decomposition analysis, within the Quantum Theory of Atoms in Molecules, along with the electron and electron spin population changes upon reduction nicely rationalise the observed potential trends. While 1,2- and 2,3-isomers show the highest/lowest redox potential in the biphenylene-quinone series, a reverse trend is observed for the naphtho-quinone, the compound having the two carbonyl groups on distinct rings being characterized by an intermediate value in both cases. There is instead almost no differentiation between 1,2 and 2,3 isomers for the biphenyl-quinone family.

  7. Metabolism of a Representative Oxygenated Polycyclic Aromatic Hydrocarbon (PAH) Phenanthrene-9,10-quinone in Human Hepatoma (HepG2) Cells

    PubMed Central

    2014-01-01

    Exposure to polycyclic aromatic hydrocarbons (PAHs) in the food chain is the major human health hazard associated with the Deepwater Horizon oil spill. Phenanthrene is a representative PAH present in crude oil, and it undergoes biological transformation, photooxidation, and chemical oxidation to produce its signature oxygenated derivative, phenanthrene-9,10-quinone. We report the downstream metabolic fate of phenanthrene-9,10-quinone in HepG2 cells. The structures of the metabolites were identified by HPLC–UV–fluorescence detection and LC–MS/MS. O-mono-Glucuronosyl-phenanthrene-9,10-catechol was identified, as reported previously. A novel bis-conjugate, O-mono-methyl-O-mono-sulfonated-phenanthrene-9,10-catechol, was discovered for the first time, and evidence for both of its precursor mono conjugates was obtained. The identities of these four metabolites were unequivocally validated by comparison to authentic enzymatically synthesized standards. Evidence was also obtained for a minor metabolic pathway of phenanthrene-9,10-quinone involving bis-hydroxylation followed by O-mono-sulfonation. The identification of 9,10-catechol conjugates supports metabolic detoxification of phenanthrene-9,10-quinone through interception of redox cycling by UGT, COMT, and SULT isozymes and indicates the possible use of phenanthrene-9,10-catechol conjugates as biomarkers of human exposure to oxygenated PAH. PMID:24646012

  8. Cp*Rh(III) and Cp*Ir(III)-catalysed redox-neutral C-H arylation with quinone diazides: quick and facile synthesis of arylated phenols.

    PubMed

    Zhang, Shang-Shi; Jiang, Chun-Yong; Wu, Jia-Qiang; Liu, Xu-Ge; Li, Qingjiang; Huang, Zhi-Shu; Li, Ding; Wang, Honggen

    2015-06-25

    Cp*Rh(III)- and Cp*Ir(III)-catalysed direct C-H arylation with quinone diazides as efficient coupling partners is disclosed. This redox-neutral protocol offers a facile, operationally simple and environmentally benign access to arylated phenols. The reaction represents the first example of Cp*Ir(III)-catalysed C-H direct arylation reaction.

  9. Generalized Mulliken-Hush analysis of electronic coupling interactions in compressed pi-stacked porphyrin-bridge-quinone systems.

    PubMed

    Zheng, Jieru; Kang, Youn K; Therien, Michael J; Beratan, David N

    2005-08-17

    Donor-acceptor interactions were investigated in a series of unusually rigid, cofacially compressed pi-stacked porphyrin-bridge-quinone systems. The two-state generalized Mulliken-Hush (GMH) approach was used to compute the coupling matrix elements. The theoretical coupling values evaluated with the GMH method were obtained from configuration interaction calculations using the INDO/S method. The results of this analysis are consistent with the comparatively soft distance dependences observed for both the charge separation and charge recombination reactions. Theoretical studies of model structures indicate that the phenyl units dominate the mediation of the donor-acceptor coupling and that the relatively weak exponential decay of rate with distance arises from the compression of this pi-electron stack.

  10. Quinone derivatives isolated from the endolichenic fungus Phialocephala fortinii are Mdr1 modulators that combat azole resistance in Candida albicans

    PubMed Central

    Xie, Fei; Chang, Wenqiang; Zhang, Ming; Li, Ying; Li, Wei; Shi, Hongzhuo; Zheng, Sha; Lou, Hongxiang

    2016-01-01

    One of the main azole-resistance mechanisms in Candida pathogens is the upregulation of drug efflux pumps, which compromises the efficacy of azoles and results in treatment failure. The combination of azole-antifungal agents with efflux pump inhibitors represents a promising strategy to combat fungal infection. High-throughput screening of 150 extracts obtained from endolichenic fungal cultures led to the discovery that the extract of Phialocephala fortinii exhibits potent activity for the reversal of azole resistance. From P. fortinii cultures, a total of 15 quinone derivatives, comprising 11 new derivatives and 4 known compounds, were obtained. Among these compounds, palmarumycin P3 (3) and phialocephalarin B (8) specifically modulate the expression of MDR1 to inhibit the activity of drug efflux pumps and therefore reverse azole resistance. The present study revealed Mdr1 targeting as an alternative mechanism for the discovery of new agents to fight antifungal drug resistance. PMID:27650180

  11. Thermodynamic contribution to the regulation of electron transfer in the Na(+)-pumping NADH:quinone oxidoreductase from Vibrio cholerae.

    PubMed

    Neehaul, Yashvin; Juárez, Oscar; Barquera, Blanca; Hellwig, Petra

    2012-05-15

    The Na(+)-pumping NADH:quinone oxidoreductase (Na(+)-NQR) is a fundamental enzyme of the oxidative phosphorylation metabolism and ionic homeostasis in several pathogenic and marine bacteria. To understand the mechanism that couples electron transfer with sodium translocation in Na(+)-NQR, the ion dependence of the redox potential of the individual cofactors was studied using a spectroelectrochemical approach. The redox potential of one of the FMN cofactors increased 90 mV in the presence of Na(+) or Li(+), compared to the redox potentials measured in the presence of other cations that are not transported by the enzyme, such as K(+), Rb(+), and NH(4)(+). This shift in redox potential of one FMN confirms the crucial role of the FMN anionic radicals in the Na(+) pumping mechanism and demonstrates that the control of the electron transfer rate has both kinetic (via conformational changes) and thermodynamic components.

  12. PQQ: Biosynthetic studies in Methylobacterium AM1 and Hyphomicrobium X using specific TC labeling and NMR. [Pyrroloquinoline quinones

    SciTech Connect

    Houck, D.R.; Hanners, J.L.; Unkefer, C.J.; van Kleef, M.A.G.; Duine, J.A.

    1988-01-01

    Using TC labeling and NMR spectroscopy we have determined biosynthetic precursors of pyrroloquinoline quinone (PQQ) in two closely related serine-type methylotrophs, Methylobacterium AM1 and Hyphomicrobium X. Analysis of the TC-labeling data revealed that PQQ is constructed from two amino acids: the portion containing N-6, C-7,8,9 and the two carboxylic acid groups, C-7' and 9', is derived-intact-from glutamate. The remaining portion is derived from tyrosine; the phenol side chain provides the six carbons of the ring containing the orthoquinone, whereas internal cyclization of the amino acid backbone forms the pyrrole-2-carboxylic acid moiety. This is analogous to the cyclization of dopaquinone to form dopachrome. Dopaquinone is a product of the oxidation of tyrosine (via dopa) in reactions catalyzed by monophenol monooxygenase (EC 1.14.18.1). Starting with tyrosine and glutamate, we will discuss possible biosynthetic routes to PQQ. 29 refs., 4 figs., 2 tabs.

  13. Simultaneous Synthesis of both Rings of Chromenes via a Benzannulation/o-Quinone Methide Formation/Electrocyclization Cascade

    PubMed Central

    Majumdar, Nilanjana; Korthals, Keith A.; Wulff, William D.

    2011-01-01

    A new route to the chromene ring system has been developed which involves the reaction of an α,β-unsaturated Fischer carbene complex of chromium with a propargyl ether bearing an alkenyl group on the propargylic carbon. This transformation involves a cascade of reactions that begins with a benzannulation reaction and is followed by the formation of an o-quinone methide and finally, results in the emergence of a chromene upon an electrocyclization. This reaction was extended to the provide access to by employing an aryl carbene complex. This constitutes the first synthesis of chromenes in which both rings of the chromene system are generated in a single step and is highlighted in the synthesis of lapachenole and Vitamin E. PMID:22176537

  14. Activity-guided isolation of constituents of Tephrosia purpurea with the potential to induce the phase II enzyme, quinone reductase.

    PubMed

    Chang, L C; Gerhäuser, C; Song, L; Farnsworth, N R; Pezzuto, J M; Kinghorn, A D

    1997-09-01

    An isoflavone, 7,4'-dihydroxy-3',5'-dimethoxyisoflavone (1), and a chalcone, (+)-tephropurpurin (2), both novel compounds, as well as six constituents of known structure, (+)-purpurin (3), pongamol (4), lanceolatin B (5), (-)-maackiain (6), (-)-3-hydroxy-4-methoxy-8,9-methylene-dioxypterocarpan (7), and (-)-medicarpin (8), were obtained as active compounds from Tephrosia purpurea, using a bioassay based on the induction of quinone reductase (QR) activity with cultured Hepa 1c1c7 mouse hepatoma cells. Additionally, three inactive compounds of known structure, 3'-methoxydaidzein, desmoxyphyllin B, and 3,9-dihydroxy-8-methoxycoumestan, were isolated and identified. The structure elucidation of compounds 1 and 2 was carried out by spectral data interpretation.

  15. Membrane protein damage and repair: selective loss of a quinone-protein function in chloroplast membranes. [Chlamydomonas

    SciTech Connect

    Kyle, D.J.; Ohad, I.; Arntzen, C.J.

    1984-07-01

    A loss of electron transport capacity in chloroplast membranes was induced by high-light intensities (photoinhibition). The primary site of inhibition was at the reducing side of photosystem II (PSII) with little damage to the oxidizing side or to the reaction center core of PSII. Addition of herbicides (atrazine or diuron) partially protected the membrane from photoinhibition; these compounds displace the bound plastoquinone (designated as Q/sub B/), which functions as the secondary electron acceptor on the reducing side of PSII. Loss of function of the 32-kilodalton Q/sub B/ apoprotein was demonstrated by a loss of binding sites for (/sup 14/C)atraazine. We suggest that quinone anions, which may interact with molecular oxygen to produce an oxygen radical, selectively damage the apoprotein of the secondary acceptor of PSII, thus rendering it inactive and thereby blocking photosynthetic electron flow under conditions of high photon flux densities. 21 references, 4 figures, 2 tables.

  16. Variation of glucosinolates and quinone reductase activity among different varieties of Chinese kale and improvement of glucoraphanin by metabolic engineering.

    PubMed

    Qian, Hongmei; Sun, Bo; Miao, Huiying; Cai, Congxi; Xu, Chaojiong; Wang, Qiaomei

    2015-02-01

    The variation of glucosinolates and quinone reductase (QR) activity in fourteen varieties of Chinese kale (Brassica oleracea var. alboglabra Bailey) was investigated in the present study. Results showed that gluconapin (GNA), instead of glucoraphanin (GRA), was the most predominant glucosinolate in all varieties, and QR activity was remarkably positively correlated with the glucoraphanin level. AOP2, a tandem 2-oxoglutarate-dependent dioxygenase, catalyzes the conversion of glucoraphanin to gluconapin in glucosinolate biosynthesis. Here, antisense AOP2 was transformed into Gailan-04, the variety with the highest gluconapin content and ratio of GNA/GRA. The glucoraphanin content and corresponding QR activity were notably increased in transgenic plants, while no significant difference at the level of other main nutritional compounds (total phenolics, vitamin C, carotenoids and chlorophyll) was observed between the transgenic lines and the wide-type plants. Taken together, metabolic engineering is a good practice for improvement of glucoraphanin in Chinese kale. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Dielectric studies on the heterogeneity and interfacial property of composites made of polyacene quinone radical polymers and sulfonated polyurethanes.

    PubMed

    Zhu, Dan; Zhang, Juan; Bin, Yuezhen; Xu, Chunye; Shen, Jian; Matsuo, Masaru

    2012-03-08

    Sulfonated polyurethane (PUI, matrix) is synthesized and composited with polyacene quinone radical polymers (PAQRs, filler). The polarization mechanism of these polymers and composites were investigated in terms of their frequency, temperature, and filler-concentration-dependent dielectric properties. We found that PUI/PAQR composites have a high permittivity, which is attributed to the filler-matrix interfacial polarization and the contact effect. The PAQR-concentration-dependent permittivity of different PUI/PAQR composites reveals a percolation threshold at 20-30 wt % with scaling exponents that indicate the intercluster polarization. The frequency dependence of dielectric response is well-fitted by using the Debye and Cole-Cole functions on the basis of the structural diagrams and equivalent circuit, leading to a detailed evaluation on heterogeneous structures of different PUI/PAQR composites.

  18. Antioxidant and pro-oxidant properties of pyrroloquinoline quinone (PQQ): implications for its function in biological systems.

    PubMed

    He, Kai; Nukada, Hitoshi; Urakami, Teiji; Murphy, Michael P

    2003-01-01

    Pyrroloquinoline quinone (PQQ) is a novel redox cofactor recently found in human milk. It has been reported to function as an essential nutrient, antioxidant and redox modulator in cell culture experiments and in animal models of human diseases. As mitochondria are particularly susceptible to oxidative damage we studied the antioxidant properties of PQQ in isolated rat liver mitochondria. PQQ was an effective antioxidant protecting mitochondria against oxidative stress-induced lipid peroxidation, protein carbonyl formation and inactivation of the mitochondrial respiratory chain. In contrast, PQQ caused extensive cell death to cells in culture. This surprising effect was inhibited by catalase, and was shown to be due to the generation of hydrogen peroxide during the autoxidation of PQQ in culture medium. We conclude that the reactivities of PQQ are dependent on its environment and that it can act as an antioxidant or a pro-oxidant in different biological systems.

  19. Electron spin echo of spin-polarised radical pairs in intact and quinone-reconstituted plant photosystem I reaction centers

    NASA Astrophysics Data System (ADS)

    Dzuba, S. A.; Hara, H.; Kawamori, A.; Iwaki, M.; Itoh, S.; Tsvetkov, Yu. D.

    1997-01-01

    Light-induced spin-polarised P700 +A 1- pairs in intact and quinone-reconstituted photosystem I reaction centres were studied by electron spin echo (ESE) spectroscopy. The observed strong ESE envelope modulation was attributed to magnetic dipolar and exchange interactions in the pairs. The values of these interactions were derived from Fourier-transformed time traces and appeared to be D = -1.71 ± 0.05 G and J = 0.010 ± 0.015 G, respectively. A magnetic field effect on the radical pair lifetime induced by microwave pumping was observed. The reconstituted 2,3-dibromo-1,4-naphthoquinone was shown to be located in the same (A 1) site as the native phylloquinone.

  20. The pattern and control of isoprenoid quinone and tocopherol metabolism in the germinating grain of wheat (Triticum vulgare)

    PubMed Central

    Hall, G. S.; Laidman, D. L.

    1968-01-01

    1. The syntheses of ubiquinone-9 and plastoquinone-9 were used as parameters respectively of mitochondrial and proplastid development in the germinating wheat grain. 2. The changes in the amounts of the tocopherols were also studied and the possible biological significance of these changes is discussed. During germination, the dimethyl tocopherols of the resting grain are probably not utilized for the synthesis of α-tocopherol. 3. It was demonstrated that ubiquinone synthesis, and hence probably mitochondrial development, in the aleurone cells during germination, is independent of control by gibberellic acid from the embryo. 4. The influence of light on the syntheses of the isoprenoid quinones in the etiolated wheat shoot was investigated. In particular, illumination did not stimulate the synthesis of either α-tocopherol or α-tocopherolquinone. PMID:5667257

  1. The two common polymorphic forms of human NRH-quinone oxidoreductase 2 (NQO2) have different biochemical properties.

    PubMed

    Megarity, Clare F; Gill, James R E; Caraher, M Clare; Stratford, Ian J; Nolan, Karen A; Timson, David J

    2014-05-02

    There are two common forms of NRH-quinone oxidoreductase 2 (NQO2) in the human population resulting from SNP rs1143684. One has phenylalanine at position 47 (NQO2-F47) and the other leucine (NQO2-L47). Using recombinant proteins, we show that these variants have similar steady state kinetic parameters, although NQO2-L47 has a slightly lower specificity constant. NQO2-L47 is less stable towards proteolytic digestion and thermal denaturation than NQO2-F47. Both forms are inhibited by resveratrol, but NQO2-F47 shows negative cooperativity with this inhibitor. Thus these data demonstrate, for the first time, clear biochemical differences between the variants which help explain previous biomedical and epidemiological findings.

  2. An anthraquinone with potent quinone reductase-inducing activity and other constituents of the fruits of Morinda citrifolia (noni).

    PubMed

    Pawlus, Alison D; Su, Bao-Ning; Keller, William J; Kinghorn, A Douglas

    2005-12-01

    Morinda citrifolia, commonly known as noni, has a long history of utilization throughout much of tropical Polynesia and is considered to be the second most important medicinal plant in the Hawaiian Islands. Recently, the use of noni as a dietary supplement in the United States has greatly increased. Bioassay-guided fractionation of a dichloromethane-soluble partition of a MeOH extract of noni fruits has led to the isolation of an extremely potent quinone reductase inducer, 2-methoxy-1,3,6-trihydroxyanthraquinone (1). This new anthraquinone (1) was nearly 40 times more potent than a positive control, l-sulforaphane. Furthermore, compound 1 demonstrated no discernible cytotoxicity at the highest dose tested. In addition to compound 1, 11 known compounds were also isolated and identified in the present investigation. This is the first report of the isolation of anthraquinones from noni fruits.

  3. Electron-Transfer Pathways in the Heme and Quinone-Binding Domain of Complex II (Succinate Dehydrogenase)

    PubMed Central

    2015-01-01

    Single electron transfers have been examined in complex II (succinate:ubiquinone oxidoreductase) by the method of pulse radiolysis. Electrons are introduced into the enzyme initially at the [3Fe–4S] and ubiquinone sites followed by intramolecular equilibration with the b heme of the enzyme. To define thermodynamic and other controlling parameters for the pathways of electron transfer in complex II, site-directed variants were constructed and analyzed. Variants at SdhB-His207 and SdhB-Ile209 exhibit significantly perturbed electron transfer between the [3Fe–4S] cluster and ubiquinone. Analysis of the data using Marcus theory shows that the electronic coupling constants for wild-type and variant enzyme are all small, indicating that electron transfer occurs by diabatic tunneling. The presence of the ubiquinone is necessary for efficient electron transfer to the heme, which only slowly equilibrates with the [3Fe–4S] cluster in the absence of the quinone. PMID:24559074

  4. Pyrroloquinoline quinone from Gluconobacter oxydans fermentation broth enhances superoxide anion-scavenging capacity of Cu/Zn-SOD.

    PubMed

    Ma, Ke; Cui, Jun-Zhu; Ye, Jian-Bin; Hu, Xian-Mei; Ma, Ge-Li; Yang, Xue-Peng

    2017-09-01

    A bioassay-guided fractionation of extract from Gluconobacter oxydans fermentation broth afforded Compound 1, which was identified as pyrroloquinoline quinone (PQQ) by spectroscopic methods. PQQ has been shown to enhance the superoxide anion-scavenging capacity significantly for Cu/Zn-SOD. To illustrate the mechanism, the interaction between PQQ and Cu/Zn-SOD was investigated. The multiple binding sites involving hydrogen bonds and van der Waals force between PQQ and Cu/Zn-SOD were revealed by isothermal titration calorimetry. The α-helix content was increased in the Cu/Zn-SOD structure with the addition of PQQ into the solution through ultraviolet (UV) spectroscopy. These results indicated that PQQ could change the conformation of Cu/Zn-SOD through interaction, which could enhance its superoxide anion-scavenging capacity. Therefore, PQQ is a potential natural antioxidant. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Insertion and self-diffusion of a monotopic protein, the Aquifex aeolicus sulfide quinone reductase, in supported lipid bilayers.

    PubMed

    Harb, Frédéric; Prunetti, Laurence; Giudici-Orticoni, Marie-Thérèse; Guiral, Marianne; Tinland, Bernard

    2015-10-01

    Monotopic proteins constitute a class of membrane proteins that bind tightly to cell membranes, but do not span them. We present a FRAPP (Fluorescence Recovery After Patterned Photobleaching) study of the dynamics of a bacterial monotopic protein, SQR (sulfide quinone oxidoreductase) from the thermophilic bacteria Aquifex aeolicus, inserted into two different types of lipid bilayers (EggPC: L-α-phosphatidylcholine (Egg, Chicken) and DMPC: 1,2-dimyristoyl-sn-glycero-3-phosphocholine) supported on two different types of support (mica or glass). It sheds light on the behavior of a monotopic protein inside the bilayer. The insertion of SQR is more efficient when the bilayer is in the fluid phase than in the gel phase. We observed diffusion of the protein, with no immobile fraction, and deduced from the diffusion coefficient measurements that the resulting inserted object is the same whatever the incubation conditions, i.e. homogeneous in terms of oligomerization state. As expected, the diffusion coefficient of the SQR is smaller in the gel phase than in the fluid phase. In the supported lipid bilayer, the diffusion coefficient of the SQR is smaller than the diffusion coefficient of phospholipids in both gel and fluid phase. SQR shows a diffusion behavior different from the transmembrane protein α-hemolysin, and consistent with its monotopic character. Preliminary experiments in the presence of the substrate of SQR, DecylUbiquinone, an analogue of quinone, component of transmembrane electrons transport systems of eukaryotic and prokaryotic organisms, have been carried out. Finally, we studied the behavior of SQR, in terms of insertion and diffusion, in bilayers formed with lipids from Aquifex aeolicus. All the conclusions that we have found in the biomimetic systems applied to the biological system.

  6. Targeting heat shock protein 90 with non-quinone inhibitors: a novel chemotherapeutic approach in human hepatocellular carcinoma.

    PubMed

    Breinig, Marco; Caldas-Lopes, Eloisi; Goeppert, Benjamin; Malz, Mona; Rieker, Ralf; Bergmann, Frank; Schirmacher, Peter; Mayer, Matthias; Chiosis, Gabriela; Kern, Michael André

    2009-07-01

    The inhibition of heat shock protein 90 (Hsp90) has emerged as a promising antineoplastic strategy in diverse human malignancies. Hsp90 has been predicted to be involved in hepatocellular carcinoma (HCC) development; however, its role in hepatocarcinogenesis remains elusive. Using chemically distinctive Hsp90 inhibitors, we show that Hsp90 capacitates the aberrant expression and activity of crucial hepatocarcinogenesis-driving factors (e.g., insulin-like growth factor receptor 1, hepatocyte growth factor receptor, protein kinase B, v-raf-1 murine leukemia viral oncogene homolog 1, and cyclin-dependent kinase 4). In vitro, Hsp90 inhibition with both geldanamycin analogs (17-allylamino-17-desmethoxygeldanamycin (17-AAG) and 17-dimethylaminoethylamino-17-desmethoxygeldanamycin (17-DMAG)) and the non-quinone compound 8-(6-iodobenzo[d][1,3]dioxol-5-ylthio)-9-(3-(isopropylamino)propyl)-9H-purin-6-amine (PU-H71) reduced the viability of various HCC cell lines, induced the simultaneous degradation of numerous hepatocarcinogenic factors, and caused substantial cell cycle arrest and apoptosis. In contrast, nontumorigenic hepatocytes were less susceptible to Hsp90 inhibition. Because conventional geldanamycin-derivate Hsp90 inhibitors induce dose-limiting liver toxicity, we tested whether novel Hsp90 inhibitors lacking the benzoquinone moiety, which has been deemed responsible for hepatotoxicity, can elicit antineoplastic activity without causing significant liver damage. In HCC xenograft mouse models, PU-H71 was retained in tumors at pharmacologically relevant concentrations while being rapidly cleared from nontumorous liver. PU-H71 showed potent and prolonged in vivo Hsp90 inhibitory activity and reduced tumor growth without causing toxicity. Hsp90 constitutes a promising therapeutic target in HCC. Non-quinone Hsp90 inhibitors exhibit tumor-specific accumulation and exert potent antineoplastic activity without causing significant hepatotoxicity.

  7. Higher activity of polymorphic NAD(P)H:quinone oxidoreductase in liver cytosols from blacks compared to whites.

    PubMed

    Covarrubias, Vanessa Gonzalez; Lakhman, Sukhwinder S; Forrest, Alan; Relling, Mary V; Blanco, Javier G

    2006-07-14

    In human liver, the two-electron reduction of quinone compounds, such as menadione is catalyzed by cytosolic carbonyl reductase (CBR) and NAD(P)H:quinone oxidoreductase (NQO1) activities. We assessed the relative contributions of CBR and NQO1 activities to the total menadione reducing capacity in liver cytosols from black (n=31) and white donors (n=63). Maximal menadione reductase activities did not differ between black (13.0+/-5.0 nmol/min mg), and white donors (11.4+/-6.6 nmol/min mg; p=0.208). In addition, both groups presented similar levels of CBR activities (CBR(blacks)=10.9+/-4.1 nmol/min mg) versus CBR(whites)=10.5+/-5.8 nmol/min mg; p=0.708). In contrast, blacks showed higher NQO1 activities (two-fold) than whites (NQO1(blacks)=2.1+/-3.0 nmol/min mg versus NQO1(whites)=0.9+/-1.6 nmol/min mg, p<0.01). To further explore this disparity, we tested whether NQO1 activity was associated with the common NQO1(*)2 genetic polymorphism by using paired DNA samples for genotyping. Cytosolic NQO1 activities differed significantly by NQO1 genotype status in whites (NQO1(whites[NQO1*1/*1])=1.3+/-1.7 nmol/min mg versus NQO1(whites[NQO1*1/*2+NQO1*2/*2])=0.5+/-0.7 nmol/min mg, p<0.01), but not in blacks (NQO1(blacks[NQO1*1/*1])=2.6+/-3.4 nmol/min mg versus NQO1(blacks[NQO1*1/*2])=1.1+/-1.2 nmol/min mg, p=0.134). Our findings pinpoint the presence of significant interethnic differences in polymorphic hepatic NQO1 activity.

  8. Succinate dehydrogenase activity regulates PCB3-quinone induced metabolic oxidative stress and toxicity in HaCaT human keratinocytes

    PubMed Central

    Xiao, Wusheng; Sarsour, Ehab H.; Wagner, Brett A.; Doskey, Claire M.; Buettner, Garry R.; Domann, Frederick E.; Goswami, Prabhat C.

    2015-01-01

    Polychlorinated biphenyls (PCBs) and their metabolites are environmental pollutants that are known to have adverse health effects. 1-(4-Chlorophenyl)-benzo-2,5-quinone (4-ClBQ), a quinone-metabolite of 4-Monochlorobiphenyl (PCB3, present in the environment and human blood) is toxic to human skin keratinocytes, and breast and prostate epithelial cells. This study investigates the hypothesis that 4-ClBQ-induced metabolic oxidative stress regulates toxicity in human keratinocytes. Results from Seahorse XF96 Analyzer showed that the 4-ClBQ treatment increased extracellular acidification rate, proton production rate, oxygen consumption rate and ATP content, indicative of metabolic oxidative stress. Results from a q-RT-PCR assay showed significant increases in the mRNA levels of hexokinase 2 (hk2), pyruvate kinase M2 (pkm2) and glucose-6-phosphate dehydrogenase (g6pd), and decreases in the mRNA levels of succinate dehydrogenase (complex II) subunit C and D (sdhc and sdhd). Pharmacological inhibition of G6PD-activity enhanced the toxicity of 4-ClBQ, suggesting that the protective function of the pentose phosphate pathway is functional in 4-ClBQ treated cells. The decrease in sdhc and sdhd expression was associated with a significant decrease in complex II activity and increase in mitochondrial levels of ROS. Overexpression of sdhc and sdhd suppressed 4-ClBQ-induced inhibition of complex II activity, increase in mitochondrial levels of ROS, and toxicity. These results suggest that the 4-ClBQ treatment induces metabolic oxidative stress in HaCaT cells, and while the protective function of the pentose phosphate pathway is active, inhibition of complex II activity sensitizes HaCaT cells to 4-ClBQ induced toxicity. PMID:25417049

  9. Quinone-induced activation of Keap1/Nrf2 signaling by aspirin prodrugs masquerading as nitric oxide.

    PubMed

    Dunlap, Tareisha; Piyankarage, Sujeewa C; Wijewickrama, Gihani T; Abdul-Hay, Samer; Vanni, Michael; Litosh, Vladislav; Luo, Jia; Thatcher, Gregory R J

    2012-12-17

    The promising therapeutic potential of the NO-donating hybrid aspirin prodrugs (NO-ASA) includes induction of chemopreventive mechanisms and has been reported in almost 100 publications. One example, NCX-4040 (pNO-ASA), is bioactivated by esterase to a quinone methide (QM) electrophile. In cell cultures, pNO-ASA and QM-donating X-ASA prodrugs that cannot release NO rapidly depleted intracellular GSH and caused DNA damage; however, induction of Nrf2 signaling elicited cellular defense mechanisms including upregulation of NAD(P)H:quinone oxidoreductase-1 (NQO1) and glutamate-cysteine ligase (GCL). In HepG2 cells, the "NO-specific" 4,5-diaminofluorescein reporter, DAF-DA, responded to NO-ASA and X-ASA, with QM-induced oxidative stress masquerading as NO. LC-MS/MS analysis demonstrated efficient alkylation of Cys residues of proteins including glutathione-S-transferase-P1 (GST-P1) and Kelch-like ECH-associated protein 1 (Keap1). Evidence was obtained for alkylation of Keap1 Cys residues associated with Nrf2 translocation to the nucleus, nuclear translocation of Nrf2, activation of antioxidant response element (ARE), and upregulation of cytoprotective target genes. At least in cell culture, pNO-ASA acts as a QM donor, bioactivated by cellular esterase activity to release salicylates, NO(3)(-), and an electrophilic QM. Finally, two novel aspirin prodrugs were synthesized, both potent activators of ARE, designed to release only the QM and salicylates on bioactivation. Current interest in electrophilic drugs acting via Nrf2 signaling suggests that QM-donating hybrid drugs can be designed as informative chemical probes in drug discovery.

  10. Activities of Secreted Aryl Alcohol Quinone Oxidoreductases from Pycnoporus cinnabarinus Provide Insights into Fungal Degradation of Plant Biomass.

    PubMed

    Mathieu, Yann; Piumi, Francois; Valli, Richard; Aramburu, Juan Carro; Ferreira, Patricia; Faulds, Craig B; Record, Eric

    2016-04-01

    Auxiliary activities family 3 subfamily 2 (AA3_2) from the CAZy database comprises various functions related to ligninolytic enzymes, such as fungal aryl alcohol oxidases (AAO) and glucose oxidases, both of which are flavoenzymes. The recent study of the Pycnoporus cinnabarinus CIRM BRFM 137 genome combined with its secretome revealed that four AA3_2 enzymes are secreted during biomass degradation. One of these AA3_2 enzymes, scf184803.g17, has recently been produced heterologously in Aspergillus niger Based on the enzyme's activity and specificity, it was assigned to the glucose dehydrogenases (PcinnabarinusGDH [PcGDH]). Here, we analyze the distribution of the other three AA3_2 enzymes (scf185002.g8, scf184611.g7, and scf184746.g13) to assess their putative functions. These proteins showed the highest homology with aryl alcohol oxidase from Pleurotus eryngii Biochemical characterization demonstrated that they were also flavoenzymes harboring flavin adenine dinucleotide (FAD) as a cofactor and able to oxidize a wide variety of phenolic and nonphenolic aryl alcohols and one aliphatic polyunsaturated primary alcohol. Though presenting homology with fungal AAOs, these enzymes exhibited greater efficiency in reducing electron acceptors (quinones and one artificial acceptor) than molecular oxygen and so were defined as aryl-alcohol:quinone oxidoreductases (AAQOs) with two enzymes possessing residual oxidase activity (PcAAQO2 and PcAAQO3). Structural comparison of PcAAQO homology models with P. eryngii AAO demonstrated a wider substrate access channel connecting the active-site cavity to the solvent, explaining the absence of activity with molecular oxygen. Finally, the ability of PcAAQOs to reduce radical intermediates generated by laccase from P. cinnabarinus was demonstrated, shedding light on the ligninolytic system of this fungus.

  11. Odoriferous Defensive Stink Gland Transcriptome to Identify Novel Genes Necessary for Quinone Synthesis in the Red Flour Beetle, Tribolium castaneum

    PubMed Central

    Li, Jianwei; Lehmann, Sabrina; Weißbecker, Bernhard; Ojeda Naharros, Irene; Schütz, Stefan; Joop, Gerrit; Wimmer, Ernst A.

    2013-01-01

    Chemical defense is one of the most important traits, which endow insects the ability to conquer a most diverse set of ecological environments. Chemical secretions are used for defense against anything from vertebrate or invertebrate predators to prokaryotic or eukaryotic parasites or food competitors. Tenebrionid beetles are especially prolific in this category, producing several varieties of substituted benzoquinone compounds. In order to get a better understanding of the genetic and molecular basis of defensive secretions, we performed RNA sequencing in a newly emerging insect model, the red flour beetle Tribolium castaneum (Coleoptera: Tenebrionidae). To detect genes that are highly and specifically expressed in the odoriferous gland tissues that secret defensive chemical compounds, we compared them to a control tissue, the anterior abdomen. 511 genes were identified in different subtraction groups. Of these, 77 genes were functionally analyzed by RNA interference (RNAi) to recognize induced gland alterations morphologically or changes in gland volatiles by gas chromatography-mass spectrometry. 29 genes (38%) presented strong visible phenotypes, while 67 genes (87%) showed alterations of at least one gland content. Three of these genes showing quinone-less (ql) phenotypes – Tcas-ql VTGl; Tcas-ql ARSB; Tcas-ql MRP – were isolated, molecularly characterized, their expression identified in both types of the secretory glandular cells, and their function determined by quantification of all main components after RNAi. In addition, microbe inhibition assays revealed that a quinone-free status is unable to impede bacterial or fungal growth. Phylogenetic analyses of these three genes indicate that they have evolved independently and specifically for chemical defense in beetles. PMID:23874211

  12. Activities of Secreted Aryl Alcohol Quinone Oxidoreductases from Pycnoporus cinnabarinus Provide Insights into Fungal Degradation of Plant Biomass

    PubMed Central

    Piumi, Francois; Valli, Richard; Aramburu, Juan Carro; Ferreira, Patricia; Faulds, Craig B.; Record, Eric

    2016-01-01

    Auxiliary activities family 3 subfamily 2 (AA3_2) from the CAZy database comprises various functions related to ligninolytic enzymes, such as fungal aryl alcohol oxidases (AAO) and glucose oxidases, both of which are flavoenzymes. The recent study of the Pycnoporus cinnabarinus CIRM BRFM 137 genome combined with its secretome revealed that four AA3_2 enzymes are secreted during biomass degradation. One of these AA3_2 enzymes, scf184803.g17, has recently been produced heterologously in Aspergillus niger. Based on the enzyme's activity and specificity, it was assigned to the glucose dehydrogenases (P. cinnabarinus GDH [PcGDH]). Here, we analyze the distribution of the other three AA3_2 enzymes (scf185002.g8, scf184611.g7, and scf184746.g13) to assess their putative functions. These proteins showed the highest homology with aryl alcohol oxidase from Pleurotus eryngii. Biochemical characterization demonstrated that they were also flavoenzymes harboring flavin adenine dinucleotide (FAD) as a cofactor and able to oxidize a wide variety of phenolic and nonphenolic aryl alcohols and one aliphatic polyunsaturated primary alcohol. Though presenting homology with fungal AAOs, these enzymes exhibited greater efficiency in reducing electron acceptors (quinones and one artificial acceptor) than molecular oxygen and so were defined as aryl-alcohol:quinone oxidoreductases (AAQOs) with two enzymes possessing residual oxidase activity (PcAAQO2 and PcAAQO3). Structural comparison of PcAAQO homology models with P. eryngii AAO demonstrated a wider substrate access channel connecting the active-site cavity to the solvent, explaining the absence of activity with molecular oxygen. Finally, the ability of PcAAQOs to reduce radical intermediates generated by laccase from P. cinnabarinus was demonstrated, shedding light on the ligninolytic system of this fungus. PMID:26873317

  13. Cationic screening of charged surface groups (carboxylates) affects electron transfer steps in photosystem-II water oxidation and quinone reduction.

    PubMed

    Karge, Oliver; Bondar, Ana-Nicoleta; Dau, Holger

    2014-10-01

    The functional or regulatory role of long-distance interactions between protein surface and interior represents an insufficiently understood aspect of protein function. Cationic screening of surface charges determines the morphology of thylakoid membrane stacks. We show that it also influences directly the light-driven reactions in the interior of photosystem II (PSII). After laser-flash excitation of PSII membrane particles from spinach, time courses of the delayed recombination fluorescence (10μs-10ms) and the variable chlorophyll-fluorescence yield (100μs-1s) were recorded in the presence of chloride salts. At low salt-concentrations, a stimulating effect was observed for the S-state transition efficiency, the time constant of O2-formation at the Mn4Ca-complex of PSII, and the halftime of re-oxidation of the primary quinone acceptor (Qa) by the secondary quinone acceptor (Qb). The cation valence determined the half-effect concentrations of the stimulating salt effect, which were around 6μM, 200μM and 10mM for trivalent (LaCl3), bivalent (MgCl2, CaCl2), and monovalent cations (NaCl, KCl), respectively. A depressing high-salt effect also depended strongly on the cation valence (onset concentrations around 2mM, 50mM, and 500mM). These salt effects are proposed to originate from electrostatic screening of negatively charged carboxylate sidechains, which are found in the form of carboxylate clusters at the solvent-exposed protein surface. We conclude that the influence of electrostatic screening by solvent cations manifests a functionally relevant long-distance interaction between protein surface and electron-transfer reactions in the protein interior. A relation to regulation and adaptation in response to environmental changes is conceivable. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Electronic Connection Between the Quinone and Cytochrome c Redox Pools and Its Role in Regulation of Mitochondrial Electron Transport and Redox Signaling

    PubMed Central

    Sarewicz, Marcin; Osyczka, Artur

    2015-01-01

    Mitochondrial respiration, an important bioenergetic process, relies on operation of four membranous enzymatic complexes linked functionally by mobile, freely diffusible elements: quinone molecules in the membrane and water-soluble cytochromes c in the intermembrane space. One of the mitochondrial complexes, complex III (cytochrome bc1 or ubiquinol:cytochrome c oxidoreductase), provides an electronic connection between these two diffusible redox pools linking in a fully reversible manner two-electron quinone oxidation/reduction with one-electron cytochrome c reduction/oxidation. Several features of this homodimeric enzyme implicate that in addition to its well-defined function of contributing to generation of proton-motive force, cytochrome bc1 may be a physiologically important point of regulation of electron flow acting as a sensor of the redox state of mitochondria that actively responds to changes in bioenergetic conditions. These features include the following: the opposing redox reactions at quinone catalytic sites located on the opposite sides of the membrane, the inter-monomer electronic connection that functionally links four quinone binding sites of a dimer into an H-shaped electron transfer system, as well as the potential to generate superoxide and release it to the intermembrane space where it can be engaged in redox signaling pathways. Here we highlight recent advances in understanding how cytochrome bc1 may accomplish this regulatory physiological function, what is known and remains unknown about catalytic and side reactions within the quinone binding sites and electron transfers through the cofactor chains connecting those sites with the substrate redox pools. We also discuss the developed molecular mechanisms in the context of physiology of mitochondria. PMID:25540143

  15. Tocopherol quinone content of green algae and higher plants revised by a new high-sensitive fluorescence detection method using HPLC--effects of high light stress and senescence.

    PubMed

    Kruk, Jerzy; Szymańska, Renata; Krupinska, Karin

    2008-08-25

    A rapid, sensitive fluorescence method was applied here for detection of oxidized tocopherol quinones in total plant tissue extracts using HPLC, employing a post-column reduction of these compounds by a Zn column. Using this method, we were able to detect both alpha- and gamma-tocopherol quinones in Chlamydomonas reinhardii with a very high degree of sensitivity. The levels of both compounds increased under high light stress in the presence of pyrazolate in parallel to a decrease in the content of the corresponding tocopherols. The formation of tocopherol quinones from tocopherols was apparently due to their oxidation by singlet oxygen, which is formed in photosystem II under high light stress. alpha-Tocopherol quinone was also detected in a variety of higher plants of different age, and its level was found to increase during senescence in leaves grown under natural conditions. In contrast to alpha-tocopherol quinone, gamma-tocopherol quinone was not found in the higher plant species investigated with the exception of young runner bean leaves, where the levels of both compounds increased dramatically during cold and light stress. Taking advantage of native fluorescence of the reduced alpha-tocopherol quinone (alpha-tocopherol quinol), it can be detected in plant tissue extracts with a high sensitivity. In young runner bean leaves, alpha-tocopherol quinol was found at a level similar to alpha-tocopherol.

  16. Ligand-independent activation of aryl hydrocarbon receptor signaling in PCB3-quinone treated HaCaT human keratinocytes.

    PubMed

    Xiao, Wusheng; Son, Jyungmean; Vorrink, Sabine U; Domann, Frederick E; Goswami, Prabhat C

    2015-03-18

    Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that plays a critical role in metabolism, cell proliferation, development, carcinogenesis, and xenobiotic response. In general, dioxin-like polychlorinated biphenyls (PCBs) exhibit a ligand-dependent activation of AhR-signaling. Results from this study show that a quinone-derivative (1-(4-Chlorophenyl)-benzo-2,5-quinone; 4-ClBQ) of a non-dioxin like PCB (PCB3) also activates AhR-signaling. Treatments of HaCaT human keratinocytes with 4-ClBQ and dioxin-like PCB126 significantly increased AhR-target gene expression, CYP1A1 mRNA and protein levels. 4-ClBQ-induced increase CYP1A1 expression was associated with an increase in the nuclear translocation of AhR protein as well as an increase in the luciferase-reporter activity of a human CYP1A1 xenobiotic response element (XRE). 6,2',4'-Trimethoxyflavone (TMF), a well-characterized AhR-ligand antagonist significantly suppressed PCB126-induced increase in CYP1A1 expression, while the same treatment did not suppress 4-ClBQ-induced increase in CYP1A1 expression. However, siRNA-mediated down-regulation of AhR significantly inhibited 4-ClBQ-induced increase in CYP1A1 expression, suggesting that AhR mediates 4-ClBQ-induced increase in CYP1A1 expression. Interestingly, treatment with the antioxidant N-acetyl-l-cysteine significantly suppressed 4-ClBQ-induced increase in CYP1A1 expression. Furthermore, CYP1A1 expression also increased in cells treated with hydrogen peroxide. These results demonstrate that a ligand-independent and oxidative stress dependent pathway activates AhR-signaling in 4-ClBQ treated HaCaT cells. Because AhR signaling is believed to mediate xenobiotics response, our results may provide a mechanistic rationale for the use of antioxidants as effective countermeasure to environmental pollutant-induced adverse health effects. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  17. Ligand-independent activation of Aryl hydrocarbon receptor signaling in PCB3-quinone treated HaCaT human keratinocytes

    PubMed Central

    Xiao, Wusheng; Son, Jyungmean; Vorrink, Sabine U.; Domann, Frederick E.; Goswami, Prabhat C.

    2015-01-01

    Aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that plays a critical role in metabolism, cell proliferation, development, carcinogenesis, and xenobiotic response. In general, dioxin-like polychlorinated biphenyls (PCBs) exhibit a ligand-dependent activation of AhR-signaling. Results from this study show that a quinone-derivative (1-(4-Chlorophenyl)-benzo-2,5-quinone; 4-ClBQ) of a non-dioxin like PCB (PCB3) also activates AhR-signaling. Treatments of HaCaT human keratinocytes with 4-ClBQ and dioxin-like PCB126 significantly increased AhR-target gene expression, CYP1A1 mRNA and protein levels. 4-ClBQ-induced increase CYP1A1 expression was associated with an increase in the nuclear translocation of AhR protein as well as an increase in the luciferase-reporter activity of a human CYP1A1 xenobiotic response element (XRE). 6,2′,4′-trimethoxyflavone (TMF), a well-characterized AhR-ligand antagonist significantly suppressed PCB126-induced increase in CYP1A1 expression, while the same treatment did not suppress 4-ClBQ-induced increase in CYP1A1 expression. However, siRNA-mediated down-regulation of AhR significantly inhibited 4-ClBQ-induced increase in CYP1A1 expression, suggesting that AhR mediates 4-ClBQ-induced increase in CYP1A1 expression. Interestingly, treatment with the antioxidant N-acetyl-L-cysteine significantly suppressed 4-ClBQ-induced increase in CYP1A1 expression. Furthermore, CYP1A1 expression also increased in cells treated with hydrogen peroxide. These results demonstrate that a ligand-independent and oxidative stress dependent pathway activates AhR-signaling in 4-ClBQ treated HaCaT cells. Because AhR signaling is believed to mediate xenobiotics response, our results may provide a mechanistic rationale for the use of antioxidants as effective countermeasure to environmental pollutant-induced adverse health effects. PMID:25668756

  18. Symmetry-related mutants in the quinone binding sites of the reaction center -- The effects of changes in charge distribution

    SciTech Connect

    Hanson, D.K.; Schiffer, M.

    1997-09-01

    To probe the structural elements that contribute to the functional asymmetries of the two ubiquinone{sub 10}binding pockets in the reaction center of Rhodobacter capsulatus, the authors targeted the L212Glu-L213Asp (near Q{sub B}) and the M246Ala-M247Ala (near Q{sub A}) pairs of symmetry-related residues for site-specific mutagenesis. They have constructed site-specific mutants that eliminate the sequence differences at these positions (L212Glu-L213Asp{yields}Ala-Ala or M246Ala-M247Ala{yields}Glu-Asp), and have reversed that asymmetry by constructing a quadruple-mutant strain, RQ (L212Glu-L213Asp-M246Ala-M247Ala{yields}Ala-Ala-Glu-Asp). The mutations were designed to change the charge distribution in the quinone-binding region of the reaction center; none of the strains is capable of photosynthetic growth. In photocomponent phenotypic revertants of the RQ strain, second-site mutations which affect Q{sub B} function are coupled to mutations in the Q{sub A} site which restore an Ala or substitute a Tyr at the M247 site; one strain carries an additional Met{yields}Glu substitution at M260 near Q{sub A}. All of the RQ revertants retain the engineered M246Ala{yields}Glu mutation in the Q{sub A} site as well as the L212Ala-L213Ala mutations in the Q{sub B} site. Kinetic characterization of the RQ revertants will give them an idea of what structural and functional elements are important for restoring efficiency to electron and proton transfer pathways in the RQRC, which is far from native. To date, these preliminary results underscore the importance of an asymmetric distribution of polar amino acids in the quinone binding pockets and its influence on the functional properties of the reaction center.

  19. The Na+-Translocating NADH:Quinone Oxidoreductase Enhances Oxidative Stress in the Cytoplasm of Vibrio cholerae

    PubMed Central

    Muras, Valentin; Dogaru-Kinn, Paul; Minato, Yusuke; Häse, Claudia C.

    2016-01-01

    ABSTRACT We searched for a source of reactive oxygen species (ROS) in the cytoplasm of the human pathogen Vibrio cholerae and addressed the mechanism of ROS formation using the dye 2′,7′-dichlorofluorescein diacetate (DCFH-DA) in respiring cells. By comparing V. cholerae strains with or without active Na+-translocating NADH:quinone oxidoreductase (Na+-NQR), this respiratory sodium ion redox pump was identified as a producer of ROS in vivo. The amount of cytoplasmic ROS detected in V. cholerae cells producing variants of Na+-NQR correlated well with rates of superoxide formation by the corresponding membrane fractions. Membranes from wild-type V. cholerae showed increased superoxide production activity (9.8 ± 0.6 μmol superoxide min−1 mg−1 membrane protein) compared to membranes from the mutant lacking Na+-NQR (0.18 ± 0.01 μmol min−1 mg−1). Overexpression of plasmid-encoded Na+-NQR in the nqr deletion strain resulted in a drastic increase in the formation of superoxide (42.6 ± 2.8 μmol min−1 mg−1). By analyzing a variant of Na+-NQR devoid of quinone reduction activity, we identified the reduced flavin adenine dinucleotide (FAD) cofactor of cytoplasmic NqrF subunit as the site for intracellular superoxide formation in V. cholerae. The impact of superoxide formation by the Na+-NQR on the virulence of V. cholerae is discussed. IMPORTANCE In several studies, it was demonstrated that the Na+-NQR in V. cholerae affects virulence in a yet unknown manner. We identified the reduced FAD cofactor in the NADH-oxidizing NqrF subunit of the Na+-NQR as the site of superoxide formation in the cytoplasm of V. cholerae. Our study provides the framework to understand how reactive oxygen species formed during respiration could participate in the regulated expression of virulence factors during the transition from aerobic to microaerophilic (intestinal) habitats. This hypothesis may turn out to be right for many other pathogens which, like V. cholerae, depend on

  20. The Na+-Translocating NADH:Quinone Oxidoreductase Enhances Oxidative Stress in the Cytoplasm of Vibrio cholerae.

    PubMed

    Muras, Valentin; Dogaru-Kinn, Paul; Minato, Yusuke; Häse, Claudia C; Steuber, Julia

    2016-09-01

    We searched for a source of reactive oxygen species (ROS) in the cytoplasm of the human pathogen Vibrio cholerae and addressed the mechanism of ROS formation using the dye 2',7'-dichlorofluorescein diacetate (DCFH-DA) in respiring cells. By comparing V. cholerae strains with or without active Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR), this respiratory sodium ion redox pump was identified as a producer of ROS in vivo The amount of cytoplasmic ROS detected in V. cholerae cells producing variants of Na(+)-NQR correlated well with rates of superoxide formation by the corresponding membrane fractions. Membranes from wild-type V. cholerae showed increased superoxide production activity (9.8 ± 0.6 μmol superoxide min(-1) mg(-1) membrane protein) compared to membranes from the mutant lacking Na(+)-NQR (0.18 ± 0.01 μmol min(-1) mg(-1)). Overexpression of plasmid-encoded Na(+)-NQR in the nqr deletion strain resulted in a drastic increase in the formation of superoxide (42.6 ± 2.8 μmol min(-1) mg(-1)). By analyzing a variant of Na(+)-NQR devoid of quinone reduction activity, we identified the reduced flavin adenine dinucleotide (FAD) cofactor of cytoplasmic NqrF subunit as the site for intracellular superoxide formation in V. cholerae The impact of superoxide formation by the Na(+)-NQR on the virulence of V. cholerae is discussed. In several studies, it was demonstrated that the Na(+)-NQR in V. cholerae affects virulence in a yet unknown manner. We identified the reduced FAD cofactor in the NADH-oxidizing NqrF subunit of the Na(+)-NQR as the site of superoxide formation in the cytoplasm of V. cholerae Our study provides the framework to understand how reactive oxygen species formed during respiration could participate in the regulated expression of virulence factors during the transition from aerobic to microaerophilic (intestinal) habitats. This hypothesis may turn out to be right for many other pathogens which, like V. cholerae, depend on the Na

  1. Exploring Cancer Therapeutics with Natural Products from African Medicinal Plants, Part I: Xanthones, Quinones, Steroids, Coumarins, Phenolics and other Classes of Compounds.

    PubMed

    Simoben, Conrad V; Ibezim, Akachukwu; Ntie-Kang, Fidele; Nwodo, Justina N; Lifongo, Lydia L

    2015-01-01

    Cancer is known to be the second most common disease-related cause of death among humans. In drug discovery programs anti-cancer chemotherapy remains quite challenging due to issues related to resistance. Plants used in traditional medicine are known to contribute significantly within a large proportion of the African population. A survey of the literature has led to the identification of ~400 compounds from African medicinal plants, which have shown anti-cancer, anti-proliferation, anti-tumor and/or cytotoxic activities, tested by in vitro and in vivo assays (from mildly active to very active), mainly alkaloids, terpenoids, flavonoids, coumarins, phenolics, polyacetylates, xanthones, quinones, steroids and lignans. The first part of this review series focuses on xanthones, quinones, steroids, coumarins, phenolics and other compound classes, while part II is focused on alkaloids, terpenoids, flavonoids.

  2. NAD(P)H:quinone oxidoreductase 1 Arg139Trp and Pro187Ser polymorphisms imbalance estrogen metabolism towards DNA adduct formation in human mammary epithelial cells.

    PubMed

    Singh, Seema; Zahid, Muhammad; Saeed, Muhammad; Gaikwad, Nilesh W; Meza, Jane L; Cavalieri, Ercole L; Rogan, Eleanor G; Chakravarti, Dhrubajyoti

    2009-10-01

    Estrogens (estrone, E(1); estradiol, E(2)) are oxidized in the breast first to catechols and then to form two ortho-quinones (E(1/2)-3,4-Q) that react with DNA to form depurinating adducts, which lead to mutations associated with breast cancer. NAD(P)H:quinone oxidoreductase 1 (NQO1) reduces these quinones back to catechols, and thus may protect against this mechanism. We examined whether the inheritance of two polymorphic variants of NQO1 (Pro187Ser or Arg139Trp) would result in poor reduction of E(1/2)-3,4-Q in normal human mammary epithelial cells (MCF-10F) and increased depurinating adduct formation. An isogenic set of stably transfected normal human breast epithelial cells (MCF-10F) that express a truncated (135Stop), the wild-type, the 139Trp variant or the 187Ser variant of human NQO1 cDNA was constructed. MCF-10F cells showed a low endogenous NQO1 activity. NQO1 expression was examined by RT-PCR and Western blotting, and catalytic activity of reducing E(2)-3,4-Q to 4-hydroxyE(1/2) and associated changes in the levels of quinone conjugates (4-methoxyE(1/2), 4-OHE(1/2)-2-glutathione, 4-OHE(1/2)-2-Cys and 4-OHE(1/2)-2-N-acetylcysteine) and depurinating DNA adducts (4-OHE(1/2)-1-N3Ade and 4-OHE(1/2)-1-N7Gua) were examined by HPLC with electrochemical detection, as well as by ultra-performance liquid chromatography with tandem mass spectrometry. The polymorphic variants transcribed comparably to the wild-type NQO1, but produced approximately 2-fold lower levels of the protein, suggesting that the variant proteins may become degraded. E(1/2)-3,4-Q toxicity to MCF-10F cells (IC50=24.74 microM) was increased (IC50=3.7 microM) by Ro41-0960 (3 microM), a catechol-O-methyltransferase inhibitor. Cells expressing polymorphic NQO1 treated with E(2)-3,4-Q with or without added Ro41-0960, showed lower ability to reduce the quinone ( approximately 50% lower levels of the free catechols and approximately 3-fold lower levels of methylated catechols) compared to the wild

  3. Polar lipid fatty acids, LPS-hydroxy fatty acids, and respiratory quinones of three Geobacter strains, and variation with electron acceptor

    SciTech Connect

    Hedrick, David B.; Peacock, Aaron; Lovley, Derek; Woodard, Trevor L.; Nevin, Kelly P.; Long, Philip E.; White, David C.

    2009-02-01

    The polar lipid fatty acids, lipopolysaccharide hydroxy-fatty acids, and respiratory quinones of Geobacter metallireducens str. GS-15, Geobacter sulfurreducens str. PCA, and Geobacter bemidjiensis str. Bem are reported. Also, the lipids of G. metallireducens were compared when grown with Fe3+ or nitrate as electron acceptors and G. sulfurreducens with Fe3+ or fumarate. In all experiments, the most abundant polar lipid fatty acids were 14:0, i15:0, 16:1*7c, 16:1*5c, and 16:0; lipopolysaccharide hydroxyfatty acids were dominated by 3oh16:0, 3oh14:0, 9oh16:0, and 10oh16:0; and menaquinone-8 was the most abundant respiratory quinone. Some variation in lipid proWles with strain were observed, but not with electron acceptor.

  4. Antineoplastic agents. 552. Oxidation of combretastatin A-1: trapping the o-quinone intermediate considered the metabolic product of the corresponding phosphate prodrug.

    PubMed

    Pettit, George R; Thornhill, Andrew J; Moser, Bryan R; Hogan, Fiona

    2008-09-01

    The very unstable (<10 min at rt) o-quinone 5 derived from the vicinal diphenol anticancer drug combretastatin A-1 (1) has been obtained by careful oxidation with NaIO4 and tetrabutylammonium bromide in water/dichloromethane. Immediate reaction with phenylenediamine (6) allowed o-quinone 5 to be trapped as the stable phenazine derivative 7. For further confirmation, 5 was also captured as a dimethoxyphenylenediamine-derived phenazine (11). Both phenazines 7 and 11 significantly inhibited (ED50 approximately 0.2 microg/mL) growth of the murine P388 lymphocytic leukemia cell line and provided a new SAR insight in the combretastatin series of naturally occurring anticancer drugs.

  5. Brønsted Acid Catalyzed Addition of Enamides to ortho-Quinone Methide Imines-An Efficient and Highly Enantioselective Synthesis of Chiral Tetrahydroacridines.

    PubMed

    Kretzschmar, Martin; Hodík, Tomáš; Schneider, Christoph

    2016-08-08

    The direct and highly enantioselective synthesis of tetrahydroacridines was achieved through the phosphoric acid catalyzed addition of enamides to in situ generated ortho-quinone methide imines and subsequent elimination. This novel one-step process constitutes a very efficient, elegant, and selective synthetic approach to valuable N-heterocycles with a 1,4-dihydroquinoline motif. By subsequent highly diastereoselective hydrogenation and N-deprotection the reaction products were easily converted into free hexahydroacridines with a total of three new stereogenic centers.

  6. Characterization of mutations in the cytochrome b subunit of the bc1 complex of Rhodobacter sphaeroides that affect the quinone reductase site (Qc).

    PubMed

    Hacker, B; Barquera, B; Crofts, A R; Gennis, R B

    1993-04-27

    The cytochrome b subunit of the bc1 complex contains two heme components, cytochrome bL and cytochrome bH, and is the locus of both a quinol oxidizing site (Qo or Qz) and a quinone reducing site (Qi or Qc). The quinone reductase site has been previously characterized as the site of interaction for a set of inhibitors including antimycin A, diuron, funiculosin, and HQNO. In this paper, four highly conserved residues in the cytochrome b subunit of Rhodobacter sphaeroides (A52, H217, K251, and D252) were targeted for site-directed mutagenesis. These residues were chosen as being likely to be at or near the quinone reductase site, on the basis of known locations of missense mutations in the homologous yeast subunit that confer resistance to Qc-directed inhibitors. The site-directed mutants all exhibit a normal rate of reduction of cytochrome bH, suggesting a fully functional quinol oxidizing site. However, each of the mutants is impaired, to varying degrees, in the rate of reoxidation of cytochrome bH. Two mutants (H217A and D252A) are unable to grow photosynthetically, indicating a severe defect in the bc1 complex. In both cases, the cause of the defect is the lack of reoxidation of cytochrome bH by ubiquinone. This is the first report of mutations that selectively impair the rate of electron transfer from cytochrome bH to the Qc-site. This set of mutations will be useful not only for modeling the structure of the quinone reducing site but also in elucidating the catalytic mechanism of this portion of the Q-cycle.

  7. Perturbation of the Quinone-binding Site of Complex II Alters the Electronic Properties of the Proximal [3Fe-4S] Iron-Sulfur Cluster*

    PubMed Central

    Ruprecht, Jonathan; Iwata, So; Rothery, Richard A.; Weiner, Joel H.; Maklashina, Elena; Cecchini, Gary

    2011-01-01

    Succinate-ubiquinone oxidoreductase (SQR) and menaquinol-fumarate oxidoreductase (QFR) from Escherichia coli are members of the complex II family of enzymes. SQR and QFR catalyze similar reactions with quinones; however, SQR preferentially reacts with higher potential ubiquinones, and QFR preferentially reacts with lower potential naphthoquinones. Both enzymes have a single functional quinone-binding site proximal to a [3Fe-4S] iron-sulfur cluster. A difference between SQR and QFR is that the redox potential of the [3Fe-4S] cluster in SQR is 140 mV higher than that found in QFR. This may reflect the character of the different quinones with which the two enzymes preferentially react. To investigate how the environment around the [3Fe-4S] cluster affects its redox properties and catalysis with quinones, a conserved amino acid proximal to the cluster was mutated in both enzymes. It was found that substitution of SdhB His-207 by threonine (as found in QFR) resulted in a 70-mV lowering of the redox potential of the cluster as measured by EPR. The converse substitution in QFR raised the redox potential of the cluster. X-ray structural analysis suggests that placing a charged residue near the [3Fe-4S] cluster is a primary reason for the alteration in redox potential with the hydrogen bonding environment having a lesser effect. Steady state enzyme kinetic characterization of the mutant enzymes shows that the redox properties of the [3Fe-4S] cluster have only a minor effect on catalysis. PMID:21310949

  8. [3+2] versus [4+2] cycloadditions of quinone monoimide with azadienes: a Lewis acid-free access to 5-amino-2,3-dihydrobenzofuranes.

    PubMed

    Lomberget, Thierry; Baragona, Fabien; Fenet, Bernard; Barret, Roland

    2006-08-31

    The reaction between p-quinone monoimide 1a and various azadienes 2 is described in the absence of a Lewis acid promoter. When alpha,beta-unsaturated hydrazones are substituted by proton or alkyl groups, 2,3-dihydrobenzofuranes 4, a motif that is present in numerous biologically active products, are obtained in moderate to excellent yields. The regio- and stereoselectivity of this reaction has been proved by a complete NMR study, including 1H-15N correlations.

  9. Perturbation of the quinone-binding site of complex II alters the electronic properties of the proximal [3Fe-4S] iron-sulfur cluster.

    PubMed

    Ruprecht, Jonathan; Iwata, So; Rothery, Richard A; Weiner, Joel H; Maklashina, Elena; Cecchini, Gary

    2011-04-08

    Succinate-ubiquinone oxidoreductase (SQR) and menaquinol-fumarate oxidoreductase (QFR) from Escherichia coli are members of the complex II family of enzymes. SQR and QFR catalyze similar reactions with quinones; however, SQR preferentially reacts with higher potential ubiquinones, and QFR preferentially reacts with lower potential naphthoquinones. Both enzymes have a single functional quinone-binding site proximal to a [3Fe-4S] iron-sulfur cluster. A difference between SQR and QFR is that the redox potential of the [3Fe-4S] cluster in SQR is 140 mV higher than that found in QFR. This may reflect the character of the different quinones with which the two enzymes preferentially react. To investigate how the environment around the [3Fe-4S] cluster affects its redox properties and catalysis with quinones, a conserved amino acid proximal to the cluster was mutated in both enzymes. It was found that substitution of SdhB His-207 by threonine (as found in QFR) resulted in a 70-mV lowering of the redox potential of the cluster as measured by EPR. The converse substitution in QFR raised the redox potential of the cluster. X-ray structural analysis suggests that placing a charged residue near the [3Fe-4S] cluster is a primary reason for the alteration in redox potential with the hydrogen bonding environment having a lesser effect. Steady state enzyme kinetic characterization of the mutant enzymes shows that the redox properties of the [3Fe-4S] cluster have only a minor effect on catalysis.

  10. Rhodium-Catalyzed Hydroacylation of para-Quinone Methides with Salicylaldehydes: An Approach to α,α-Diaryl-2-Hydroxy Acetophenones.

    PubMed

    Yang, Chi; Gao, Shang; Yao, Hequan; Lin, Aijun

    2016-12-02

    A rhodium-catalyzed hydroacylation of para-quinone methides (p-QMs) with salicylaldehydes has been disclosed. This method allows for the construction of α,α-diaryl-2-hydroxy acetophenones through tandem C-H activation/C-C bond formation/aromatization process. Moreover, this unprecedented hydroacylation of trisubstituted alkenes exhibits good yields with broad functional group tolerance as well as gram-scale capacity.

  11. QSAR studies on 1,2-dithiole-3-thiones: modeling of lipophilicity, quinone reductase specific activity, and production of growth hormone.

    PubMed

    Khadikar, Padmakar; Jaiswal, Mona; Gupta, Madhu; Mandloi, Dheeraj; Sisodia, Raj Singh

    2005-02-15

    Studies on modeling of lipophilicity (logP) quinone reductase specific activity (logCDQR) and production of growth hormone (logCDGH) of 1,2-dithiole-3-thiones have been carried out using distance-based topological indices. The regression analysis of the data has shown that the set of compounds exhibit 'familial' relationships in that excellent results are obtained by dividing the data set into two or more classes (families).

  12. A physiological threshold for protection against menadione toxicity by human NAD(P)H:quinone oxidoreductase (NQO1) in Chinese hamster ovary (CHO) cells.

    PubMed

    De Haan, Laura H J; Boerboom, Anne Marie J F; Rietjens, Ivonne M C M; van Capelle, Daniëlla; De Ruijter, Annemieke J M; Jaiswal, Anil K; Aarts, Jac M M J G

    2002-12-01

    NAD(P)H:quinone oxidoreductase 1 (NQO1) has often been suggested to be involved in cancer prevention by means of detoxification of electrophilic quinones. In the present study, a series of Chinese hamster ovary (CHO) cell lines expressing various elevated levels of human NQO1 were generated by stable transfection. The level of NQO1 over-expression ranged from 14 to 29 times the NQO1 activity in the wild-type CHO cells. This panel of cell lines, allowed investigation of the protective role of NQO1 in quinone cytotoxicity. It could be demonstrated that menadione toxicity was significantly reduced in all NQO1-transfected CHO clones compared to the wild-type cells, but the clones did not show differences in their level of protection against menadione. This observation pointed at a critical threshold concentration of NQO1 above which a further increase does not provide further protection against quinone cytotoxicity. Additional studies in which the NQO1 activity was inhibited by dicoumarol showed that only dicoumarol concentrations of about five times the EC(50) for NQO1 inhibition were able to reduce NQO1 levels below the apparent threshold, making the cells more sensitive. The level of this threshold was estimated to be in the range of base line NQO1 activities observed in several tissues and species. Thus, the results of the present study indicate that beneficial effects of NQO1 induction by, for example, cruciferous vegetables might be absent or present depending on the NQO1 activity threshold for optimal protection and the basal level of NQO1 expression in the tissue and species of interest.

  13. Changes in [14C]Atrazine Binding Associated with the Oxidation-Reduction State of the Secondary Quinone Acceptor of Photosystem II 1

    PubMed Central

    Jursinic, Paul; Stemler, Alan

    1983-01-01

    One hypothesis of triazine-type herbicide action in photosynthetic material is that the herbicide molecule competes with a secondary quinone acceptor, B, for a binding site at the reaction center of photosystem II. The binding affinity of B has been suggested to change with its level of reduction, being most strongly bound in its semiquinone form. To test this hypothesis, [14C]atrazine binding studies have been carried out under different photochemically induced levels of B reduction in Pisum sativum. It is found that herbicide binding is reduced in continuously illuminated samples compared to dark-adapted samples. Decreased binding of atrazine corresponds to an increase in the semiquinone form of B. With flash excitation, the herbicide binding oscillates with a cycle of two, being low on odd-numbered flashes when the amount of semiquinone form of B is greatest. Treatment with NH2OH was found to significantly decrease the strength of herbicide binding in the dark as well as stop the ability of p-benzoquinone to oxidize the semiquinone form of B. It is suggested that the mode of action of NH2OH is disruption of quinones or their environment on both the oxidizing and reducing sides of photosystem II. Herbicide binding was found to be unaltered under conditions when p-benzosemiquinone oxidation of the reduced primary acceptor, Q−, is herbicide insensitive; weak herbicide binding cannot explain this herbicide insensitivity. It is concluded that the quinone-herbicide competition theory of herbicide action is correct. Also, since quinones are lipophilic the importance of the lipid composition of the thylakoid membrane in herbicide interactions is stressed. PMID:16663286

  14. Free radical-derived quinone methide mediates skin tumor promotion by butylated hydroxytoluene hydroperoxide: expanded role for electrophiles in multistage carcinogenesis.

    PubMed Central

    Guyton, K Z; Bhan, P; Kuppusamy, P; Zweier, J L; Trush, M A; Kensler, T W

    1991-01-01

    Free radical derivatives of peroxides, hydroperoxides, and anthrones are thought to mediate tumor promotion by these compounds. Further, the promoting activity of phorbol esters is attributed, in part, to their ability to stimulate the cellular generation of oxygen radicals. A hydroperoxide metabolite of butylated hydroxytoluene, 2,6-di-tert-butyl-4-hydroperoxyl-4-methyl-2,5-cyclohexadienone (BHTOOH), has previously been shown to be a tumor promoter in mouse skin. BHTOOH is extensively metabolized by murine keratinocytes to several radical species. The primary radical generated from BHTOOH is a phenoxyl radical that can disproportionate to form butylated hydroxytoluene quinone methide, a reactive electrophile. Since electrophilic species have not been previously postulated to mediate tumor promotion, the present study was undertaken to examine the role of this electrophile in the promoting activity of BHTOOH. The biological activities of two chemical analogs of BHTOOH, 4-trideuteromethyl-BHTOOH and 4-tert-butyl-BHTOOH, were compared with that of the parent compound. 4-Trideuteromethyl-BHTOOH and 4-tert-butyl-BHTOOH have a reduced ability or inability, respectively, to form a quinone methide; however, like the parent compound, they both generate a phenoxyl radical when incubated with keratinocyte cytosol. The potency of BHTOOH, 4-trideuteromethyl-BHTOOH, and 4-tert-butyl-BHTOOH as inducers of ornithine decarboxylase, a marker of tumor promotion, was commensurate with their capacity for generating butylated hydroxytoluene quinone methide. These initial results were confirmed in a two-stage tumor promotion protocol in female SENCAR mice. Together, these data indicate that a quinone methide is mediating tumor promotion by BHTOOH, providing direct evidence that an electrophilic intermediate can elicit this stage of carcinogenesis. PMID:1846971

  15. Identifying involvement of Lys251/Asp252 pair in electron transfer and associated proton transfer at the quinone reduction site of Rhodobacter capsulatus cytochrome bc1.

    PubMed

    Kuleta, Patryk; Sarewicz, Marcin; Postila, Pekka; Róg, Tomasz; Osyczka, Artur

    2016-10-01

    Describing dynamics of proton transfers in proteins is challenging, but crucial for understanding processes which use them for biological functions. In cytochrome bc1, one of the key enzymes of respiration or photosynthesis, proton transfers engage in oxidation of quinol (QH2) and reduction of quinone (Q) taking place at two distinct catalytic sites. Here we evaluated by site-directed mutagenesis the contribution of Lys251/Asp252 pair (bacterial numbering) in electron transfers and associated with it proton uptake to the quinone reduction site (Qi site). We showed that the absence of protonable group at position 251 or 252 significantly changes the equilibrium levels of electronic reactions including the Qi-site mediated oxidation of heme bH, reverse reduction of heme bH by quinol and heme bH/Qi semiquinone equilibrium. This implicates the role of H-bonding network in binding of quinone/semiquinone and defining thermodynamic properties of Q/SQ/QH2 triad. The Lys251/Asp252 proton path is disabled only when both protonable groups are removed. With just one protonable residue from this pair, the entrance of protons to the catalytic site is sustained, albeit at lower rates, indicating that protons can travel through parallel routes, possibly involving water molecules. This shows that proton paths display engineering tolerance for change as long as all the elements available for functional cooperation secure efficient proton delivery to the catalytic site.

  16. Regiospecific attack of nitrogen and sulfur nucleophiles on quinones derived from poison oak/ivy catechols (urushiols) and analogues as models for urushiol-protein conjugate formation.

    PubMed

    Liberato, D J; Byers, V S; Dennick, R G; Castagnoli, N

    1981-01-01

    Attempts to characterize potential biologically important covalent interactions between electrophilic quinones derived from catechols present in poison oak/ivy (urushiol) and biomacromolecules have led to the analysis of model reactions involving sulfur and amino nucleophiles with 3-heptadecylbenzoquinone. Characterization of the reaction products indicates that this quinone undergoes regiospecific attack by (S)-N-acetylcysteine at C-6 and by 1-aminopentane at C-5. The red solid obtained with 1-aminopentane proved to be 3-heptadecyl-5-(pentylamino)-1,2-benzoquinone. Analogous aminobenzoquinones were obtained with the quinones derived from the 4- and 6-methyl analogues of 3-pentadecylcatechol. All three adducts absorbed visible light at different wavelengths. When the starting catechols were incubated with human serum albumin almost identical chromophores were formed. These results establish that cathechols responsible for the production of the poison oak/ivy contact dermatitis in humans undergo a sequence of reactions in the presence of human serum albumin that lead to covalent attachment of the catechols to the protein via carbon-nitrogen bonds. Estimations of the extent of this binding indicate that, at least with human serum albumin, the reaction is quantitative.

  17. Photosensitized Oxidation of Hypoxanthine and Xanthine by Aluminum Phthalocyanine Tetrasulfonate. Role of the Alkylating Quinone 2,5-Dichloro-diaziridinyl-1,4-benzoquinone

    PubMed Central

    Alegria, Antonio E.; Inostroza, Yaritza; Kumar, Ajay

    2009-01-01

    Photoirradiation of nitrogen-saturated aqueous solutions containing aluminum phthalocyanine tetrasulfonate (AlPcS4) at 675 nm in the presence of 2,5-dichloro-diaziridinyl-1,4-benzoquinone (AZDClQ) and hypoxanthine (HX) produces the oxidized HX derivatives, xanthine (X) and uric acid (UA). Concentrations of the AZDClQ semiquinone, X and UA increase at the expense of HX with an increase in irradiation time. Almost negligible decomposition of HX, as well as very low amounts of X, are detected if photolysis occurs under identical conditions but in the absence of AZDClQ. Addition of calf-thymus DNA produces quinone-DNA covalent adducts after photolysis of anaerobic samples containing quinone, DNA and AlPcS4, in the presence or absence of HX and at pH 5.5. However, larger amounts of quinone-DNA adducts are detected if HX is present. The results presented here could have applications in the photodynamic treatment of hypoxic tissues such as solid tumors, under conditions of high HX concentration, where Type-I pathways could be more important than singlet oxygen generation. PMID:18627517

  18. The structure and function of quinones in biological solar energy transduction: a cyclic voltammetry, EPR, and hyperfine sub-level correlation (HYSCORE) spectroscopy study of model naphthoquinones.

    PubMed

    Coates, Christopher S; Ziegler, Jessica; Manz, Katherine; Good, Jacob; Kang, Bernard; Milikisiyants, Sergey; Chatterjee, Ruchira; Hao, Sijie; Golbeck, John H; Lakshmi, K V

    2013-06-20

    Quinones function as electron transport cofactors in photosynthesis and cellular respiration. The versatility and functional diversity of quinones is primarily due to the diverse midpoint potentials that are tuned by the substituent effects and interactions with surrounding amino acid residues in the binding site in the protein. In the present study, a library of substituted 1,4-naphthoquinones are analyzed by cyclic voltammetry in both protic and aprotic solvents to determine effects of substituent groups and hydrogen bonds on the midpoint potential. We use continuous-wave electron paramagnetic resonance (EPR) spectroscopy to determine the influence of substituent groups on the electronic properties of the 1,4-naphthoquinone models in an aprotic solvent. The results establish a correlation between the presence of substituent group(s) and the modification of electronic properties and a corresponding shift in the midpoint potential of the naphthoquinone models. Further, we use pulsed EPR spectroscopy to determine the effect of substituent groups on the strength and planarity of the hydrogen bonds of naphthoquinone models in a protic solvent. This study provides support for the tuning of the electronic properties of quinone cofactors by the influence of substituent groups and hydrogen bonding interactions.

  19. Structure and function of quinones in biological solar energy transduction: a high-frequency D-band EPR spectroscopy study of model benzoquinones.

    PubMed

    Chatterjee, Ruchira; Coates, Christopher S; Milikisiyants, Sergey; Poluektov, Oleg G; Lakshmi, K V

    2012-01-12

    Quinones are utilized as charge-transfer cofactors in a wide variety of reactions that are crucial for photosynthesis and respiration. In photosynthetic protein complexes, both Type I and Type II, including oxygenic and anoxygenic reaction centers contain quinone cofactors that are known to participate in electron- and proton-transfer processes. Type II reaction centers, purple bacterial reaction centers, and photosystem II utilize benzoquinone molecules, ubiquinone, and plastoquinone, respectively, to facilitate proton-coupled electron transfer reactions. Here, we report a systematic study of the principal components of the g-tensor of an extensive library of model benzosemiquinone anion radicals in both protic (2-isopropanol) and aprotic (dimethyl sulfoxide) solvents using high-frequency EPR spectroscopy. A detailed comparison of the experimental g-values of the benzosemiquinone models at D-band EPR frequency allows for the discrimination of substituent effects and solvent hydrogen bonds on the principal components of the g-tensor. Further, we compare the primary plastosemiquinone, Q(A)(-), of photosystem II with the substituent and solvent hydrogen bond effects of benzosemiquinone models in vitro. This study significantly extends the experimental basis for elucidating the role of both molecular structure and interactions with environment on the functional tuning of quinone cofactors in biological solar energy transduction.

  20. Characterization of two quinone radicals in the NADH:ubiquinone oxidoreductase from Escherichia coli by a combined fluorescence spectroscopic and electrochemical approach.

    PubMed

    Hielscher, Ruth; Yegres, Michelle; Voicescu, Mariana; Gnandt, Emmanuel; Friedrich, Thorsten; Hellwig, Petra

    2013-12-17

    The NADH:ubiquinone oxidoreductase (complex I) couples the transfer of electrons from NADH to ubiquinone with the translocation of protons across the membrane. It was proposed that the electron transfer involves quinoid groups localized at the end of the electron transfer chain. To identify these groups, fluorescence excitation and emission spectra of Escherichia coli complex I and its fragments, namely, the NADH dehydrogenase fragment containing the flavin mononucleotide and six iron-sulfur (Fe-S) clusters, and the quinone reductase fragment containing three Fe-S clusters were measured. Signals sensitive to reduction by either NADH or dithionite were detected within the complex and the quinone reductase fragment and attributed to the redox transition of protonated ubiquinone radicals. A fluorescence spectroscopic electrochemical redox titration revealed midpoint potentials of -37 and- 235 mV (vs the standard hydrogen electrode) for the redox transitions of the quinone radicals in complex I at pH 6 with an absorption around 325 nm and a fluorescence emission at 460/475 nm. The role of these cofactor(s) for electron transfer is discussed.

  1. Quinone 1 e and 2 e /2 H + Reduction Potentials: Identification and Analysis of Deviations from Systematic Scaling Relationships

    SciTech Connect

    Huynh, Mioy T.; Anson, Colin W.; Cavell, Andrew C.; Stahl, Shannon S.; Hammes-Schiffer, Sharon

    2016-11-10

    Quinones participate in diverse electron transfer and proton-coupled electron transfer processes in chemistry and biology. An experimental study of common quinones reveals a non-linear correlation between the 1 e and 2 e/2 H+ reduction potentials. This unexpected observation prompted a computational study of 128 different quinones, probing their 1 e reduction potentials, pKa values, and 2 e/2 H+ reduction potentials. The density functional theory calculations reveal an approximately linear correlation between these three properties and an effective Hammett constant associated with the quinone substituent(s). However, deviations from this linear scaling relationship are evident for quinones that feature halogen substituents, charged substituents, intramolecular hydrogen bonding in the hydroquinone, and/or sterically bulky substituents. These results, particularly the different substituent effects on the 1 e versus 2 e /2 H+ reduction potentials, have important implications for designing quinones with tailored redox properties.

  2. Accurate calculation of absolute one-electron redox potentials of some para-quinone derivatives in acetonitrile.

    PubMed

    Namazian, Mansoor; Coote, Michelle L

    2007-08-02

    Standard ab initio molecular orbital theory and density functional theory calculations have been used to calculate absolute one-electron reduction potentials of several para-quinones in acetonitrile. The high-level composite method of G3(MP2)-RAD is used for the gas-phase calculations and a continuum model of solvation, CPCM, has been employed to calculate solvation energies. To compare the theoretical reduction potentials with experiment, the reduction potentials relative to a standard calomel electrode (SCE) have also been calculated and compared to experimental values. The average error of the calculated reduction potentials using the proposed method is 0.07 V without any additional approximation. An ONIOM method in which the core is studied at G3(MP2)-RAD and the substituent effect of the rest of the molecule is studied at R(O)MP2/6-311+G(3df,2p) provides an accurate low-cost alternative to G3(MP2)-RAD for larger molecules.

  3. Regulation of the primary quinone binding conformation by the H subunit in reaction centers from Rhodobacter sphaeroides.

    PubMed

    Sun, Chang; Taguchi, Alexander T; Beal, Nathan J; O'Malley, Patrick J; Dikanov, Sergei A; Wraight, Colin A

    2015-11-19

    Unlike photosystem II (PSII) in higher plants, bacterial photosynthetic reaction centers (bRCs) from Proteobacteria have an additional peripheral membrane subunit "H". The H subunit is necessary for photosynthetic growth, but can be removed chemically in vitro. The remaining LM dimer retains its activity to perform light-induced charge separation. Here we investigate the influence of the H subunit on interactions between the primary semiquinone and the protein matrix, using a combination of site-specific isotope labeling, pulsed electron paramagnetic resonance (EPR), and density functional theory (DFT) calculations. The data reveal substantially weaker binding interactions between the primary semiquinone and the LM dimer than observed for the intact bRC; the amount of electron spin transferred to the nitrogen hydrogen bond donors is significantly reduced, the methoxy groups are more free to rotate, and the spectra indicate a heterogeneous mixture of bound semiquinone states. These results are consistent with a loosening of the primary quinone binding pocket in the absence of the H subunit.

  4. Synthesis, spectral characterization, molecular structure and pharmacological studies of N'-(1, 4-naphtho-quinone-2yl) isonicotinohyWdrazide

    NASA Astrophysics Data System (ADS)

    Kavitha Rani, P. R.; Fernandez, Annette; George, Annie; Remadevi, V. K.; Sudarsanakumar, M. R.; Laila, Shiny P.; Arif, Muhammed

    2015-01-01

    A simple and efficient procedure was employed for the synthesis of N'-(1,4-naphtho-quinone-2-yl) isonicotinohydrazide (NIH) by the reaction of 2-hydroxy-1,4-naphthaquinone (lawsone) and isonicotinoyl hydrazine in methanol using ultrasonic irradiation. Lawsone is the principal dye, isolated from the leaves of henna (Lawsonia inermis). Structural modification was done on the molecule aiming to get a more active derivative. The structure of the parent compound and the derivative was characterized by elemental analyses, infrared, electronic, 1H, 13C NMR and GC-MS spectra. The fluorescence spectral investigation of the compound was studied in DMSO and ethanol. Single crystal X-ray diffraction studies reveal that NIH crystallizes in monoclinic space group. The DNA cleavage study was monitored by gel electrophoresis method. The synthesized compound was found to have significant antioxidant activity against DPPH radical (IC50 = 58 μM). The in vitro cytotoxic studies of the derivative against two human cancer cell lines MCF-7 (human breast cancer) and HCT-15 (human colon carcinoma cells) using MTT assay revealed that the compound exhibited higher cytotoxic activity with a lower IC50 value indicating its efficiency in killing the cancer cells even at low concentrations. These results suggest that the structural modifications performed on lawsone could be considered a good strategy to obtain a more active drug.

  5. Differently substituted sulfonated polyanilines: the role of polymer compositions in electron transfer with pyrroloquinoline quinone-dependent glucose dehydrogenase.

    PubMed

    Sarauli, David; Xu, Chenggang; Dietzel, Birgit; Schulz, Burkhard; Lisdat, Fred

    2013-09-01

    Sulfonated polyanilines have become promising building blocks in the construction of biosensors, and therefore we use here differently substituted polymer forms to investigate the role of their structural composition and properties in achieving a direct electron transfer with the redox enzyme pyrroloquinoline quinone-dependent glucose dehydrogenase (PQQ-GDH). To this end, new copolymers containing different ratios of 2-methoxyaniline-5-sulfonic acid (MAS), 3-aminobenzenesulfonic acid (ABS) and 3-aminobenzoic acid (AB) units have been chemically synthesized. All polymers have been studied with respect to their ability to react directly with PQQ-GDH. This interaction has been monitored initially in solution, and subsequently on electrode surfaces. The results show that only copolymers with MAS and aniline units can directly react with PQQ-GDH in solution; the background can be mainly ascribed to the emeraldine salt redox state of the polymer, allowing rather easy reduction. However, when polymers and the enzyme are immobilized on the surface of carbon nanotube-containing electrodes, direct bioelectrocatalysis is also feasible in the case of copolymers composed of ABS/AB and MAS/AB units, existing initially in pernigraniline base form. This verifies that a productive interaction of the enzyme with differently substituted polymers is feasible when the electrode potential can be used to drive the reaction towards the oxidation of the substrate-reduced enzyme. These results clearly demonstrate that enzyme electrodes based on sulfonated polyanilines and direct bioelectrocatalysis can be successfully constructed.

  6. Synthesis and in vitro evaluation of radioiodinated indolequinones targeting NAD(P)H: quinone oxidoreductase 1 for internal radiation therapy.

    PubMed

    Sasaki, Junichi; Sano, Kohei; Hagimori, Masayori; Yoshikawa, Mai; Maeda, Minoru; Mukai, Takahiro

    2014-11-01

    quinone oxidoreductase 1 (NQO1) is an obligate two-electron reductase and is highly expressed in many human solid cancers. Because NQO1 can be induced immediately after exposure to ionizing radiation, we aimed to develop an NQO1-targeted radiolabeled agent to establish a novel internal radiation therapy that amplifies the therapeutic effects when combined with external radiation therapy. We designed three NQO1-targeted radioiodinated compounds including two ether linkage compounds ([(125)I]1 and [(125)I]2) and a sulfide linkage compound ([(125)I]3) based on the selective binding of indolequinone analogs to the active site of NQO1 by the stacking effect. These compounds were successfully prepared using an oxidative iododestannylation reaction with high radiochemical yields and purity. In NQO1-expressing tumor cells, [(125)I]1 and [(125)I]2 were readily metabolized to p-[(125)I]iodophenol or m-[(125)I]iodophenol and [(125)I]I(-), whereas over 85% of the initial radioactivity of [(125)I]3 was observed as an intact form at 1h after incubation. The cellular uptake of [(125)I]3 was significantly higher than those of [(125)I]1 and [(125)I]2. The uptake of [(125)I]3 was specific and was dependent on the expression of NQO1. These data suggest that the novel NQO1-targeted radioiodinated compound [(125)I]3 could be used as a novel internal radiation agent for the treatment of cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  7. Mechanism of proton-coupled electron transfer for quinone (Q{sub B}) reduction in reaction centers of Rb sphaeroides

    SciTech Connect

    Graige, M.S.; Paddock, M.L; Feher, G.; Okamura, M.Y.; Bruce, J.M.

    1996-09-25

    The mechanism of the proton-coupled electron transfer reaction, Q{sub A}{sup -}Q{sub B}{sup -} + H{sup +} {yields} Q{sub A}(Q{sub B}H){sup -} (i.e. k{sup (2)}{sub AB}), was studied in reaction centers (RCs) from the photosynthetic bacterium Rb. sphaeroides by substituting quinones with different redox potentials into the Q{sub A} site. These substitutions change the driving force for electron transfer without affecting proton transfer rates or proton binding equilibria around the Q{sub B} site. The measured rate constants, k{sup (2)}{sub AB}, increased with increasing electron driving force (by a factor of 10 per 160 meV change in redox free energy). The proton-coupled electron transfer was modeled. The free energy dependencies of these possible mechanisms were predicted using Marcus theory and were compared to the observed dependence. The best agreement with the experimental data is given by a two-step mechanism in which fast reversible proton transfer is followed by rate limiting electron transfer. For this mechanism the observed free energy dependence for k{sup (2)}{sub AB} can be fitted using reasonable parameters of the Marcus theory. The free energy dependence predicted using a simple model for a concerted reaction also provides a reasonable fit to the data. 75 refs., 9 figs., 2 tabs.

  8. Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer

    SciTech Connect

    Sun, Bin; Hoshino, Juma; Jermihov, Katie; Marler, Laura; Pezzuto, John M.; Mesecar, Andrew D.; Cushman, Mark

    2012-07-11

    A series of new resveratrol analogues were designed and synthesized and their inhibitory activities against aromatase were evaluated. The crystal structure of human aromatase (PDB 3eqm) was used to rationalize the mechanism of action of the aromatase inhibitor 32 (IC{sub 50} 0.59 {mu}M) through docking, molecular mechanics energy minimization, and computer graphics molecular modeling, and the information was utilized to design several very potent inhibitors, including compounds 82 (IC{sub 50} 70 nM) and 84 (IC{sub 50} 36 nM). The aromatase inhibitory activities of these compounds are much more potent than that for the lead compound resveratrol, which has an IC{sub 50} of 80 {mu}M. In addition to aromatase inhibitory activity, compounds 32 and 44 also displayed potent QR2 inhibitory activity (IC{sub 50} 1.7 {mu}M and 0.27 {mu}M, respectively) and the high-resolution X-ray structures of QR2 in complex with these two compounds provide insight into their mechanism of QR2 inhibition. The aromatase and quinone reductase inhibitors resulting from these studies have potential value in the treatment and prevention of cancer.

  9. Voltammetric method for determining the trace moisture content of organic solvents based on hydrogen-bonding interactions with quinones.

    PubMed

    Hui, Yanlan; Chng, Elaine Lay Khim; Chua, Louisa Pei-Lyn; Liu, Wan Zhen; Webster, Richard D

    2010-03-01

    Voltammetry experiments were performed on the natural quinone, vitamin K(1) (VK(1)), in a range of organic solvents of varying dielectric constant that are commonly used for electrochemical measurements [dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), acetonitrile (MeCN), propionitrile (EtCN), butyronitrile (PrCN), 1,2-dichloroethane (DCE), dichloromethane (DCM), and 1,1,2,2-tetrachloroethane (TCE)]. The water content of the solvents was accurately measured using Karl Fischer (KF) coulometric titrations, and the voltammetric data were used to estimate the degree of hydrogen-bonding interactions between the reduced forms of VK(1) and variable levels of water, thereby allowing a ranking of water-substrate interactions in the different solvents. The voltammetric data were analyzed based on interactions that occur between reduced forms of VK(1) and the water, the solvent, and the supporting electrolyte. Calibration data were obtained that are independent of the nature of the reference electrode and allow the water content of the solvents to be calculated by performing a single voltammetric scan in the presence of VK(1) and 0.2 M supporting electrolyte (Bu(4)NPF(6)).

  10. Role of quinones in electron transfer of PQQ–glucose dehydrogenase anodes—mediation or orientation effect

    SciTech Connect

    Babanova, Sofia; Matanovic, Ivana; Chavez, Madelaine Seow; Atanassov, Plamen

    2015-06-16

    In this study, the influence of two quinones (1,2- and 1,4-benzoquinone) on the operation and mechanism of electron transfer in PQQ-sGDH anodes has been determined. Benzoquinones were experimentally explored as mediators present in the electrolyte. The electrochemical performance of the PQQ–sGDH anodes with and without the mediators was examined and for the first time molecular docking simulations were used to gain a fundamental understanding to explain the role of the mediator molecules in the design and operation of the enzymatic electrodes. It was proposed that the higher performance of the PQQ–sGDH anodes in the presence of 1,2- and 1,4-benzoquinones introduced in the solution is due to the shorter distance between these molecules and PQQ in the enzymatic molecule. It was also hypothesized that when 1,4-benzoquinone is adsorbed on a carbon support, it would play the dual role of a mediator and an orienting agent. At the same time, when 1,2-benzoquinone and ubiquinone are adsorbed on the electrode surface, the enzyme would transfer the electrons directly to the support, and these molecules would primarily play the role of an orienting agent.

  11. Pyrroloquinoline quinone increases the expression and activity of Sirt1 and -3 genes in HepG2 cells.

    PubMed

    Zhang, Jian; Meruvu, Sunitha; Bedi, Yudhishtar Singh; Chau, Jason; Arguelles, Andrix; Rucker, Robert; Choudhury, Mahua

    2015-09-01

    Sirtuin (Sirt) 1 and Sirt 3 are nicotinamide adenine dinucleotide ((+))-dependent protein deacetylases that are important to a number of mitochondrial-related functions; thus, identification of sirtuin activators is important. Herein, we hypothesize that pyrroloquinoline quinone (PQQ) can act as a Sirt1/Sirt3 activator. In HepG2 cell cultures, PQQ increased the expression of Sirt1 and Sirt3 gene, protein, and activity levels (P < .05). We also observed a significant increase in nicotinamide phosphoribosyltransferase gene expression (as early as 18 hours) and increased NAD(+) activity at 24 hours. In addition, targets of Sirt1 and Sirt3 (peroxisome proliferator-activated receptor γ coactivator 1α, nuclear respiratory factor 1 and 2, and mitochondrial transcription factor A) were increased at 48 hours. This is the first report that demonstrates PQQ as an activator of Sirt1 and Sirt3 expression and activity, making it an attractive therapeutic agent for the treatment of metabolic diseases and for healthy aging. Based on our study and the available data in vivo, PQQ has the potential to serve as a therapeutic nutraceutical, when enhancing mitochondrial function.

  12. Spectrofluorimetric determination of gemifloxacin mesylate and linezolid in pharmaceutical formulations: Application of quinone-based fluorophores and enhanced native fluorescence.

    PubMed

    Moussa, Bahia Abbas; Mahrouse, Marianne Alphonse; Hassan, Mahmoud Ali; Fawzy, Michael Gamal

    2014-03-01

    Quinone-based fluorophores and enhanced native fluorescence techniques were applied for a fast quantitative analysis of gemifloxacin mesylate (GEM) and linezolid (LIN) in pharmaceutical formulations. For this purpose, three sensitive, accurate and precise spectrofluorimetric methods were developed. GEM, as an n-electron donor, reacts with 7,7,8,8-tetracyanoquinodimethane (method A) and 2,5-dichloro-3,6-dihydroxy-p-benzoquinone (method B) as п-electron acceptors, forming charge transfer complexes that exhibit high fluorescence intensity at 441 and 390 nm upon excitation at 260 and 339 nm, respectively. Method C depends on measurement of enhanced native fluorescence of LIN in phosphate buffer (pH 5) at 380 nm upon excitation at 260 nm. Experimental factors affecting fluorescence intensity were optimized. Linearity was obtained over concentration ranges 50-500, 10-60 and 20-400 ng mL-1 for methods A, B and C, respectively. The developed methods were validated and successfully applied for determination of the cited drugs in tablets.

  13. Quinone-modified NH2-MIL-101(Fe) composite as a redox mediator for improved degradation of bisphenol A.

    PubMed

    Li, Xianghui; Guo, Weilin; Liu, Zhonghua; Wang, Ruiqin; Liu, Hua

    2017-02-15

    A novel quinone-modified metal-organic frameworks NH2-MIL-101(Fe) was synthesized using a simple chemical method under mild condition. The introduced 2-anthraquinone sulfonate (AQS) can be covalently modified with NH2-MIL-101(Fe) and acts as a redox mediator to enhance the degradation of bisphenol A (BPA) via persulfate activation. The obtained AQS-NH-MIL-101(Fe) was characterized by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectra, cyclic voltammetry and electrochemical impedance spectroscopy. AQS-NH-MIL-101(Fe) exhibited better catalytic performance compared with NH2-MIL-101(Fe) and NH2-MIL-101(Fe) with free AQS (NH2-MIL-101(Fe)/AQS). That is, AQS-NH-MIL-101(Fe) was proved to be the most effective in that more than 97.7% of BPA was removed. The degradation rate constants (k) of AQS-NH-MIL-101(Fe) was 9-fold higher than that of NH2-MIL-101(Fe) and 7-fold higher than NH2-MIL-101(Fe)/AQS, indicating that AQS is a great electron-transfer mediator when modified with NH2-MIL-101(Fe). Based on the above results, the possible mechanism of catalytic reaction has been investigated in view of the trapping experiments. In addition, the AQS-NH-MIL-101(Fe) catalyst exhibited excellent stability and can be used several times without significant deterioration in performance.

  14. "Quinone Millipedes" Reconsidered: Evidence for a Mosaic-Like Taxonomic Distribution of Phenol-Based Secretions across the Julidae.

    PubMed

    Bodner, Michaela; Vagalinski, Boyan; Makarov, Slobodan E; Antić, Dragan Ž; Vujisić, Ljubodrag V; Leis, Hans-Jörg; Raspotnig, Günther

    2016-03-01

    The defensive chemistry of juliformian millipedes is characterized mainly by benzoquinones ("quinone millipedes"), whereas the secretions of the putative close outgroup Callipodida are considered to be exclusively phenolic. We conducted a chemical screening of julid secretions for phenolic content. Most species from tribes Cylindroiulini (15 species examined), Brachyiulini (5 species examined), Leptoiulini (15 species examined), Uncigerini (2 species examined), Pachyiulini (3 species examined), and Ommatoiulini (2 species examined) had non-phenolic, in most cases exclusively benzoquinonic secretions. In contrast, tribes Cylindroiulini, Brachyiulini, and Leptoiulini also contained representatives with predominantly phenol-based exudates. In detail, p-cresol was a major compound in the secretions of the cylindroiulines Styrioiulus pelidnus and S. styricus (p-cresol content 93 %) and an undetermined Cylindroiulus species (p-cresol content 51 %), in the brachyiulines Brachyiulus lusitanus (p-cresol content 21 %) and Megaphyllum fagorum (p-cresol content 92 %), as well as in an undescribed Typhloiulus species (p-cresol content 32 %, Leptoiulini). In all species, p-cresol was accompanied by small amounts of phenol. The secretion of M. fagorum was exclusively phenolic, whereas phenols were accompanied by benzoquinones in all other species. This is the first incidence of clearly phenol-dominated secretions in the Julidae. We hypothesize a shared biosynthetic route to phenols and benzoquinones, with benzoquinones being produced from phenolic precursors. The patchy taxonomic distribution of phenols documented herein supports multiple independent regression events in a common pathway of benzoquinone synthesis rather than multiple independent incidences of phenol biosynthesis.

  15. Design, synthesis, and biological evaluation of resveratrol analogues as aromatase and quinone reductase 2 inhibitors for chemoprevention of cancer.

    PubMed

    Sun, Bin; Hoshino, Juma; Jermihov, Katie; Marler, Laura; Pezzuto, John M; Mesecar, Andrew D; Cushman, Mark

    2010-07-15

    A series of new resveratrol analogues were designed and synthesized and their inhibitory activities against aromatase were evaluated. The crystal structure of human aromatase (PDB 3eqm) was used to rationalize the mechanism of action of the aromatase inhibitor 32 (IC50 0.59 microM) through docking, molecular mechanics energy minimization, and computer graphics molecular modeling, and the information was utilized to design several very potent inhibitors, including compounds 82 (IC50 70 nM) and 84 (IC50 36 nM). The aromatase inhibitory activities of these compounds are much more potent than that for the lead compound resveratrol, which has an IC50 of 80 microM. In addition to aromatase inhibitory activity, compounds 32 and 44 also displayed potent QR2 inhibitory activity (IC50 1.7 microM and 0.27 microM, respectively) and the high-resolution X-ray structures of QR2 in complex with these two compounds provide insight into their mechanism of QR2 inhibition. The aromatase and quinone reductase inhibitors resulting from these studies have potential value in the treatment and prevention of cancer.

  16. Pyrroloquinoline quinone nutritional status alters lysine metabolism and modulates mitochondrial DNA content in the mouse and rat.

    PubMed

    Bauerly, K A; Storms, D H; Harris, C B; Hajizadeh, S; Sun, M Y; Cheung, C P; Satre, M A; Fascetti, A J; Tchaparian, E; Rucker, R B

    2006-11-01

    Pyrroloquinoline quinone (PQQ) added to purified diets devoid of PQQ improves indices of perinatal development in rats and mice. Herein, PQQ nutritional status and lysine metabolism are described, prompted by a report that PQQ functions as a vitamin-like enzymatic cofactor important in lysine metabolism (Nature 422 [2003] 832). Alternatively, we propose that PQQ influences lysine metabolism, but by mechanisms that more likely involve changes in mitochondrial content. PQQ deprivation in both rats and mice resulted in a decrease in mitochondrial content. In rats, alpha-aminoadipic acid (alphaAA), which is derived from alpha-aminoadipic semialdehyde (alphaAAS) and made from lysine in mitochondria, and the plasma levels of amino acids known to be oxidized in mitochondria (e.g., Thr, Ser, and Gly) were correlated with changes in the liver mitochondrial content of PQQ-deprived rats, but not PQQ-supplemented rats. In contrast, the levels of NAD dependent alpha-aminoadipate-delta-semialdehyde dehydrogenase (AASDH), a cytosolic enzyme important to alphaAA production from alphaAAS, was not influenced by PQQ dietary status. Moreover, the levels of U26 mRNA were not significantly changed even when diets differed markedly in PQQ and dietary lysine content. U26 mRNA levels were measured, because of U26's proposed, albeit questionable role as a PQQ-dependent enzyme involved in alphaAA formation.

  17. Effects of psoralen from Psoralea corylifolia on quinone reductase, ornithine decarboxylase, and JB6 cells transformation promotion.

    PubMed

    Lee, Sung-Jin; Nam, Kung-Woo; Mar, Woongchon

    2011-01-01

    The cancer chemopreventive effect of psoralen isolated from the seeds of Psoralea corylifolia was investigated in the induction of quinone reductase (QR) activity, intracellular detoxification enzyme, inhibition of 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ornithine decarboxylase (ODC) activity, a key regulatory enzyme for polyamine metabolism, and tumor promotion in mouse epidermal JB6 cells, sensitive to tumor promoters (clone 415a P+ cells), which are related to suppress multistage carcinogenesis including initiation and promotion. Psoralen was isolated and identified from the ethyl acetate-soluble fraction of the methanolic extract from the seeds. Psoralen was active in induction of QR activity, the concentration of psoralen required to induce 1.5 fold QR activity was 14.8 μg/mL. Also, this pure compound inhibited TPA-induced ODC activity by 50% (designated IC(50)) at the concentration 15.6 μg/mL and exhibited inhibition of TPA-induced tumor promotion in mouse epidermal JB6 cells with an IC(50) value of 17.1 μg/mL. Therefore, it is extrapolated that psoralen has the potential capable of inhibiting the initiation and/or promotion stage of carcinogenesis by induction of QR activity, inhibition of TPA-induced ODC activity and mouse epidermal JB6 cells tumor promotion.

  18. Thymoquinone: An edible redox-active quinone for the pharmacotherapy of neurodegenerative conditions and glial brain tumors. A short review.

    PubMed

    Elmaci, Ilhan; Altinoz, Meric A

    2016-10-01

    There exist few efficient agents in the neurological and neurosurgical armamentarium for treatment of neurotrauma, refractory seizures and high grade glial tumors. Pathophysiological conditions of diverse neural injuries have converging common pathways including oxidative stress and apoptosis. Targeted therapies have been throughly investigated, but limited success has been achieved until now. Phytochemical drugs may provide easily achievable and cheap adjunctive sources. Thymoquinone is an edible quinone obtained from Nigella sativa seed oil and exerts powerful antiinflammatory, antioxidant and antitumor activities in experimental models. Recently emerging studies conducted with animal models suggest that thymoquinone - bearing a very simple molecular structure - significantly crosses the blood brain barrier and exerts neuromodulatory activities. Indeed, in animal studies, the following actions of thymoquinone were demonstrated: 1-Protection against ischemic brain damage. 2-Reduction of epileptic seizures and associated cerebral oxidative injury. 3-Reduction of morphine tolerance and associated oxidative brain damage. 4-Anxiolytic effects and reduction of immobility stress-associated cerebral oxidative injury. 5-Reduction of diabetes-induced cerebral oxidative stress, 6-Reduction of cerebral oxidative injuries induced by noxious exposures including toluene, lead and ionizing radiation. Substantial in vitro data suggest that thymoquinone may be beneficial in treatment of glial tumors. However, there is no clinical study investigating its antitumor effects. In fact, thymoquinone suppresses growth and invasion, and induces apoptosis of glial tumor cells via degrading tubulins and inhibiting 20S proteasome, telomerase, autophagy, FAK and metalloproteinases. A simple and easily available agent may be a promising adjunctive treatment option in neurological and neurosurgical practice.

  19. In vitro investigation of enhanced hemocompatibility and endothelial cell proliferation associated with quinone-rich polydopamine coating.

    PubMed

    Luo, Rifang; Tang, Linlin; Zhong, Si; Yang, Zhilu; Wang, Jin; Weng, Yajun; Tu, Qiufen; Jiang, Chongxi; Huang, Nan

    2013-03-13

    Recent investigations have demonstrated that polydopamine (PDA)-modified surfaces were beneficial to the proliferation of endothelial cells (ECs). In this work, PDA coated 316L stainless steels (316L SS) were thermally treated at 50, 100, and 150 °C respectively (hereafter designated as Th50, Th100, and Th150) and consequently produced diverse surface chemical components. In vitro hemocompatibility and vascular cell-material interactions with ECs and smooth muscle cells (SMCs) affected by surface characteristics have been investigated. The Th150, rich in quinone, showed the best hemocompatibility and could effectively inhibit platelet adhesion, activation, and fibrinogen conformation transition. The polydopamine-modified surfaces were found to induce dramatic cell-material interaction with enhanced ECs proliferation, viability and migration, release of nitric oxide (NO), and reduced SMCs proliferation. The inhibitory effect of SMCs proliferation might be associated with the surface catechol content. The coating on Th150 showed a good resistance to the deformation of compression and expansion of vascular stents. These results effectively suggested that the Th150 coating might be promising when served as a stent coating platform.

  20. Sensitivity of hiPSC-derived neural stem cells (NSC) to Pyrroloquinoline quinone depends on their developmental stage.

    PubMed

    Augustyniak, J; Lenart, J; Zychowicz, M; Lipka, G; Gaj, P; Kolanowska, M; Stepien, P P; Buzanska, L

    2017-05-31

    Pyrroloquinoline quinone (PQQ) is a factor influencing on the mitochondrial biogenesis. In this study the PQQ effect on viability, total cell number, antioxidant capacity, mitochondrial biogenesis and differentiation potential was investigated in human induced Pluripotent Stem Cells (iPSC) - derived: neural stem cells (NSC), early neural progenitors (eNP) and neural progenitors (NP). Here we demonstrated that sensitivity to PQQ is dependent upon its dose and neural stage of development. Induction of the mitochondrial biogenesis by PQQ at three stages of neural differentiation was evaluated at mtDNA, mRNA and protein level. Changes in NRF1, TFAM and PPARGC1A gene expression were observed at all developmental stages, but only at eNP were correlated with the statistically significant increase in the mtDNA copy numbers and enhancement of SDHA, COX-1 protein level. Thus, the "developmental window" of eNP for PQQ-evoked mitochondrial biogenesis is proposed. This effect was independent of high antioxidant capacity of PQQ, which was confirmed in all tested cell populations, regardless of the stage of hiPSC neural differentiation. Furthermore, a strong induction of GFAP, with down regulation of MAP2 gene expression upon PQQ treatment was observed. This indicates a possibility of shifting the balance of cell differentiation in the favor of astroglia, but more research is needed at this point. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Pyrroloquinoline Quinone Induces Cancer Cell Apoptosis via Mitochondrial-Dependent Pathway and Down-Regulating Cellular Bcl-2 Protein Expression

    PubMed Central

    Min, Zhihui; Wang, Lingyan; Jin, Jianjun; Wang, Xiangdong; Zhu, Bijun; Chen, Hao; Cheng, Yunfeng

    2014-01-01

    Pyrroloquinoline quinone (PQQ) has been reported as a promising agent that might contribute to tumor cell apoptosis and death, yet little is known on its mechanisms. In current study, the effect of PQQ on cell proliferation and mitochondrial-dependent apoptosis were examined in 3 solid tumor cell lines (A549, Neuro-2A and HCC-LM3). PQQ treatment at low to medium dosage exhibited potent anti-tumor activity on A549 and Neuro-2A cells, while had comparably minimal impact on the viabilities of 2 human normal cell lines (HRPTEpiC and HUVEC). The apoptosis of the 3 tumor cell lines induced by PQQ were increased in a concentration-dependent manner, which might be attributed to the accumulation of intracellular reactive oxygen species (ROS), decline in ATP levels and dissipation of mitochondrial membrane potential (MMP), in conjunction with down-regulation of Bcl-2 protein expression, up-regulation of activated caspase-3, and disturbed phosphorylated MAPK protein levels. PQQ induced tumor cells apoptosis was significantly alleviated by pan-caspase inhibitor Z-VAD-FMK. The present work highlights the potential capability of PQQ as an anti-tumor agent with low toxicity towards normal cells through activating mitochondrial-dependent apoptosis pathways, and warrants its development for cancer therapy. PMID:25161699

  2. Role of Quinones in Electron Transfer of PQQ-Glucose Dehydrogenase Anodes—Mediation or Orientation Effect.

    PubMed

    Babanova, Sofia; Matanovic, Ivana; Chavez, Madelaine Seow; Atanassov, Plamen

    2015-06-24

    In this study, the influence of two quinones (1,2- and 1,4-benzoquinone) on the operation and mechanism of electron transfer in PQQ-dependent glucose dehydrogenase (PQQ-sGDH) anodes has been determined. Benzoquinones were experimentally explored as mediators present in the electrolyte. The electrochemical performance of the PQQ-sGDH anodes with and without the mediators was examined and for the first time molecular docking simulations were used to gain a fundamental understanding to explain the role of the mediator molecules in the design and operation of the enzymatic electrodes. It was proposed that the higher performance of the PQQ-sGDH anodes in the presence of 1,2- and 1,4-benzoquinones introduced in the solution is due to the shorter distance between these molecules and PQQ in the enzymatic molecule. It was also hypothesized that when 1,4-benzoquinone is adsorbed on a carbon support, it would play the dual role of a mediator and an orienting agent. At the same time, when 1,2-benzoquinone and ubiquinone are adsorbed on the electrode surface, the enzyme would transfer the electrons directly to the support, and these molecules would primarily play the role of an orienting agent.

  3. The chloroplast membrane associated ceQORH putative quinone oxidoreductase reduces long-chain, stress-related oxidized lipids.

    PubMed

    Curien, Gilles; Giustini, Cécile; Montillet, Jean-Luc; Mas-Y-Mas, Sarah; Cobessi, David; Ferrer, Jean-Luc; Matringe, Michel; Grechkin, Alexander; Rolland, Norbert

    2016-02-01

    Under oxidative stress conditions the lipid constituents of cells can undergo oxidation whose frequent consequence is the production of highly reactive α,β-unsaturated carbonyls. These molecules are toxic because they can add to biomolecules (such as proteins and nucleic acids) and several enzyme activities cooperate to eliminate these reactive electrophile species. CeQORH (chloroplast envelope Quinone Oxidoreductase Homolog, At4g13010) is associated with the inner membrane of the chloroplast envelope and imported into the organelle by an alternative import pathway. In the present study, we show that the recombinant ceQORH exhibits the activity of a NADPH-dependent α,β-unsaturated oxoene reductase reducing the double bond of medium-chain (C⩾9) to long-chain (18 carbon atoms) reactive electrophile species deriving from poly-unsaturated fatty acid peroxides. The best substrates of ceQORH are 13-lipoxygenase-derived γ-ketols. γ-Ketols are spontaneously produced in the chloroplast from the unstable allene oxide formed in the biochemical pathway leading to 12-oxo-phytodienoic acid, a precursor of the defense hormone jasmonate. In chloroplasts, ceQORH could detoxify 13-lipoxygenase-derived γ-ketols at their production sites in the membranes. This finding opens new routes toward the understanding of γ-ketols role and detoxification.

  4. Central role of the Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR) in sodium bioenergetics of Vibrio cholerae.

    PubMed

    Steuber, Julia; Halang, Petra; Vorburger, Thomas; Steffen, Wojtek; Vohl, Georg; Fritz, Günter

    2014-12-01

    Vibrio cholerae is a Gram-negative bacterium that lives in brackish or sea water environments. Strains of V. cholerae carrying the pathogenicity islands infect the human gut and cause the fatal disease cholera. Vibrio cholerae maintains a Na(+) gradient at its cytoplasmic membrane that drives substrate uptake, motility, and efflux of antibiotics. Here, we summarize the major Na(+)-dependent transport processes and describe the central role of the Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR), a primary Na(+) pump, in maintaining a Na(+)-motive force. The Na(+)-NQR is a membrane protein complex with a mass of about 220 kDa that couples the exergonic oxidation of NADH to the transport of Na(+) across the cytoplasmic membrane. We describe the molecular architecture of this respiratory complex and summarize the findings how electron transport might be coupled to Na(+)-translocation. Moreover, recent advances in the determination of the three-dimensional structure of this complex are reported.

  5. Discovery of quinone-directed antitumor agents selectively bioactivated by NQO1 over CPR with improved safety profile.

    PubMed

    Bian, Jinlei; Li, Xiang; Wang, Nan; Wu, Xingsen; You, Qidong; Zhang, Xiaojin

    2017-03-31

    In this work, we mainly focused on discovering compounds with good selectivity for NQO1 over CPR. The NQO1-mediated two-electron reduction of compounds would kill cancer cells selectively, while CPR-mediated one-electron reduction would induce potential hepatotoxicity. Several novel quinone-directed antitumor agents were discovered as specific NQO1 substrates through structure-activity relationship studies. Among them, compound 3,7,8-trimethylnaphtho[1,2-b]furan-4,5-dione (12b) emerged as the most specific substrate of the two-electron oxidoreductase NQO1 and could hardly be reduced by CPR. It afforded the highest selectivity between NQO1/CPR (selectivity ratio = 6.37), much higher than the control β-lapachone (selectivity ratio = 1.36), indicated 12b may possess superior safety profile. The electrochemical studies provided a reasonable explanation to the good selectivity toward NQO1. Molecular docking studies supported that 12b was capable of forming additional C-H … π interactions with Trp105 and Phe178 residues compared to the control β-lap. In addition, compound 12b was shown to kill cancer cells efficiently both in vitro and in vivo model. This work gave us a promising and novel scaffold for further investigation.

  6. Synergistic effect of pyrroloquinoline quinone and graphene nano-interface for facile fabrication of sensitive NADH biosensor.

    PubMed

    Han, Shanying; Du, Tianyu; Jiang, Hui; Wang, Xuemei

    2017-03-15

    A self-assembly composite of graphene-pyrroloquinoline quinone (PQQ) was fabricated and modified on glassy carbon electrode (GCE) for sensitive detection of nicotinamide adenine dinucleotide (NADH). Chitosan (CTS) was applied to disperse graphene to form a stable robust film on GCE. A synergistic effect between PQQ and graphene was observed during the electrocatalytic oxidation of NADH, with about 260mV reduction in the oxidation potential and 2.5-fold increase in the oxidation current compared with those on the bare GCE. The electrochemical sensors based on the modified electrodes allowed the detection of NADH with a good linear dependence from 0.32 to 220µM with a high sensitivity of 0.421µAµM(-1)cm(-2) and a low detection limit of 0.16µM (S/N=3). It could also eliminate the interference of electroactive substances like ascorbic acid (AA), uric acid, and dopamine and its derivatives. The outstanding performances of graphene-PQQ/CTS composite capable of improving the electrical conductivity and accelerating the electron transport suggested its promising applications for design of different graphene based composites used in electrochemical sensing and energy fields.

  7. Profiles of Glucosinolates, Their Hydrolysis Products, and Quinone Reductase Inducing Activity from 39 Arugula (Eruca sativa Mill.) Accessions.

    PubMed

    Ku, Kang-Mo; Kim, Moo Jung; Jeffery, Elizabeth H; Kang, Young-Hwa; Juvik, John A

    2016-08-31

    Glucosinolates, their hydrolysis product concentrations, and the quinone reductase (QR) inducing activity of extracts of leaf tissue were assayed from 39 arugula (Eruca sativa Mill.) accessions. Arugula accessions from Mediterranean countries (n = 16; Egypt, Greece, Italy, Libya, Spain, and Turkey) and Northern Europe (n = 2; Poland and United Kingdom) were higher in glucosinolates and their hydrolysis products, especially glucoraphanin and sulforaphane, compared to those from Asia (n = 13; China, India, and Pakistan) and Middle East Asia (n = 8; Afghanistan, Iran, and Israel). The QR inducing activity was also the highest in Mediterranean and Northern European arugula accessions, possibly due to a significant positive correlation between sulforaphane and QR inducing activity (r = 0.54). No nitrile hydrolysis products were found, suggesting very low or no epithiospecifier protein activity from these arugula accessions. Broad sense heritability (H(2)) was estimated to be 0.91-0.98 for glucoinolates, 0.55-0.83 for their hydrolysis products, and 0.90 for QR inducing activity.

  8. U-shaped temperature dependence of rate constant of intramolecular photoinduced charge separation in zinc-porphyrin-bridge-quinone compounds.

    PubMed

    Kichigina, Anna O; Ionkin, Vladimir N; Ivanov, Anatoly I

    2013-06-20

    The multichannel stochastic point transition model of photoinduced electron transfer from both a vibrationally unrelaxed and a relaxed states involving the vibrational relaxation in donor-acceptor pairs has been elaborated. The U-shaped temperature dependencies of the rate constants of the intramolecular photoinduced charge separation from both the vibrationally unrelaxed and the relaxed states observed in Zn-porphyrin-bridge-quinone compounds in 2-methyltetrahydrofuran solvent have been reproduced in the framework of the proposed model that accounts for the temperature dependencies of the charge separation free energy gap and the medium reorganization energy. This modeling has allowed uncovering the mechanism of such a variation of the rate constant with the temperature. In the high temperature region, 310-125 K, the charge separation proceeds in the solvent controlled regime and its rate constant decreases with decreasing the temperature mirroring the temperature dependence of the medium relaxation rate. Further lowering the temperature leads to a rise of the reaction free energy gap so that it becomes larger than the medium reorganization energy. In this region the dynamic solvent effect is strongly suppressed and the charge separation rate constant becomes independent from the solvent relaxation rate. Although the medium relaxation rate continues to decrease with decreasing the temperature, the charge separation rate constant starts to rise because the reaction proceeds in the barrierless region.

  9. NAD(P)H quinone oxidoreductase 1 inhibits the proteasomal degradation of homocysteine-induced endoplasmic reticulum protein

    SciTech Connect

    Maeda, Tomoji; Tanabe-Fujimura, Chiaki; Fujita, Yu; Abe, Chihiro; Nanakida, Yoshino; Zou, Kun; Liu, Junjun; Liu, Shuyu; Nakajima, Toshihiro; Komano, Hiroto

    2016-05-13

    Homocysteine-induced endoplasmic reticulum (ER) protein (Herp) is an ER stress-inducible key regulatory component of ER-associated degradation (ERAD) that has been implicated in insulin hypersecretion in diabetic mouse models. Herp expression is tightly regulated. Additionally, Herp is a highly labile protein and interacts with various proteins, which are characteristic features of ubiquitinated protein. Previously, we reported that ubiquitination is not required for Herp degradation. In addition, we found that the lysine residues of Herp (which are ubiquitinated by E3 ubiquitin ligase) are not sufficient for regulation of Herp degradation. In this study, we found that NAD(P)H quinone oxidoreductase 1 (NQO1)-mediated targeting of Herp to the proteasome was involved in Herp degradation. In addition, we found that Herp protein levels were markedly elevated in synoviolin-null cells. The E3 ubiquitin ligase synoviolin is a central component of ERAD and is involved in the degradation of nuclear factor E2-related factor-2 (Nrf2), which regulates cellular reactive oxygen species. Additionally, NQO1 is a target of Nrf2. Thus, our findings indicated that NQO1 could stabilize Herp protein expression via indirect regulation of synoviolin. -- Highlights: •Herp interacts with NQO1. •NQO1 regulates Herp degradation.

  10. Hydrogen peroxide formation in a surrogate lung fluid by transition metals and quinones present in particulate matter.

    PubMed

    Charrier, Jessica G; McFall, Alexander S; Richards-Henderson, Nicole K; Anastasio, Cort

    2014-06-17

    Inhaled ambient particulate matter (PM) causes adverse health effects, possibly by generating reactive oxygen species (ROS), including hydrogen peroxide (HOOH), in the lung lining fluid. There are conflicting reports in the literature as to which chemical components of PM can chemically generate HOOH in lung fluid mimics. It is also unclear which redox-active species are most important for HOOH formation at concentrations relevant to ambient PM. To address this, we use a cell-free, surrogate lung fluid (SLF) to quantify the initial rate of HOOH formation from 10 transition metals and 4 quinones commonly identified in PM. Copper, 1,2-naphthoquinone, 1,4-naphthoquinone, and phenanthrenequinone all form HOOH in a SLF, but only copper and 1,2-naphthoquinone are likely important at ambient concentrations. Iron suppresses HOOH formation in laboratory solutions, but has a smaller effect in ambient PM extracts, possibly because organic ligands in the particles reduce the reactivity of iron. Overall, copper produces the majority of HOOH chemically generated from typical ambient PM while 1,2-naphthoquinone generally makes a small contribution. However, measured rates of HOOH formation in ambient particle extracts are lower than rates calculated from soluble copper by an average (±1σ) of 44 ± 22%; this underestimate is likely due to either HOOH destruction by Fe or a reduction in Cu reactivity due to organic ligands from the PM.

  11. Lifespan extension by peroxidase and dual oxidase-mediated ROS signaling through pyrroloquinoline quinone in C. elegans.

    PubMed

    Sasakura, Hiroyuki; Moribe, Hiroki; Nakano, Masahiko; Ikemoto, Kazuto; Takeuchi, Kosei; Mori, Ikue

    2017-08-01

    Reactive oxygen species (ROS), originally characterized based on their harmful effects on cells or organisms, are now recognized as important signal molecules regulating various biological processes. In particular, low levels of ROS released from mitochondria extend lifespan. Here, we identified a novel mechanism of generating appropriate levels of ROS at the plasma membrane through a peroxidase and dual oxidase (DUOX) system, which could extend lifespan in Caenorhabditis elegans A redox co-factor, pyrroloquinoline quinone (PQQ), activates the C. elegans DUOX protein BLI-3 to produce the ROS H2O2 at the plasma membrane, which is subsequently degraded by peroxidase (MLT-7), eventually ensuring adequate levels of ROS. These ROS signals are transduced mainly by the oxidative stress transcriptional factors SKN-1 (Nrf2 or NFE2L2 in mammals) and JUN-1, and partially by DAF-16 (a FOXO protein homolog). Cell biology experiments demonstrated a similarity between the mechanisms of PQQ-induced activation of human DUOX1 and DUOX2 and that of C. elegans BLI-3, suggesting that DUOXs are potential targets of intervention for lifespan extension. We propose that low levels of ROS, fine-tuned by the peroxidase and dual oxidase system at the plasma membrane, act as second messengers to extend lifespan by the effect of hormesis. © 2017. Published by The Company of Biologists Ltd.

  12. Hydrogen Peroxide Formation in a Surrogate Lung Fluid by Transition Metals and Quinones Present in Particulate Matter

    PubMed Central

    2015-01-01

    Inhaled ambient particulate matter (PM) causes adverse health effects, possibly by generating reactive oxygen species (ROS), including hydrogen peroxide (HOOH), in the lung lining fluid. There are conflicting reports in the literature as to which chemical components of PM can chemically generate HOOH in lung fluid mimics. It is also unclear which redox-active species are most important for HOOH formation at concentrations relevant to ambient PM. To address this, we use a cell-free, surrogate lung fluid (SLF) to quantify the initial rate of HOOH formation from 10 transition metals and 4 quinones commonly identified in PM. Copper, 1,2-naphthoquinone, 1,4-naphthoquinone, and phenanthrenequinone all form HOOH in a SLF, but only copper and 1,2-naphthoquinone are likely important at ambient concentrations. Iron suppresses HOOH formation in laboratory solutions, but has a smaller effect in ambient PM extracts, possibly because organic ligands in the particles reduce the reactivity of iron. Overall, copper produces the majority of HOOH chemically generated from typical ambient PM while 1,2-naphthoquinone generally makes a small contribution. However, measured rates of HOOH formation in ambient particle extracts are lower than rates calculated from soluble copper by an average (±1σ) of 44 ± 22%; this underestimate is likely due to either HOOH destruction by Fe or a reduction in Cu reactivity due to organic ligands from the PM. PMID:24857372

  13. Pyrroloquinoline quinone and a quinoprotein kinase support γ-radiation resistance in Deinococcus radiodurans and regulate gene expression.

    PubMed

    Rajpurohit, Yogendra Singh; Desai, Shruti Sumeet; Misra, Hari Sharan

    2013-06-01

    Deinococcus radiodurans is known for its extraordinary resistance to various DNA damaging agents including γ-radiation and desiccation. The pqqE:cat and Δdr2518 mutants making these cells devoid of pyrroloquinoline quinone (PQQ) and a PQQ inducible Ser/Thr protein kinase, respectively, became sensitive to γ-radiation. Transcriptome analysis of these mutants showed differential expression of the genes including those play roles in oxidative stress tolerance and (DSB) repair in D. radiodurans and in genome maintenance and stress response in other bacteria. Escherichia coli cells expressing DR2518 and PQQ showed improved resistance to γ-radiation, which increased further when both DR2518 and PQQ were present together. Although, profiles of genes getting affected in these mutants were different, there were still a few common genes showing similar expression trends in both the mutants and some others as reported earlier in oxyR and pprI mutant of this bacterium. These results suggested that PQQ and DR2518 have independent roles in γ-radiation resistance of D. radiodurans but their co-existence improves radioresistance further, possibly by regulating differential expression of the genes important for bacterial response to oxidative stress and DNA damage. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Aripiprazole increases NAD(P)H-quinone oxidoreductase-1 and heme oxygenase-1 in PC12 cells.

    PubMed

    Kaneko, Yoko S; Takayanagi, Takeshi; Nagasaki, Hiroshi; Kodani, Yu; Nakashima, Akira; Mori, Keiji; Suzuki, Atsushi; Itoh, Mitsuyasu; Kondo, Kazunao; Nagatsu, Toshiharu; Ota, Miyuki; Ota, Akira

    2015-06-01

    We previously showed that aripiprazole increases intracellular NADPH and glucose-6-phosphate dehydrogenase mRNA in PC12 cells. Aripiprazole presumably activates a system that concurrently detoxifies reactive oxygen species and replenishes NADPH. Nrf2, a master transcriptional regulator of redox homeostasis genes, also activates the pentose phosphate pathway, including NADPH production. Therefore, our aim was to determine whether aripiprazole activates Nrf2 in PC12 cells. Aripiprazole increased mRNA expression of Nrf2-dependent genes (NAD(P)H-quinone oxidoreductase-1, Nqo1; heme oxygenase-1, HO1; and glutamate-cysteine ligase catalytic subunit) and protein expression of Nqo1 and HO1 in these cells (p < 0.05). To maintain increased Nrf2 activity, it is necessary to inhibit Nrf2 degradation; this is done by causing Nrf2 to dissociate from Keap1 or β-TrCP. However, in aripiprazole-treated cells, the relative amount of Nrf2 anchored to Keap1 or β-TrCP was unaffected and Nrf2 in the nuclear fraction decreased (p < 0.05). Aripiprazole did not affect phosphorylation of Nrf2 at Ser40 and decreased the relative amount of acetylated Nrf2 (p < 0.05). The increase in Nqo1 and HO1 in aripiprazole-treated cells cannot be explained by the canonical Nrf2-degrading pathways. Further experiments are needed to determine the biochemical mechanisms underlying the aripiprazole-induced increase in these enzymes.

  15. Metal-independent production of hydroxyl radicals by halogenated quinones and hydrogen peroxide: an ESR spin trapping study.

    PubMed

    Zhu, Ben-Zhan; Zhao, Hong-Tao; Kalyanaraman, Balaraman; Frei, Balz

    2002-03-01

    The metal-independent production of hydroxyl radicals (*OH) from H(2)O(2) and tetrachloro-1,4-benzoquinone (TCBQ), a carcinogenic metabolite of the widely used wood-preservative pentachlorophenol, was studied by electron spin resonance methods. When incubated with the spin trapping agent 5,5-dimethyl-1-pyrroline N-oxide (DMPO), TCBQ and H(2)O(2) produced the DMPO/*OH adduct. The formation of DMPO/*OH was markedly inhibited by the *OH scavenging agents dimethyl sulfoxide (DMSO), ethanol, formate, and azide, with the concomitant formation of the characteristic DMPO spin trapping adducts with *CH(3), *CH(CH(3))OH, *COO(-), and *N(3), respectively. The formation of DMPO/*OH and DMPO/*CH(3) from TCBQ and H(2)O(2) in the absence and presence, respectively, of DMSO was inhibited by the trihydroxamate compound desferrioxamine, accompanied by the formation of the desferrioxamine-nitroxide radical. In contrast, DMPO/*OH and DMPO/*CH(3) formation from TCBQ and H(2)O(2) was not affected by the nonhydroxamate iron chelators bathophenanthroline disulfonate, ferrozine, and ferene, as well as the copper-specific chelator bathocuproine disulfonate. A comparative study with ferrous iron and H(2)O(2), the classic Fenton system, strongly supports our conclusion that *OH is produced by TCBQ and H(2)O(2) through a metal-independent mechanism. Metal-independent production of *OH from H(2)O(2) was also observed with several other halogenated quinones.

  16. High and low potential forms of the QA quinone electron acceptor in Photosystem II of Thermosynechococcus elongatus and spinach.

    PubMed

    Ido, Kunio; Gross, Christine M; Guerrero, Fernando; Sedoud, Arezki; Lai, Thanh-Lan; Ifuku, Kentaro; Rutherford, A William; Krieger-Liszkay, Anja

    2011-01-01

    The redox potential of Q(A) in Photosystem II (PSII) from Thermosynechococcus elongatus was titrated monitoring chlorophyll fluorescence. A high potential form (E(m)=+60 ± 25 mV) was found in the absence of Mn(4)Ca, the active site for water oxidation. The low potential form (E(m)=-60 ± 48 mV), which is difficult to measure in conventional titration experiments, could be "locked in" by cross-linking the active enzyme. This indicates that the presence of Mn(4)Ca is relayed to the quinone site by significant structural changes in the protein. The presence of high and low potential forms agrees with what has been seen in plants, algae from our lab and in T. elongatus (Shibamoto et al., Biochemistry 48 (2009) 10682-10684). In the latter work, the potentials of Q(A) were shifted to lower potentials compared to other measurements. The redox potential of Q(A) in Mn-depleted PSII from spinach was titrated in the presence of redox mediators and the midpoint potential was shifted by 80 mV towards a more negative value compared to titrations without mediators. The lower values of the midpoint potential of the (Q(A)/Q(A)(-)) redox couple in the literature could be due to a perturbation due to a specific mediator.

  17. Cellobiose quinone oxidoreductase from the white rot fungus Phanerochaete chrysosporium is produced by intracellular proteolysis of cellobiose dehydrogenase.

    PubMed

    Raíces, Manuel; Montesino, Raquel; Cremata, José; García, Bianca; Perdomo, Walmer; Szabó, István; Henriksson, Gunnar; Hallberg, B Martin; Pettersson, Göran; Johansson, Gunnar

    2002-06-07

    The fungus Phanerochaete chrysosporium was grown in a 10-l automatic fermenter using cellobiose as carbon source to monitor the induction of cellobiose dehydrogenase (CDH) and cellobiose quinone oxidoreductase (CBQ) enzymes, and to search for tentative cbq and cdh genes and their transcriptional products. After 24 h of induction, CDH was detected in the culture supernatant and a protein was recognized by a specific anti-CDH polyclonal antibody in the sonicated biomass. Northern blot experiments performed with several fungal RNA samples showed, after 24 h of induction, only one single species of an mRNA transcript corresponding in size to the cdh gene (2.5 kb) The relative amount of this transcript decreased as a function of time. Southern blot experiments done with genomic DNA and database search in the recently available genome information also ruled out the presence in this strain of a separate cbq gene distinct from the cdh gene. Taken together, these results demonstrated that CBQ originates from the cdh gene. Furthermore, it is not produced by differential splicing but by a posttranslational, predominantly intracellular, proteolytic cleavage.

  18. Role of the Na(+)-translocating NADH:quinone oxidoreductase in voltage generation and Na(+) extrusion in Vibrio cholerae.

    PubMed

    Vorburger, Thomas; Nedielkov, Ruslan; Brosig, Alexander; Bok, Eva; Schunke, Emina; Steffen, Wojtek; Mayer, Sonja; Götz, Friedrich; Möller, Heiko M; Steuber, Julia

    2016-04-01

    For Vibrio cholerae, the coordinated import and export of Na(+) is crucial for adaptation to habitats with different osmolarities. We investigated the Na(+)-extruding branch of the sodium cycle in this human pathogen by in vivo (23)Na-NMR spectroscopy. The Na(+) extrusion activity of cells was monitored after adding glucose which stimulated respiration via the Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR). In a V. cholerae deletion mutant devoid of the Na(+)-NQR encoding genes (nqrA-F), rates of respiratory Na(+) extrusion were decreased by a factor of four, but the cytoplasmic Na(+) concentration was essentially unchanged. Furthermore, the mutant was impaired in formation of transmembrane voltage (ΔΨ, inside negative) and did not grow under hypoosmotic conditions at pH8.2 or above. This growth defect could be complemented by transformation with the plasmid encoded nqr operon. In an alkaline environment, Na(+)/H(+) antiporters acidify the cytoplasm at the expense of the transmembrane voltage. It is proposed that, at alkaline pH and limiting Na(+) concentrations, the Na(+)-NQR is crucial for generation of a transmembrane voltage to drive the import of H(+) by electrogenic Na(+)/H(+) antiporters. Our study provides the basis to understand the role of the Na(+)-NQR in pathogenicity of V. cholerae and other pathogens relying on this primary Na(+) pump for respiration. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Quenching Enhancement of the Singlet Excited State of Pheophorbide-a by DNA in the Presence of the Quinone Carboquone

    PubMed Central

    Díaz-Espinosa, Yisaira; Crespo-Hernández, Carlos E.; Alegría, Antonio E.; García, Carmelo; Arce, Rafael

    2011-01-01

    Changes in the emission fluorescence intensity of pheophorbide-a (PHEO) in the presence of carboquone (CARBOQ) were used to obtain the association constant, the number of CARBOQ molecules interacting with PHEO, and the fluorescence quantum yield of the complex. Excitation spectra of mixtures of PHEO and CARBOQ in ethanol (EtOH) show an unresolved doublet in the red-most excitation band of PHEO, indicating the formation of a loose ground-state complex. The 1:1 CARBOQ–PHEO complex shows a higher fluorescence quantum yield in EtOH (0.41 ± 0.02) than in buffer solution (0.089 ± 0.002), which is also higher than that of the PHEO monomer (0.28). Quenching of the PHEO fluorescence by DNA nucleosides and double-stranded oligonucleotides was also observed and the bimolecular quenching rate constants were determined. The quenching rate constant increase as the oxidation potential of the DNA nucleoside increases. Larger quenching constants were obtained in the presence of CARBOQ suggesting that CARBOQ enhances DNA photo-oxidation, presumably by inhibiting the back–electron-transfer reaction from the photoreduced PHEO to the oxidized base. Thus, the enhanced DNA-base photosensitized oxidation by PHEO in the presence of CARBOQ may be related to the large extent by which this quinone covalently binds to DNA, as previously reported. PMID:21138440

  20. Role of Quinones in Electron Transfer of PQQ–Glucose Dehydrogenase Anodes—Mediation or Orientation Effect

    SciTech Connect

    Babanova, Sofia; Matanovic, Ivana; Chavez, Madelaine Seow; Atanassov, Plamen

    2015-06-24

    In this study, the influence of two quinones (1,2- and 1,4-benzoquinone) on the operation and mechanism of electron transfer in PQQ-dependent glucose dehydrogenase (PQQ–sGDH) anodes has been determined. Benzoquinones were experimentally explored as mediators present in the electrolyte. The electrochemical performance of the PQQ–sGDH anodes with and without the mediators was examined and for the first time molecular docking simulations were used to gain a fundamental understanding to explain the role of the mediator molecules in the design and operation of the enzymatic electrodes. It was proposed that the higher performance of the PQQ–sGDH anodes in the presence of 1,2- and 1,4-benzoquinones introduced in the solution is due to the shorter distance between these molecules and PQQ in the enzymatic molecule. It was also hypothesized that when 1,4-benzoquinone is adsorbed on a carbon support, it would play the dual role of a mediator and an orienting agent. At the same time, when 1,2-benzoquinone and ubiquinone are adsorbed on the electrode surface, the enzyme would transfer the electrons directly to the support, and these molecules would primarily play the role of an orienting agent.

  1. Role of quinones in electron transfer of PQQ–glucose dehydrogenase anodes—mediation or orientation effect

    DOE PAGES

    Babanova, Sofia; Matanovic, Ivana; Chavez, Madelaine Seow; ...

    2015-06-16

    In this study, the influence of two quinones (1,2- and 1,4-benzoquinone) on the operation and mechanism of electron transfer in PQQ-sGDH anodes has been determined. Benzoquinones were experimentally explored as mediators present in the electrolyte. The electrochemical performance of the PQQ–sGDH anodes with and without the mediators was examined and for the first time molecular docking simulations were used to gain a fundamental understanding to explain the role of the mediator molecules in the design and operation of the enzymatic electrodes. It was proposed that the higher performance of the PQQ–sGDH anodes in the presence of 1,2- and 1,4-benzoquinones introducedmore » in the solution is due to the shorter distance between these molecules and PQQ in the enzymatic molecule. It was also hypothesized that when 1,4-benzoquinone is adsorbed on a carbon support, it would play the dual role of a mediator and an orienting agent. At the same time, when 1,2-benzoquinone and ubiquinone are adsorbed on the electrode surface, the enzyme would transfer the electrons directly to the support, and these molecules would primarily play the role of an orienting agent.« less

  2. Detoxication of structurally diverse polycyclic aromatic hydrocarbon (PAH) o-quinones by human recombinant catechol-O-methyltransferase (COMT) via O-methylation of PAH catechols.

    PubMed

    Zhang, Li; Jin, Yi; Chen, Mo; Huang, Meng; Harvey, Ronald G; Blair, Ian A; Penning, Trevor M

    2011-07-22

    Polycyclic aromatic hydrocarbons (PAH) are environmental and tobacco carcinogens. Metabolic activation of intermediate PAH trans-dihydrodiols by aldo-keto reductases (AKRs) leads to the formation of electrophilic and redox-active o-quinones. We investigated whether O-methylation by human recombinant soluble catechol-O-methyltransferase (S-COMT) is a feasible detoxication step for a panel of structurally diverse PAH-catechols produced during the redox-cycling process. Classes of PAH non-K-region o-quinones (bay region, methylated bay region, and fjord region o-quinones) produced by AKRs were employed in the studies. PAH o-quinones were reduced to the corresponding catechols by dithiothreitol under anaerobic conditions and then further O-methylated by human S-COMT in the presence of S-[³H]adenosyl-l-methionine as a methyl group donor. The formation of the O-methylated catechols was detected by HPLC-UV coupled with in-line radiometric detection, and unlabeled products were also characterized by LC-MS/MS. Human S-COMT was able to catalyze O-methylation of all of the PAH-catechols and generated two isomeric metabolites in different proportions. LC-MS/MS showed that each isomer was a mono-O-methylated metabolite. ¹H NMR was used to assign the predominant positional isomer of benzo[a]pyrene-7,8-catechol as the O-8-monomethylated catechol. The catalytic efficiency (k(cat)/K(m)) varied among different classes of PAH-catechols by 500-fold. The ability of S-COMT to produce two isomeric products from PAH-catechols was rationalized using the crystal structure of the enzyme. We provide evidence that O-8-monomethylated benzo[a]pyrene-7,8-catechol is formed in three different human lung cell lines. It is concluded that human S-COMT may play a critical role in the detoxication of PAH o-quinones generated by AKRs.

  3. DNA strand scission by polycyclic aromatic hydrocarbon o-quinones: role of reactive oxygen species, Cu(II)/Cu(I) redox cycling, and o-semiquinone anion radicals,.

    PubMed

    Flowers, L; Ohnishi, S T; Penning, T M

    1997-07-15

    In previous studies, benzo[a]pyrene-7,8-dione (BPQ), a polycyclic aromatic hydrocarbon (PAH) o-quinone, was found to be 200-fold more potent as a nuclease than (+/-)-anti-7,8-dihydroxy-9,10-epoxy-7,8,9, 10-tetrahydrobenzo[a]pyrene, a suspect human carcinogen. The mechanism of strand scission mediated by naphthalene-1,2-dione (NPQ) and BPQ was further characterized using either phiX174 DNA or poly(dG).poly(dC) as the target DNA. Strand scission was extensive, dependent on the concentration of o-quinone (0-10 microM), and required the presence of NADPH (1 mM) and CuCl2 (10 microM). The production of reactive species, i.e., superoxide anion radical, o-semiquinone anion (SQ) radical, hydrogen peroxide (H2O2), hydroxyl radical (OH.), and Cu(I), was measured in the incubation mixtures. The formation of SQ radicals was measured by EPR spectroscopy under anaerobic conditions in the presence of NADPH. A Cu(II)/Cu(I) redox cycle was found to be critical for DNA cleavage. No strand scission occurred in the absence of Cu(II) or when Cu(I) was substituted, yet Cu(I) was required for OH* production. Both DNA strand scisson and OH. formation were decreased to an equal extent, albeit not completely, by the inclusion of OH. scavengers (mannitol, soduim benzoate, and formic acid) or Cu(I) chelators (bathocuproine and neocuproine). In contrast, although the SQ radical signals of NPQ and BPQ were quenched by DNA, no strand scission was observed. When calf thymus DNA was treated with PAH o-quinones, malondialdehyde (MDA) was released by acid hydrolysis. The formation of MDA was inhibited by OH. scavengers suggesting that OH* cleaved the 2'-deoxyribose moiety in the DNA to produce base propenals. These studies indicate that for PAH o-quinones to act as nucleases, NADPH, Cu(II), Cu(I), H2O2, and OH*, were necessary and that the primary species responsible for DNA fragmentation was OH., generated by a Cu(I)-catalyzed Fenton reaction. The genotoxicity of PAH o-quinones may play a role in

  4. EGF-receptor phosphorylation and downstream signaling are activated by benzo[a]pyrene 3,6-quinone and benzo[a]pyrene 1,6-quinone in human mammary epithelial cells

    SciTech Connect

    Rodriguez-Fragoso, Lourdes; Melendez, Karla; Hudson, Laurie G.; Lauer, Fredine T.; Burchiel, Scott W.

    2009-03-15

    Benzo[a]pyrene (BaP) is activated by xenobiotic-metabolizing enzymes to highly mutagenic and carcinogenic metabolites. Previous studies in this laboratory have shown that benzo[a]pyrene quinones (BPQs), 1,6-BPQ and 3,6-BPQ, are able to induce epidermal growth factor receptor (EGFR) cell signaling through the production of reactive oxygen species. Recently, we have reported that BPQs have the potential to induce the expression of genes involved in numerous pathways associated with cell proliferation and survival in human mammary epithelial cells. In the present study we demonstrated that BPQs not only induced EGFR tyrosine autophosphorylation, but also induced EGFR-dependent tyrosine phosphorylation of phospholipase C-{gamma}1 and several signal transducers and activators of transcription (STATs). The effects of BPQs were evaluated in a model of EGF withdrawal in MCF10-A cells. We found that BPQs (1 {mu}M), induced EGFR tyrosine phosphorylation at positions Y845, Y992, Y1068, and Y1086. PLC-{gamma}1 phosphorylation correlated with the phosphorylation of tyrosine-Y992, a proposed docking site for PLC-{gamma}1 on the EGFR. Additionally, we found that BPQs induced the activation of STAT-1, STAT-3, STAT-5a and STAT-5b. STAT5 was shown to translocate to the nucleus following 3,6-BPQ and 1,6-BPQ exposures. Although the patterns of phosphorylation at EGFR, PLC-{gamma}1 and STATs were quite similar to those induced by EGF, an important difference between BPQ-mediated signaling of the EGFR was observed. Signaling produced by EGF ligand produced a rapid disappearance of EGFR from the cell surface, whereas BPQ signaling maintained EGFR receptors on the cell membrane. Thus, the results of these studies show that 1,6-BPQ and 3,6-BPQ can produce early events as evidenced by EGFR expression, and a prolonged transactivation of EGFR leading to downstream cell signaling pathways.

  5. Activation of dioxin response element (DRE)-associated genes by benzo(a)pyrene 3,6-quinone and benzo(a)pyrene 1,6-quinone in MCF-10A human mammary epithelial cells

    SciTech Connect

    Burchiel, Scott W. . E-mail: SBurchiel@salud.unm.edu; Thompson, Todd A.; Lauer, Fredine T.; Oprea, Tudor I.

    2007-06-01

    Benzo(a)pyrene (BaP) is a known human carcinogen and a suspected breast cancer complete carcinogen. BaP is metabolized by several metabolic pathways, some having bioactivation and others detoxification properties. BaP-quinones (BPQs) are formed via cytochrome P450 and peroxidase dependent pathways. Previous studies by our laboratory have shown that BPQs have significant growth promoting and anti-apoptotic activities in human MCF-10A mammary epithelial cells examined in vitro. Previous results suggest that BPQs act via redox-cycling and oxidative stress. However, because two specific BPQs (1,6-BPQ and 3,6-BPQ) differed in their ability to produce reactive oxygen species (ROS) and yet both had strong proliferative and EGF receptor activating activity, we utilized mRNA expression arrays and qRT-PCR to determine potential pathways and mechanisms of gene activation. The results of the present studies demonstrated that 1,6-BPQ and 3,6-BPQ activate dioxin response elements (DRE, also known as xenobiotic response elements, XRE) and anti-oxidant response elements (ARE, also known as electrophile response elements, EpRE). 3,6-BPQ had greater DRE activity than 1,6-BPQ, whereas the opposite was true for the activation of ARE. Both 3,6-BPQ and 1,6-BPQ induced oxidative stress-associated genes (HMOX1, GCLC, GCLM, and SLC7A11), phase 2 enzyme genes (NQO1, NQO2, ALDH3A1), PAH metabolizing genes (CYP1B1, EPHX1, AKR1C1), and certain EGF receptor-associated genes (EGFR, IER3, ING1, SQSTM1 and TRIM16). The results of these studies demonstrate that BPQs activate numerous pathways in human mammary epithelial cells associated with increased cell growth and survival that may play important roles in tumor promotion.

  6. NqrM (DUF539) Protein Is Required for Maturation of Bacterial Na+-Translocating NADH:Quinone Oxidoreductase

    PubMed Central

    Kostyrko, Vitaly A.; Bertsova, Yulia V.; Serebryakova, Marina V.; Baykov, Alexander A.

    2015-01-01

    ABSTRACT Na+-translocating NADH:quinone oxidoreductase (Na+-NQR) catalyzes electron transfer from NADH to ubiquinone in the bacterial respiratory chain, coupled with Na+ translocation across the membrane. Na+-NQR maturation involves covalent attachment of flavin mononucleotide (FMN) residues, catalyzed by flavin transferase encoded by the nqr-associated apbE gene. Analysis of complete bacterial genomes has revealed another putative gene (duf539, here renamed nqrM) that usually follows the apbE gene and is present only in Na+-NQR-containing bacteria. Expression of the Vibrio harveyi nqr operon alone or with the associated apbE gene in Escherichia coli, which lacks its own Na+-NQR, resulted in an enzyme incapable of Na+-dependent NADH or reduced nicotinamide hypoxanthine dinucleotide (dNADH) oxidation. However, fully functional Na+-NQR was restored when these genes were coexpressed with the V. harveyi nqrM gene. Furthermore, nqrM lesions in Klebsiella pneumoniae and V. harveyi prevented production of functional Na+-NQR, which could be recovered by an nqrM-containing plasmid. The Na+-NQR complex isolated from the nqrM-deficient strain of V. harveyi lacks several subunits, indicating that nqrM is necessary for Na+-NQR assembly. The protein product of the nqrM gene, NqrM, contains a single putative transmembrane α-helix and four conserved Cys residues. Mutating one of these residues (Cys33 in V. harveyi NqrM) to Ser completely prevented Na+-NQR maturation, whereas mutating any other Cys residue only decreased the yield of the mature protein. These findings identify NqrM as the second specific maturation factor of Na+-NQR in proteobacteria, which is presumably involved in the delivery of Fe to form the (Cys)4[Fe] center between subunits NqrD and NqrE. IMPORTANCE Na+-translocating NADH:quinone oxidoreductase complex (Na+-NQR) is a unique primary Na+ pump believed to enhance the vitality of many bacteria, including important pathogens such as Vibrio cholerae, Vibrio

  7. NqrM (DUF539) Protein Is Required for Maturation of Bacterial Na+-Translocating NADH:Quinone Oxidoreductase.

    PubMed

    Kostyrko, Vitaly A; Bertsova, Yulia V; Serebryakova, Marina V; Baykov, Alexander A; Bogachev, Alexander V

    2015-12-07

    Na(+)-translocating NADH:quinone oxidoreductase (Na(+)-NQR) catalyzes electron transfer from NADH to ubiquinone in the bacterial respiratory chain, coupled with Na(+) translocation across the membrane. Na(+)-NQR maturation involves covalent attachment of flavin mononucleotide (FMN) residues, catalyzed by flavin transferase encoded by the nqr-associated apbE gene. Analysis of complete bacterial genomes has revealed another putative gene (duf539, here renamed nqrM) that usually follows the apbE gene and is present only in Na(+)-NQR-containing bacteria. Expression of the Vibrio harveyi nqr operon alone or with the associated apbE gene in Escherichia coli, which lacks its own Na(+)-NQR, resulted in an enzyme incapable of Na(+)-dependent NADH or reduced nicotinamide hypoxanthine dinucleotide (dNADH) oxidation. However, fully functional Na(+)-NQR was restored when these genes were coexpressed with the V. harveyi nqrM gene. Furthermore, nqrM lesions in Klebsiella pneumoniae and V. harveyi prevented production of functional Na(+)-NQR, which could be recovered by an nqrM-containing plasmid. The Na(+)-NQR complex isolated from the nqrM-deficient strain of V. harveyi lacks several subunits, indicating that nqrM is necessary for Na(+)-NQR assembly. The protein product of the nqrM gene, NqrM, contains a single putative transmembrane α-helix and four conserved Cys residues. Mutating one of these residues (Cys33 in V. harveyi NqrM) to Ser completely prevented Na(+)-NQR maturation, whereas mutating any other Cys residue only decreased the yield of the mature protein. These findings identify NqrM as the second specific maturation factor of Na(+)-NQR in proteobacteria, which is presumably involved in the delivery of Fe to form the (Cys)4[Fe] center between subunits NqrD and NqrE. Na(+)-translocating NADH:quinone oxidoreductase complex (Na(+)-NQR) is a unique primary Na(+) pump believed to enhance the vitality of many bacteria, including important pathogens such as Vibrio cholerae

  8. Leflunomide induces NAD(P)H quinone dehydrogenase 1 enzyme via the aryl hydrocarbon receptor in neonatal mice.

    PubMed

    Shrestha, Amrit Kumar; Patel, Ananddeep; Menon, Renuka T; Jiang, Weiwu; Wang, Lihua; Moorthy, Bhagavatula; Shivanna, Binoy

    2017-03-25

    Aryl hydrocarbon receptor (AhR) has been increasingly recognized to play a crucial role in normal physiological homeostasis. Additionally, disrupted AhR signaling leads to several pathological states in the lung and liver. AhR activation transcriptionally induces detoxifying enzymes such as cytochrome P450 (CYP) 1A and NAD(P)H quinone dehydrogenase 1 (NQO1). The toxicity profiles of the classical AhR ligands such as 3-methylcholanthrene and dioxins limit their use as a therapeutic agent in humans. Hence, there is a need to identify nontoxic AhR ligands to develop AhR as a clinically relevant druggable target. Recently, we demonstrated that leflunomide, a FDA approved drug, used to treat rheumatoid arthritis in humans, induces CYP1A enzymes in adult mice via the AhR. However, the mechanisms by which this drug induces NQO1 in vivo are unknown. Therefore, we tested the hypothesis that leflunomide will induce pulmonary and hepatic NQO1 enzyme in neonatal mice via AhR-dependent mechanism(s). Leflunomide elicited significant induction of pulmonary CYP1A1 and NQO1 expression in neonatal mice. Interestingly, the dose at which leflunomide increased NQO1 was significantly higher than that required to induce CYP1A1 enzyme. Likewise, it also enhanced hepatic CYP1A1, 1A2 and NQO1 expression in WT mice. In contrast, leflunomide failed to induce these enzymes in AhR-null mice. Our results indicate that leflunomide induces pulmonary and hepatic CYP1A and NQO1 enzymes via the AhR in neonatal mice. These findings have important implications to prevent and/or treat disorders such as bronchopulmonary dysplasia in human infants where AhR may play a crucial role in the disease pathogenesis.

  9. Inhibition of melanoma cell proliferation by resveratrol is correlated with upregulation of quinone reductase 2 and p53

    SciTech Connect

    Hsieh Tzechen; Wang Zhirong; Hamby, Carl V.; Wu, Joseph M. . E-mail: Joseph_Wu@nymc.edu

    2005-08-19

    Resveratrol (trans-3,4',5-trihydroxystilbene) is a grape-derived polyphenol under intensive study for its potential in cancer prevention. In the case of cultured human melanoma cells, no one to our knowledge has investigated whether resveratrol exerts similar anti-proliferative activities in cells with different metastatic potential. Therefore, we examined the effects of this polyphenol on the growth of weakly metastatic Line IV clone 3 and on autologous, highly metastatic Line IV clone 1 cultured melanoma cells. Comparable inhibition of growth and colony formation resulted from treatment by resveratrol in both cell lines. Flow cytometric analysis revealed that resveratrol-treated clone 1 cells had a dose-dependent increase in S phase and a concomitant reduction in the G{sub 1} phase. No detectable change in cell cycle phase distribution was found in similarly treated clone 3 cells. Western blots demonstrated a significant increase in the expression of the tumor suppressor gene p53, without a commensurate change in p21 and several other cell cycle regulatory proteins in both cell types. Chromatography of Line IV clone 3 and clone 1 cell extracts on resveratrol affinity columns revealed that the basal expression of dihydronicotinamide riboside quinone reductase 2 (NQO2) was higher in Line IV clone 1 than clone 3 cells. Levels of NQO2 but not its structural analog NQO1 were dose-dependently increased by resveratrol in both cell lines. We propose that induction of NQO2 may relate to the observed increased expression of p53 that, in turn, contributes to the observed suppression of cell growth in both melanoma cell lines.

  10. Photoinduced [4 + 4], [4 + 2], and [2 + 2] cycloadditions of o-quinones with oxazoles: chemo-, regio-, and diastereoselectivity.

    PubMed

    Wang, Lei; Huang, Yu-Cheng; Liu, Yang; Fun, Hoong-Kun; Zhang, Yan; Xu, Jian-Hua

    2010-11-19

    Photoinduced reactions of the 1,2-dicarbonyl compounds phenanthrenequinone (PQ), 1-acetylisatin (IS), and benzil (BZ) with the oxazoles 1a-j have been investigated. In photoreactions of PQ with the oxazoles, in addition to the 1,4-dioxins derived from [4 + 2] cycloaddition and the oxetanes from the Paternó-Büchi [2 + 2] reactions, [4 + 4] cycloaddition products are formed in the reactions with 1a, 1c, 1g, 1i, and 1j, with the quinone's dicarbonyl unit (O═C-C═O) and the oxazole's C═N-C═C moiety as two 4π addends. Photoreactions of IS with the oxazoles 1f and 1g give the [4 + 4] cycloaddition products exclusively, while in photoreactions of IS with 1a, 1c, 1e, 1h, and 1i, [4 + 4] products are formed together with the [2 + 2] products. Reaction pathway partitioning in these photocycloaddtions strongly depends on the substitution pattern on the oxazole ring. The presence of a substituent at the oxazole's C2 atom hampers the [4 + 4] pathway by causing steric hindrance to radical pair recombination in the corresponding 1,7-diradical intermediate to form the [4 + 4] cycloaddition products. A substituent at the C4 atom results in steric hindrance for ring closure of the 1,4-diradicals in the [2 + 2] cycloaddition pathway, therefore favoring the [4 + 4] and [4 + 2] cycloaddition pathways. Regio- and diastereoselectivity in the [2 + 2] and [4 + 4] cycloadditions have been discussed based on the thermodynamic stability of the relevant triplet diradical intermediates and the conformations of these diradicals suitable for the intersystem crossing process. Photoreactions of BZ with the oxazoles afford only [2 + 2] cycloaddition products.

  11. Selective photocytotoxicity of anthrols on cancer stem-like cells: The effect of quinone methides or reactive oxygen species.

    PubMed

    Uzelac, Lidija; Škalamera, Đani; Mlinarić-Majerski, Kata; Basarić, Nikola; Kralj, Marijeta

    2017-09-08

    Cancer stem cells (CSCs) are a subpopulation of cancer cells that share properties of embryonic stem cells like pluripotency and self-renewal and show increased resistance to chemo- and radiotherapy. Targeting CSC, rather than cancer cells in general, is a novel and promising strategy for cancer treatment. Novel therapeutic approaches, such as photodynamic therapy (PDT) have been investigated. A promising group of phototherapeutic agents are reactive intermediates - quinone methides (QMs). This study describes preparation of QM precursor, 2-hydroxy-3-hydroxymethylanthracene (2) and a detailed photochemical and photobiological investigation on similar anthracene derivatives 3 and 4. Upon photoexcitation with near visible light at λ > 400 nm 1 and 2 give QMs, that were detected by laser flash photolysis and their reactivity with nucleophiles has been demonstrated in the preparative irradiation experiments where the corresponding adducts were isolated and characterized. 3 and 4 cannot undergo photodehydration and deliver QM, but lead to the formation of phenoxyl radical and singlet oxygen, respectively. The activity of 1-4 was tested on a panel of human tumor cell lines, while special attention was devoted to demonstrate their potential selectivity towards the cells with CSC-like properties (HMLEshEcad). Upon the irradiation of cell lines treated with 1-4, an enhancement of antiproliferative activity was demonstrated, but the DNA was not the target molecule. Confocal microscopy revealed that these compounds entered the cell and, upon irradiation, reacted with cellular membranes. Our experiments demonstrated moderate selectivity of 2 and 4 towards CSC-like cells, while necrosis was shown to be a dominant cell death mechanism. Especially interesting was the selectivity of 4 that produced higher levels of ROS in CSC-like cells, which forms the basis for further research on cancer phototherapy, as well as for the elucidation of the underlying mechanism of the observed

  12. A molecular level mechanism for uranium (VI) toxicity through Ca(2+) displacement in pyrroloquinoline quinone-dependent bacterial dehydrogenase.

    PubMed

    Burbank, Katherine A; Walker, Robert A; Peyton, Brent M

    2015-08-01

    Dipicolinic acid (DPA), a small molecule analogue for the pyrroloquinoline quinone (PQQ) bacterial dehydrogenase cofactor, was used to model displacement of the complexing ion, Ca(2+), by a uranium (VI) dioxo-cation, UO2(2+). Complexation of UO2(2+) with DPA through the displacement of Ca(2+) was examined with UV/visible spectroscopy, ESI (electrospray ionization)-Mass spectrometry, and density functional theory based-modeling. The UO2(2+) displacement of other biologically important metal cations (Zn(2+), Cu(2+), Ni(2+), and Fe(3+)) from DPA was also examined. Results show that UO2(2+) has a distinctly higher binding affinity (logβ = 10.2 ± 0.1) for DPA compared to that of Ca(2+) (logβ = 4.6 ± 0.1), and provide molecular level insight into the mechanism of uranium toxicity associated with the {ONO} site. These results support those of VanEngelen et al. (2011) where a key interaction between PQQ and UO2(2+) produced significant uranium toxicity in bacteria. The observed toxicity mechanism was determined to be the displacement of a Ca(2+) cation bound to the {ONO} site on PQQ and was observed even at submicromolar UO2(2+) concentrations. Here we couple experimental findings with density functional theory (DFT) calculations to investigate the electronic and structural properties that make the {ONO} site so distinctively favorable for UO2(2+) binding. This novel approach using integrated experimental and fundamental atomic based models opens the path to identify a library of potential uranium interactions with critical biological molecules. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Prodrugs Bioactivated to Quinones Target NF-κB and Multiple Protein Networks: Identification of the Quinonome.

    PubMed

    Pierce, Emily N; Piyankarage, Sujeewa C; Dunlap, Tareisha; Litosh, Vladislav; Siklos, Marton I; Wang, Yue-Ting; Thatcher, Gregory R J

    2016-07-18

    Electrophilic reactive intermediates resulting from drug metabolism have been associated with toxicity and off-target effects and in some drug discovery programs trigger NO-GO decisions. Many botanicals and dietary supplements are replete with such reactive electrophiles, notably Michael acceptors, which have been demonstrated to elicit chemopreventive mechanisms; and Michael acceptors are gaining regulatory approval as contemporary cancer therapeutics. Identifying protein targets of these electrophiles is central to understanding potential therapeutic benefit and toxicity risk. NO-donating NSAID prodrugs (NO-NSAIDs) have been the focus of extensive clinical and preclinical studies in inflammation and cancer chemoprevention and therapy: a subset exemplified by pNO-ASA, induces chemopreventive mechanisms following bioactivation to an electrophilic quinone methide (QM) Michael acceptor. Having previously shown that these NO-independent, QM-donors activated Nrf2 via covalent modification of Keap-1, we demonstrate that components of canonical NF-κB signaling are also targets, leading to the inhibition of NF-κB signaling. Combining bio-orthogonal probes of QM-donor ASA prodrugs with mass spectrometric proteomics and pathway analysis, we proceeded to characterize the quinonome: the protein cellular targets of QM-modification by pNO-ASA and its ASA pro-drug congeners. Further comparison was made using a biorthogonal probe of the "bare-bones", Michael acceptor, and clinical anti-inflammatory agent, dimethyl fumarate, which we have shown to inhibit NF-κB signaling. Identified quinonome pathways include post-translational protein folding, cell-death regulation, protein transport, and glycolysis; and identified proteins included multiple heat shock elements, the latter functionally confirmed by demonstrating activation of heat shock response.

  14. Methyl Jasmonate and 1-Methylcyclopropene Treatment Effects on Quinone Reductase Inducing Activity and Post-Harvest Quality of Broccoli

    PubMed Central

    Ku, Kang Mo; Choi, Jeong Hee; Kim, Hyoung Seok; Kushad, Mosbah M.; Jeffery, Elizabeth H.; Juvik, John A.

    2013-01-01

    Effect of pre-harvest methyl jasmonate (MeJA) and post-harvest 1-methylcyclopropene (1-MCP) treatments on broccoli floret glucosinolate (GS) concentrations and quinone reductase (QR, an in vitro anti-cancer biomarker) inducing activity were evaluated two days prior to harvest, at harvest and at 10, 20, and 30 days of post-harvest storage at 4 °C. MeJA treatments four days prior to harvest of broccoli heads was observed to significantly increase floret ethylene biosynthesis resulting in chlorophyll catabolism during post-harvest storage and reduced product quality. Post-harvest treatment with 1-methylcyclopropene (1-MCP), which competitively binds to protein ethylene receptors, maintained post-harvest floret chlorophyll concentrations and product visual quality in both control and MeJA-treated broccoli. Transcript abundance of BoPPH, a gene which is responsible for the synthesis of pheophytinase, the primary enzyme associated with chlorophyll catabolism in broccoli, was reduced by 1-MCP treatment and showed a significant, negative correlation with floret chlorophyll concentrations. The GS, glucobrassicin, neoglucobrassicin, and gluconasturtiin were significantly increased by MeJA treatments. The products of some of the GS from endogenous myrosinase hydrolysis [sulforaphane (SF), neoascorbigen (NeoASG), N-methoxyindole-3-carbinol (NI3C), and phenethyl isothiocyanate (PEITC)] were also quantified and found to be significantly correlated with QR. Sulforaphane, the isothiocyanate hydrolysis product of the GS glucoraphanin, was found to be the most potent QR induction agent. Increased sulforaphane formation from the hydrolysis of glucoraphanin was associated with up-regulated gene expression of myrosinase (BoMyo) and the myrosinase enzyme co-factor gene, epithiospecifier modifier1 (BoESM1). This study demonstrates the combined treatment of MeJA and 1-MCP increased QR activity without post-harvest quality loss. PMID:24146962

  15. Phylogenomic Analysis and Predicted Physiological Role of the Proton-Translocating NADH:Quinone Oxidoreductase (Complex I) Across Bacteria

    PubMed Central

    Spero, Melanie A.; Aylward, Frank O.; Currie, Cameron R.

    2015-01-01

    ABSTRACT The proton-translocating NADH:quinone oxidoreductase (complex I) is a multisubunit integral membrane enzyme found in the respiratory chains of both bacteria and eukaryotic organelles. Although much research has focused on the enzyme’s central role in the mitochondrial respiratory chain, comparatively little is known about its role in the diverse energetic lifestyles of different bacteria. Here, we used a phylogenomic approach to better understand the distribution of complex I across bacteria, the evolution of this enzyme, and its potential roles in shaping the physiology of different bacterial groups. By surveying 970 representative bacterial genomes, we predict complex I to be present in ~50% of bacteria. While this includes bacteria with a wide range of energetic schemes, the presence of complex I is associated with specific lifestyles, including aerobic respiration and specific types of phototrophy (bacteria with only a type II reaction center). A phylogeny of bacterial complex I revealed five main clades of enzymes whose evolution is largely congruent with the evolution of the bacterial groups that encode complex I. A notable exception includes the gammaproteobacteria, whose members encode one of two distantly related complex I enzymes predicted to participate in different types of respiratory chains (aerobic versus anaerobic). Comparative genomic analyses suggest a broad role for complex I in reoxidizing NADH produced from various catabolic reactions, including the tricarboxylic acid (TCA) cycle and fatty acid beta-oxidation. Together, these findings suggest diverse roles for complex I across bacteria and highlight the importance of this enzyme in shaping diverse physiologies across the bacterial domain. PMID:25873378

  16. NAD(P)H: Quinone Oxidoreductase 1 Deficiency Conjoint with Marginal Vitamin C Deficiency Causes Cigarette Smoke Induced Myelodysplastic Syndromes

    PubMed Central

    Das, Archita; Dey, Neekkan; Ghosh, Arunava; Das, Tanusree; Chatterjee, Indu B.

    2011-01-01

    Background The etiology of myelodysplastic syndromes (MDS) is largely unknown. Exposure to cigarette smoke (CS) is reported to be associated with MDS risk. There is inconsistent evidence that deficiency of NAD(P)H-quinone: oxidoreductase 1 (NQO1) increases the risk of MDS. Earlier we had shown that CS induces toxicity only in marginal vitamin C-deficient guinea pigs but not in vitamin C-sufficient ones. We therefore considered that NQO1 deficiency along with marginal vitamin C deficiency might produce MDS in CS-exposed guinea pigs. Methodology and Principal Findings Here we show that CS exposure for 21 days produces MDS in guinea pigs having deficiency of NQO1 (fed 3 mg dicoumarol/day) conjoint with marginal vitamin C deficiency (fed 0.5 mg vitamin C/day). As evidenced by morphology, histology and cytogenetics, MDS produced in the guinea pigs falls in the category of refractory cytopenia with unilineage dysplasia (RCUD): refractory anemia; refractory thrombocytopenia that is associated with ring sideroblasts, micromegakaryocytes, myeloid hyperplasia and aneuploidy. MDS is accompanied by increased CD34(+) cells and oxidative stress as shown by the formation of protein carbonyls and 8-oxodeoxyguanosine. Apoptosis precedes MDS but disappears later with marked decrease in the p53 protein. MDS produced in the guinea pigs are irreversible. MDS and all the aforesaid pathophysiological events do not occur in vitamin C-sufficient guinea pigs. However, after the onset of MDS vitamin C becomes ineffective. Conclusions and Significance CS exposure causes MDS in guinea pigs having deficiency of NQO1 conjoint with marginal vitamin C deficiency. The syndromes are not produced in singular deficiency of NQO1 or marginal vitamin C deficiency. Our results suggest that human smokers having NQO1 deficiency combined with marginal vitamin C deficiency are likely to be at high risk for developing MDS and that intake of a moderately large dose of vitamin C would prevent MDS. PMID:21655231

  17. Inhibitory effects of different forms of tocopherols, tocopherol phosphates, and tocopherol quinones on growth of colon cancer cells.

    PubMed

    Dolfi, Sonia C; Yang, Zhihong; Lee, Mao-Jung; Guan, Fei; Hong, Jungil; Yang, Chung S

    2013-09-11

    Tocopherols are the major source of dietary vitamin E. In this study, the growth inhibitory effects of different forms of tocopherols (T), tocopheryl phosphates (TP), and tocopherol quinones (TQ) on human colon cancer HCT116 and HT29 cells were investigated. δ-T was more active than γ-T in inhibiting colon cancer cell growth, decreasing cancer cell colony formation, and inducing apoptosis; however, α-T was rather ineffective. Similarly, the rate of cellular uptake also followed the ranking order δ-T > γ-T ≫ α-T. TP and TQ generally had higher inhibitory activities than their parent compounds. Interestingly, the γ forms of TP and TQ were more active than the δ forms in inhibiting cancer cell growth, whereas the α forms were the least effective. The potencies of γ-TQ and δ-TQ (showing IC50 values of ∼0.8 and ∼2 μM on HCT116 cells after a 72 h incubation, respectively) were greater than 100-fold and greater than 20-fold higher, respectively, than those of their parent tocopherols. Induction of cancer cell apoptosis by δ-T, γ-TP, and γ-TQ was characterized by the cleavage of caspase 3 and PARP1 and DNA fragmentation. These studies demonstrated the higher growth inhibitory activity of δ-T than γ-T, the even higher activities of the γ forms of TP and TQ, and the ineffectiveness of the α forms of tocopherol and their metabolites against colon cancer cells.

  18. Anticancer activity of Nigella sativa (black seed) and its relationship with the thermal processing and quinone composition of the seed.

    PubMed

    Agbaria, Riad; Gabarin, Adi; Dahan, Arik; Ben-Shabat, Shimon

    2015-01-01

    The traditional preparation process of Nigella sativa (NS) oil starts with roasting of the seeds, an allegedly unnecessary step that was never skipped. The aims of this study were to investigate the role and boundaries of thermal processing of NS seeds in the preparation of therapeutic extracts and to elucidate the underlying mechanism. NS extracts obtained by various seed thermal processing methods were investigated in vitro for their antiproliferative activity in mouse colon carcinoma (MC38) cells and for their thymoquinone content. The effect of the different methods of thermal processing on the ability of the obtained NS oil to inhibit the nuclear factor kappa B (NF-κB) pathway was then investigated in Hodgkin's lymphoma (L428) cells. The different thermal processing protocols yielded three distinct patterns: heating the NS seeds to 50°C, 100°C, or 150°C produced oil with a strong ability to inhibit tumor cell growth; no heating or heating to 25°C had a mild antiproliferative effect; and heating to 200°C or 250°C had no effect. Similar patterns were obtained for the thymoquinone content of the corresponding oils, which showed an excellent correlation with the antiproliferative data. It is proposed that there is an oxidative transition mechanism between quinones after controlled thermal processing of the seeds. While NS oil from heated seeds delayed the expression of NF-κB transcription, non-heated seeds resulted in only 50% inhibition. The data indicate that controlled thermal processing of NS seeds (at 50°C-150°C) produces significantly higher anticancer activity associated with a higher thymoquinone oil content, and inhibits the NF-κB signaling pathway.

  19. Effects of dietary pyrroloquinoline quinone disodium on growth performance, carcass yield and antioxidant status of broiler chicks.

    PubMed

    Samuel, K G; Zhang, H J; Wang, J; Wu, S G; Yue, H Y; Sun, L L; Qi, G H

    2015-03-01

    Pyrroloquinoline quinone (PQQ), a putative essential nutrient and redox modulator in microorganisms, cell and animal models, has been recognized as a growth promoter in rodents. Growth performance, carcass yield and antioxidant status were evaluated on broiler chickens fed different levels of PQQ disodium (PQQ.Na2). A total of 784 day-old male Arbor Acres (AA) broilers were randomly allotted into seven dietary groups: ne